Title of Invention

1,3-DIAMINO-2-HYDROXYPROPANE PRODRUG DERIVATIVES

Abstract

The present invention relates to compounds of formula (I): useful in treating Alzheimer's disease and other similar diseases. Compounds of formula (I) include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of formula (I) are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

Full Text

l,3-DIAMINO-2-HYDROXYPROPANE PRODRUG DERIVATIVES CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority from U.S. Provisional Application Serial No. 60/408,783, filed September 6, 2002, which is incorporated herein by reference in its entirety. BACKGROUND OF THE INVENTION Field of the Invention The invention relates to l,3-diamino-2- hydroxypropane prodrug derivatives and to such compounds that are useful in the treatment of Alzheimer's disease and related diseases. More specifically, it relates to such compounds that are capable of yielding or generating, either in vitro or in vivo, compounds that inhibit beta-secretase, an enzyme that cleaves amyloid precursor protein to produce amyloid beta peptide (A beta), a major component of the amyloid plagues found in the brains of Alzheimer's sufferers. Background of the Invention Alzheimer's • disease (AD) is a progressive degenerative disease of the brain primarily associated with aging. Clinical presentation of AD i characterized by loss of memory, cognition, reasoning, judgment, and orientation. As the disease progresses, motor, sensory, and linguistic abilities are also affected until there is global impairment of multiple cognitive functions. These cognitive losses occur gradually, but typically lead to severe impairment and eventual death in the range of four to twelve years. Alzheimer's disease is characterized by two major pathologic observations in the brain: neurofibrillary tangles and beta amyloid (or neuritic) plaques, comprised predominantly of an aggregate of a peptide fragment know as A beta. Individuals with AD exhibit characteristic beta-amyloid deposits in the brain (beta amyloid plaques) and in cerebral blood vessels (beta amyloid angiopathy) as well as neurofibrillary tangles. Neurofibrillary tangles occur not only in Alzheimer's disease but also in other dementia-inducing disorders. On autopsy, large numbers of these lesions are generally found in areas of the human brain important for memory and cognition. Smaller numbers of these lesions in a more restricted anatomical distribution are found in the brains of most aged humans who do not have clinical AD. Amyloidogenic plaques and vascular amyloid angiopathy also characterize the brains of individuals with Trisomy 21 (Down's Syndrome), Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type (HCHWA-D) , and other neurodegenerative disorders. Beta-amyloid is a defining feature of AD, now believed to be a causative precurscr or factor in the development of disease. Deposition of A beta in areas of the brain responsible for cognitive activities is a major factor in the development of AC. Beta-amyloid plaques are predominantly composed of amyloid beta peptide (A beta, also sometimes designated betaA4). A beta peptide is derived by proteolysis of the amyloid precursor protein (APP) and is comprised of 39-42 amino acids. Several proteases called secretases are involved in the processing of APP. Cleavage of APP at the N-terminus of the A beta peptide by beta-secretase and at the C-terminus by one or more gamma-secretases constitutes the beta-amyloidogenic pathway, i.e. the pathway by which A beta is formed. Cleavage of APP by alpha-secretase produces alpha-sAPP, a secreted form of APP that does not result in beta-amyloid plaque formation. This alternate pathway precludes the formation of A beta peptide. A description of the proteolytic processing fragments of APP is found, for example, in U.S. Patent Nos. 5,441,870; 5,721,130; and 5,942,400. An aspartyl protease has been identified as the enzyme responsible for processing of APP at the beta- secretase cleavage site. The beta-secretase enzyme has been disclosed using varied nomenclature, including BACE, Asp, and Memapsin. See, for example, Sinha et al., 1999, Nature 402:537-554 (p501) and published PCT application WO00/17369. Several lines of evidence indicate that progressive cerebral deposition of beta-amyloid peptide (A beta) plays a seminal role in the pathogenesis of AD and can precede cognitive symptoms by years or decades. See, for example, Selkoe, 19.91, Neuron 6:487. Release of A beta from neuronal cells grown in culture and the presence of A beta in cerebrospinal fluid (CSF) of both normal individuals and AD patients has been demonstrated. See, for example, Seubert et al., 1992, Nature 359:325-327. It has been proposed that A beta peptide accumulates as a result of APP processing by beta-secretase, thus inhibition of this enzyme's activity is desirable for the treatment of AD. In vivo processing of APP at the beta- secretase cleavage site is thought to be a rate-limiting step in A beta production, and is thus a therapeutic target for the treatment of AD. See for example, Sabbagh, M., et al., 1997, Alz. Dis. Rev. 3, 1-19. BACEl knockout mice fail to produce A beta, and present a normal phenotype. When crossed with transgenic mice that over express APP, the progeny show reduced amounts of A beta in brain extracts as compared with control animals (Luo et al., 2001 Nature Neuroscience 4:231-232). This evidence further supports the proposal that inhibition of beta-secretase activity and reduction of A beta in the brain provides a therapeutic method for the treatment of AD and other beta amyloid disorders. At present there are no effective treatments for halting, preventing, or reversing the progression cf Alzheimer's disease. Therefore, there is an urgent need for pharmaceutical agents capable of slowing the progression of Alzheimer's disease and/or preventing it in the first place. Compounds that are effective inhibitors of beta- secretase, that inhibit beta-secretase-mediated cleavage of APP, that are effective inhibitors of A beta production, and/or are effective to reduce amyloid beta deposits or plaques, are needed for the treatment and prevention of disease characterized by amyloid beta deposits or plaques, such as AD. SUMMARY OF THE INVENTION The invention encompasses the compounds of formula (AA) , (I) and (X) shown below, pharmaceutical compositions containing the compounds and methods employing such compounds or compositions in the treatment of Alzheimer's disease and more specifically compounds that are capable of inhibiting beta-secretase, an enzyme that cleaves amyloid precursor protein to produce A-beta peptide, a major component of the amyloid plaques found in the brains of Alzheimer's sufferers. In one aspect, the invention provides compounds of the formula AA: R4-6 is-H or C1-C6 alkyl; R5 is selected from the group consisting of C3-C7 cycloalkyl; C1-C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, -NR6R7, C1-C4 alkoxy, C5-C6 heterocycloalkyl, C5-C6 heteroaryl, C6-C10 aryl, C3-C7 cycloalkyl C1-C4 alkyl, -S-C1-C4 alkyl, -SO2-C1-C4 alkyl, -CO2H, -CONR6R7, -C02-C1-C4 alkyl, C6-C10 aryloxy; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, C1-C4 haloalkyl, or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, or C2-C4 alkanoyl; aryl optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 haloalkyl; and -NR6R7; wherein R6 and R7 are independently selected from the group consisting of H, C1-C4 alkyl, C1-C4 alkanoyl, phenyl, -SO2-C1-C4 alkyl, phenyl C1-C4 alkyl; R8 is selected from the group consisting of -SO2- heteroaryl, -SO2-aryl, -SO2-heterocycloalkyl, -SO2-C1-C4 alkyl, -C(O)NHR9, heterocycloalkyl, -S-C1-C6 alkyl, -S-C2-C4 alkanoyl, wherein R9 is aryl C1-C6 alkyl, C1-C6 alkyl, or H; R51 is H or C1-C6 alkyl; R51 is selected from the group consisting of aryl C1_- C4 alkyl; C1-C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, heteroaryl, -NR6R7, -C(O)NRSR7, C3-C7 cycloalkyl, or C1-C6 alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, C2-C4 alkanoyl, aryl C1-C4 alkyl, and -SO2 C1-C4 alkyl; alkenyl; alkynyl; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently OH, C1-C4 alkyl, C1-C4 alkoxy, halogen, NH2, NH (C1-C4 alkyl) or N(C1-C6 alkyl) (C1-C4 alkyl); heteroarylalkyl optionally substituted with l, 2, or 3 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, NH2, NH(C1-C6 alkyl) or N(C1-C6 alkyl) (C1-C6 alkyl); aryl; heterocycloalkyl; C1-C6 cycloalkyl; and cycloalkylalkyl; wherein the aryl; heterocycloalkyl, C3-C8 cycloalkyl, and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5 groups that are independently halogen, CN, N02, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkanoyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxy, C1-C6 hydroxyalkyl, C1-C6 alkoxy C1-C6 alkyl, C1-C6 thioalkoxy, C1-C6 thioalkoxy C1-C6 alkyl, or C1-C6 alkoxy C1-C6 alkoxy; R52 is heterocycloalkyl, heteroaryl, aryl, cycloalkyl., -S(0) 0-2-C1-C6 alkyl, CO2H, -C(O)NH2, -C(O)NH(alkyl), -C(O)N(alkyl)(alkyl), -C02- alkyl, -NHS(0)o-2-C1-C6 alkyl, -N(alkyl)S (0)0-2- C1-C6 alkyl, -S (O) 0_2-heteroaryl, -S (0) 0-2-aryl, -NH(arylalkyl), -N(alkyl) (arylalkyl) , thioalkoxy, or alkoxy, each of which is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkyl, alkoxy, thioalkoxy, halogen, haloalkyl, haloalkoxy, alkanoyl, NO2, CN, alkoxycarbonyl, or aminocarbonyl; R53 is absent, -O-, -C(O)-, -NH-, -M(alkyl)-, -NH- S(O)O-2-r -N(alkyl)-S(O)0-2-/ -S (O) 0-2-NH-, -S (O) o,- 2- N(alkyl)-, -NH-C(S)-, or -N(alkyl)-C(S)-; RS4 is heteroaryl, aryl, arylalkyl, heterocycloalkyl, CO2H, -CO2-alkyl, -C(O)NH(alkyl), -C(O)N(alky.l) (alkyl), -C(O)NH2, C1-C6, alkyl, OH, aryloxy, alkoxy, arylalkoxy, NH2, NH(alkyl), N (alkyl) (alkyl) , or -C1-Cs alkyl-CO2-C1-C6 alkyl, each of which is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkyl, alkoxy, CO2H, -CO2-alkyl, thioalkoxy, halogen, haloalkyl, haloalkoxy, hydroxyalkyl, alkanoyl, N02, CN, alkoxycarbonyl, or aminocarbonyl; X is selected from the group consisting of -C1-C6 alkylidenyl optionally optionally substituted with 1, 2, or 3 methyl groups; and -NR4_6-,- or R4 and R4_6 combine to form -(CH2)n10-, wherein n10 is 1, 2, 3, or 4; Z is selected from the group consisting of a bond; S02; SO; S; and C(0); Y is selected from the group consisting of H; C1-C6 haloalkyl; C1-C6 heterocycloalkyl; C1-C6 aryl; OH; -N(Y1) (Y2) ; C1-C6 alkyl optionally substituted with 1 thru 3 substituents which can be the same or different and are selected from the group consisting of halogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy; C3-C8 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from C1-C6 alkyl, and halogen; alkoxy; aryl optionally substituted with halogen, alkyl, alkoxy, CN or N02; arylalkyl optionally substituted with halogen., alkyl, alkoxy, CN or NO2; wherein Y2 and Y2 are the same or different and are H; C1-C10 alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, C1-C6 alkoxy, C3-C8 cycloalkyl, and OH; C2-Cs alkenyl; C2-C6 alkanoyl; phenyl; -SO2- C3-C4 alkyl; phenyl C3.-C4 alkyl; or C3-CB cycloalkyl C1-C4 alkyl; or Y1 Y2 and the nitrogen to which they are attached form a ring selected from the group consisting of piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxy C1-C6 alkyl, or halogen; R1 is -(CH2)1-2-S(O)0-2-(C1-C6 alkyl), or C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OK, =0, -SH, -C=N, -CF3, -C1-C3 alkoxy, amino, mono- or dialkylamino, -N(R)C(O)R'-, -OC(=O)-amino and -OC(=O)-mono- or dialkylamino, or C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, C1-C3 alkoxy, amino, and mono- or dialkylamino, or aryl, heteroaryl, heterocyclyl, -C1-C6 alkyl-aryl, -C1-C6 alkyl-heteroaryl, or -C1-C6 alkyl- heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, -OH, -SH, -C=N, -NR105R'105, -CO2R, -N(R)COR', or -N(R)SO2R', -C(=O)-(c1-C4) alkyl, -SO2-amino, -SO2-mono or dialkylamino, -C(=O)-amino, -C(=O)- mono or dialkylamino, -SO2- (c1-C4) alkyl, or -c1-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently a halogen, or C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, C1-C3 alkoxy, amino, -C1-C6 alkyl and mono- or dialkylamino, or c1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CP3, -C1-C3 alkoxy, amino, mono- or dialkylamino and -C1-C3 alkyl, or C2-C10 alkenyl or C2-G10 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, C1-C3 alkoxy, amino, Ci-Cs alkyl and mono- cr dialkylamino; and the heterocyclyl group is optionally further substituted with oxo; R and R' independently are hydrogen or C1-C10 alkyl; R2 is selected from the group consisting of H; C1-Cs alkyl, optionally substituted with 1, 2, or 3 substituents that are independently selected from the group consisting of C1-C3 alkyl, halogen, -OH, -SH, -C=N, -CF3, C1-C3 alkoxy, and -NR1 aR1-b; wherein R1-a and R1_b are -H or C1-C6 alkyl ; - (CH2)o-4-aryl; - (CH2) 0..4-heteroaryl; C2-C6 alkenyl; C2- Cs alkynyl; -CONRH_2Rn-3; -SO2NRn_2RN-3; -CO2H; and -CO2- (C1-C4 alkyl) ; R3 is selected from the group consisting of H; C1-C6 alkyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of C1-C3 alkyl, halogen, -OH, -SH, -C=V!, -CF3, Ci-C3 alkoxy, and -NRi_aRi-b; - (CH2)0-4-aryl; - (CH2) 0.4-heteroaryl; C2-C6 alkenyl; C2-C6 alkynyl; -CO- NRN-2Rn-3; -SO2-NRN-2Rn.3; -CO2H; and - CO-O-(C1-C4 alkyl); or R2, R3 and the carbon to which they are attached form a carbocycle of three thru seven carbon atoms, wherein one carbon atom is optionally replaced by a group selected from-O-, -S-, -SO2-, or -NRN-2-; Rc is selected from the grcup consisting of Ci-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, -OC=ONR235R240, -S (=0) 0-2 (Ci-C6 alkyl) , -SH, -NR235C=ONR23SR24o, -C=ONR235R24o, and -S (=O) 2MR235R24o; - (CH2) 0-3- (C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R2o5 0-4-aryl ; - (CR24SR25o) 0-4-heteroaryl; - (CR245R2So) 0-4- heterocycloalkyl; - (CR245R25o)o-4-aryl-heteroaryl; - (CR245R25o) o-4-aryl-heterocycloalkyl; - (CR245R2So) 0-4- aryl-aryl; - (CR24sR25o) c-4-heteroaryl-aryl; - (CR245R25o) 0- 4-heteroaryl-heterocycloalkyl; - (CR245R250)0-4- heteroaryl-heteroaryl; - (CR245R250) 0-4- heterocycloalkyl-heteroaryl; - {CR24sR25o) 0-4- heterocycloalkyl-heterocycloalkyl; - (CR245R25O)o-4- 11 heterocycloalkyl-aryl; - [C (R2S5) (Rzso) 11-3-CO-N- (R2ss) 2; -CH(aryl)2; -CH(heteroaryl)2; -CH{heterocycloalkyl)2; -CH(aryl)(heteroaryl); cyclopentyl, cyclohexyl, or cycloheptyl ring fused to aryl, heteroaryl, or heterocycloalkyl wherein one carbon of the cyclopentyl, cyclohexyl, or cycloheptyl is optionally replaced with NH, NR215, O, or S(=O)0-2, and wherein the cyclopentyl, cyclohexyl, or cycloheptyl group can be optionally substituted with 1 or 2 groups that are independently R205 or =O; -CO- NR235R24o; -SO2- (C1-C4 alkyl) ,- C2-C10 alkenyl optionally substituted with 1, 2, or 3 R2os groups; C2-C10 alkynyl optionally substituted with 1, 2, or 3 R205 groups; -(CH2)o.i-CH((CH2)o-6-OH)-(CH2)o-1-aryl; -(CH2)0- 3,-CHRc-s-(CH2) 0-1-heteroaryl; -CH(-ary.l or -heteroaryl) -CO-O(d-C4 alkyl) ; -CH(-CH2-OH) -CH(OH) - phenyl-NO2; (Ci-Cs alkyl) -O- (Cx-Cs alkyl) -OH; -CH2-NH- CH2-CH(-O-CH2-CH3)2; -H; and -(CH2)0.s- C(=NR235) (NR235R24o) ; wherein each aryl is optionally substituted with 1, 2, or 3 R200 ; each heteroaryl is optionally substituted with 1, 2, 3, or 4 R200; each heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R2io; R200 at each occurrence is independently selected from the group consisting of Ci-C6 alkyl optionally substituted with 1, 2, or 3 R205 groups; OH; -NO2; halogen; -CO2H; CsN; -(CH2)0-4- C0-NR220R225; - (CH2) 0-4-CO- (Ci-C12 alkyl) ,- - (CH2) 0-t~ CO- (C2-CX2 alkenyl) ,- - (CH2)0-4-CO- (C2-C12 alkynyl) ; - (CH2)0-4-CO-(C3-C7 cycloalkyl) ; - (CH2) 0.4-CO-aryl ; - (CH2)0-4-CO-heteroaryl; - (CH2)o-4-CO- 12 heterocycloalkyl;- (CH2) 0-4-CO2R2a5; - (CH2) 0-4-SO;.- NR220R225; -(CH2)0-4-SO-(Ci-C8 alkyl); - (CH2) 0-4-SO2- {Cx-C^ alkyl); - (CH2) 0-4-SO2- (C3-C7 cycloalkyl) ; - (CH2)0-4-M(H or R215) -CO2R2i5; - (CH2) 0-4~N(H or R2i5)-CO-N(R215)2; -(CH2)0-4-N-CS-N (1*215)2; - (CH2) 0.4:- N(-H or R2i5)-CO-R220; - (CH2) 0-4-NR220R225,- - (CH2) 0- O-CO-(C1-C6 alkyl); -(CH2)0-4-O-P(O)-(OR240) -(CH2)0_4-O-CO-N(R215)2 -(CH2)0-4-O-CS-N(R215)2; - (CH2)o-4-O"(R215)2; -(CH2) 0-4-O- (R215)2-COOH; - (CH2) 0- 4-S-(R215)2; - (CH2) 0-4-O- (C1-Cs alkyl optionally substituted with 1, 2, 3, or 5 -F) ; C3-C7 cycloalkyl; C2-C6 alkenyl optionally substituted with 1 or 2 R20S groups; C2-C6 alkynyl optionally substituted with 1 or 2 R205 groups; - (CH2) 0-4-N(H or R21S) -SO2-R220; and -(CH2)0-4- C3-C7 cycloalkyl; wherein each aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205, R210 or C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210; wherein each heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R210 ; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205, R210; or C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 OR R210; R205 at each occurrence is independently selected from the group consisting of C1-C6 alkyl, halogen, -OH, -O-phenyl, -SH, -C=N, -CF3; C1-C6 alkoxy, NH2, NH(C1-C6 alkyl) , and N-(C1-C6 alkyl) (C1-C6 alkyl) ; R210 at each occurrence is independently selected from the group consisting of C1-C6 alkyl optionally substituted with 1, 2, or 3 R205 groups; C2-C6 alkenyl optionally substituted with 1, 2, or 3 R205 groups; C2-Cs alkynyl optionally substituted with 1, 2, or 3 R205 groups; halogen; C1-C6 alkoxy;C1-C6 haloalkoxy; -NR220R225; OH; O=N; C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R205 groups; -CO-(C- C4 alkyl); .S02-NR235R240; -CO-NR23SR240; -SO2- (C1-C6 alkyl); and =O; wherein R215 at each occurrence is independently selected from the group consisting of Ci-Cs alkyl, (CH2) o-2- (aryl) , C2-Cs alkenyl, C2-Cs alkynyl, C3_ C7 cycloalkyl, and - (CH2) 0-2- (heteroaryl) , - (CH2)0-2- (heterocycloalkyl) ; wherein the aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R2t,5 or R210; wherein the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R210; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R210; R22o and R225 at each occurrence are independently selected from the group consisting of -H, -C1-C6 alkyl, hydroxy C1-C6 alkyl, amino C1-C6 alkyl; halo Ci-Cs alkyl; -C3-C7 cycloalkyl, - (C1-C6 alkyl)-(C3-C7 cycloalkyl), - (C1-C6 alkyl)-O- (C1- C3 alkyl), -C2-C6 alkenyl, -C2-C6 alkynyl, -C1-C6 alkyl chain with one double bond and one triple bond, -aryl, -heteroaryl, and heterocycloalkyl; wherein the aryl group at each occurrence is optionally substituted with 1, 2, or 3 R27o groups, wherein R27o at each occurrence is independently R20s, Ci~Ce alkyl optionally substituted with 1, 2, or 3 R205 groups,- C2-C6 alkenyl optionally substituted with l, 2, or 3 R205 groups;' C2-C6 alkynyl optionally substituted with 1, 2, or 3 R2D5 groups; halogen; Ci-Cs alkoxy; Ci-Cs haloalkoxy; NR235R240; OH; C=N; C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R205 groups; -CO- (Ci- C4 alkyl); .SO2_NR23SR240; -CO-NR23SR24o; -SO2-(Cx-C4 alkyl); and =0; wherein the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R205 groups; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R205 groups; R235 and R240 at each occurrence are independently H, or Ci-C6 alkyl; R24s and R2B0 at each occurrence are independently selected from the group consisting of H, C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, - (CH2) 0-4-C3-C7 cycloalkyl, C2-Cs alkenyl, C2-Cs alkynyl, aryl C1-C4 alky!., heteroaryl C1-C4 alkyl, and phenyl; or R24S and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of -O-, -S-, -SO2-, and -NR220-; RaS5 and R26t, at each occurrence are independently selected from the group consisting of H; Ci-Cs alkyl optionaXly substituted with 1, 2, or 3 R2Q5 groups; Ci-Cs alkenyl optionally substituted with l, 2, or 3 R205 groups; C2-Cs alkynyl optionally stibstituted with 1, 2, or 3 R205 groups; - (CH2) i_2-S (O) 0.2- (Ci-C6 alkyl) ; - (CHa) 0-4- C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R20S groups; - (Cx-CU alkyl) -aryl; -\C1-C4 alkyl) -heteroaryl; - (Cj-C^ alkyl)- heterocycloalkyl ,¦ -aryl; -heteroaryl; -heterocycloalkyl; . (CH2)i.4-R2S5- (CH2) 0-4-aryl; - (CH2) i-4-Rss5- (CH2) o-4-heteroaryl; and; - (CH2) i-«- R2S5- (CH2) e-4-iieterocycloalkyl; wherein R265 at eacli occurrence is independently -O-. -S- or -N(Ci-Cs alXyl)-; each aryl or phenyl is optionally substituted with 1, 2, or 3 groups that are independently R20s, R210, or d-Cs alkyl substituted with 2, 2, or 3 groups that are independently R3CS or R310; each heteroaryl is optionally substituted with 1, 2, 3, or 4 R200/ each heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R2io; Rioo and R'ioo independently represent aryl, heteroaryl, heterocyclyl, -aryl-W-aryl, -aryl-W-heteroaryl, ~aryl-W-heterocyclyl, -heteroaryl-W-aryl, heteroaryl-W-heteroaryl, -heteroaryl-w- heterocyclyl, -heterocyclyl-W-aryl, -heterocyclyl-W- heteroaryl, -heterocyclyl-W-heterocyclyl, -Cni(CH2)Q, a-O-Riso} - (CHa) 0-2-aryl, -CHI (CH2) o-2-O-RX50] - (CH2) 0.2- heterocyclyl or ~CHl (CH2) o.2-O~Rl5al - (CH2)0-2- heteroaryl, where the ring portions of each are optionally substituted with 1, 2, or 3 groupis independently selected from -OR, -NO2, Cx-C6 alkyl, halogen, -CsN, -OCF3, -CP3, - (CH2)0-4-O-P(=O) (OR) (OR') , -(CH2)o-4-CO-NRXosR'i05, - (CH2) o-4-0- (CH2) o-4-CONR102R102', - (CH2) 0.4-Cb- (Ci-Ci2 alkyl) , - (CH2) 0-4-CO- (C2-Ci2 alkenyl) , - (CH2) 0_4- CO-(C2-C12 alkynyl)/ - (CH2)0.4-CO- (CH2) 0.4 (C3-C7 cycloalkyl) , - (CH2) 0-4-R110- - (CH2) 0-4-R120; - (CH2)O-4-Ri3o/ - (CH2)o-4-CO-Riio, - (CH2) 0-4-CO-Ri20, -(CH2)0-4-CO-R13o, -(CH2)0.4-CO-Rl40, - (CH2) 0.4-C0-0- Riso, ~ (CH2) o-4-S02-NRlosR'io5, - (CH2) 0-4-SO-(Ci-CB alkyl), -(CH2)o-4-S02. (d-Ci2 alkyl), - (CH2) 0-4-SO2- (CH2) 0-4-(C3-C7-cycloalkyl) , - (CH2) 0-4-N(R1S0j -C0-0- Riso, -(CH2)o-4-N(R15o)-CO-N(R15o)2, - (CH2) 0-4- N(Ri5O)-CS-N(Ri5o)2, -(CH2)0-4-N(R1So)-CO-Rio5, -(CH2)o-4-NRio5R'io5/ -(CH2)o-4-Ri4Q, -(CH2)0.4-O-CO- (Ci-C6 alkyl), - :CH2)0-4-O-P(O)-(O-R1io)2, -(CH2)0- 4-O-CO-N(R1S0)2, -(CH2)o-4-O-CS-N(R150)2, -(CH2)0-4- O-(Riso), -(CH2)0-4-O-R15o'-COOH, - (CH2) 0.4-S- (R1S0) , -(CH2)o-4-N(Ri5o)-SO2-RXOs, -(CH2)0,4- C3-C7 cycloalkyl, (C2-Ci0) alkenyl, and (C2- C10) alkynyl, or R100 is Ci-Cxo. alkyl optionally substituted with 1, 2, or 3 R115 groups, or Rloo is -(Cx-Cg alkyl)-O-Cr-Cs alkyl) or - (Ci-C6 alkyl) -S- (Ci-C6 alkyl) , each of which is optionally substituted with 1, 2, or 3 Rn5 groups, or R100 is C3-C8 cycloalkyl optionally substituted with 1, 2, or 3 Rus groups; W is -(CH2)0-4-/ -0-, -S (O0-2-, -N(R135)-, -CR(OH)- or - C(O)- ; R-102 and R102' independently are hydrogen, or 17 Ci-Cio alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, aryl or Rio5 and R'ios independently represent -H, -Ruo, -Ri2ew C3-C7 cycloalkyl, - (Ci-C2 alkyl) - (C3-C7 cycloalkyl) , - (d-C6 alkyl)-O-(C1-C3 alkyl), C2-Cs alkenyl, C2-Ce alkynyl., or Cx-Cs alkyl chain with one double bond and one triple bond, or Ci-C6 alkyl optionally substituted with -OH or -NH2; or, C1-C6 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, or R105 and R'105 together with the atom to which they are attached form a 3 to 7 membered carbocylic ring, where one member is optionally a heteratom selected from -0-, -S{O)0.2-, -N(R135)-, the ring being optionally substituted with 1, 2 or 3 independently selected R14Q groups; Rii5 at each occurrence is independently halogen, -OH, -CO2R102, -Ci-C6 thioalkoxy, -CO2-phenyl, -NR105R'135, -SO2-{Ci-CB alkyl), -C(=0)Riao, Rise, - CONR105R' 10s, -SO2NR105R'105, -NH-CO-(Cx-Cg alkyl), -NH-C(=O) -OH, - NH-C(=O)-OR, -NH-C(=O)-O-phenyl, -O-C(=O)-(C^-Cc alkyl), -O-C(=O)-amino, -O-C(=O)-mono- or dialkylamino, -O-C(=O)-phenyl, -O-(Ci-C6 alkyl)-CO2H, -NH-SO2-(Ci-C6 alkyl), Ci.-C6 alkoxy or Cj.-C6 haloalkoxy; R135 is Ci-Cs alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3.C7 cycloalkyl, - (CH2) O-2- (aryl) , - (CH2) 0.2- (heteroaryl) , or - (CH2) 0-2- (heterocyclyl) ; R140 is heterocyclyl optionally substituted with 1, 2, 3, or 4 groups independently selected from CfCs alkyl, Ci-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, 18 mono(Ci-C6)alkylamino, di (Cx-Cs) alkylamino, C2-G6 alkenyl, C2-C6 alkynyl, Ci-C6 haloalkyl, Ci-Cs haloalkoxy, amino (Cx-Cg) alkyl, mono (C:L- Cs) alkylamino (Cj_-Ce) alkyl, di (Ci-Cs) alkylamino (C-_- C6)alkyl, and =O; Ri4S is Cx-C6 alkyl or CF3; Ri5o is hydrogen, C3-C7 cycloalkyl, - (C].-C2 alkyl) - (C3-C7 cycloalkyl), C3-Cs alkenyl, C2-C6 alkynyl, C!-C6 alkyl with one double bond and one triple bond, -Rno, - R120, or Ci-C6 alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from -OH, -NH2, Ci-C3 alkoxy, RiU, and halogen; R1S0' is C3-C7 cycloalkyl, - (C1-C3 alkyl) - (C3-C7 cycloalkyl), C2-C6 alkenyl, C2-Cs alkynyl, Cj.-Cs alkyl with one double bond and one triple bond, -E110, Ruo# or Ci-Cs alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from -OH, -NH2, C1-C3 alkoxy, R110, and halogen,- R1S5 is C3-C7 cycloalkyl, - (-i-C2 alkyl) - (C3-C7 cycloalkyl), C2-C6 alkenyl, C2-C5 alkynyl, C].-C6 alkyl with one double bond and one triple bond, -Rno, -R120, or Ci-C6 alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from -OH, -NH2, C1-C3 alkoxy, and halogen; Ribo is selected from morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl £5, S- dioxide, pyrrol inyl and pyrrolidinyl, each of which is optionally substituted with 1, 2, 3, or 4 groups independently selected from C^-Ce alkyl, C^-Cs alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(Ci-C6) alkylaminc, di (Ci-Cs)alkylamino, C2-C6 alkenyl, C2-Cs alkynyl, Ci- Ce haloalkyl, C^-Cg haloalkoxy, amino (Cx-Cg) alkyl, mono (Cx-Cg) alkylamino (Ci-C6) alkyl, di (Cx- Cg) alkylaraino (Ci-Cs) alkyl, and =O ; Euo is aryl optionally substituted with 1 or 2 Ra;!5 groups ,- R12S at each occurrence is independently halogen, amino, mono- or dialkylamino, -OH, -ON, -SO2-NH2, -SO2-NH- d-Cg alkyl, -SO2-N(C!-C6 alkyl) 2, -SO2- (C3.-C4 alkyl), -CO-NH2, -CO-NH-^-Cg alkyl, or -CO-N(Ca-Cs alkyl) 2, or Cx-Cg alkyl, C2-Cs alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups that are independently selected from Ci- C3 alkyl, halogen, -OH, -SH, -C=N, -CF3, C1-C3 alkoxy, arnino, and mono- and dialkylamino, or Ci-Cs alkoxy optionally substituted with one, two or three of halogen; Ri20 is heteroaryl, which is optionally substituted with 1 or 2 R12S groups; and Ri30 is heterocyclyl optionally substituted with 1 or 2 R125 groups. The invention also provides compounds of the formula I: Rn is -C (CRR' ) .i-s-S-R' ioo, -C (=O) - (CRR') i-S-C (=O) -Rla0, -C (=O) - (CRR') i-6-SO2-RXOo, ~C (=O) - (CRR' ) i-s-NRioo-R' aoo, or Rn is .Z ^(CH2)n7—CHC(O>- Y X I R4 wherein R4 is selected from the group consisting of H; NH2; --NH- (CH2)n6-R4-i; -NHR8; -NR5oC(O)Rs; d-C4 alkyl-NHC (O) R5; -(CH2)0-4R8; -O-C1-C4 alkanoyl; OH; Cs-C10 aryloxy optionally substituted with 1, 2, or 3 groups that are independently halogen., C1-C4 alkyl, -CO2H, -C(O)- Cx-Ct alkoxy, or CX-C4 alkoxy; Ci-C6 alkoxy; aryl Cx-C4 alkoxy; -NR5BCO2RSi; -C3-C4 alkyl-NR50CO2R51; -CsN; -CP3; -CF2-CF3; -CsCH; -CH2-CH=CH2; - (CH2) 1-4-R4-1;- (CH2) ^4- NH-R4-1; -O-(CH2)nS-R4-i; -S-(CH2)n6-R4-i; -(CH2)0.4- NHC (O) - (CH2) 0-6-Rs2; - (CH2) 0-4-R53- (CH2) 0-4-R54 ; wherein n6 is 0, 1, 2, or 3,¦ n7 is 0, 1, 2, or 3; R4-1 is selected from the group consisting of -S02- (d-Cg alkyl) , -SO- (Ci-CB alkyl) , -S- (d-C8 alkyl), -S-CO-(d-C6 alkyl), -SO2-NR,-2R4-3; -C0- Ci-C2 alkyl; -CO-NR4-3R4-4; R4.2 and R4-3 are independently H, d-C3 alkyl, or C3-Cs cycloalkyl; R4_4 is alkyl, arylalkyl, alkanoyl, or arylalkanoyl; R4.6 is-H or Ci-C« alkyl ; R5 is selected from the group consisting of C3-C7 cycloalkyl; d-C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, -NR6R7, Ci-C4 alkoxy, CE-C5 heterocycloalkyl, C5-C6 heteroaryl, C5-C10 aryl, C3-C7 cycloalkyl d-C* alkyl, -S-C1-C4 alkyl, -SO2-C1-C4 alkyl, -CO2H, -CONR6R7, -CO2-C1-C4 alkyl, Cs-Cio aryloxy; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, Ci-C4 alkoxy, halogen, CJ.-C4 haloalkyl, or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groups that are independently Cx-C4 alkyl, C1-C4 alkoxy, halogen, or C2-C4 alkanoyl; aryl optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, or C1.-C4 haloalkyl; and -NR6R7; wherein Rs and R7 are independently selected from the group consisting of H, Ci-Cs alkyl, C2-C6 alkanoyl, phenyl, -SO2-Ci-C4 alkyl, phenyl C1-C4 alkyl; RB is selected from the group consisting of -SO:,- heteroaryl, -SO2-aryl, -SO2-heterocycloalkyl, -SO2-C1-Ci0 alkyl, -C(O)NHR9/ heterocycloalkyl, -S-Ci-Cs alkyl, -S-C2-C4 alkanoyl, wherein R9 is aryl Q1-C4 alkyl, Ct-C6 alkyl, or H; R50 is H or Ci-Cg alkyl; RS1 is selected from the group consisting of aryl C:.- C4 alkyl,- Ci-C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, heteroaryl, -NR6R7, -C(O)NR6R7, C3-Cn cycloalkyl, or -Ci-Ct alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, C2-C4 alkanoyl, aryl C!-C4 alkyl, and -SO2 C1-C4 alkyl; alkenyl; alkynyl; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently OH, C1-C4 alkyl, Ql-CU alkoxy, halogen, NH2, NH(Ci-Cs alkyl) or N(Ci-C6 alkyl) (Ci-C6 alkyl); heteroarylalkyl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C!-C4 alkoxy, halogen, NH2, NH (Ci-Cs alkyl) or N(Ci-Cs alkyl) (Ci-C6 alkyl); aryl; heterocycloalkyl; C3- CB cycloalkyl; and cycloalkylalkyl; wherein the aryl; heterocycHoalkyl, C3-C8 cycloalkyl, and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5 groups thsit are independently halogen, CN, NO2, C!-C6 alkyl, C1-C6 alkoxy, C2-C6 alkanoyl, Ci-C6 haloalkyl, C:L- Cs haloalkoxy, hydroxy, Ci-Cs hydroxyalkyl, Cl-C6 alkoxy Ci-Cs alkyl, Ci-C6 thioalkoxy, Ci-C6 thioalkoxy Ci-C6 alkyl, or Ci-C6 alkoxy Ci-Cs alkoxy; R52 is heterocycloalkyl, heceroaryl, aryl, cycloalkyl, -S (O) 0-2-Ci-C6 alkyl, CO2H, -C(O)NH2, -C(O)NH(alkyl) , -C(O)N(alkyl) (alkyl), -CO2- alkyl, -NHS(O)0.-2-Ci-Cs alkyl, -N (alkyl) S (O) 0-2- Ci-C6 alkyl, -S (O) 0-2-heteroaryl, -S (O) 0-2-aryl, -NH(arylalkyl), -N(alkyl)(arylalkyl), thioalkoxy, or alkoxy, each of which is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkyl, alkoxy, thioalkoxy, halogen, haloalkyl, haloalkoxy, alkanoyl, NO2, CN, alkoxycarbonyl, or aminocarbonyl; R53 is absent, -O-, -C(O)-, -NH-, -N (alkyl)-, -KH- S(O)0-2-, -N(alkyl)-S(O)0-2-, -S (O) 0-2-NH-, -S(O)0- 2- N(alkyl)-, -NH-C(S)-, or -N(alkyl)-C(S)-; R54 is heteroaryl, aryl, arylalkyl, heterocycloalkyl, CO2H, -CO2-alkyl, -C(O)NH(alkyl) , -C(O)N(alkyl) (alkyl), -C(O)NH2, C!-C8 alkyl, OH, aryloxy, alkoxy, arylalkoxy, NH2, NH (alkyl), N(alkyl) (alkyl), or -d-C6 alkyl-CC^-Cx-Cg alkyl, each cf which is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkyl, alkoxy, CO2H, -CO2-alkyl, thioalkoxy, halogen, haloalkyl, haloalkoxy, hydroxyalkyl, alkanoyl, NO2, CN, alkoxycarbonyl, or aminocarbonyl; X is selected from the group consisting of -C1-C6 alkylidenyl optionally optionally substituted with 1, 2, or 3 methyl groups; and -NR4-6-; or R4 and R4-6 combine to form - (CH2)mo-, wherein n10 is 1, 2, 3, or 4; Z is selected from the group consisting of a bond; SO2; SO; S; and C(O); Y is selected from the group consisting of H; Cj-C^ haloalkyl; C5-C6 heterocycloalkyl; Cs-C10 aryl; OH; -N(YX) (Y2) ; Cx-Cio alkyl optionally substituted with 1 thru 3 substituents which can be the same or different and are selected from the group consisting of halogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy; C3-C8 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from C1-C3 alkyl, and halogen; alkoxy; aryl optionally substituted with halogen, alkyl, alkoxy, CN or NO2; arylalkyl optionally substituted with halogen, alkyl, alkoxy, CN or KTO2; wherein Yi and Y2 are the same or different and are H; C1-C10 alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, C!-C4 alkoxy, C3-CB cycloalkyl, and OH; C2-Cs alkenyl; C2-Cs alkanoyl; phenyl; -SO2- C!-C4 alkyl; phenyl Ci-C4 alkyl; or C3-C8 cycloalkyl C1-C4 alkyl; or Yi, Y2 and the nitrogen to which they are attached form a ring selected from the group consisting of piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently Cx-Cs alkyl, C1-C6 alkoxy, Ci-C6 alkoxy Ci-Cs alkyl, or halogen; Rioo and R'ioo independently represent aryl, heteroaryl, heterocyclyl, -aryl-W-aryl, -aryl-W-heteroaryl, -aryl-W-heterocyclyl, -heteroaryl-W-aryl, heteroaryl-W-heteroaryl, -heteroaryl-W- heterocyclyl, -heterocyclyl-W-aryl, -heterocyclyl-W- heteroaryl, -heterocyclyl-W-heterocyclyl, -CH[(CH2)0_ 2-O-Riso] - (CHa) 0-2-aryl, -CH[(CH2) 0-2-O-Ri5o3 - (CH2) 0-z- heterocyclyl or -CH [ (CH2) 0.2-O-R150] - (CH2) 0-j- heteroaryl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from -OR, -NO2, Cx-Cs alkyl, halogen, -C=N, -OCF3, -CF3, - (CHa) o-4-O-P (=O) (OR) (OR' ) , - (CH2) a-4-CO-NR10SR' 10,, - (CH2) o-4-O- (CH2) o-4-CONR102Rio2' , - (CH2) o-4"CO- (Ca-C12 alkyl), -(CH2)o-4-CO-(C2-C12 alkenyl), - (CH2) 0-4- CO-(C2-C12 alkynyl) , - (CH2) o-4-CO- (CH2) 0-4 (C3-C7 cycloalkyl) , - (CH2) 0-4-R110, - (CH2) 0-4-R120, -(CH2)O-4-Ri3o, " (CH2)o-4-CO-Ruo, - (CH2) a-4-CO-Ri20, - (CH2) 0-4-CO-R13o, - (CH2) t,.4-CO-Ri4o, " (CH2) 0-4-CO-O- R150, - (CH2) 0-4-SO2-NRlq5R' 10s, " (CH2) 0-4-SO- (Ci-Cg alkyl) , - (CH2) o-4-S02- (Ca.-C12 alkyl) , - (CH2) 0-4-SO2- (CH2) 0-4- (C'3-C7 cycloalkyl) , - (CH2) 0-4-N (R150) -CO-O- R150, -(CH2)o-4-M(Ri5o)-CO-N(Ri50)2/ -(CH3)0-4- N(R15o) -CS-N(R150)2/ - (CH2)o-4-N(Riso) -CO-R105, -(CH2)0-4-NRiosR'ios/ - (CH2) 0.4-RW0, - (CH2) 0-4-O-CO- (Ca-Cg alkyl) , - (CH2) 0-*-0-P(O) - (O-Ri10)2, -(CH2)0- 4-O-CO-N(R1S0)2, -(CH2)0-4-O-CS-N(R15o)2, - (CH2) O- (Riso) , - (CH2) o-4-O-Rlso' -COOH, - (CHa) 0-4-S- (R150) , -(CH2)0-4-N(R1S0)-SO2-R105, -(CH2)0-4- C3-C7 cycloalkyl, (C2-C10) alkenyl, and (C2- C10)alkynyl, or R100 is Ca-Cio alkyl optionally substituted with 1, 2, or 3 R115 groups, or R100 is -(Ci.-C6 alkyl)-O-Ci-C6 alkyl) or -{Ci-C6 alkyl) -S- (Ci-Cs alkyl) , each of which is optionally substituted with 1, 2, or 3 Rn5 groups, or R100 is C3-Cb cycloalkyl optionally substituted with 1, 2, or 3 R115 groups; W is -(CH2)0.4-, -C-, -S {0)0-2-, -N(R135)-, -CR(OH)- or - C(0)-; Rio2 and R102' independently are hydrogen, or Ci-Cio alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, aryl or "Rno; R105 and R'iob independently represent -H, -Ruo, -R120, C3-C7 cycloalkyl, - (Cx-C2 alkyl)-(C3-C7 cycloalkyl), - (Ci-Cs alkyl)-O-(Ci-C3 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, or Ci-Cz alkyl chain with one double bond and one triple bond, or Ci-Cs alkyl optionally substituted with -OH or -NH2; or, Cj.-C6 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, or R105 and R'ios together with the atom to which they are attached form a 3 to 7 membered carbocylic ring, where one member is optionally a heteratom selected from -O-, -S(O)0-a-, -N(Ri3S)-, the ring being optionally substituted with 1, 2 or 3 independently- selected R14o groups,- Riis at each occurrence is independently halogen, -OH, -CO2R102/ -Ca-Cg thioalkoxy, -CO2-phenyl, -NRiosR'us, -SOa-CCi-Cg alkyl), -C(=O)R1B0, Rl80/ - CONR10SR' ins, -SO2NR105R'105, -NH-CO-(Ci-Cs alkyl), -NH-C (=O)-OH, - NH-C(=O)-OR, -NH-C(=O)-Ophenyl, -O-C (=O) - (Cx-C6 alkyl), -O-C(=O) -atnino, -O-C (=O)-mono- or dialkylamino, -O-C(=O)-phenyl, -O-(d-Cg alkyl)-CO2H, -NH-SO2-(Cx-Cs alkyl), d-C6 alkoxy or Ci-C6 haloalkoxy; R135 is Cx-Cs alkyl, C2-Cs alkenyl, C2--Cs alkynyl, C3_C7 cycloalkyl, - (CH2) 0-2- (aryl) , - (CH2) 0-2- (heteroaryl) , or - (CH2)o-2- (heterocyclyl) ; R14o is heterocyclyl optionally substituted with 1, 2, 3, or 4 groups independently selected from Ci-Cs alkyl, Ci-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (Cx-Cs) alkylamino, di (Cj.-Cs) alkylamino, C2-C6 alkenyl, C2-C6 alkynyl, d-Cg haloalkyl, d-Cg haloalkoxy, amino(Ci-C6)alkyl, mono(Ci- C6) alkylamino (Ci-C6) alkyl, di (Ci-Cs) alkylamino (Ci- Cs) alkyl, and -O; R14S is d-Cs alkyl or CF3; Riso is hydrogen, ' C3-C7 cycloalkyl, - (d~C2 alkyl) - (C3-C7 cycloalkyl) , C2-C6 alkenyl, C2-C6 alkynyl, Ci-C6 alkyl with one double bond and one triple bond, -Rno, - Rizof or Cj-C6 alkyl optionally substituted with 1, 2, 3, or groups independently selected from -OH, -NH2, d-C3 alkoxy, Ruo, and halogen,- Riso' is C3-Cy cycloalkyl, - (d-C3 alkyl) - (C3-d cycloalkyl), C2-C6 alkenyl, C2-C6 alkynyl, Ci-Cs alkyl with one double bond and one triple bond, -Rllo, - R120/ or Ci-C6 alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from -OH, -NH2, C3.-C3 alkoxy, Rno, and halogen; Riss is C3-C7 cycloalkyl, - (Ci-C2 alkyl) - (C3-C7 cycloalkyl) , C2-C6 alkenyl, C2-C6 alkynyl, Ci-Cg alkyl with one double bond and one triple bond, -R110, -Ri2o, or Ci-Cs alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from -OH, -NH2( C1-C3 alkoxy, and halogen; Riso is selected from morpholinyl, . thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl, each of which is optionally substituted with 1, 2, 3, or 4 groups independently selected from Ci-Cs alkyl, Ci-Cs alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (Ci-C6) alkylamino, di (Ci-Cs) alkylamino, C2-C6 alkenyl, C2-C6 alkynyl, Ci- Cs haloalkyl, Ci-C'g haloalkoxy, amino (C^Cg) alkyl, mono (Cx-C6} alkylamino (Ci-C6) alkyl, di (Ci- C6) alkylamino (C:i-C6) alkyl, and =O; R110 is aryl optionally substituted with 1 or 2 Ri25 groups; R125 at each occurrence is independently halogen, amino,. mono- or dialkylamino, -OH, -C=N, -SO2-NH2, -SO2-NH- Ci-C6 alkyl, -SOz-NtCi-Cs alkyl) 3, -SO2-(C1-C4 alkyl),, -CO-NH2, -CO-NH-d-Cg alkyl, or -CO-N(Ci-C6 alkyl) 2. or Ci-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups that are independently selected from Ci- C3 alkyl, halogen, -OH, -SH, -C=N, -CF3, C1-C3 alkoxy, ainino, and mono- and dialkylamino, or C].-C6 alkoxy optionally substituted with one, two or three of halogen; R120 is heteroaryl, which is optionally substituted with 1 or 2 R12s groups; and R130 is heterocyclyl optionally substituted with 1 or 2 R125 groups. The invention also provides compounds of the formula X: and pharmaceutically acceptable salts thereof, wherein R:., R2, R3, RN and Rc ares as defined for formula (I) . The invention also provides methods of generating compounds of formula (Y) from the compounds of formulae (AA) , (I) or (X) : wherein Rl7 R2, R3, Rn and Rc are as defined for formula (I) . The generation of compounds of formula (Y) from compounds of formulae (AA), (I) or (X) can occur in vivo or in vitro. Compounds of formula Y are useful for treating and/or preventing Alzheimer's disease. The invention also provides processes for converting compounds of formula AA, I or X to the compounds of 29 formula Y. The conversion and/or generation of compounds of formula Y involves contacting the compounds of formula I and/or X with an aqueous medium. The conversion can occur in vitro or in vivo. The invention also provides methods for the treatment or prevention of Alzheimer's disease, mild cognitive impairment Down's syndrome, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloid angiopathy, other degenerative dementias, dementias of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimer's disease compriseing administration of a therapeutically effective amount of a compound or salt of formula AA, I or X, to a patient in need thereof. Preferably, the patient is a human. More preferably, the disease is Alzheimer's disease. More preferably, the disease is dementia. The invention also provides pharmaceutical compositions comprising a compound or salt of formula AA, I or X and at least one pharmaceutically acceptable carrier, solvent, adjuvant or diluent. The invention also provides the use of a compound or salt according to formula AA, I or X for the manufacture of a medicament. The invention also provides the use of a compound or salt of formula (AA) , formula (I) or formula (X) for the treatment or prevention of Alzheimer's disease, mild cognitive impairment Down's syndrome, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloid angiopathy, other degenerative dementias. deaientias of mixed vascular and degenerative origin, dementia associated with. Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, or diffuse Lewy body type of Alzheimer's disease. The invention also provides compounds, pharmaceutical compositions, kits, and methods for inhibiting beta-secretase-mediated cleavage of amyloid precursor protein (APP) . More particularly, the compounds, compositions, and methods of the invention are effective to inhibit the production of A-beta peptide and to treat or prevent any human or veterinary disease or condition associated with a pathological form of A-beta peptide. The invention also provides methods of preparing the compounds of the invention and the intermediates used in those methods. The compounds, compositions, and methods of the invention are useful for treating humans who have Alzheimer's Disease (AD), for helping prevent or delay the onset of AD, for treating patients with mild cognitive impairment (MCI), and preventing or delaying the onset of AD in those patients who would otherwise be expected to progress from MCI to AD, for treating Down's syndrome, for treating Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch Type, for treating cerebral beta-amyloid angiopathy and preventing its potential consequences such as single and recurrent lobar hemorrhages, for treating other degenerative dementias, including dementias of mixed vascular and degenerative origin, for treating dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, and diffuse Lewy body type AD, and for treating frontotemporal dementias with parkinsonism (FTDP). The compounds of formula Y possess beta-secretase inhibitory activity. The inhibitory activities of the compounds of the invention is readily demonstrated, for example, using one or more of the assays described herein or known in the art. Unless the substituents for a particular formula are expressly defined for that formula, they are understood to carry the definitions set forth in connection with the preceding formula to which the particular formula makes reference. DETAILED DESCRIPTION OF THE INVENTION As noted above, the invention provides compounds of formulae (AA) , (I) and (X) that are useful in the treatment and prevention of Alzheimer's disease. These compounds can be viewed as prodrugs of the active compounds of Formula Y since they generate the activs compound both in vivo and in vitro. The compounds of formula AA, I and X undergo acyl group migration of the RN group when in contact with water, as depicted in Scheme I. The migration associated with compounds of formula (I) is referred to herein as "N-acyl migration." The migration associated with compounds of formula (X) is referred to herein as wO-acyl migration." The migrations depicted in SCHEME 1 can occur either in vitro or in vivo and occur when the compounds are contacted with aqueous media, including water itself. The aqueous medium can be neutral, acidic or basic. It is preferred that the media have a pH of about 2 to abou~ 10, more preferably, about 3 to about 7. The amount of water required for the migration is not critical. A catalytic amount of aqueous media will suffice to cause the migration. Aqueous buffer solutions as well as gastric fluid are satisfactory media for the migration to occur. The products of the rearrangements of the compounds of formula AA, formula I and/or formula X are the compounds of formula (Y) . The substituents Ri, R2, R3, Rn and Rc in the compounds (Y) are as defined above fo:r compounds of formula (I). Preferred compounds of formula AA include those of formula AA-1, i.e., compounds of formula AA wherein Ri is aryl, heteroaryl, heterocyclyl, -Ct.-Cs alkyl-aryl, - Ci-C6 alkyl-heteroaryl, or -Ci-C6 alkyl- heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, - OH, -SH, -CsN, -NO2, -NRiosR'ios, -CO2R, N(R)COR', or -N(R)SO2R', -C (=O) - (C!-C4) alkyl, -SO2-amino, -SO2-mono or dialkylamino, -C(=O)- amino, -C(=O)-mono or dialkylamino, -SO2-(Ci-C4l) alkyl, or Ci-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen, or C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -CsN, -CF3, C1-C3 alkoxy, amino, -Ci-C6 alkyl and mono- or dialkylamino, or Ca-Cio alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -CsN, -CF3, -C^C^ alkoxy, amino, mono- or dialkylamino and -Ci-C3 alkyl, or C2-C10 alkenyl or C2-C10 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -CsN, -CF3, C1-C3 alkoxy, amino, Ci-CE alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo. Preferred compounds of formula AA-1 also include those wherein Rj. is -Ci-Cs alkyl-aryl, -Ci-C6 alkyl-heteroaryl, or -Ca-Cfi alkyl-heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, -OH, -SH, -C-N, -NO2, -NRiO5R'ios, -CO2R, -N(R)COR', or -N(R)SO2R', -C (=O) - (C1-C4) alkyl, -SO2-amino, -SO2-mono or dialkylamino, -C(=O)- amino, -C(=O)-mono or dialkylamino, -SO2-(C1-C4) alkyl, or Ci-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen, or C3-C7 cycloalkyl optionally substituted with :., 2, or 3 groups independently selected from halogen, -OH, -SH, -O-N, -CF3, d-C^ alkoxy, amino, -Ci-C5 alkyl and mono- or dialkylamino, or Ci-Cao alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, -Ci-C3 alkoxy, amino, mono- or dialkylamino and -C1-C3 alkyl, or C2-Cio alkenyl or C2-C10 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, Ql-Cj alkoxy, amino, Ci-Cs alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo. Preferred compounds of formula AA-1 further include those wherein R.! is -(CH2)-aryl, - (CH2) -heteroaryl, or - (CH2) - heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, - OH, -SH, -C^N, -NO2, -NR1OSR'1O5, -CO2R, - N(R)COR', or -N(R)SO2R', -C (=O) - (C!-C4) alkyl, -SO2-amino, -SO2-mono or dialkylamino, -C(=O)- t amino, -C(=O)-mono or dialkylamino, -SO2- (C1-C4) alkyl, or Cx-Cj alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen, or C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -G=N, -CF3, C1-C3 alkoxy, amino, -Ci-Cs alkyl and mono- or dialkylamino, or Ci-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, -Q1.-C3 alkoxy, amino, mono- or dialkylamino and -C1-C3 alkyl, or C2-Ci0 alkenyl or C2-Ca0 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, Ci-C3 alkoxy, amino, Ci-Cs alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo. Preferred compounds of formula AA-1 also include those wherein Ri is -CH2-phenyl or -CH2-pyridinyl where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, C1-C4 alkoxy, hydroxy, -NO2, and C1.-C4 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from halogen, OH, SH, NHa, NH(C!-C6 alkyl), N-(d-Cs alkyl) (Ci-Cs alkyl), ON, CF3. Preferred compounds of formula AA-1 further include those wherein Ri is -CH2-phenyl or -CH2-pyridinyl where the phenyl or pyridinyl rings are each optionally substituted with 1 or 2 groups independently selected from halogen, Ci-C2 alkyl, Ci--C2 alkoxy, hydroxy, -CF3, and -NO2. Preferred compounds of formula AA-1 include those wherein Ri is -CH2-phenyl where the phenyl ring is optionally substituted with 2 groups independently selected from halogen, Cx-C2 alkyl, Ci-C2 alkoxy, hydroxy, and -NO2. Preferred compounds of formula AA-1 also include those wherein Rj is benzyl, or 3,5-difluorobenzyl. Preferred compounds of formula AA and AA-1 include those of formula AA-2, i.e., compounds of formula AA or AA-1 wherein R2 and R3 are independently selected from H or C^-Cg alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of C;,.-C3 alkyl, halogen, -OH, -SH, -C=N, -CF3, C1.-C3 alkoxy, and -NRi- aRl-b. Preferred compounds of formula AA-2 include those wherein Re is selected from the group consisting of C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, -OC=ONR235R24o/ -S (=0) 0-2 (Ci-C6 alkyl), -SH, -NR235C=ONR23sR240, -C=ONR235R240, and -S (=O) 2NR23SR24(,; - (CH2) 0-3- (C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, -CO2H, and -CO2-(Ci-C4 alkyl); - (CR245R250) 0-4-aryl; - (CR245R250) 0-4-heteroaryl; - (CR245R2S0) 0-4- heterocycloalkyl; - [C (R255) (R26o) ] 1-3-CO-N- (R255) 2; CH(aryl)2; -CH(heteroaryl)2; -CH(heterocycloalkyl)2; -CH(aryl) (heteroaryl) ; -CO-NR235R24o; -(CH2)0-:l- CH( (CH2)o-s-OH) - (CH2)0-i-aryl; - (CH2) 0-i-CHRC-6- (CH2)0-:l- heteroaryl; -CH(-aryl or -heteroaryl)-CO-O(C!-C4 alkyl); -CH (-CH2-C>H) -CH(OH) -phenyl-NO2; (Ci-Cs alkyl)- O-(Ci-C6 alkyl)-OH; -CH2-NH-CH2-CH (-O-CH2-CH3) 2; -H; and - (CH2)o-6-C(=NR23S) (NR235R24o) ; wherein each aryl is optionally substituted with 1, 2, or 3 R200! each heteroaryl is optionally substituted with l, 2, 3, or 4 R200; each heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R21o; R200 at each occurrence is independently selected from the group consisting of Ci-C6 alkyl optionally substituted with 1, 2, or 3 R:;05 groups; OH; -N02; halogen; -CO2H; feN; -(CH2)o-4- CO-NR220R225; -(CH2)0-4-CO-(C1-C12 alkyl) ; -(CH2)0-4- CO2R21S; and - (CH2) 0-4-O-(Ci-Cs alkyl optionally substituted with 1, 2, 3, or 5 -F) ; wherein each aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R2os, R210 or Ci-C,; alkyl substituted with 1, 2, or 3 groups that are independently R2os or R2io; wherein each heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R210/ wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205» R210, or Ci-C6 alkyl substituted with 1, 2, or 3 groups that are independently R2os or R210; R205 at each occurrence is independently selected from the group consisting of Ci-Cs alkyl, halogen, -OH, -O-phenyl, -SH, -ON, -CP3, Ci-Cs alkoxy, NH2, NH(d-Cs alkyl), and N- (Ci-Cg alkyl) (Ci-Cfi alkyl); R2io at each occurrence is independently selected from the group consisting of Cx-C6 alkyl optionally substituted with 1,' 2, or 3 R:;05 groups; halogen; Cx-C^ alkoxy; C^-Cg haloalkoxy; -NR220R22s; OH; CteN; C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R205 groups,- -CO-(d- C4 alkyl); .S02-NR23sR24o; -CO-NR23ER240; -SO2-(C1-C4 alkyl); and =O; wherein R215 at each occurrence is independently selected from the group consisting of Ci-C6 alkyl., - (CH2)0-2- (aryl) , C3.C7 cycloalkyl, and -(CH2)0-2- (heteroaryl) , - wherein the aryl group at each occurrence :.s optionally substituted with 1, 2, or 3 groups that are independently R20s or R2io; wherein the heterocycloalkyl group at each occurrence :.s optionally substituted with 1, 2, or 3 R2id; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R2i0; R22o and R225 at each occurrence are independently selected from the group consisting of -H, -CX~CS alkyl, hydroxy Ci-C6 alkyl, amino Ci-Cs alkyl; halo Ci-Cs alkyl; -C3-C7 cycloalkyl, - (Cx-Cg alkyl)-O-(d-Cs alkyl), -aryl, -heteroaryl, and -heterocycloalkyl; wherein the aryl group at each occurrence is optionally substituted with 1, 2, or 3 R27o groups, each heteroaryl is optionally substituted with 1, 2, 3, or 4 R2Oo, each 'heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R210 wherein R27o at each occurrence is independently R20s/ Ci-CE alkyl optionally substituted with 1, 2, or 3 R20S groups; halogen; Ci-C6 alkoxy; Cx-Cfi haloalkoxy; NR23sR24o; OH; CsN; -CO- (Ci-C4 alkyl); and =O; wherein the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R205 groups; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R205 groups; R235 and R240 at each occurrence are independently H, or Cx-Cs alkyl; R24S and R25o at . each occurrence are independently selected from the group consisting of H, Ci-CU alkyl, C1.-C4 hydroxyalkyl, Cx~C4 alkoxy, C1-C4 haloalkoxy, or R24s and R2S0 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms, wherein the carbocycle is optionally substituted with 1 or 2 groups that are independently OH, methyl, Cl, F, OCH3, CP3, NO2, or CN; R255 and R2f;o at each occurrence are independently selected from the group consisting of H; Ci-C6 alkyl optionally substituted with 1, 2, or 3 R20S groups; - (CH2) 0-4-C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 RZOs groups; - (C1-C4 alkyl)-aryl; - [C^-Ci alkyl)-heteroaryl; -(C1-C4 alkyl)-heterocycloalkyl; aryl; heteroaryl; heterocycloalkyl; . (CH2) ^4 -R2Ss- (CH2) 0.4-aryl; - (CH2) i-4-R265- (CH2) 0.4-heteroaryl; and; - (CH2) 1.4- R26S- (CH2) 0-4-h.eterocycloalkyl; wherein R26S at each occurrence is independently -0--, -S- or -N(Ca-C6 alkyl)-; each aryl or phenyl is optionally substituted with 1, 2, or 3 groups that are independently R2os, R210/ or Ci-C6 alkyl substituted with 1, 2, or 3 groups that are independently R20S or R2io. Preferred compounds of formula AA-2 include those wherein: Rc is - (CR245R25o) 0-4-aryl, or - (CR245R250) 0-4-heteroaryl, wherein aryl and heteroaryl are optionally substituted with 1, 2, or 3 R200 groups. Preferred compounds of formula AA-2 also include compounds wherein Rc is - (CR24SR2bo) -aryl, or - (CR245R250) -heteroaryl wherein each aryl and heteroaryl is optionally substituted with 1, 2, or 3 R200 groups. Preferred compounds of formula AA-2 also include compounds wherein Rc is -(CH2)-aryl, or - (CH2)-heteroaryl, wherein each aryl and heteroaryl is optionally substituted with 1, 2, or 3 groups selected from OH, -NO2, halogen, -CO2H, C=N, - (CH2) 0-4-CO-NR220R225/ -(CH^o.-i-CO-Cd-da alkyl), and - (CH2) 0_4-SO2- NR220R225 • Preferred compounds of formula AA-2 also include compounds wherein Rc is -(CH2)-aryl, wherein aryl is optionally substituted with 1, 2, or 3 groups selected from OH, -N02, halogen, -CO2H, and C=N. Preferred compounds of formula AA-2 also include compounds wherein Rc is - (CH2)-phenyl, wherein phenyl is optionally substituted with 1, 2, or 3 groups selected from OH, -NO2, halogen, -CO2H, and CsN. Preferred compounds of formula AA-2 also include compounds wherein Rc is benzyl. Other preferred compounds of formulas AA, AA-1 and AA-2 include compounds of formula AA-3, i.e., those of formulas AA, AA-1 or AA-2 wherein one of RN and RN' is hydrogen and the other is: Y,Z.x^(CH2)n7-CHC(O> wherein R4 is NH2; -NH-(CH2)nS-R4.i; -NHR8; -NR50C(O)R5; or - NR5oCO2R5i; wherein n6 is 0, 1, 2, or 3; n7 is 0, 1, 2, or 3; R4_i is selected from the group consisting of -SO2- (Ci-Cg alkyl), -SO-(d-Ce alkyl) , -S- (C^Ce alkyl), -S-CO-tCj-Cs alkyl), -SO2-NR4.2R4.3; -C0-- C!-C2 alkyl; -CO-NR4-3R4-4; R4-2 and R4.3 are independently H, C1-C3 alkyl, or C3-Ca cycloalkyl; R4-4 is alkyl, phenylalkyl, C2-C4 alkanoyl, or phenylalkanoyl; R5 is ' cyclopropyl; cyclobutyl; cyclopentyl; and cyclohexyl; wherein each cycloalkyl group is optionally substituted with one or two groups that are CX~C6 alkyl, more preferably C1-C2 alkyl, Ci-Cs alkoxy, more preferably Ci-C2 alkoxy, CF3, OH, NH2, NH(C!-C6 alkyl), N(Ci-C6 alkyl) (Cx-Ce alkyl), halogen, CN, or NO2; or the cycloalkyl group is substituted with 1 or 2 groups that are independently CF3, Cl, F, methyl, ethyl or cyano; Cz-C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, -NRSR7, Ci-CU alkoxy, C5-C6 heterocycloalkyl, Cs-Cs heteroaryl, phenyl, C3-C7 cycloalkyl, -S-C1-C4 alkyl, -SO2-Ci-C4 alkyl, -CO2K, -CONR6R7, -CO2-C1-C4 alkyl, or phenyloxy; heteroaryl optionally substituted with. 1, 2, or 3 groups that are independently Cx-C4 alkyl, Cx-CU alkoxy, haloger., Ci-C4 haloalkyl, or OH,- heterocycloalkyl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, or C2-C4 alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, OH, Cx-C4 alkyl, CJ-C4 alkoxy, or C1-C4 haloalkyl; and -NR6R7; wherein R6 and R7 are independently selected from the group consisting of H, Ci-C6 alkyl, C2-C6 alkanoyl, phenyl, -SO2-C].-C4 alkyl, and phenyl Ci-C4 alkyl; Re is selected from the group consisting of -SO:>- heteroaryl optionally substituted with 1 or 2 groups that are independently C1-C4 alkyl or halogen;, -SO2-aryl, -SO2-heterocycloalkyl, -C(O)NHR9, heterocycloalkyl, "S-C2-C4 alkanoyl, wherein R9 is phenyl C1-C4 alkyl, C^-Cg alkyl, or H; R50 is H or Cx-Ce alkyl; R51 is selected from the group consisting of phenyl Ci-C4 alkyl; Ci-C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, -NR6R7, -C(O)NR6R7, C3-C7 or -C.L- C4 alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups that are independently C3.-C4 alkyl, Q1.-C4 alkoxy, halogen, C2-C4 alkanoyl, phenyl C!-C4 alkyl, and -SO2 Cx--4 alkyl; heterocycloalkylalkyl optionally substituted with 1 or 2 groups that are independently Ci-C4 alkyl, Ql-C4 alkoxy, halogen, C2-C4 alkanoyl, phenyl Ci-C4 alkyl, and -SO2 C1-C4 alkyl; alkenyl; alkynyl; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently OH, Ci-C4 alkyl, Ci-C4 alkoxy, halogen, NH2; NH^-Cg alkyl) or N(C1-C6 alkyl)(Ci-Cg alkyl); heteroarylalkyl optionally substituted with 1, 2, or 3 groups that are independently Ci-C4 alkyl, Ci-C4 alkoxy, halogen, NH2, NHCCi-Cg alkyl) or N^-Cg alkyl) (d-C6 alkyl); phenyl; C3-C8 cycloalkyl, and cycloalkylalkyl, wherein the phenyl; C3-CB cycloalkyl, and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5 groups that are independently halogen, CN, NO2, Ci-C6 alkyl, Ci-C6 alkoxy, C2-C6 alkanoyl, Ci-C6 haloalkyl,. Cx-Cg haloalkoxy, hydroxy, Ci-Cs hydroxyalkyl, Ci-C6 alkoxy Ci-C6 alkyl, Ci-C6 thioalkoxy, C3.-C6 thioalkoxy Ci-Cs alkyl, or Ci- Cs alkoxy Ca-C6 alkoxy. Preferred compounds of formula. AA-3 include compounds wherein one of RN and R»' is hydrogen and the other is Y'Z^X-CHC(O)- NH2 wherein X is Ci-C4 alkylidenyl optionally substituted with 1, 2, or 3 methyl groups; or -NR4-6-; or R4 and R4_6 combine to form -(CH2)nio-> wherein ni0 is 1, 2, 3, or .4; Z is selected from a bond; SO2/- SO; S; and C(O); Y is selected from H; Ci-C4 haloalkyl; C5-C6 heterocycloalkyl containing at least one N, O, or S; phenyl; OH; -NCYJ (Y2) ; C!-Clo alkyl optionally substituted with 1 thru 3 substituents which can be the same or different and are selected from halogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy,- C3-CB cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from Ci-C3 alkyl, and halogen; alkoxy; phenyl optionally substituted wi;h halogen, Ci-C4 alkyl, Ci-C4 alkoxy, CN or NO2,- phenyl Ci-C4 alkyl optionally substituted with halogen, C1-C4 alkyl, C1-C4 alkoxy, CN or NO2; wherein Ya and Y2 are the same or different and are H; C1-C10 alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, C1-C4 alkoxy, C3-C8 cycloalkyl, and OH; C2-Cs alkenyl; C2-C6 alkanoyl; phenyl; -SO;>- C1-C4 alkyl; phenyl C1-C4 alkyl; and C3-Ca cycloalkyl C1-C4 alkyl; or -N(Yi) (Y2) forms a ring selected from piperazinyl, piperidinyl, tnorpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently C-i-Ce alkyl, Ci-C6 alkoxy, Cx-C6 alkoxy Cx-C6 alkyl, or halogen. Preferred compounds of formula AA-3 include compounds wherein X is Ci-C4 alkylidenyl optionally optionally substituted with 1, 2, or 3 methyl groups; Z is selected from SO2; SO; S; and C[O); Y is selected from H; C1-C4 haloalkyl; C5-Cs heterocycloalkyl containing at least, one N, O, or S; phenyl; OH; -N(Yi) (Y2) ; Ci-Cio alkyl optionally substituted with 1 thru 3 substituents which can be the same or different and are selected from the group consisting of halogen, hydroxy, alkoxy. thioalkoxy, and haloalkoxy; C3-C8 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from C1-C3 alkyl, and halogen; alkoxy; phenyl optionally substituted with halogen, Ci-C4 alkyl, Ci-C4 alkoxy, CN or NO2; phenyl C1-C4 alkyl optionally substituted with halogen, C1--C4 alkyl, C1-C4 alkoxy, CK or NO2; wherein Y], and Y2 are the same or different and are H; Ci-es alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, C3.-C4 alkoxy, C3-C8 cycloalkyl, and OH; C2-C6 alkenyl; C2-Cs alkanoyl; phenyl; -SO2- C!-C4 alkyl; phenyl C1-C4 alkyl; or C3-CB cycloalkyl C1-C4 alkyl; or -N(Yi) (Y2) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently Ci-C« alkyl, Ql-Cs alkoxy, Ci~C6 alkoxy Ci-C6 alkyl, or halogen. Preferred compounds of formula AA-3 include compounds one of RH and RN' is hydrogen and the other is: ' R4 0 wherein R4 is NH2; -NH-(CH2)n6-R4-i; -NHRB; -NR50C(O)Rs; or -NR50CO2R5i wherein jit is 0, 1, 2, or 3; n7 is 0, 1, 2, or 3; R4-! is selected from the group consisting of -S02- (Ci-C8 alkyl), -SO- (Ci-C8 alkyl), -S- (d-C8 alkyl) , -S-CO-IQl-Cs alkyl) , -SO2-NR4.2R4.-3; -CO- C!-C2 alkyl; -CO-NR4_3R4-4; R4-2 and R4-3 are independently H, Ci-C3 alkyl, or C2-C6 cycloalkyl; R4.4 is alkyl, phenylalkyl, C2-C4 alkanoyl, or phenylalkanoyl; R5 is cyclopropyl; cyclobutyl; cyclopentyl; or cyclohexyl; wherein each cycloalkyl group is optionally substituted with one or two groups that are C3.-Cs alkyl, more preferably Ci-C2 alkyl, Ql-Cs alkoxy, more preferably Ci-C2 alkoxy, CF3, OH, NH2, NH(C1-CS alkyl), N(Ci-Cs alkyl) (Ci-C6 alkyl), halogen, CN, or NO2; or the cycloalkyl group is substituted with 1 or 2 groups that are independently CF3, Cl, F, methyl, ethyl or cyano,- Cx-C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, -NRSR7, C^-d alkoxy, C5- Cs heterocycloalkyl, Cs-Cs heteroaryl, phenyl, C3-C7 cycloalkyl, -S-Ci-C4 alkyl, -SO2-CJ.-C4 alkyl, --CO2H, -CONR6R7, -CO2-C1-C4 alkyl, or phenyloxy; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, C!-C4 haloalkyl, or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groups that are independently Cr-C4 alkyl, C3.-C4 alkoxy, halogen, or C2-C4 alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, OH, Cx-d alkyl, C!-C4 alkoxy, or C1-C4 haloalkyl; and -NR6R7; wherein Rs and R7 are independently selected from the group consisting of H, Ci-C6 alkyl, C2-C6 alkanoyl, phenyl, -SC^-Cx-C^ alkyl, and phenyl Ci-C4 alkyl; Re is selected from the group consisting of -SO2- heteroaryl optionally substituted with 1 or 2 groups that are independently C3.-C4 alkyl or halogen;, -SO2~aryl, -SO2-heterocycloalkyl, -C(O)NHR9, heterocycloalkyl, -S-C2-C4 alkanoyl, wherein R9 is phenyl C1-C4 alkyl, Ci-C6 alkyl, or H; R50 is H or Ci-C6 alkyl; and R51 is selected from the group consisting of phenyl Ci-C4 alkyl; Cx-Cs alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, -NR6R7, -C(O)NRSR7, C3-C7 or -Ci- C4 alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups that are independently C1-C4 alkyl, Cx-C^, alkoxy, halogen, C2-C4 alkanoyl, phenyl C^-Ci alkyl, and -SO2 C1-C4 alkyl; heterocycloalkylalkyl optionally substituted with 1 or 2 groups that are independently Ci-C4 alkyl, C1-C4 alkoxy, haloger., C2-C4 alkanoyl, phenyl C1-C4 alkyl, and -SO2 C1-C4 alkyl; alkenyl; alkynyl; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently OH, Ci-C4 alkyl, C3.-C4 alkoxy, halogen, NH2, NH (Cx-Cs alkyl) or N(Ci-Cs alkyl) (Ci-Cg alkyl); heteroarylalkyl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, Ci-C4 alkoxy, halogen, NH2, NH(Ci-C6 alkyl) or N(C1-C6 alkyl) (Cx-Cg alkyl) ,- phenyl; C3-C8 cycloalkyl, and cycloalkylalkyl, wherein the phenyl; C3-CB cycloalkyl, and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5 groups that are independently halogen, CN, NO2, Ci-C6 alkyl, Cx-Cs alkoxy, C2-C6 alkanoyl, Ci-C6 haloalkyl, Ci-C6 haloalkoxy, hydroxy, Ci-C6 hydroxyalkyl, Ci-Cs alkoxy Ci-Cs alkyl, Ci-C6 thioalkoxy, Ci-C6 thioalkoxy Cj.-C6 alkyl, or Ci- Cs alkoxy Ci-C6 alkoxy; and Y is Ci-Cio alkyl optionally substituted with 1 thru 3 substituents which, can be the same or different and are selected from halogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy. Preferred compounds of formula AA-3 further include compounds wherein Re is Ci-C8 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R2osr -OC=ONR235R24o/ -S(=O) 0-2 (Ci-C6 alkyl), -SH, -C=ONR7.35IW and -S (=O) 2NR235R240; -(CH2)0. 3- (C3-Ca) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, -CO2H, and -CO2- (C1-C4 alkyl); - (CR245R250) 0-4- phenyl; - (CR245R250) 0-4-heteroaryl; - (CR245R250) 0-4- heterocycloalkyl; - {CH2) o-i-CH ( (CH2) o-4-OH) - (CH2) 0-1- phenyl; - (CH2) 0-i-CHRc..6- (CH2) O.i-heteroaryl; -CH (-CH2- OH)-CH(OH) -phenyl-NO2; (Ci-Cs alkyl)-O-(d-Cg alkyl)- OH; or - (CH2)o-6-C(=NR235) (NR23SR24o) ; wherein each aryl is optionally substituted with 1, 2, or 3 R200; . each heteroaryl is optionally substituted with 1, 2, 3, or 4 R200; each heterocycloalkyl is optionally substituted with 1, 2, 3, or A R210; R200 at each occurrence is independently Cj-C6 alkyl optionally substituted with 1, 2, or 3 R2os groups; OH; -NO2; halogen; -CO2H; CsN; -(CH2)0-4- CO-NR220R225; - (CH:|) 0-4-CO- (d-C12 alkyl) ,- - (CH2) 0.4- CO2R21S; or - (CH2) 0-4-O- (Ci-C6 alkyl optionally substituted with 1, 2, 3, or 5 -F); R205 at each occurrence is independently Ci-Cs alkyl, halogen, -OH, -O-phenyl, -SH, -CeN, -CF3, Ci-C6 alkoxy, NH2/ NHfd-Cg alkyl), or N- (d-Cg alkyl)(Ci-Cs alkyl); R2io at each occurrence is independently d-Cg alkyl optionally substituted with 1, 2, or 3 R2oS groups; halogen; C1-C6 alkoxy; Ci-C6 haloalkoxy; -NR220R225; OH; C^N; C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R205 groups; -CO-(d- C4 alkyl); _SO2-NR235R24o; -CO-NR23SR24o; -SO2-(C1-C4 alkyl); and =O; wherein R2i5 at each occurrence is independently Ci-C6 alkyl, - (CH2) 0-2- (phenyl) , C3_C7 cycloalkyl, and - (CH2) 3_ 2-(heteroaryl), - (CH2) 0-2-(heterocycloalkyl); wherein the phenyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205 or R2io; wherein the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R2iC; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R2i0; R220 and R2ZS at each occurrence are independently -H, -Cx-Cg alkyl, hydroxy Ci-Cs alkyl, halo Cx-Cg alkyl; -C3-C7 cycloalkyl, and - (Ci-C6 alkyl)-O- (Ci-Ca alkyl) ; R235 and R24o at each occurrence are independently H, or Ql-Cs alkyl; R245 and R2so at each occurrence are independently E, C1-C4 alkyl, C1-C4 hydroxyalkyl, C!-C4 alkoxy, Ca- C4 haloalkoxy, or R245 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon .atoms. Preferred compounds of formula AA-3 include compounds wherein Ri is benzyl which is optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, d.- C4 alkoxy, hydroxy, and C1-C4 alkyl optionally substituted with 1, 2, or 3 substituents halogen, OH, SH, NH2, NH(d-C6 alkyl), N-(Cx-Cs alkyl) (Ci-C« alkyl), CsN, CF.3; R2 and R3 are independently selected from H or Cx-CU alkyl optionally substituted with 1 substituent selected from halogen, -OH, -SH, -CaN, -CF3, C1-C3 alkoxy, NH2, NHfCi-Cg alkyl), and NH(Ci-Cs alkyl) (Ca-C6 alkyl); Rc is Ci-Ca alkyl optionally substituted with 1, 2, or 3 groups independently selected from R2os, -SH, -C=ONR235R240/ and -S (=O) 2NR23sR24 0-3- (C3-Cs) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from R205/ -CO2H, and -CO2- [C^-d alkyl); - (CR24sR2so) O-4-phenyl optionally substituted v;ith l, 2, or 3 R200; -(CRa45R25o)o-3-pyridyl; - (CR245R2so) 0-3- pyridazinyl; - (CR24sR2so) 0-3-pyrimidinyl; - (CR24SR25o) 0-3- pyrazinyl; - (CR245R250) 0-3 - fury 1; - (CR245R250) 0-3-indolyl ; - (CR245R2St)) 0-3-thienyl; - (CR24SRzso) 0-3-pyrrolyl; - (CR245R250) o-3-PYrazolyl; (CR245R250) 0-3-benzoxazolyl; - (CR24sR25o)o-3-iniMazolyl; each of the above heteroaryl groups is optionally substituted with 1, 2, 3, or 4 R200;-(CR24sR25o)o-3-imidazolidinyl; (CR245R2S0) 0-3-tetrahydrofuryl; (CR245R250) 0-3- tetrahydropyranyl; (CR24SR250) o-3-piperazir.yl ; (CR245R250) 0-3-pyrrolidinyl; {CR245R250) 0-3-piperidir.yl ; (CR245R250) 0-3-indolinyl; each of the above heterocycloalkyl groups is optionally substituted with 1, 2, 3, or 4 R210; (CHa) 0-1-CH ( {CH2) 0-4-OH) - (CHa) 0- i-phenyl; - (CH2) 0-i-CH(C1-C4 hydroxyalkyl) - (CH2) 0-i- pyridyl; R200 at each occurrence is independently Ci-C6 alkyl optionally substituted with 1, 2, or 3 R20s groups; OH; -NO2; halogen; -CO2H; CsN; -(CHa)0-4- CO-NR220R225; - (CH2) 0-4-CO- (Ci-C8 alkyl) ; - (CH2) 0-«- CO2R2i5/ and - (CH2) 0-4-O-(Ci-C6 alkyl optionally substituted with 1, 2, 3, or 5 -F); R205 at each occurrence is independently d-C6 alkyl, halogen, -OH, -O-phenyl, -SH, -C=N, -CF3, C:-Cs alkoxy, NH2, NH(Ci-C6 alkyl), and N-(C:-CS alkyl) (d-Cg alkyl) ; R210 at each occurrence is independently Ci.-Cs alkyl optionally substituted with 1 or 2 R20s groups; halogen; Cj-C* alkoxy; Ci-C4 haloalkoxy; -NR220R225; OH; C=N; C3-C7 cycloalkyl optionally substituted with 1 or 2 R205 groups; -CO-(C1-C4 alkyl); _SO2.NR235R24o; -CO-NR235R240; -S02-(C1-C4 alkyl); and =O; wherein R215 at each occurrence is independently Ci-C6 alkyl, - (CH2)0-2- (phenyl) , C3_C6 cycloalkyl, -(CH2)0-2- (pyridyl) , - (CH2) 0-2- (pyrrolyl) , - (CHa) 0-2- (imidazolyl) , - (CH2) 0-2- (pyrimidyl) , - (CH2) (l_2- (pyrrolidinyl) , - (CH2) 0-2- (imidazolidinyl) - (CH2) 0-2- (piperazinyl) , - (CH2) 0-2- (piperidinyl) , and - (CH2)0-2- (morpholinyl) ; wherein the phenyl group at each occurrence is optionally substituted with 1 or 2 groups that are independently R205 or R210; wherein each heterocycloalkyl group at each occurrence is optionally substituted with 1 or 2 R210; wherein each heteroaryl group at each occurrence is optionally substituted with 1 or 2 R210! R220 and R225 at each occurrence are independently -H, -C1-C4 alkyl, hydroxy C1-C4 alkyl, halo C1-C4 alkyl; -C3-C6 cycloalkyl, and -(C1-C4 alkyl)-0- (Ci-Ca alkyl); R-235 and R240 at each occurrence are independently H, or Ci-Cg alkyl; R245 and R2so at each occurrence are independently H, C1-C4 alkyl, C1-C4 hydroxyalkyl, CV-C4 alkoxy, Ci- C4 haloalkoxy, or R345 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, or 6 carbon atoms. Other preferred compounds of formula AA-3 include compounds wherein X is-Ci-C3 alkylidenyl optionally optionally substituted with 1 or 2 methyl groups; Z is SO2; SO; S; or C(0); Y is C1-C4 haloalkyl; OH; -N(Yi) (Y2) ,- Ci-C10 alkyl optionally substituted with 1 or 2 substituents which can be the same or different and are selected from halogen, hydroxy, C1-C4 alkoxy, Ci~C4 thioalkoxy, and C1-C4 haloalkoxy; C1-C4 alkoxy; phenyl optionally substituted with halogen, Cx-CU alkyl, CX-C4 alkoxy, CN or NO2; and benzyl optionally substituted with halogen, Ca-C4 alkyl, Cx-d alkoxy, CN or NO2; wherein Yi and Y2 are the same or different and are H; Ci-Cs alkyl optionally substituted with 1, 2, or 3 substituents selected from halogen, Cx-C2 alkoxy, C3-Ce cycloalkyl, and OH; C2-C6 alka:aoyl; phenyl; -SO2-Ci-C4 alkyl; benzyl; and C3-Cs cycloalkyl C2.-C2 alkyl; or -N(Yi) (Y2) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently Cx-Cs alkyl, Cj-Cg alkoxy, Cx-C6 alkoxy Ci-Cs alkyl, or halogen. Preferred compounds of formula AA-3 also include those of formula AA-4, i.e., compounds of formula AA-3 wherein X is-Ci-Cs alkylidenyl optionally optionally substituted with 1 methyl group; Z is SO2; SO; S; or C(O); Y is OH; -N(Y.O (Y2) ; phenyl; benzyl; or C3.-CK, alkyl optionally substituted with 1 or 2 substituents which can be the same or different and are selected from halogen, hydroxy, methoxy, ethoxy, thiomethoxy, thioethoxy, and CF3; wherein Yi and Y2 are the same or different and are H; C!-C4 alkyl optionally substituted with 1 or 2 substituents selected from halogen, methoxy, ethoxy, cyclopropyl, and OH; or -N(Yi) (Y2) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1 or 2 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, or halogen; Ri is benzyl which is optionally substituted.with 1, 2, or 3 groups independently selected from methyl, ethyl, n-propyl, isopropyl, hydroxymethyl, monohalomethyl, dihalomethyl, trihalomethyl, -CH2CF3, methoxymethyl, halogen, methoxy, ethoxy, n-propyloxy, isopropyloxy, and OH; R2 and R3 are independently H or C3.-C4 alkyl, Rc is Ci-Cs alkyl optionally substituted with 1, 2, or 3 R205 groups; cyclopropyl, cyclopropyltnethyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cyclohexylmethyl; - (CR245R250) 0-3-phenyl optionally substituted with 1 or 2 R200 groups; - (CR245R250) 0-3- pyridyl optionally substituted with 1 or 2 R2oo; - (CR245R25o)o-3-piperazinyl; or (CR245R25o) 0-3- pyrrolidinyl; - (CR24SR25o) 0-3-piperidir.yl; each of the above heterocycloalkyl groups is optionally substituted with 1 or 2 R2io groups; R200 at each occurrence is independently selected from Ci-C4 alkyl optionally substituted with 1 or 2 R205 groups; OH; and halogen; R20S at each occurrence is independently selected from C3.-C4 alkyl, halogen, -OH, -SH, -G=N, -CF3, and C!-C4 alkoxy; R210 at each occurrence is independently selected from C1-C4 alkyl optionally substituted with 1 or 2 R205 groups; halogen; C1-C4 alkoxy; OCF3; NH2, NH(Ci-Cs alkyl); N(Ci-Cs alkyl) (d-Cs alkyl); OH; and -CO- (C1-C4 alkyl); wherein R245 and R25o at each occurrence are independently selected from H, Cx-C4 hydroxyalkyl, C1-C4 alkoxy, or R.245 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 5,or 6 carbon atoms. Preferred compounds of formulas AA, AA-1 and AA-2 include compounds of formula AA-5, i.e., those of formulae AA., AA-1 or AA-2 wherein one of RN and RN' is hydrogen and the other is -C(=O)- (CRR') o-sRioo; and R1Oo represents aryl, heteroaryl, or heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from -OR, -NO2, Ci-C6 alkyl, halogen, -ON, -OCF3, -CF3, - (CH2) o-4-O-P (=O) (OR) (OR') , - (CH2) 0.4-CO-NRiosR' ios, - (CH2) o-4-O- (CH2) 0-4-CONR102Ri02', - (CH2) 0-4-CO- (Ca-C12 alkyl), -(CH2)0_4-CO-(C2-C13 alkenyl) , -(CHz)0.4- CO- (C2-Cw. alkynyl) , - (CH2)0-4-C0- (CH2) 0-4 (C3-C-, cycloalkyl) , - (CH2) 0-4-Rno/ - (CH2) 0-4-R12i], -(CH2)O-4-R13o, -(CH2)0-4-CO-R110, - (CH2) o-4-CO-Ra21), -(CH2)0.4-CO-R13o, -(CHzJo^-CO-R^o, - (CH2) 0-4-CO-O- Riso, -(CH2)o-4-SO2-NRi05R'ios/ - (CH2) 0-4-S0-(Ca-Cg alkyl) , - (CH2) o-4-SL2. (Ci-da alkyl) , - (CH2) 0-4-SO2- (CH2) 0.4- (C3-C7 cycloalkyl) , - (CH2) o-4-N(Ri5o) -C0-L- R1S0, -(CH2)0-4-N(Riso)-CO-N(R15o)2, -(CH2)0-4- N(R150) -CS-N(Ri5o)2, ~ (CH2)0-4-N(R15o)-CO-Rios, -(CH2)0.4-NRiosR'ios, -(CH2)0-4-R140, - (CH2) 0-4-O-CO- (d-C6 alkyl), - (CH2)0-4-O-P(O)-(O-Rno)2, -(CH2)0- 4-O-CO-N(R15Q)2, - (CH2)o-4-O-CS-N(Riso)2, - (CH2) 0-4- O- (R150) , - (CH2) o-4-O-Riso' -COOH, - (CH2) 0-4-S- (Riso) , - (C^Jo^-NCRjlboJ-SOj-Rhjs, -(CH2)0-4- C3-C7 cycloalkyl, (C2-C10) alkenyl, or (C2-C10)alkynyl. Preferred compounds of formula AA-5 include compounds wherein one of RN and RN' is hydrogen and the other is -C(=O)-R10o; and Rj.00 represents aryl, or heteroaryl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from -OR, -NO2, Ci-C6 alkyl, halogen, -C=N, -OCF3, -CF3, - (CH2) o-4-O-P (=O) (OR) (OR') , - (CH2) 0-4-CO-NRi05R' ios. - (CH2)0-4-O- (CH2)0-4-CONRi02Rioa', - (CH2)0-4-CO- (d-C12 alkyl), - (CH2) o_4-CO-(C2-C12 alkenyl) , - (CH2) 0_4- C0- (C2-C12 alkynyl) , - (CH2) 0-4-CO- (CH2) 0-4 (C3-C7 cycloalkyl) , - (CH2) 0-4-R110; - (CH2)0-4-Ri2o, - (CH2)0-4-Ri30r - (CH2)o-4-CO-R110, - (CH2) o-4-CO-Ri20, - (CH2)0-4-CO-Ri3o, - (CH2)0-4-CO-Ri4o, - (CH2) 0-4-CO-O- Riso, -(CH2)o-4-S02-NR105R'ios/ - (CH2) 0-4-SO-(Ci-CB alkyl), -(CH2)o-4-S02. (Ci-C12 alkyl) , - (CH2)0-4-SO2- (CH2)0-4-(C3-C7 cycloalkyl), - (CH2; o.4-N{R15o)-CO-O- Riso, -(CH2)0-4-N(R15o)-CO-N(R15o)2, - (CH2) 0.4- N (R150) -CS-N (R150) 2, - (CH2) 0-4-N (R1S0) -CO-R105, - (CH2)o-4-NRio5R'iO5/ -(CH2)0-4-Ri40, - (CH2) 0-4-O-CO- (Ci-Cs alkyl), -(CH2)0-4-O-P(O)- (O-RU0)2, -(CH2)0- 4-O-CO-N(Rlso)2, -(CH2)0-4-O-CS-N(R15o)2, -(CH2)0-4- O-(Ribo), -(CH2)0.4-O-R15o'-COOH, - (CH2) 0-4-S-(R150) / -(CH2) 0-4-N(R1So)-SO02-R105, -(CH2)O-4- C3-C7 cycloalkyl, (C2-C10) alkenyl, or (C2-C10) alkynyl. Preferred compounds of formula AA-5 also include compounds wherein one of Rn and RNT is hydrogen and the other is -C(=O)-aryl or -C(=O)-heteroaryl where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from -OR, -NO2, Ci-C6 alkyl, halogen, -C^Sf, -OCF3, -CF3, - (CH2)o-4-CO-NRio5R'io5- " (CH2) 0-4-O-(CH2) 0-4- CONR102Ri02', -(CH2) 0-4-CO-(d-C12 alkyl), -(CH2)0-4- CO- (C2-Ci2 alkenyl) , - (CH2) 0-4-CO- (C2-Ci2 alkynyl) , - (CH2) o-4-Riio, - (CH2) 0-4-R120, " (CH2) 0-4-R130, -(CH2)0.4-CO-R110, -(CH2)o-4-CO-R120, - (CH2) 0..4-CO- Ruo, -(CH2)0.4-CO-R140, -(CH2)0.4-CO-O-R150, - (CH2) 0- 4-SO2-NRlosR'ios, - (CH2) 0-4-SO- (Ci-Ce alkyl) , - (CH2) 0-i-SO2. (Ca-C12 alkyl) , - (CH2; 0-4-N (Ri50) -CO-O- R150, -(CH2)0.4-N(Rlso)-CO-N(R15o)2, - (CH2) 0.4- N(Ri5o) -CO-Rj.05, - (CH2)o-4-NRidsR'ios, - (CH2) O-4-Ri«o, - (CH2) 0-4-0-CO- (d-C6 alkyl) , - (CH2) 0.4-O-CO- N(Ri5o)2, - (CH2) o-4-O-(R1So) , -(CH2)0.4-N(R150;-SO2- R105, -(CH2)0-4- C3-C7 cycloalkyl, (C2- C10) alkenyl, or (C2-Ci0) alkynyl. Other preferred compounds of formulla AA-5 include compounds wherein one of RN and RN' is hydrogen and the other is -C(=O)-aryl or -C(=O)-heteroaryl where the ring portions of each are optionally substituted with 1 or 2 groups independently selected from Cx-Cg alkyl, halogen, - (CH2) o-4-CO-NR1(iSR'ios, - (CH2) 0-4- O-CO-N(Ri50)2, - (CH2)o-4-N(R1so)-SO2-R105, -(CH2)0-4- SO2-NR105R'105/ C3-C7 cycloalkyl, (C2-C10) alkenyl, - (CH2)o-4-Ruo, -(CH2)0-4-Ri20, - (CH2)o-4-Ri3o, or (C2-C10) alkynyl. Other preferred compounds of formula AA-5 include compounds wherein one of RN and RN' is hydrogen and the other is -C(=O)- phenyl, where the phenyl ring is optionally substituted with 1 or 2 groups independently selected from Ci-C6 alkyl, halogen, - (CH2) 0-4-CO-NR105R'105/ -(CH2)0-4- O-CO-N(R15O)2, - (CH2)0.4-N(R15o)-SO2-Ri05, - (CH2) O-4- S02-NRi05R'ios» C3-C7 cycloalkyl, (C2-C1O) alkenyl, 59 - (CH2)o-4-Riio, -(CH2)o-4-Ri2o# -(CH2)o-4-Ri3o, or (C2-Cio)alkynyl. Other preferred compounds of formula AA-5 also include compounds wherein one of Rn and Rn' is hydrogen and the other is: wherein sub is hydrogen or is Ci-Cg alkyl, halogen, - (CH2)o-4-CO-NR105R'105, -(CH2)0-4-O-CO-N(R1S0)2, C3-C7 cycloalkyl, - (C2-Cio)alkenyl, - (CH2) o-4-Riu, - (CH2)o-4-Ri2o/ - (CH2)0-4-Ri30; or (C2-C10)alkyny:i. A preferred stereochemistry for compounds of formula AA is as follows: Preferred compounds of formula I include those of formula 1-1, i.e., compounds of formula I wherein Rx is aryl, heteroaryl, heterocyclyl, -CX~C& cilkyl-aryl, - Ci-C6 alkyl-heteroaryl, or -Ci-Cs alkyl- heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected frotr. halogen, - OH, -SH, -GsN, -NO2, -NRio5R'io5r -CO2R, N(R)COR', or -N(R)SO2R', -C(=O)- (C!-C4) alkyl, -S02-amino, -SO2-mono or dialkylamino, -C(=O)- amino, -C(=O)-mono or dialkylami.no, -SO2- (Ci-C4) alkyl, or Ci-Cs alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen, or C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -CsN, -CF3, d-C3 alkoxy, amino, -C^Cg alkyl and mono- or dialkylamino, or C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, -C!-C3 alkoxy, amino, mono- or dialkylamino and -Ci-C3 alkyl, or C2-Cio alkenyl or C2-C10 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=M, -CF3, C1-C3 alkoxy, amino, Ci-C6 alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo. Preferred compounds of formula 1-1 also include those wherein Ri is -Ci-C6 alkyl-aryl, -Cx-Cf; alkyl-heteroaryl, or -Ci-Cs alkyl-heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, -OH, -SH, -G=N, -NO2, -NR1OsR'105, -CO2R, -N(R)COR', or -N(R)SO2R', -C (=0) - (d-C4) alkyl, -SO2-amino, -SO2-mono or dialkylamino, -C(=O)- amino, -C(=O)-mono or dialkylamino, -SO2-(Ci-C4) alkyl, or Ci-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen, or C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen', -OH, -SH, -ON, -CF3, C1-C3 alkoxy, amino, -Ci-Cs alkyl and mono- or dialkylamino, or Ci-Cj.0 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C^N, -CF3, -C1-C3 alkoxy, amino, mono- or dialkylamino and -C1-C3 alkyl, or C2-C10 alkenyl or C2-Ci0 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -ON, -CP3, d-C3 alkoxy, amino, Ci-Cs alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo. Preferred compounds of formula 1-1 further include those wherein Ri is -(CH2)-aryl, - (CH2) -heteroaryl, or - (CH2) - heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, - OH, -SH, -CsN, -NO2, -NR1OSR'1O5, -CO2R, - N(R)COR', or -N(R)SO2R', -C(=C)- (Ca-CJ alkyl, -SO2-amino, -SO2-mono or dialkylamino, -C(=O)- amino, -C(=O)-mono or dialkylamino, -SO2-(C1-C4) alkyl, or Ci-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen, or C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, C3.-C3 alkoxy, amino, -Ci-C6 alkyl and mono- or dialkylamino, or C3.-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, -C!-C3 alkoxy, amino, mono- or dialkylamino and -Cj.-C3 alkyl, or C2-C10 alkenyl or C2-C10 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -CsK, -CF3, C1-C3 alkoxy, amino, Ci-C6 alkyl and mono- or dialkylamino,- and the heterocyclyl group is optionally further substituted with oxo. Preferred compounds of formula 1-1 also include those wherein Ri is -CH2-phenyl or -CH2-pyridinyl where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, C1-C4 alkoxy, hydroxy, -NO2, and C1-C4 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from halogen, OH, SH, NH2, NH(Ci-Cs alkyl), N-(d-Cs alkyl) (Ci-Cs alkyl) , ON, CF3. Preferred compounds of formula 1-1 further include those wherein R2 is ~CH2-phenyl or -CH2-pyridinyl where the phenyl or pyridinyl rings are each optionally substituted with 1 or 2 groups independently selected from halogen, C1-C2 alkyl, C!-C2 alkoxy, hydroxy, -CF3/ and -NO2. Preferred compounds of formula 1-1 include those wherein Rj. is -CH2-phenyl where the phenyl ring is optionally substituted with 2 groups independently selected from halogen, Ci-C2 alkyl, Ci-C2 alkoxy, hydroxy, and -NO2. Preferred compounds of formula 1-1 also include those wherein Rj, is benzyl, or 3,5-difluoro!benzyl. Preferred compounds of formula I and 1-1 include those of formula 1-2, i.e., compounds of formula I or 1-1 wherein R2 and R3 are independently selected from H or Ca.-C6 alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of C].-C3 alkyl, halogen, -OH, -SH, -GsN, -CF3, C1-C3 alkoxy, and -NRj.. aRl-b. Preferred compounds of formula 1-2 include those wherein Rc is selected from the group consisting of Ci-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R20S, -OC=ONR235R24o, -S(=O)o-2(Ci-Cs alkyl), -SH, -NR235C=ONR235R240, -C=ONR23SR24o/ and -S (=O) 2NR235R2.so; - (CH2)0-3- (C3-Ce) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of Rzos/ -CO2H, and -CO2-(Ci-C4 alkyl) ; - (CR245R250) 0-4-aryl; - (CR245R2S0) o-4-heteroaryl; - (CR245R2S0) 0-4- heterocycloalkyl; - [C (R255) (R26o) 11-3-CO-N- (R255) 2; CH(aryl)2; -CH(heteroaryl)2; -CH(heterocycloalkyl)2; -CH(aryl) (heteroaryl) ; -CO-NR235R24o; -(CH2)0-i- CH ( (CH2) 0-6-OH) - (CH2) 0-1-aryl; - (CH2) o-i-CHRc-s- (CH2) 0-1 - heteroaryl; -CH(-aryl or -heteroaryl)-CO-O(Ci-C4 alkyl); -CH(-CH2-OH) -CH (OH)-phenyl-NO2; (Ci-C6 alkyl) - O- (Cx-Cg alkyl)-OH; -CH2-NH-CH2-CH (-O-CH2-CH3) 2; -H; and - (CH2) o-6-C(=NR23S) (NR235R24o) ; wherein each aryl is optionally substituted with 1, 2, or 3 R200; each heteroaryl is optionally substituted with 1, 2, 3, or 4 R200; each heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R2io; R2Oo at each occurrence is independently selected from the group consisting of Ci-C6 alkyl optionally substituted with 1, 2, or 3 R205 groups; OH; -NO2; halogen; -CO2H; C=N; - (CH2) 0-4- CO-NR220R225; - (CH2) 0-4-CO- (C!-C12 alkyl) ; - (CH2) 0-4- CO2R215; and - (CH2) 0-4-O- (Ci~Cs alkyl optionally substituted with 1, 2, 3, or 5 -F) ; wherein each aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205, R2io or Cx-C6 alkyl substituted with 1, 2, or 3 groups that are independently R2os or R210; wherein each heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R210; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R-205J R210/ or C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210; R205 at each occurrence is independently selected from the group consisting of C1-C6 alkyl, halogen, -OH, -O-phenyl, -SH, -C=N, -CF3, C1-C6 alkoxy, NH2, NH(C1-C6 alkyl), and N- (C1-C6 alkyl) (C1-C6 alkyl) ; R210 at each occurrence is independently selected from the group consisting of C1-C6 alkyl optionally substituted with 1, 2, or 3 R2os groups; halogen; C1-C6 alkoxy; C1-C6 haloalkoxy; -NR220R225; OH; C=N; C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R205 groups; -CO-(d- C4 alkyl); .SO2-NR235R240; -CO-NR235R240; -SO2-(C1-C4 alkyl); and =O; wherein R215 at each occurrence is independently selected from the group consisting of C1-C6 alkyl, - (CH2)0.2- (aryl) , C3.C7 cycloalkyl, and -(CH2)0-2- (heteroaryl), - (CH2) 0-2-(hsterocycloalkyl); wherein the aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205 or R210; wherein the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R210; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R210; R22o and R225 at each occurrence are independently selected from the group consisting of -H, -C1-C6 alkyl, hydroxy Ci-C6 'alkyl, amino Ci-Cs alkyl; halo Ci-C6 alkyl; -C3-C7 cycloalkyl, - (Ci-C6 alkyl)-O-(C!-C3 alkyl), -aryl, -heteroaryl, and -heterocycloalkyl; wherein the aryl group at each occurrence is optionally substituted with 1, 2, or 3 R270 groups, each heteroaryl is optionally substituted with 1, 2, 3, or 4 R200, each heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R2io wherein R270 at each occurrence is independently R2osr Ci-Cg alkyl optionally substituted with 1, 2, or 3 R205 groups; halogen; Ci-CS' alkoxy; Ci-Cs haloalkoxy; NR235R240; OH; C=N; -CO-(Cx-C* alkyl); and =0; wherein the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R205 groups; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R2os groups; R235 and R240 at each occurrence are independently H, or Cx-Cs alkyl; R245 and R25o at each occurrence are independently selected from the group consisting of H, C1--C4 alkyl, Ci-04 hydroxyalkyl, Q1.-C4 alkoxy, Ci~C4 haloalkoxy, or R245 and R25o are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, ox 1 carbon atoms, wherein the carbocycle is optionally substituted with 1 or 2 groups that are independently OH, methyl, Cl, F, OCH3, CF3, N02, or CN; R255 and R26o at each occurrence are independently selected from the group consisting of H; Ci~Cs alkyl optionally substituted with 1, 2, or 3' R205 groups,- - (CH2)o-4-C3-C7 cycloalkyl optionally- substituted with l, 2, or 3 R205 groupia; - (C1-C4 alkyl)-aryl; - (Cx-Ct alkyl)-heteroaryl; -(C1-C4 alkyl)-heterocycloalkyl; aryl; heteroaryl; heterocycloalkyl; . (CH2) -..-4-R26S- (CH2) 0_4-aryl ; -(CH2)i-4-R2ss-(CH2)o-4-heteroar/l; and; -(CH2)i-4- R265- (CH2) 0-4-heterocycloalkyl; wherein R26S at each occurrence is independently -0-, -S- or -N(Ci-C6 alkyl)-; each aryl or phenyl is optionally substituted with 1, 2, or 3 groups that are independently R2os/ R210/ or Cl-Cs alkyl substituted with 1, 2, or 3 groups that are independently R2os or R210. Preferred compounds of formula 1-2 include those wherein: Rc is - (CR245R2so) 0-4-aryl, or - (CR245R2S0) o-4-heteroaryl, wherein aryl and heteroaryl are optionally substituted with 1, 2, or 3 R2Oo groups. Preferred compounds of formula 1-2 also include compounds wherein Rc is - (CR245R2eo)-aryl, or - (CR24sR2so) -heteroaryl wherein each aryl and heteroaryl is optionally substituted with 1, 2, or 3 R200 groups. Preferred compounds of formula 1-2 also include compounds wherein Rc is -(CH2)-aryl, or - (CH2)-heteroaryl, wherein each aryl and heteroaryl is optionally substituted with 1, 2, or 3 groups selected from OH,. -M02, halogen, -CO2H, GsN, - (CH2) o-4-CO-NR220R22s; -(CH2)0-4-CO-(C1-C12 alkyl), and - (CH2)CM-SO2- NR22pR225 • Preferred compounds of 'formula 1-2 also include compounds wherein Rc is -(CH2)-aryl, wherein aryl is optionally substituted with 1, 2, or 3 groups selected from OH, -N02, halogen, -CO2H, and C^N. Preferred compounds of formula 1-2 also include compounds wherein Rc is - (CH2) -phenyl, wherein phenyl is optionally substituted with 1, 2, or 3 groups selected from OH, -N02, halogen, -CO2H, and C=N. Preferred compounds of formula 1-2 also include compounds wherein Rc is benzyl. Other preferred compounds of formulas I, 1-1 and 1-2 include compounds of formula 1-3, i.e., those of formulas I, I-lorI-2 wherein RN is: ,Z _{CH2)n7-CHC(O)- Y X R4 wherein R4 is NH2; ~NH-(CH2)nS-R4-i; -NHR8; -NR50C (0) R5; or - NRS0CO2R51 ; wherein n6 is 0, 1, 2, or 3; n7 is 0, 1, 2, or 3; R4_i is selected from the group consisting of -S02- (Cx-Cs alkyl) , -SO-Cd-Cs alkyl) , -S- (C^Ce alkyl) , -S-CO-(Ci-c6 alkyl), -SO2-NR4.2R4.3; -C0- C1-C2 alkyl; -CO-NR4_3R4.4; R4-2 and R4.3 are independently H, C1-C3 alkyl, or C3-C6 cycloalkyl ; R4.4 is alkyl, phenylalkyl, C2-C4 alkanoyl, or phenylalkanoyl; R; is cyclopropyl; cyclobutyl; cyclopentyl; and cyclohexyl; wherein each cycloalkyl group is optionally substituted with one or two groups that are Ci-C6 alkyl, more preferably C3-C2 alkyl, Cx-C6 alkoxy, more preferably C1-C2 alkoxy, CF3, OH, NH2, NHfCi-Cg alkyl), N(Ci-C6 alkyl) (Cx-Cs alkyl), halogen, CN, or N02; or the cycloalkyl group is substituted with 1 or 2 groups that are independently CF3, Cl, F, methyl, ethyl or cyano; Cx-Cs alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, -NRgR7, Ci-CU alkoxy, C5-C6 heterocycloalkyl, C5-C6 heteroaryl, phenyl, C3-C7 cycloalkyl, -S-Ci-C4 alkyl, -SO2-Ci-C4 alkyl, -CO2H, -CONRSR7, -CO2-C!-C4 alkyl, or phenyloxy; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently Ci-C4 alkyl, Ci-C4 alkoxy, halogen, Ca.-C4 haloalkyl, or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groups that are independently C!-C4 alkyl, Ci-C4 alkoxy, halogen, or C2-C4 alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, OH, C1-C4 alkyl, Q1.-C4 alkoxy, or Ci-C4 haloalkyl; and -NR6R7; wherein R6 and R7 are independently selected from the group consisting of H, Ci-Cs alkyl, C2-C6 alkanoyl, phenyl, -SO2-Cj.-C4 alkyl, and phenyl Cx-C4 alkyl; Rg is selected from the group consisting of -S02- heteroaryl optionally substituted with 1 or 2 groups that are independently Ci-C4 alkyl or halogen,-, -SO2-aryl, -S02-heterocycloalkyl, -C(O)NHRa, heterocycloalkyl, -S-C2-^4 alkanoyl, wherein Rs is phenyl C1-C4 alkyl, Ci-C6 alkyl, or H; Rso is H or Ql-Cs alkyl; R5i is selected from the group consisting of phenyl C1-C4 alkyl; Ci-Cs alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, -NR6R7, -C(O)NR6R7, C3-C7 or -Cj.- C4 alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups that are independently C3.-C4 alkyl, C!-C4 alkoxy, halogen, C2-C4 alkanoyl, phenyl CJ.-C4 alkyl, and -SO2 Cx-C4 alkyl; heterocycloalkylalkyl optionally substituted with l or 2 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, C2-C4 alkanoyl, phenyl C1-C4 alkyl, and -S02 C 3.-04 alkyl; alkenyl; alkynyl; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently OH, C1-C4 alkyl, C!-C4 alkoxy, halogen, NH2; NH (Cz-C6 alkyl) or N (Ci-Cs alkyl) (Ci-Cs alkyl) ; heteroarylalkyl optionsilly substituted with 1, 2, or 3 groups that are independently Q1.-C4 alkyl, C1-C4 alkoxy, halogen, NH2, NH(Ci-C6 alkyl) or N(Ci-C6 alkyl) (d-Cs alkyl); phenyl; C3-C8 cycloalkyl, and cycloalkylalkyl, wherein the phenyl; C3-C8 cycloalkyl, and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5 groups that are independently halogen, CN, N02, Ci-Cs alkyl, Ci-Cg alkoxy, C2-Cs alkanoyl, Ci-C6 haloalkyl, Ci-C6 haloalkoxy, hydroxy, C;l-C6 hydroxyalkyl, Ci-C6 alkoxy Ci-Cs alkyl, Ci-C6 thioalkoxy, Ci-Cs thioalkoxy Ci-Cs alkyl, or Ci- C6 alkoxy Ci-C6 alkoxy. Preferred compounds of formula 1-3 include compounds wherein wherein X is C!-C4 alkylidenyl optionally substituted with 1, 2, or 3 methyl groups,- or -NR4.6-; or R4 and R4_6 combine to form -(CH2)ni0-/ wherein nio is 1, 2, 3, or 4; Z is selected from a bond; S02; SO; S; and C(0); Y is selected from H; Cx-C4 haloalkyl; Cs-C6 heterocycloalkyl containing at least one N, 0, or S; phenyl; OH; -N{?i) (Y3) ; Ci-C10 alkyl optionally substituted with 1 thru 3' substituents which can be the same or different and are selected from halogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy; C3-C8 cycloalkyl optionally substituted with 1, 2, cr 3 groups independently selected from C1-C3 alkyl, and halogen; alkoxy; phenyl optionally substituted with halogen, Cj.-^ alkyl, C1-C4 alkoxy, CN or N02; phenyl C1-C4 alkyl optionally substituted with halogen, C^d alkyl, Ci-C4 alkoxy, CN or N02; wherein Yj. and Y2 are the same or different and are H; C1-C10 alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, C!-C4 alkoxy, C3-C8 cycloalkyl, and OH; C2-C6 alkenyl; C;,-C6 alkanoyl; phenyl; -S02- C!-C4 alkyl; phenyl C^d alkyl; and C3-C8 cycloalkyl C1-C4 alkyl; or -N{Y!) (Y2) forms a ring selected from piperaziryl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently Ci-C6 alkyl, C^-Cg alkoxy, Ci-Cs alkoxy Cx-C6 alkyl, or halogen. Preferred compounds of formula 1-3 include compounds wherein X is Ci-C4 alkylidenyl optionally optionally substituted with 1, 2, or 3 methyl groups; Z is selected from SO2; SO; S; and C(0); Y is selected ' from H; Ci.-C4 haloalkyl; Cs-Cs heterocycloalkyl containing at least one N, 0, or S; phenyl; OH; -N^) (Y2); Ci-C10 alkyl optionally substituted with 1 thru 3 substituents which can be the same or different and are selected from the group consisting of halogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy; C3-C8 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from C1-C3 alkyl, and halogen; alkoxy; phenyl optionally substituted with halogen, C!-C4 alkyl, C!-C4 alkoxy, CN or N02; phenyl Ca-C4 alkyl optionally substituted with halogen, C1-C4 alkyl, Ca-C4 alkoxy, CN or N02; wherein Yi and Y2 are the same or different and are H; Cx-Cg alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, Ci-C4 alkoxy, C3-C8 cycloalkyl, and OH; C2-C6 alkenyl; C2-C6 alkanoyl; phenyl; -S02- Ci-C4 alkyl; phenyl Cx-C4 alkyl; or Ca-C8 cycloalkyl Ci-C4 alkyl; or -N(Yi) (Y2) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently Ci-C6 alkyl, Ci-C6 alkoxy, Cx-Cg alkoxy Ci-C6 alkyl, or halogen. and wherein R4 is NH2; -NH- (CH2)nS-R4-i; -NHR8; - NR50C(O)R5; or -NR50C02R51 wherein n6 is 0, 1,2, or 3; n7 is 0, 1, 2, or 3; R4-1 is selected from the group consisting of -S02- (d-Ca alkyl) , -SO-(Ci-C8 alkyl) , -S-(Ci-Cb alkyl) , -S-CO-(d-Cg alkyl), -SO2-NR4-2R4-3; -CO- Ci-C2 alkyl; -CO-NR4.3R4-4; R4.2 and R4.3 are independently H, C1-C3 alkyl, or C3-C6 cycloalkyl; R4.4 is alkyl, phenylalkyl, C2-C4 alkanoyl, or phenylalkanoyl; R5 is cyclopropyl,- cyclobutyl; cyclopentyl; or cyclohexyl; wherein each cycloalkyl group is optionally substituted with one or two groups that are d-C,; alkyl, more preferably Ci-C2 alkyl, Ci-Cs alkoxy, more preferably d-C2 alkoxy, CF3, OH, NH2, NH(d-C6 alkyl), N(d-C6 alkyl) (d-Cs alkyl), halogen, CN, or NO2; or the cycloalkyl group is substituted with 1 or 2 groups that are independently CF3, Cl, F, methyl, ethyl or cyano; d-C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, -NRSR7, C1--C4 alkoxy, C5- Ce heterocycloalkyl, C5-C6 heteroaryl, phenyl, C3-C7 cycloalkyl, -S-C1-C4 alkyl, -SO2-d-C4 alkyl, -CO2H, -CONRSR7, -CO2-CX-C4 alkyl, or phenyloxy; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently Cx-C4 alkyl, Ci-C4 alkoxy, halogen, Ca-C4 haloalkyl, or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, or C2-C4 alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, OH, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 haloalkyl; and -NRgR7; wherein R6 and R7 are independently selected from the group consisting of H, Ci-C6 alkyl, C2-C6 alkanoyl, phenyl, -SO2-C1-C4 alkyl, and phenyl C1-C4 alkyl; R8 is selected from the group consisting of -S02- heteroaryl optionally substituted with 1 or 2 groups that are independently C1-C4 alkyl or halogen;, -SO2-aryl, -S02-heterocycloalkyl, -C(O)NHR9, heterocycloalkyl, -S-C2-C4 alkanoyl, wherein Rg is phenyl Ci-C4 alkyl, Ci-Cs alkyl, or H; R50 is H or Ci-Cs alkyl; and R51 is selected from the group consisting of phenyl C1-C4 alkyl; Ci-Cs alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, -NR6R7, -C(O)NR6R7, C3-C7 or -Ci- C4 alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups that are independently Ci-C4 alkyl, Ci-C4 alkoxy, halogen, C2-C4 alkanoyl, phenyl C1-C4 alkyl,. and -S02 Ci-C4 alkyl; heterocycloalkylalkyl optionally substituted with 1 or 2 groups that are independently Ci-C4 alkyl, C1-C4 alkoxy, halogen, C2-C4 alkanoyl, phenyl C1-C4 alkyl, and -S02 C1-C4 alkyl; alkenyl; alkynyl; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently OH, C1-C4 alkyl, Ci-C4 alkoxy, halogen, NH2, NH(C!-C6 alkyl) or N(Ci-Cs alkyl) {C-j_-Cs alkyl) ; heteroarylalkyl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, NH2, NH(Ci-C6 alkyl) or N(d-C6 alkyl) (C3.-Ce alkyl); phenyl; C3-C8 cycloalkyl, and cycloalkylalkyl, wherein the phenyl; Ca-Cs cycloalkyl, and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5 groups that are independently halogen, CN, N02, Ci-C6 alkyl', Ci-C6 alkoxy, C2-C6 alkanoyl, CL-C6 haloalkyl, Ci-C6 haloalkoxy, hydroxy, C].-C6 hydroxyalkyl, C3.-C6 alkoxy C!-C6 alkyl, Cn-Cs thioalkoxy, Ci-C6 thioalkoxy Ci-C6 alkyl, or Ci- Cg alkoxy Ci-C6 alkoxy; and Y is C1-C10 alkyl optionally substituted with 1 thru 3 substituents which can be the same or different and are selected from halogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy. Preferred compounds of formula 1-3 further include compounds wherein Re is Ci-C8 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, -OC=ONR235R24o, -S (=O)0.2(Ci-C6 alkyl), -SH, -C=ONR235R240, and -S (=0) 2NR235R24o; -(CH2)o- 3-(C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R20S, -CO2H, and -C02- (Ci-C4 alkyl); - (CR24SR25o)o-4- phenyl; - (CR245R25o) 0-4-heteroaryl; - (CR245R2So) 0-4- heterocycloalkyl; - (CH2) o-i-CH ((CH2) 0-4-OH) - (CH2) 0-1- phenyl; - (CH2) o-i-CHRc-6-(CH2) o-i-heteroairyl; -CH(-CH2- OH)-CH(OH)-phenyl-NO2; (d-Cs alkyl)-O-(Cx-C6 alkyl)- OH? or -(CH2!o-6-C(=NR23S) (NR235R24o) ; wherein each aryl is optionally substituted with 1, 2, or 3 R200; each heteroaryl is optionally substituted with 1, 2, 3, or 4 R200; each heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R210; R200 at each occurrence is independently Cx-C6 alkyl optionally substituted with 1, 2, or 3 R20S groups; OH; -N02; halogen; -CO2H; ;>N; -(CH2)0_4- CO-NR220R22S; - CO2R2a5; or - (CH2) 0-4-O- (d-C6 alkyl optionally substituted with 1, 2, 3, or 5 -F) ? R2o5 at each occurrence is independently d-C6 alkyl, halogen, -OH, -O-phenyl, -SH, -C=N, -CF3, d-C6 alkoxy, NH2, NH(d"Cs alkyl), or N- (d.-C6 alkyl) (d-C6 alkyl) ; R210 at each occurrence is independently d-C6 alkyl optionally substituted with 1, 2, or 3 R2os groups; halogen; Ci-Cs alkoxy; d-Cs haloalko:Ky; -NR220R22S; OH; ON; C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R205 groups; -CO- (d- C4 alkyl) ; .S02.NR235R24o; -CO-NR235R240; -S02- (d"C4 alkyl); and =0; wherein R2is at each occurrence is independently d-C6 alJc^l, -(CH2)0.2-(phenyl) , d-d- cycloalkyl, and -(CH2)0- 2- (heteroaryl) , - (CH2) 0-2- (heterocycloalkyl) ; wherein the phenyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R20s or R210; wherein the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R2i0; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 Raio; R220 and R225 at each occurrence are independently -H, -Ci-Cs alkyl, hydroxy Cj-Cs alkyl, halo Ci-C6 alkyl; -C3-C7 cycloalkyl, and - (Ci-C6 alkyl)-0- (C1-C3 alkyl) ; R235 and R240 at each occurrence are independently H, or Ci-Cs alkyl; R24S and R2s0 at each occurrence are independently H, Ci-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, Ci- C4 haloalkoxy, or R245 and R2So are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms. Preferred compounds of formula 1-3 include compounds wherein Ri is benzyl which is optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, Ci- C4 alkoxy, hydroxy, and Cx-C4 alkyl optionally substituted with 1, 2, or 3 substituents halogen, ¦OH, SH, NH2, NH(Ci-Cs alkyl), N-(d-Cs alkyl) (C^-Cg alkyl) , Cs=N, CF3; R2 and R3 are independently selected from H or C1-C4 alkyl optionally substituted with 1 substituent selected from halogen, -OH, -SH, -CsN, -CF3, C1-C3 alkoxy, NH2, NH(Ci-Cs alkyl), and NH(C!-CS alkyl) (Ci-C6 alkyl); Rc is Cx-Cs alkyl optionally substituted with 1, 2, or 3 groups independently selected from R205» -SH, -C=ONR235R24o, and -S (=0) 2NR235R240; - (CH2) 0-3-(C3-Cs) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from R20S, -CO2H, and -C02- (Ci-C4 alkyl); - (CR245R250) o-4-phenyl optionally substituted with 1, 2, or 3 R2oo; - (CR24sR2so) 0-3-pyridyl; - (CR245R250) 0-3- pyridazinyl; - (CR24SR25o) 0.3-pyrimidinyl; - (CR245R2so) 0-3- pyrazinyl; - (CR24sRa5o) 0-3-furyl; - (CR24sR25o) 0-3-indolyl ; - {CR245R2Bo) 0-3-thienyl; - (CR245R2S0) 0-3-pyrrolyl; - (CR245R25o) 0-3-pyrazolyl; (CR245R25o) 0-3-benzoxazolyl ; - (CR245R2So) 0-3-itnidazolyl; each of the above heteroaryl groups is optionally substituted with 1, 2, 3, or 4 R200;- {CRZ45R250) 0-3-imidazolidinyl; (CR24SR2So) 0-3 -tetrahydrof uryl; {CR245K250) 0-3- fcetrahydropyranyl; (CR245R2so) 0-3-piperazinyl; (CR245R2so) 0-3-pyrrolidinyl; {CR245R25o) 0-3-piperidinyl ; (CR24sR25o)o-3-indolinyl; each of the above heterocycloalkyl groups is optionally substituted with 1, 2, 3, or 4 R210; (CH2) 0-i-CH( (CH2) 0-4-OH) - (CH2) 0. a-phenyl,- - (CH2) 0-i-CH [C^-Ci hydroxyalkyl) - (CH2) 0-i~ pyridyl; R20o at each occurrence is independently CX~C6 alkyl optionally substituted with 1, 2, or 3 R205 groups; OH; -N02; halogen; -CO2H; CfeN; -(CH2)0-4- CO-NR220R22s; - {Cn2) a-i-CO-(Cx-Ca alkyl)? -(CH2)0.4- CO2R2iS; and - (CH2)0-4-O- (Cx-Ce alkyl optionally substituted with 1, 2, 3, or 5 -F) ; R2os at each occurrence is independently Ci-C6 alkyl, halogen, -OH, -O-phenyl, -SH, -CaKT, -CF3, Ci-C6 alkoxy, NH2, NHfCx-Cs alkyl), and N-(Ci-Cg alkyl) (Ci-Cs alkyl); Raio at each occurrence is independently Ci-Cs alkyl optionally substituted with 1 or 2 R205 groups; halogen; Ci~C4 alkoxy; Cx-C* haloalkoxy; -NR220R225; OH; CsN; C3-C7 cycloalkyl optionally substituted with 1 or 2 R2os groups; -CO- (C1-C4 alkyl) ; -SO2-NR235R240; -CO-NR235R2«o; -S02- (C1-C4 alkyl); and =0; wherein R215 at each occurrence is independently Ci-C6 alkyl, - (CH2) 0-2- (phenyl) , C3.C6 cycloalkyl, - (CH2) 0-2- (pyridyl) , - (CH2) 0-2- (pyrrolyl) , - (CH2) 0-2- (imidazolyl) , - (CH2) 0-2- (pyrimidyl) , - (CH2) 0-2- (pyrrolidinyl) , - (CH2) 0.2- (imidazolidinyl) - (CH2) 0_2- (piperazinyl) , - (CH2) 0-2- (piperidinyl) , and - (CH2) 0-2-(morpholinyl) ; wherein the phenyl group at each occurrence is optionally substituted with 1 or 2 groups that are independently R205 or R2io; wherein each heterocycloalkyl group at each occurrence is optionally substituted with 1 or 2 R210; wherein each heteroaryl group at each occurrence, is optionally substituted with 1 or 2 R210; R22o and R22S at each occurrence are independently -H, -C1-C4 alkyl, hydroxy C1.-C4 alkyl, halo Cj,-C4 alkyl; -C3-Cs cycloalkyl, and - (Q1.-C4 alkyl) -0- (d-Ca alkyl) ; R235 and R240 at each occurrence are independently H, or C1-C6 alkyl; R24s and R250 at each occurrence are independently H, C1-C4 alkyl, C1-C4 hydroxyalkyl, Ca-C4 alkoxy, Cx- C4 haloalkoxy, or R245 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, or 6 carbon atoms. Other preferred compounds of formula 1-3 include compounds wherein X is-Ci-C3 alkylidenyl optionally optionally substituted with. 1 or 2 methyl groups; Z is S02; SO; S; or C(0); Y is C1-C4 haloalkyl; OH; -N(Ya)(Y2); Ci-C10 alkyl optionally substituted with 1 or 2 substituents which can be the same or different and are selected from halogen, hydroxy, Cj.-C4 alkoxy, Cj.-C4 thioalkoxy, and C].-C4 haloalkoxy; C1-C4 alkoxy; phenyl optionally substituted with halogen, Cx-04 alkyl, C1-C4 alkoxy, CN or NO2; and benzyl optionally substituted with halogen, C1-C4 alkyl, C1-C4 alkoxy, CN or N02; wherein Yi and Y2 are the same or different and are H; Ci-Cs alkyl optionally substituted with 1, 2, cr 3 substituents selected from halogen, C3.-C2 alkoxy, C3-Cs cycloalkyl, and OH; C2-C6 alkanoyl; phenyl; -SO2-Ci-C4 alkyl; benzyl; and C3-C6 cycloalkyl Ci-C2 alkyl; or -N(Yi) (Y2) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidi:ayl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently Ci-Cs alkyl, Ci-C6 alkoxy, Ci-C6 alkoxy d-C6 alkyl, or halogen. Preferred compounds of formula 1-3 also include those of formula 1-4, i.e., compounds of formula 1-3 wherein X is-Ci-C3 alkylidenyl optionally optionally substituted with 1 methyl group; Z is S02; SO; S; or C(0); Y is OH; -N(YX)(Y2); phenyl; benzyl; or d-C10 alkyl optionally substituted with 1 or 2 substituents which can be the same or different and are selected from halogen, hydroxy, methoxy, ethoxy, thiomethoxy, thioethoxy, and CF3; wherein Yi and Y2 are the same or different and are H; Cj,-C4 alkyl optionally siibstituted with 1 or 2 substituents selected from halogen, methoxy, ethoxy, cyclopropyl, and OH; or -N(Yi) (Y2) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with l or 2 groups that are independently CJ-C4 alkyl, Ci-C4 alkoxy, or halogen; Ri is benzyl which is optionally substituted with 1, 2, or 3 groups independently selected from methyl, ethyl, n-propyl, isopropyl, hydroxymethyl, monohalomethyl, dihalomethyl, trihalomethyl, -CH2CF3, methoxymethyl, halogen, methoxy, ethoxy, n-propyloxy, isopropyloxy, and OH; R2 and R3 are independently H or C1-C4 alkyl, Rc is Ci-Cg alkyl optionally siibstituted with 1, 2, or 3 R205 groups; cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cyclohexylmethyl; - (CR24SR2so) 0-3-phenyl optionally substituted with 1 or 2 R2oo groups; - (CR245R25o)o-3- pyridyl optionally substituted with 1 or 2 R200; - {CR245R250) 0-3 -piperazinyl; or (CR245R2so) 0-3 - pyrrolidinyl; - (CR24sR2so) 0-3-piperidinyl; each of the above heterocycloalkyl groups ia optionally substituted with 1 or 2 R210 groups; R200 at each occurrence is independently selected from Cx-Ci alkyl optionally substituted with 1 or 2 R205 groups; OH; and halogen; R2os at each occurrence is independently selected from C1-C4 alkyl, halogen, -OH, -SH, -CsN, -CF3, and d~c4 alkoxy; R210 at each occurrence is independently selected from C1-C4 alkyl optionally substituted with 1 or 2 R20S groups; halogen; C1-C4 alkoxy; OCF3/- NH2, NH(d-CG alkyl); N(d-C6 alkyl) (d-C6 alkyl); OH; and -CO-(C1-C4 alkyl); wherein R245 and R2so at each occurrence are independently selected from H, d~CU hydroxyalkyl, d~C4 alkoxy, or R24S and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 5,or 6 carbon atoms. Preferred compounds of formulas I, 1-1 and 1-2 include compounds of formula 1-5, i.e., those of formulae I, 1-1 or 1-2 wherein RK is -C(=O) - (CRR')o.sR1Oo; and R100 represents aryl, heteroaryl, or heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from -OR, -N02, d-C6 alkyl, halogen, -CsN, -OCF3, -CF3, - (CH2)0-4-O-P(=O) (OR) (OR') , -(CH2)o-4-CO-NR10sR'ios, - (CH2) 0-4-O- (CH2) o-4-CONR102R102' , - (CH2) 0-4-CO- (d"dz alkyl) , - (CH2) 0-4-CO- (Ca-da alkenyl) , - (CH2) 0-4- CO- (C2-d2 alkynyl), - (CH2)p-4-CO- (CH2)0.4 (C3-C7 cycloalkyl) , - (CH2) 0-4-R110, - (CH2) 0-4-R120, -(CH2)0-4-Ri30, -(CH2)0.4-CO-Riia, - (CH2) o-4-CO-RX2o, - (CH2) o-4-CO-Ru0j - (CH2) o.4-CO-R14o, - (CH2) 0-4-CO-0- Riso, - (CH2) 0-4-S02-NRio5R'io5, - (CH2) 0-4-SO-- (d-Ca alkyl) , - (CH2) 0-4-S02. {Cx-Zx2 alkyl) , - (CH2) 0.4-SO2- (CH2)o-4-(C3-C7 cycloalkyl), - (CH2) 0-4-N(R150)-C0-0- Riso, -(CH2)0.4-N(R1So}-CO-N(Riso)3/ -(CH2)0-4- N(R15o)-CS-N(R15o)2, -(CH2)o-4-:S(Riso)-CO-R105, -(CH2)o-4-NRiosR'iO5, -(CH2)o-4-Ri4O/ - (CH2) 0-4-O-CO- (Ca-C6 alkyl), - (CH2) 0-4-O-P(O) - (0-R110)2, -(CH2)0- 4-O-CO-N(R150)2/ -(CH2)o-4-0-CS-N(RiEio)2, - (CH2J 0.4- O- (Riso) , - (CH2) o-4-O-Riso' -COOH, - (CH2) 0.4-S- (Rlso) , -(CH2)0-4-N(R150)-SO2-R105, -(CH2)0_4- C3-C7 cycloalkyl, (C2-C10) alkenyl, or (C2-Ci0) alkynyl. Preferred compounds of formula 1-5 include compounds wherein RN is -C(=O)-R100; and Rioo represents aryl, or heteroaryl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from -OR, -N02, Ci~C6 alkyl, halogen, -C=N, -OCF3, -CF3, - (CH2) o-4-O-P (=0) (OR) (OR' ) , - (CH2) 0..4-CO-NR10sR' ios- - (CH2) o-4-O- (CH2) 0-4-CONRio2Rio2', - (CH2) 0-4-CO- (C1-C12 alkyl) , - (CH2) 0-4-CO- (C2-Ci2 alkenyl) , - (CH2) o-4- CO- (C2-Ci2 alkynyl) , - (CH2) 0-4-CO- (CH2) 0-4 (C3-C7 cycloalkyl), - (CH2) 0-4-R110/ - (CH2) 0-4-^i2o; - (CH2)0.4-R130, - (CH2)o-4-CO-Rii0, - (CH2) 0-4-CO-:S.i20, -(CH2)0.4-CO-Ri30, -(CH2)o-4-CO-R140, - (CH2) 0-4-CO-O- Ri5o, " (CH2) 0-4-SO2-NR105R' 1D5, - (CH2) 0-4-SO- (C^-Cs alkyl), -(CH2)o-4-SO2.(Ci-C12 alkyl) , - (CH2) 0.4-S02- (CH2)0-4-(C3-C7 cycloalkyl), - (CH2) O-4-N(Ri5o) -C0-0- Riso, -(CH2)o-4-N(Ri5o)-CO-N(R150)2, - (CH2) 0.4- N(R15O)-CS-N(R15o)2, -(CH2)0.4-N(R15o)-CO-R105, -(CH2)0-4-NRi05R'l05, -(CH2)0-4-Ri40, -(CH2)0-4-O-CO- (d-Cs alkyl), -(CH2)0-4-O-P(O)-(O-R110)2, -(CH2)0- 4-0-CO-N(RiSo)2, -(CH2)0.4-0-CS-N(R1.5o)2, -(CH2)0.4- 0- (Riso) , - (CH2) o-4-O-Rxso' -COOH, - (CH2) 0-«-S- (R150) , -(CH2)0-4-N(RiSo)-S02-R105, • -(CH2)0-4- C3-C7 cycloalkyl, (C2-C10)alkenyl, or (C2-Ci0) alkynyl. Preferred compounds of formula 1-5 also include compounds wherein RN is -C(=O)-aryl or -C(=0)-heteroaryl where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from -OR, -N02, Cx-Ce alkyl,. halogen, -CsN, -OCF3, -CF3, - (CH2) 0.4-C0-NR105R' io5, - (CH2) o-4-0- (CH2) 0_4- CONR102R102' r - (CH2) o-4-CO- (Ci-Ci2 alkyl) , - (CH2) 0_4- CO- {C2-C12 alkenyl) , - (CH2)0.4-CO- (C2-Cij alkynyl) , - (CH2) 0-4-RllO, " (CH2) 0-4~R-X20f ~ (CH2) 0-4-J-130, -(CH2)0- R130, - (CH2)0-4-CO-Ri4o, - (CH2)0-4-CO-O-R1S0, -(CH2)o- 4-S02-NRlosR'io5, - (CH2) 0.4-SO- (Ci-C8 alkyl) , - Ribo, -(CH2)o.4-N(R150)-CO-N(R150)2, - (CH2) 0-4- N(Riso) -CO-Rios, -(CH2)o-4-NRiosR'ios/ - (CH2) 0-4-Rwo, - (CH2) o-4-O-CO- (Ci-Cs alkyl) , - (CH2) 0-4-0-CO- N(Riso)2, - (CH2) o-4-O-(R150) , - (CH2) o-4-N(R15o)-S02- Rios; -(CH2)0-4- C3-C7 cycloalkyl, (C2- C10)alkenyl, or (C2-Ci0)alkynyl. Other preferred compounds of formula 1-5 include compounds wherein RN is -C(=O)-aryl or -C(=0)-heteroaryl where the ring portions of each are optionally substituted with 1 or 2 groups independently selected from Ci-C6 alkyl, halogen, - (CH2) o-4-CO-NRiOSR'ios, -(CH2)0-4- O-CO-N(R1S0)2, -(CH2)0-4-N(R1So)-S02-R105, - (CH2) 0-4- S02-NRi05R'iosi C3-C7 cycloalkyl, (C2-C10) alkenyl, - (CH2)O-4-Riio/ -(CH2)o-4-Ri2o/ - (CH2)0-4-Ri30, or (Ca-do) alkynyl. Other preferred compounds of formula 1-5 also include compounds wherein R» is: wherein sub is hydrogen or is Ci-C6 alkyl, halogen, (Ct^Jo^-CO-NRiosR'xosi - (CH2) o-4-0-CO-N(R150) 2, - (CH2) 0-4- N(Ri50) -SO2-R105/ - (CH2)o-4-S02-NRiOSR'iob, C3-C7 cycloalkyl, - (C2-Ci0)alkenyl, - (CH2) 0-4-R110/ - (CHa) 0-4- R12l3, -(CH2)o-4-Ri3o, or {C2-Ci0)alkynyl. A preferred stereochemistry for compounds of formula I ia as follows: Preferred compounds of formula X include those of formula X-l, i.e., compounds of formula X wherein Ri is aryl, heteroaryl, heterocyclyl, -Ci.-Cs alkyl-aryl, - Ci-C6 alkyl-heteroaryl, . or -Ci-Cg alkyl- heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, OH, -SH, -CNN, -NO2, -NRiO5R'io5, -CO2R, N(R)COR', or -N(R)SO2R', -C(=0) - (Ci~C4) alkyl, -S02-amino, -S02-mono or dialkylamino, -C(=0)- amino, -C(=0)-mono or dialkylamino, -S02- (C1-C4) alkyl, or Ql-Cs alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen, or C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, Ci-C3 alkoxy, amino, -C^-Cs alkyl and mono-- or dialkylamino, or Ci-C10 alkyl optionally substituted with 1,. 2, or 3 groups independently selected from halogen, -OH, -SH, -ON,, -CF3, -C1-C3 alkoxy, amino, mono- or dialkylamino and -C1-C3 alkyl, or C2-C10 alkenyl or C2-Ci0 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, C1-C3 alkoxy, amino, Ci-C6 alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo. Preferred compounds of formula X-l also include those wherein Ri is -Ci-Cs alkyl-aryl, -C^Cs alkyl-heteroaryl, or -Ci-C6 alkyl-heterocyclyl, where the ring portions; of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, -OH, .-SH, -CsN, -N02, -NRiosR'ios, -CO2R, -N(R)COR', or -N(R)SO2R', -C(=0) - (d-d) alkyl, -S02-amino, ~so2-mono or dialkylamino, -C(=0)- amino, -C(=0)-mono or dialkylamino, -S02-(C1-C4) alkyl, or Ci-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen, or C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, C1-C3 alkoxy, amino, -Ci-Cg alkyl and mono- or dialkylamino, or Ci-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -CsN, -CF3, -C1-C3 alkoxy, amino, mono- or diatlkylamino and -Q1.-C3 alkyl, or C2-C10 alkenyl or C2-Ci0 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -CsN, -CF3, C!-C3 alkoxy, amino, Ci-Cg alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo. Preferred compounds of formula X-l further include those wherein Ri is -(CH2)-aryl, - (CH2) -heteroaryl, or - (CE2) - heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, - OH, -SH, -CsN, -N02, -NR1O5R'ios/ -CO2R, - N(R)COR', or -N(R)SO2R', -C(=0)- (C1-C4) alkyl, -S02-amino, -S02-mono or dialkylamino, -C(=0)~ amino, -C(=0)-mono or dialkylamino, -S02-(C1-C4) alkyl, or Ci-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen, or C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -CsN, -CF3, C!-C3 alkoxy, amino, -C^-Os alkyl and mono- or dialkylamino, or Ci-C10 alkyl optionally substituted with l, 2, or 3 groups independently selected from halogen, -OH, -SH, -ON, -CF3/ -Ci-C3 alkoxy, amino, mono- or dialkylamino and -Ci-C3 alkyl, or C2-C10 alkenyl or C2-Clo alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, C3-C3 alkoxy, amino, Ci-Cg alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo. Preferred compounds of formula X-i also include those wherein Ri is -CH2-phenyl or -CH2-pyridinyl where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, C1-C4 alkoxy, hydroxy, -N02, and C1-C4 alkyl optionally subatituted with 1, 2, or 3 substituents independently selected from halogen, OH, SH, NH2, m.(Cx-C6 alkyl), N- (d-C6 alkyl) (Ci-Cg alkyl), ON, CP3. Preferred compounds of formula X-l further include those wherein Ri is -CH2-phenyl or -CH2-pyridinyl where the phenyl or pyridinyl rings are each optionally substituted with 1 or 2 groups independently selected from halogen, Ci-C2 alkyl, C3.-C2 alkoxy, hydroxy, -CF;i, and -N02. Preferred compounds of formula X-l include those wherein Ri is -GH2-phenyl where the phenyl ring is optionally substituted with 2 groups independently selected from halogen, Ci-C2 alkyl, Cj-^ alkoxy, hydroxy, and -N02. Preferred compounds of formula X-l also include those wherein Rx is benzyl, or 3,5-difluoz"obenzyl. Preferred compounds of formula X cr X-l include those of formula X-2, i.e., compounds of formula X or X-l wherein R2 and R3 are independently selected from H or Cx-C6 alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of C!-C3 alkyl, halogen, -OH, -SH, -C=N, -CP3, C!-C3 alkoxy, and -NRi_ aRi-b. Preferred compounds of formula X-2 include those wherein Rc is selected from the group consisting of Ci-Cio alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of Raos, -OC=ONR23sR24o, -S (=0)0.2(^-06 alkyl), -SH, -NR235C=ONR23sR24o, -C=ONRZ35R24o, and -S (=0}2NR235R34o; - (CH2) 0-3-(C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, -CO2H, and -CO2-(C1-C4 alkyl); - (CR245R250) 0-4-aryl; - (CR24sR2so) 0-4-heteroaryl; - (CR24sR2so) 0-4- heterocycloalkyl; - [C (R2S5) (Rzso) 31-3-CO-N- (R255) zi CH(aryl)2; -CH(heteroaryl)2; -CH(heterocycloalkyl)2; -CH(aryl) (heteroaryl) ; -CO-NR23sR;4o; -(CH2)0-i- CH ((CH2) o-s-OH) - (CH2) o-i-aryl; - (CH2) 0-i-CHRc-6- (CH2) o-i- heteroaryl; -CH(-aryl or -heteroaryl)-CO-O(Ci-C4 alkyl); -CH(-CH2-OH)-CH(OI0-phenyl-NO2; (Cx-C6 alkyl) - O-(Ci-C6 alkyl)-OH; -CH2-NH-CH2-CH(-O-CH2-CH3)2; -H; and - (CH2)0.6-C{=NR23s) (NR23SR24o) ; wherein each aryl is optionally substituted with 1, 2, or 3 R2OO/ each heteroaryl is optionally substituted with 1, 2, 3, or 4 R2Oo; each heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R210; R2Oo at each occurrence is independently selected from the group consisting of Cx-Cs alkyl optionally substituted with 1, 2, . or 3 R205 groups; OH; -N02; halogen; -CO2H; C=N; -(CH2;0-4- CO-NR220R225; - (CH2)o-4-CO- (Cx-Cx2 alkyl) ; - (CH2; 0-4- CO2R2is; and - (CH2) 0-4-O- (Ci-Cs alkyl optionally substituted with 1, 2, 3, or 5 -F); wherein each aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205/ R210 or Cx-C6 alkyl substituted with 1, 2, or 3 groups that are independently R2os or R2io; wherein each heterocycloalkyl group at 'each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R210? wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205/ R210/ or Ci-C6 alkyl substituted with 1, 2, or 3 groups that are independently R20S or R2i0; R205 at each occurrence is independently selected from the group consisting of C!-C6 alkyl, halogen, -OH, -O-phenyl, -SH, -G=N, -CF3, Cj.-Cs alkoxy, NH2, NH(Ci-Cs alkyl) , and N- (d-C6 alkyl) (Ql-Cs alkyl); R210 at each occurrence is independently selected from the group consisting of Ci-C6 alkyl optionally substituted with 1, 2, or 3 R205 groups; halogen; Ci-C5 alkoxy; Ci-C6 haloalkoxy; -NR220R22s; OH,- CsN; C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R205 groups; -CO-(Ci- C4 alkyl); -SO2-NR235R240; -CO-NR235R240; -SO2-(Ci-C4 alkyl); and =0; wherein R215 at each occurrence is independently selected from the group consisting of C3.-C6 alkyl, - (CH2)o-2-(aryl), C3_C7 cycloalkyl, and -(CH2)0-2- (heteroaryl), - (CH2) 0-2-(heterocycloalkyl); wherein the aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205 or R210; wherein the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R2io; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R2i0; R220 and R225 at each occurrence are independently selected from the group consisting of -H, -Ci-C6 alkyl, hydroxy C^-Cg alkyl, amino Cx-Cg alkyl; halo Ci-C6 alkyl; -C3-C7 cycloalkyl, - (Ci-C6 alkyl)-0-(C1-C3 alkyl), -aryl, -heteroaryl, and -heterocycloalkyl; wherein the aryl group at each occurrence is optionally substituted with 1, 2, or 3 R270 groups, each heteroaryl is optionally substituted with 1, 2, 3, or 4 Raoo^ each heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R2i0 wherein R27o at each occurrence is independently R20s/ Cn.-C6 alkyl optionally substituted with 1, 2, or 3 R-205 groups; halogen; Cf-Cs alkoxy; Ci-C6 haloalkoxy; NR23SR24o; OH; Q=N; -CO-(Ql^ alkyl); and =0; wherein the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R2o5 groups; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R205 groups; R235 and R240 at each occurrence are independently H, or Ci-C6 alkyl; R24S and R2So at each occurrence are independently selected from the group consisting of H, C1-C4 alkyl, C1-C4 hydroxyalkyl, Ci-C4 alkoxy, C1-C4 haloalkoxy, or R245 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, ox 1 carbon atoms, wherein the carbocycle is optionally substituted with 1 or 2 groups that are independently OH, methyl, Cl, F, OCH3, CF3/ N02, or CN; R255 and R26o at each occurrence are independently selected from the group consisting of H; Cx-C6 alkyl optionally substituted with 1, 2, or 3 R20S groups; - (CH2)o-4-C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R205 groups; - (C1-C4 alkyl)-aryl; - (C1-C4 alkyl)-heteroaryl; - (C!-C4 alkyl)-heterocycloalkyl; aryl; heteroaryl; heterocycloalkyl; . (CH2) 1-4-R2S5- (CH2) 0-4-aryl; - (CH2) 1-4-R265- (CH2)0-4-heteroaryl; and; -(CRz)^- R2s5- (CH2) 0-4-heterocycloalkyl; wherein R2SS at each occurrence is independently -O-, -S- or -NCCi-Cs alkyl)-; each aryl or phenyl is optionally substituted with 1, 2, or 3 groups that are independently R20si R2ior or Ci-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R2io- Preferred compounds of formula X-2 include those wherein: Re is - (CR24sR25o)o-«-aryl, or - (CR245R250) o-4-heteroaryl, wherein aryl and heteroaryl are optionally substituted with 1, 2, or 3 R200 groups. Preferred compounds of formula X-2 also include compounds wherein Rc is - (CR24SR2so) -aryl, or - (CR245R250) -heteroaryl wherein each aryl and heteroaryl is optionally substituted with 1, 2, or 3 R2Oo groups. Preferred compounds of formula X-2 also include compounds wherein Rc is -(CH2)-aryl, or -(CH2) -heteroaryl, wherein each aryl and heteroaryl is optionally substituted with 1, 2, or 3 groups selected from OH, -N02, halogen, -CO2H, C=N, - (CH2) o-4-CO-NR220R225/ - (CH2) 0-4-CO- (Ci-C12 alkyl) , and - (CH2) 0-4"SO2- NR220R225 • Preferred compounds of formula X-2 also include compounds wherein Rc is -(CH2)-aryl, wherein aryl is optionally substituted with 1, 2, or 3 groups selected from OH, -N02, halogen, -CO2H, and CsN. Preferred compounds of formula X-2 also include compounds wherein Rc is - (CH2)-phenyl, wherein phenyl is optionally substituted with 1, 2, or 3 groups selected from OH, -N02, halogen, -C02H, and ON. Preferred compounds of formula X-2 also include compounds wherein Rc is benzyl. Other preferred compounds of formulas X, X-l or X-2 include compounds of formula X-3, i.e., those of formulas X, X-l or X-2 wherein RN is: rZ.x.(CH2)n7-CHC(O)- wherein R4 is NH2; -NH-(CHa)n6-Rj-i; -NHR8; -NRS0C (0) R5; or - NRS0CO2RSi ; wherein ns is 0, 1, 2, or 3; n7 is 0, 1, 2, or 3; R4-i is selected from the group consisting of -S02- (Ci-Cf, alkyl), -SO-CCx-Cs alkyl) , -S-(d-Cfl alkyl) , -S-CO- (Cx-Cg alkyl) , -SO2-NR4-2R4-3; -CO- Ci-C2 alkyl; -CO-NR4.3R4.4; R4.2 and R4.3 are independently H, C0.-C3 alkyl, or C3-Cs cycloalkyl; R4-4 is alkyl, phenylalkyl, C2-C4 alkanoyl, or phenylalkanoyl; Rs is cyclopropyl; cyclobutyl; cyclopentyl; or cyclohexyl; wherein each cycloalkyl group is optionally substituted with one or two groups that are Ci-C6 alkyl, more preferably Ci-C2 alkyl, Ci-Cs alkoxy, more preferably d-C2 alkoxy, CF3, OH, NH2, NH(C1-CS alkyl), N(CX-C6 alkyl) (d-Cs alkyl), halogen, CN, or N02; or the cycloalkyl group is substituted with 1 or 2 groups that are independently CF3, Cl, F, methyl, ethyl or cyano; C^-Cg alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, -NR6R7, Ci-C4 alkoxy, Cs-Cs heterocycloalkyl, CS-CE heteroaryl, phenyl, C3-C7 cycloalkyl, -S-C1-C4 alkyl, -SO2-C1-C4 alkyl, -CO2H, -CONR6R7, -C02-Ci-C4 alkyl, or phenyloxy; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently Ci-C4 alkyl, Ci-C4 alkoxy, halogen, Cx- C4 haloalkyl, or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, Ci-C4 alkoxy, halogen, or C2-C4 alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, OH, Ci-C4 alkyl, C^-d alkoxy, or Ci-C4 haloalkyl; and -NR6R7; wherein R6 and R7 are independently selected from the group consisting of H, Ci-C6 alkyl, C2-C6 alkanoyl, phenyl, -SO2-Ci-C4 alkyl, and phenyl Ci-C4 alkyl; R8 is selected from the group consissting of -S02- heteroaryl optionally substituted with 1 or 2 groups that are independently C1-C4 alkyl or halogen;, -SO2-aryl, -S02-heterocycloalkyl, -C(O)NHR3, heterocycloalkyl, -S-C2-C4 alkanoyl, wherein R9 is phenyl Ci-C4 alkyl, Ci-C6 alkyl, or H; RSo is H or Ci-Cg alkyl; R51 is selected from the group consisting of phenyl Ci-d alkyl; Cx-Cf; alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, -NRSR7, -C(O)NRsR7/ C3-C7 or -Cl- C4 alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups that are independently C1-C4 alkyl, CJ.-C4 alkoxy, halogen, C2-C4 alkanoyl, phenyl C].-C4 alkyl, and -S02 C'i-C4 alkyl; heterocycloalkylalkyl optionally substituted with 1 or 2 groups that are independently C^-d alkyl, C1-C4 alkoxy, halogen, C2-C4 alkanoyl, phenyl C!-C4 alkyl, and -S02 Ci-C4 alkyl; alkenyl; alkynyl; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently OH, Ci-C4 alkyl, C1-C4 alkoxy, halogen, NH3, NH(C!-C6 alkyl) or N(d-C6 alkyl) (Cj-Cb alkyl); heteroarylalkyl optionally substituted with 1, 2, or 3 groups that are independently C!-C4 alkyl, C1-C4 alkoxy, halogen, NH2, NHfCi-Cg alkyl) or N(Ci-Cs alkyl) (Ci-C6 alkyl); phenyl; C3-C8 cycloalkyl, and cycloalkylalkyl, wherein the phenyl; C3-C8 cycloalkyl, and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 cr 5 groups that are independently halogen, CN, N02, Ci-C6 alkyl, Ci-C6 alkoxy, C2-C6 alkanoyl, Ci-C6 haloalkyl, Ci-C6 haloalkoxy, hydroxy, Ci-C6 hydroxyalkyl, Ci-C6 alkoxy Ci-C6 alkyl, Ci-Cs thioalkoxy, Ci-Cs thioalkoxy Cx-Cs alkyl, or Ci- C6 alkoxy Ci-C6 alkoxy. Preferred compounds of formula X-3 include compounds wherein RN is Y'ZnX—CHC(O)- NH2 wherein X is Ci-C4 alkylidenyl optionally substituted with 1, 2, or 3 methyl groups; or -NR4.6-; or R4 and R4_6 combine to form -(CH2)nio-, wherein n10 is 1, 2, 3, or 4; Z is selected from a bond; SO2; SO; S; and C (0) ,- Y is selected from H; C3.-C4 haloalkyl; C5-C6 heterocycloalkyl containing at least one KT, 0, or S; phenyl; OH; -N(YX) (Y2) ,- C^-d,, alkyl optionally substituted with 1 thru 3 substituents which can be the same or different and are selected from halogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy; Cs-Ca cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from C1-C3 alkyl, and halogen; alkoxy; phenyl optionally substituted with halogen, C1-C4 alkyl, C1-C4 alkoxy, CN or N02; phenyl C1-C4 alkyl optionally substituted with halogen, C3.-C4 alkyl, Ca-C4 alkoxy, CN or N02; wherein Yi and Y2 are the same or different and are H; CL-Cio alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, C1-C4 alkoxy, C3-C8 cycloalkyl, and OH; C2-C6 alkenyl; C2-C6 alkanoyl; phenyl; -S02- C!-C4 alkyl; phenyl C].-C4 alkyl; and C3-Ca cycloalkyl C1-C4 alkyl; or -N(Yi) (Y2) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently Ci-C6 alkyl, Ci-Cs alkoxy, Cx-Cg alkoxy Ci-C6 alkyl, or halogen. Preferred compounds of formula X-3 include compounds wherein X is C!-C4 alkylidenyl optionally substituted with 1,. 2, or 3 methyl groups; Z is selected from S02; SO; S; and C(0); Y is selected from H; Ci-C4 haloalkyl; C5-C6 heterocycloalkyl containing at least one N, 0, or S; phenyl; OH; -N(Yi) (Y2) ; Ci-Cio alkyl optionally substituted with 1 thru 3 substituents which can be the same or different and are selected from the group consisting of halogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy; C3-Ca cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from CrC3 alkyl, and halogen; alkoxy; phenyl optionally substituted with halogen, Ci-C4 alkyl, C1-C4 alkoxy, CN or NO5,; phenyl C3.-C4 alkyl optionally substituted with halogen, C3.-C4 alkyl, C1-C4 alkoxy, CN or N02; wherein Yi and Y2 are the same or different and are H; Ci-CG alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, C1-C4 alkoxy, C3-C8 cycloalkyl, and OH; C2-Cs alkenyl; C2-C6 alkanoyl; phenyl; -S02- C1-C4 alkyl; phenyl C1-C4 alkyl; or C3-C8 cycloalkyl C1-C4 alkyl; or -N(Yi) (Y2) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently Ci-Cs alkyl, Ci-Cf; alkoxy, Cx-Cg alkoxy Ci-Cs alkyl, or halogen. Preferred compounds of formula X-3 include compounds wherein RN is and wherein R4 is NH2; -NH-(CH2)n6-R4.1; -NHR8; NR50C(O)R5; or -NR50CO2R51 wherein ns is 0, 1, 2, or 3; n.7 is 0, 1, 2, or 3; R4-i is selected from the group consisting of -S02- (Ci-C8 alkyl), -SO- (Ci-C8 alkyl), -S-(Ci-C8 alkyl) , -S-C0-(C1-C6 alkyl), -SO--NR4-2R4-3; -C0- Ci-C2 alkyl; -CO-NR4.3R4-4; R4-2 and R4.3 are independently H, C;l-C3 alkyl, or C3-C6 cycloalkyl ; R4-4 is alkyl, phenylalkyl, C2-C4 alkanoyl, or phenylalkanoyl; Rs is cyclopropyl; cyclobutyl; cyclopentyl; or cyclohexyl; wherein each cycloalkyl group is optionally substituted with one or two groups that are Ci-C6 alkyl, more preferably Ci-C2 alkyl, Ci-C6 alkoxy, more preferably Ci-C2 alkoxy, CF3, OH, NH2, NH(Ca-Cs alkyl), N(Ci-Cs alkyl) (Ci-c6 alkyl), halogen, CN, or N02; or the cycloalkyl group is substituted with 1 or 2 groups that are independently CF3, Cl, F, methyl, ethyl or cyano; Ci-C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, -NR6R7, Cx-C4 alkoxy, C5- C« heterocycloalkyl, Cs-Cs heteroaryl, phenyl, C3-C7 cycloalkyl, -S~Ci-C4 alkyl, -SO2-Ci-C4 alkyl, -C02H, -CONRSR7, -CO2-CX-C4 alkyl, or phenyloxy; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently C!-C4 alkyl, Cx-e4 alkoxy, halogen, Ci-C4 haloalkyl, or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groups that are independently C!-C4 alkyl, Cx-C4 alkoxy, halogen, or C2-C4 alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, OH, Cr-C4 alkyl, C1-C4 alkoxy, or Ci-C4 haloalkyl; and -NR6R7; wherein R6 and R7 are independently selected from the group consisting of H, Ci-C6 alkyl, C2-C6 alkanoyl, phenyl, -SO2-C1-C4 alkyl, and phenyl Ci-C* alkyl; R$ is selected from the group consisting of ~S02- heteroaryl optionally substituted with 1 or 2 groups that are independently C1-C4 alkyl or halogen,-, -SO2-aryl, -S02-heterocycloalkyl, -C(O)NHR9, heterocycloalkyl, -S-C2-C4 alkanoyl, wherein R9 is phenyl Cx-Gj alkyl, C;-C6 alkyl, or H; R50 is H or Ci-C6 alkyl; and R51 is selected from the group consisting of phenyl Cj-04 alkyl; Cx-Cg alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, -NR6R7, -C(O)NR6R7, C3-C7 or -Ci- C4 alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups that are independently Ci-C4 alkyl, Ci-C4 alkoxy, halogen, C2-C4 alkanoyl, phenyl C1-C4 alkyl., and -S02 C3.-C4 alkyl; heterocycloalkylalkyl optionally substituted with 1 or 2 groups that are independently Ci-C4 alkyl, C3.-C4 alkoxy, halogen, C2-C4 alkanoyl, phenyl Ci.-C4 alkyl., and -S02 C1-C4 alkyl; alkenyl; alkynyl; heteroe.ryl optionally substituted with 1, 2, or 3 groups that are independently OH, Ci-C4 alkyl, Ci-C4 alkoxy, halogen, NH2, NHfCx-Cs alkyl) or N(Ci-C6 alkyl)(C1-C6 alkyl); heteroarylalkyl optionally substituted with 1, 2, or 3 groups that are independently C!-C4 alkyl, C^C^ alkoxy, halogen, NH2, NH(C1-C6 alkyl) or N{C:,-C6 alkyl) (Ql-Cs alkyl); phenyl; C3-CB cycloalkyl, and cycloalkylalkyl, wherein the phenyl; C3-C8 cycloalkyl, and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5 groups that are independently halogen, CN, N02, Ci-C6 alkyl, Ci-C6 alkoxy, C2-C6 alkanoyl, Ci-C6 haloalkyl, C1-C5 haloalkoxy, hydroxy, C1-C6 hydroxyalkyl, C!-Cs alkoxy Cx-Cg alkyl, Ci-C6 thioalkoxy, Cx-Cg thioalkoxy Ci~C6 alkyl, or Ci- C6 alkoxy Ci-Cg alkoxy; and Y is C1-C10 alkyl optionally substituted with 1 thru 3 substituents which can be the same or different and are selected from halogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy. Preferred compounds of formula X-3 further include compounds wherein Rc is Ci-C8 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R2o5r -OC=ONR235R240 7 -S (=0) 0-2 (C1-C6 alkyl), -SH, -C=ONR23bR240/ and -S (=0) 2NR23SR240; -(CH2)0- 3- (C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, -CO2H, and -C02- (Q1.-C4 alkyl); - (CR245R250) 0-4- phenyl; - (CR245R2S0) 0-4-heteroaryl; - (CR245R250) 0-4- heterocycloalkyl; - (CH2)0-i-CH( (CH2)0-4-OH) - (CH2)0-i- phenyl; - (CH2) 0-i-CHRc-s- (CH2) 0-i-heteroa:ryl; -CH(-CH2- 0H)-CH(0H)-phenyl-N02; (Ci-Cs alkyl)-0-(Ci-C6 alkyl)- OH; or - (CH2)o-6-C(=NR235) (NR23SR24o) ; wherein each aryl is optionally substituted with 1, 2, or 3 R200; each heteroaryl is optionally substituted with 1, 2, 3 , or 4 R2Oo ; each heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R2io; R200 at each occurrence is independently Ci-C6 alkyl optionally substituted with 1, 2, or 3 R205 groups; OH; -N02; halogen; -CO2H; C=N; -(CH2)0-4- CO-NR220R225; - (CH2)o-4-CO- (C1-C12 alkyl); -(CH2)o-4- CO2R2i5; or - (CH2) 0-4-0-(Ci-Cs alkyl optionally substituted with 1, 2, 3, or 5 -F); R205 at each occurrence is independently Ci-Cs alkyl, halogen, -OH, -O-phenyl, -SH, -C^N, -CF3, d-C6 alkoxy, NH2, NH(Ci-C6 alkyl), or N- {Cx-C6 alkyl) (Ci-Cs alkyl) ; R210 at each occurrence is independently Ci-C6 alkyl optionally substituted with 1, 2, or 3 R20s groups; halogen; Ci-C6 alkoxy; Ci-C6 haloalkoxy; -NR22oR22s; OH; C=N; C3-C7 cyclosilkyl optionally substituted with 1, 2, or 3 R205 groups; -CO-(Ca- C4 alkyl); .SO2-NR235R240; -CO-NR23bR24o; -S02-(C1-C4 alkyl); and =0; wherein R215 at each occurrence is independently Ci-Cs alkyl, - (CH2) 0-2- (phenyl) , C3-C7 cycloalkyl, and -(CH2)0- 2-(heteroaryl), - (CH2) 0.2-(heterocycloalkyl) ; wherein the phenyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R2os or R2i0; wherein the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R2i0; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R210; R22o and R225 at each occurrence are independently -H, -Ci-Cg alkyl, hydroxy Ci-Cs alkyl, halo Cx-C6 alkyl; -C3-C7 cycloalkyl, and - (Cx-C6 alkyl)-O- (Ci-C3 alkyl) ; R235 and R2«o at each occurrence are independently H, or Ci-Cg alkyl; R24S and R2S0 at each occurrence are independently H, Ci-C4 alkyl, C1-C4 hydroxyalkyl, C1.-C4 alkoxy, Ci- C4 haloalkoxy, or R245 and R25o are taken together with the carbcn to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms. Preferred compounds of formula X-3 include compounds wherein R2. is benzyl which is optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, Ci- C4 alkoxy, hydroxy, and C1-C4 alkyl optionally substituted with 1, 2, or 3 substituents halogen, OH, SH, NH2, NH(C1-CS alkyl), N- (Ci-C6 alkyl) (d-C6 alkyl), CNN, CF3; Rz and R3 are independently selected from E or C1-C4 alkyl optionally substituted with 1 substituent selected from halogen, -OH, -SH, -CsN, -CP3, C1-C3 alkoxy, NH2, NH(C!-C6 alkyl) , and NH(C!-C6 alkyl) (d~Ce alkyl) ; Rc is Ci-C8 alkyl optionally substituted with 1, 2, or 3 groups independently selected from R205, -SH, -C=ONR23SR240/ and -S (=0) 2NR23SR24o; - (CH2) 0.3-(C3-C6) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from R205, -C02H, and -CO2- (C1-C4 alkyl) ; - (CR245R2so)o-4-p5ienyl optionally substituted with 1, 2, or 3 R200; - (CR245R25o)o-3-pyridyl; - (CR245R25D) 0-3- pyridazinyl; - (CR24SR2So) 0-3-PYrimidinyl; - (CR245R2s0)0-3- pyrazinyl; - (CR245R25 - (CR245R250) 0-3-thienyl; - {CR245H250) 0-3-pyrrolyl ; - (CR245R250) 0-3-pyrazolyl; (CR24SR2so) 0-3-benzoxazolyl; - (CR245R25o) 0-3-imidazolyl; each of the above heteroaryl groups is optionally substituted with. 1, 2, 3, or 4 R200;- (CR245R250)0_3-imidazolid:Lnyl; (CR245R2so) 0-3-tetrahydrofuryl; (CR245R2S0) 0-3- tetrahydropyranyl; (CR24SR25o) 0-3-piperazinyl ; (CR24sR25o) o-3-pyrrolidinyl ,• (CR24SR25o) 0-3-piperidinyl ,¦ (CR245R25o)o-3-indolinyl; each of the above heterocycloalkyl groups is optionally substituted with 1, 2, 3, or 4 R210; (CH3) 0-i-CH( (CH2) 0-4-OH) - (CHa) 0- i-phenyl; - {CH2} 0-i-CH (C1-C4 hydroxyalkyl) - (CH2) 0-1- pyridyl ,- R200 at each occurrence is independently Ci-C6 alkyl optionally substituted with 1, 2, or 3 R20s groups; OH; -NO2; halogen; -CO2H; C^N; -(CH2)o-4- CO-NR220R22s; -(CH2)0-4-CO-(C1-C8 alkyl); -(CH::)0-4- CO2R21S; and - (CH2) 0-4-O- (Ci-C6 alkyl optionally substituted with 1, 2, 3, or 5 -F) ; R205 at each occurrence is independently Ci-Cs alkyl, halogen, -OH, -O-phenyl, -SH, -CaN, -CF3, Ci-C6 alkoxy, NH2, NH(C!-CS alkyl), and N-(d-C6 alkyl)(cx-C6 alkyl); R210 at each occurrence is independently C^-Cg alkyl optionally substituted with 1 or 2 R2Os groups; halogen; Ca-C4 alkoxy; C1-C4 haloalkoxy; -NR220R22s; OH; C=N; C3-C7 cycloal.'tyl optionally substituted with 1 or 2 R205 gro\ips; -CO- (Ci-C4 alkyl); _S02-NR235R24o; -CO-NR23SR240; -S03-(C1-C4 alkyl); and =0; wherein R2is at each occurrence is independently Ci-C6 alkyl, - (CH2)o-2- (phenyl), C3-C6 cycloalkyl, -(CH2)o-2- (pyridyl) , - (CH2) 0-2- (pyrrolyl) , - (CH2) 0_2- (imidazolyl) , - (CH2) 0-2- (pyrimidyl) , - (CH2) 0.2- (pyrrolidinyl) , - (CH2) 0-2- (imidazolidinyl) - (CH2) 0-2- (piperazinyl) , - (CH2) 0-2- (piperidinyl) , and - (CH2)0-2- (morpholinyl) ; wherein the phenyl group at each occurrence is optionally substituted with 1 or 2 groups that are independently R205 or R210; wherein each heterocycloalkyl group at each occurrence is optionally substituted with 1 or 2 R210; wherein each heteroaryl group at each occurrence is optionally substituted with 1 or 2 R210; R220 and R225 at each occurrence are independently -H, -C1-C4 alkyl, hydroxy C!-C4 alkyl, halo C1-C4 alkyl; -C3-C6 cycloalkyl, and - (C1-C4 alkyl)-0- (Ci-C2 alkyl) ; R235 and R240 at each occurrence are independently H, or Ci-Cs alkyl; R245 and R250 at each occurrence are independently H, C1-C4 alkyl, C1-C4 hydroxyalkyl, Cx-C4 alkoxy, Ci- C4 haloalkoxy, or R245 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, or S carbon atoms. Other preferred compounds of formula X-3 include compounds wherein X is-Ci-C3 alkylidenyl optionally optionally substituted with 1 or 2 methyl groups; Z is S02; SO; S; or C(0); Y is C.-C4 haloalkyl; OH; -N^) (Ya) ; Cx-Cio alkyl optionally substituted with 1 or 2 substituents which can be the same or different and are selected from halogen, hydroxy, Cj.-C4 alkoxy, C'i-C4 thioalkoxy, and Ci-C4 haloalkoxy; C1-C4 alkoxy; phenyl optionally substituted with halogen, C!-C4 alkyl, C;t-C4 alkoxy, CN or N02; and benzyl optionally substituted with halogen, Ci-C4 alkyl, C1-C4 alkoxy, CN or N02; wherein Yi and Y2 are the same or different and are H; Ci-Ce alkyl optionally substituted with 1, 2, or 3 substituents selected from halogen, Ci-C2 alkoxy, C3-CB cycloalkyl, and OH; C2-C6 alkanoyl; phenyl; -S02-C1-C4 alkyl; benzyl; and C3-C6 cycloalkyl C!-C2 alkyl; or -N(Yj.) (Y2) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently Ca-C6 alkyl, Ci-Cs alkoxy, C'i-C6 alkoxy Ci-C6 alkyl, or halogen. Preferred compounds of formula X-3 also include those of formula X-4, i.e., compounds of formula X-3 wherein X is-Cn-Cs alkylidenyl optionally optionally substituted with 1 methyl group ,- Z is S02; SO; S; or C(0); Y is OH; -N(Y1)(Y2); phenyl; benzyl; or Ci-do alkyl optionally substituted with 1 or 2 substituents which can be the same or different and are selected from halogen, hydroxy, methoxy, ethoxy, thiomethojjy, thioethoxy, and CF3; wherein Yi and Y2 are the same or different and are H; Cr-C4 alkyl optionally substituted with 1 or 2 substituents selected from halogen, methoxy, ethoxy, cyclopropyl, and OH; or. -N{Yx) (Y2) forms a ring selected from piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1 or 2 groups that are independently Ca-C4 alkyl, Ci-C4 alkoxy, or halogen; Ri is benzyl which is optionally substituted with 1, 2, or 3 groups independently selected from methyl, ethyl, n-propyl, isopropyl, hydroxymethyl, monohalomethyl, dihalomethyl, trihalomethyl, -CH2CF3/ methoxymethyl, halogen, methoxy, ethoxy, n-propyloxy, isopropyloxy, and OH; R2 and R3 are independently H or C1-C4 alkyl; Rc is Ci-Cs alkyl optionally substituted with 1, 2, or 3 R205 groups; cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cyclohexylmethyl; - (CR24sR2so)o-3-phenyl optionally substituted with 1 or 2 R2oo groups,- - (CR245R250) 0-3- pyridyl optionally substituted with 1 or 2 R200; - (CR245R250) 0-3-piperazinyl; or (CR24SR250) 0-3- pyrrolidinyl; - (CR345R25o) 0-3-piperidinyl; each of the above heterocycloalkyl groups is optionally substituted with 1 or 2 R210 groups; R200 at each occurrence is independently selected from Ci-C4 alkyl optionally substituted with 1 or 2 R205 groups; OH; and halogen; R205 at each occurrence is independently selected from C1-C4 alkyl, halogen, -OH, -SH, -ON, -CF3, and C1-C4 alkoxy; R210 at each occurrence is independently selected from C!-C4 alkyl optionally substituted witn 1 or 2 R2os groups; halogen; Ci-C4 alkoxy; OCF3; NH2, NH(Ci-Cs alkyl); N(Ci-C6 alkyl) {C^-Cg alkyl); OH; and -CO-(C1-C4 alkyl); wherein R245 and R250 at each occurrence are independently selected from H, Ca-C4 hydroxyalkyl, d-C4 alkoxy, or R245 and R2so are taken together with the carbon to which they are attached to form a. carbocycls of 3, 5,or 6 carbon atoms. Preferred compounds of formulas X, X-l and X.-2 include compounds of formula X-5, i.e., those of formulae X, X-l or X-2 wherein RN is -C(=0)-(CRR')0_6Raoo; and R100 represents aryl, heteroaryl, or heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from -OR, -N02, Ci-Cs alkyl, halogen, -C=N, -OCF3, -CF3, - (CH2)0-4-O-P(=O) (OR) (OR') , -(CH2)0-4-CO-NR10SR'io5, - (CH2) 0.4-O- (CH2)0-4-CONR1D2R102' , - (CH2) 0.4-C0- (d-da alkyl) , - (CH2) o-4-CO- (C2-Ci2 alkenyl) , - (CH2) 0-4- C0- (C2-C12 alkynyl) , - (CH2) 0-4-CO- (CH2) 0-4 (C3-C7 cycloalkyl) , - (CH2) 0-4-R110/ - (CH2)o-4-R12o, - (CH2) o-4~R-i3o» - (CH2) o-4"CO-Rno? "" (CH2) o-4~CO-R120, -(CH2)o-4-CO-R130, -(CH2)0-4-CO-R140, - (CH2) 0-4-CO-O- Rlso, - (CH2)0.4-SO2-NR10sR'i05- - (CH2) 0.4-S0-(d-Ca alkyl), -(CH2)0.4-SO2. (d-C12 alkyl) , - (CH2)0-4-SO2- (CH2) 0-4- (C3-C7 cycloalkyl) , - (CH2) o-4-N(Ri5o) -C0-0- R150, -(CH2)o-4-N(Ri5o)-CO-N(Rlso)2, -(CH2)0-4- N (R150) -CS-N (R150) 2, ~ (CH2) 0-4-N (R150) -CO-R105, - (CH2)0-4-NRiosR'i05/ - (CH2) o-4"Ri4O/ - (CH2)o-4-0-CO- (d-Cs alkyl), -(CH2)o-4-0-P(0)-(0-Riio)2, -(CH2)0- 4-O-CO-N(Ri50)2, -(CH2)0.4-0-CS-N(R15o)2, - (CH2) 0.4- 0- (Riso) , - (CH2) 0-4-0-R15o' -CO0H, - (CH2) 0.4-S- (R150) , -(CH2)0_4-N(R1So)-S02-R105, -(CH2)0.4- C3-C7 cycloalkyl, (d~do) alkenyl, or (C2-do) alkyryl. Preferred compounds of formula X-5 include compounds wherein RN is -C(=0) -Rioo; and R10Q represents aryl, or heteroaryl, where the ring portions of each are optionally substibuted with 1, 2, or 3 groups independently selected from -OR, -N02, Ci-C6 alkyl, halogen, -OsN, -OCF3, -CF3, - (CH2) o-4-O-P (=0) (OR) (OR') , - (CHa) 0-4-CO-NR105R' 105, - (CHa) o-4-O- (CH2) o-4-CONR102R102' , - (CH2) 0-4-CO- (Cr-C12 alkyl) , - (CH2) 0-4-CO- (C2-C12 alkenyl) , - (CHa) 0.4- C0- (C2-C12 alkynyl) , - (CH2) 0-4-CO- (CH2) 0.4 (C3-C7 cycloalkyl) , - (CH2) 0-4-R110. - (CHa) 0-4-R120, - (CH2)0-4-Ri30f ~ (CH2)0-4-CO-Riio, - (CH2) 0-4-CO-R120, -(CH2)0-4-CO-Ri3o, -(CH2)0-4-CO-R14o, - (CH2) a.4-C0-0- Risof -(CH2)o-4-S02-NRio5R'io5/ - (CH2) 0-4-SO-(C:i-C8 alkyl), -(CH2)o-4-S02.(d-C12 alkyl) , - (CH2)0-4-SO2- (CH2)0.4-(C3-C7 cycloalkyl), - (CH2) 0-4-N(Ri50) -C0-0- Riso, ' -(CH2)0-4-N(R1Eo)-CO-N(R1So)2, -(CH2)0_4- N(R150) -CS-N(R1S0)2, - (CH2)o-4-N(Riso) -CO-R10S, - (CH2)o.4-NR1O5R'ios, -(CH2)0-4-Ri40, - (CH2) 0_4-O-CO- (Ci-C6 alkyl), -(CH2)0.4-O-P(O)-(O-R110)2, -(CH2)0- 4-O-CO-N(R150)2, -(CH2)O-4-O-CS-N(R150)2, - (CH2) 0.4- 0- (R150) , - (CH2) o-4-O-Riso' -COOH, - (CH2) 0-4-S- (R130) , -(CH2)0.4-N(R1So)-S02-R105, -(CH2)0-4- C.3-C7 cycloalkyl, (C2-C10)alkenyl, or (C2-C10)alkynyl. Preferred compounds of formula X-5 also include compounds wherein RN is -C(=0)-aryl or -C(=0)-heteroaryl where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from -OR, -NO2, d-Cg alkyl, halogen, -CsN, -OCF3, -CF3, - (CHa) 0-4-CO-NR105R' 105, " (CH2) o-4-O- (CH2) 0-4- CONR102R102', - (CH2) 0-4-CO- (C1-C12 alkyl) , - (CH2) 0.4- CO-(C2-Ci2 alkenyl) , - (CH2) 0-4-CO- (C2-Ci2 alkynyl) , -(CH2)o-4-Rno, -(CH2)o-4-Ri2o, -(CH2)o-4-Ri3o, -(CH2)0-4-CO-R110, -(CH2)0-4-CO-Ri2o, - (CH2) 0.4-C0- Ri30, -(CH2)o-4-CO-R14o, -(CH2)o-4-CO-0-Ri50, - (CH2) 0- 4-S02-NRlosR'10s, -(CH2)0.4-SO-(d-C8 alkyl) , - (CH2) o-4-S02. (Ci-C12 alkyl) , - (CH2) 0-4-N (R150) -CO-0- R1S0, -(CH2)o-4-N(Ri5o)-CO-N(RiSO)2, -(CH2)0-4- N(R150)-CO-Rio5, - (CH2)o-4-NRio5R'ao5, - (CH2) 0-4-R140, - (CH2) 0-4-O-CO- (d-Cs alkyl) , - (CH2) 0-4-O-CO- N(Riso)2, -(CH2) 0-4-0-(R150), -(CH2) 0-4-N (Ribo)-S02- Riosr -(CH2)0-4- C3-C7 cycloalkyl, (C2- Clo) alkenyl, or (C2-do) alkynyl. Other preferred compounds of formula X-5 include compounds wherein RN is -C(=0)-aryl or -C(=0)-heteroaryl where the ring portions of each are optionally substituted with 1 or 2 groups independently selected from Ci-C6 alkyl, halogen, - (CH2)o-4-CO-NRlosR'iosi -(CH2)0-4- 0-CO-N(R1So)2, -(CH2) 0-4-N(Ri5o)-S02-R105, - (CH2) 0-4~ S02-NRlosR'io5, C3-C7 cycloalkyl, (C2-C10) alkenyl, - (CH2) 0-4-R110, ~ (CH2) 0-4-R120, - (CH2) 0-4-R130/ or (C2-C10) alkynyl. Other preferred compounds of formula X-5 also include compounds wherein RM is: CrC4alkJl V^ sub wherein sub is hydrogen or is d-Cg alkyl, halogen, - (CH2)0-4-CO-NR105R'10S/ -(CH2)o-4-0-CO-N(Ri50)2, (CH2) 0-4-N (Riso) -S02-Rios, - (CH2) 0-4-S02-NRio5R'ios, C3-C7 cycloalkyl, - (C2-Ci0) alkenyl, - (CH2) 0-4-R110, - (CH2) 0-4-R120/ -(CH2)o-4-Ri3o/ or (Ca-Cio)alkynyl. A preferred stereochemistry for compounds of formula X is as follows: In another aspect, the invention provides intermediates of the formula (IA): wherein Ri, R2, R3, Rn/ and Re are as defined above for compounds of formula I, and PROT is an amine protecting group as defined below. In another aspect, the invention provides intermediates of the formula (XA): wherein R1# R2, R3, RM, and Rc are as defined above for compounds of formula I, and PROT is an amine protecting group as defined below The invention also provides methods of generating compounds of formula (Y) from the compounds of formula (AA) , formula (I) or formula (X) , which are useful for treating and/or preventing Alzheimer's disease. The generation of compounds of formula (Y) from compounds of formulae (AA) , (I) or (X) can occur in vivo or in vitro. The invention also provides processes for converting compounds of formula AA, I or X to the compounds of formula Y by exposing compounds of formula AA, I or X to aqueous media. The conversion can occur in vitro or in vivo. The invention also provides methods for treating a patient who has, or in preventing a patient from getting, a disease or condition selected from the group consisting of Alzheimer's disease, for helping prevent or delay the onset of Alzheimer's disease, for treating patients with mild cognitive impairment (MCI) and preventing or delaying the onset of Alzheimer's disease in those who would progress from MCI to AD, for treating Down's syndrome, for treating humans who have Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, for treating cerebral amyloid angiopathy and preventing its potential consequences, i.e. single and recurrent lobar hemorrhages, for treating other degenerative dementias, including dementias of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, or diffuse Lewy body type of Alzheimer's disease and who is in need of such treatment which includes administration of a therapeutically effective amount of a compound of formula (AA) , (I) or (X) or a pharmaceutically acceptable salts thereof. In an embodiment, this method of treatment can be used where the disease is Alzheimer's disease. In an embodiment, this method of treatment can help prevent or delay the onset of Alzheimer's disease. In an embodiment, this method of treatment car. be used where the disease is mild cognitive impairment. In an embodiment, this method of treatment can be used where the disease is Down's syndrome. In an embodiment, this method of treatment can be used where the disease is Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type. In an embodiment, this method of treatment can be used where the disease is cerebral amyloid angiopathy. In an embodiment, this method of treatment can be used where the disease is degenerative dementias. In an embodiment, this method of treatment can be used where the disease is diffuse Lewy body type of Alzheimer's disease. In an embodiment, this method of treatment can treat an existing disease. In an embodiment, this method of treatment can prevent a disease from developing. In an embodiment, this method of treatment can employ therapeutically effective amounts: for oral administration from about 0.1 mg/day to about 1,000 mg/day; for parenteral, sublingual, intranasal, intrathecal administration from about 0.5 to about 100 mg/day; for depo administration and implants from about 0.5 mg/day to about 50 mg/day; for topical administration from about 0.5 mg/day to about 200 mg/da.y; for rectal administration from about 0.5 mg to about 500 mg. In an embodiment, this method of treatment can employ therapeutically effective amounts: for oral administration from about 1 mg/day to about 100 mg/day; and for parenteral administration from about 5 to about 50 mg daily. In an embodiment, this method of treatment can employ therapeutically effective amounts for oral administration from about 5 mg/day to about 50 mg/day. The invention also includes pharmaceutical compositions which include a compound of formula (AA) , (I) or (X) or a pharmaceutically acceptable salts thereof. The invention also includes the use of a compound of formula (AA) , (I) or (X) or pharmaceutically acceptable salts thereof for the manufacture of a medicament. The invention also includes methods for inhibiting beta-secretase activity, for inhibiting cleavage of amyloid precursor protein (APP), in a reaction mixture, at a site between Met596 and Asp597, numbered for the APP-695 amino acid isotype, or at a corresponding site of an isotype or mutant thereof; for inhibiting production of amyloid beta peptide (A beta) in a cell; for inhibiting the production of beta-amyloid plaque in an animal; and for treating or preventing a disease characterized by beta-amyloid deposits in the brain. These methods each include administration of a therapeutically effective amount of a compound of formula (AA) , (I) or (X) or a pharmaceutically acceptable salts thereof. The invention also includes a method for inhibiting beta-secretase activity, including exposing said beta- secretase to a compound of formula (AA) , (I) or (X), under conditions whereby an effective inhibitory amount of a compound of formula (V) , or a pharmaceutically acceptable salt thereof, is formed. In an embodiment, this method employs a compound that inhibits 50% of the enzyme's activity at a concentration of less than 50 micromolar. In an embodiment, this method employs a compound that inhibits 50% of the enzyme's activity at a concentration of 10 micromolar or less. In an embodiment, this method employs a compound that inhibits 50% of the enzyme's activity at a concentration of 1 micromolar or less. In an embodiment, this method employs a compound that inhibits 50% of the enzyme's activity at a concentration of 10 nanomolar or less. In an embodiment, this method includes exposing said beta-secretase to said compound in vitro. In an embodiment, this method includes exposing said beta-secretase to said compound in a cell. In an embodiment, this method includes exposing said beta-secretase to said compound in a cell in an animal. In an embodiment, this method includes exposing said beta-secretase to said compound in a human. The invention also includes a method for inhibiting cleavage of amyloid precursor protein (APP), in a reaction mixture, at a site between Met5S>6 and Asp597, numbered for the APP-695 amino acid isotype; or at a corresponding site of an isotype or mutant thereof, including exposing said reaction mixture to an effective inhibitory amount of a compound of formula (AA) , (I) or (X), or a pharmaceutically acceptable salt thereof. In an embodiment, this method employs a cleavage site: between Met652 and Asp653, numbered for the APP- 751 isotype,- between Met 671 and Asp 672, numbered for the APP-770 isotype; between Leu.596 and Asp597 of the APP-695 Swedish Mutation; between LeuS52 and Asp653 of the APP-751 Swedish Mutation; or between Leu671 and Asp672 of the APP-770 Swedish Mutation. In an embodiment, this method exposes; said reaction mixture in vitro. In an embodiment, this method exposes said reaction mixture in a cell. In an embodiment, this method exposes said reaction mixture in an animal cell. In an embodiment, this method exposes said reaction mixture in a human cell. The invention also includes a method for inhibiting production of amyloid beta peptide (A beta) in a cell, including administering to said cell a compound of formula (AA), (I) or (X) , under conditions whereby an effective inhibitory amount of a compound of formula (Y), or a pharmaceutically acceptable salt thereof, is formed. In an embodiment, this method includes administering to an animal. In an embodiment, this method includes administering to a human. The invention also includes a method for inhibiting the production of beta-amyloid plague in an animal, including administering to said animal a compound of formula (AA.) , (I) or {X) , under conditions whereby an effective inhibitory amount of a compound of formula. (Y) , or a pharmaceutically acceptable salt thereof, is formed. In an embodiment, this method includes administering to a human. The invention also includes a method for treating or preventing a disease characterized by beta-amyloid deposits in the brain including administering to a patient an effective therapeutic amount of a compound of formula (AA) , (I) or (X) , under conditions whereby an effective inhibitory amount of a compound of formula (Y), or a pharmaceutically acceptable salt thereof, is formed. In an embodiment, this method results in a compound of formula (Y) that inhibits 50% of the enzyme's activity at a concentration of less than 50 micromolar. In an embodiment, this method results in a compound of formula (Y) that inhibits 50% of the enzyme's activity at a concentration of 10 micromolar or less. In an embodiment, this method results in a compound of formula (Y) that inhibits 50% of the enzyme's activity at a concentration of 1 micromolar or less. In an embodiment, this method results in a compound of formula (Y) that inhibits 50% of the enzyme's activity at a concentration of 10 nanomolar or less. In an embodiment, this method employs a compound at a therapeutic amount in the range of from about 0.1 to about 1500 mg/day. In an embodiment, this method employs a compound at a therapeutic amount in the range of from about 15 to about 1000 mg/day. In an embodiment, this method employs a compound at a therapeutic amount in the range of from about 1 to about 100 mg/day. In an embodiment, this method employs a compound at a therapeutic amount in the range of from about 5 to about 50 mg/day. In an embodiment, this method can be used where said disease is Alzheimer's disease. In an embodiment, this method can be used where said disease is Mild Cognitive Impairment, Down's Syndrome, or Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch Type. The invention also includes a component kit including component parts capable of being assembled, in which at least one component part includes a compound of formula AA, I or X enclosed in a container. In an embodiment, this component kit includes lyophilized compound, and at least one further component part includes a diluent. The invention also includes a container kit including a plurality of containers, each container including one or more unit dose of a compound of formula (AA) , (I) or (X) :, or a pharmaceutically acceptable salt thereof. In an embodiment, this container kit includes each container adapted for oral delivery and includes a tablet, gel, or capsule. In an embodiment, this container kit includes each container adapted for parenteral delivery and includes a depot product, syringe, ampoule, or vial. In an embodiment, this container kit includes each container adapted for topical delivery and includes ' a patch, medipad, ointment, or cream. The invention also includes an agent kit including a compound of formula (AA),¦ (I) or (X), or a pharmaceutically acceptable salt thereof; and one or more therapeutic agent selected from the group consisting of an antioxidant, an anti-inflammatory, a gamma secretase inhibitor, a neurotrophic agent, an acetyl cholinesterase inhibitor, a statin, an A beta peptide, and an anti-A beta antibody. The invention also includes a composition including a compound of formula (AA) , (I) or (X) , or a pharmaceutically acceptable salt thereof; and an inert diluent or edible carrier. In an embodiment, this composition includes a carrier that is an oil. The invention also includes a composition including: a compound of formula (AA) , (I) or (X) , or a pharmaceutically acceptable salt thereof; and a binder, excipient, disintegrating agent, lubricant, or gildant. The invention also includes a composition including a compound of formula (AA) , (I) or (X) , or a pharmaceutically acceptable salt thereof; disposed in a cream, ointment, or patch. The invention provides compounds of formula (AA) , formula (I) and (X) that can be used to generate compounds of formula (Y), that are useful in treating and preventing Alzheimer's disease. The compounds of the invention can be prepared by one skilled in the art based only on knowledge of the compound's chemical structure. The chemistry for the preparation of the compounds of this invention is known to those skilled in the art. In fact, there is more than one process to prepare the compounds of the invention. Specific examples of methods of preparation can be found in the art. For examples, see J. Org. Chem. 1998, 63, 4898-4906; J. Org. Chem. 1997, 62, 9348-9353; J. Org. Chem. 1996, 61, 5528-5531; Chem. 1993, 36, 320-330; J. Am. Chem. 3oc. 1999, 121, 1145-1155; and references cited therein. See also U.S. Patent Nos. 6,150,530, 5,892,052, 5,696,270, and 5,362,912, which are incorporated herein by reference, and references cited therein. Examples of various processes that can be used to prepare the compounds of the invention are set forth below. A general process to prepare the compounds of formula I and X is set forth in SCHEME A. The chemistry is straight forward and in summary involves the steps of N-protecting the amino acid (A) starting material to produce the corresponding protected amino acid (II), reaction of the protected amino acid (II) with diazomethane followed by work-up to add a carbon atom to produce the corresponding protected compound (III), reduction of the protected halide to the corresponding alcohol (IV), formation of the corresponding epoxide (V), opening of the epoxide (V) with a C-terminal amine, RC-NH2 (VI) to produce the corresponding protected alcohol (VII). Compounds of formula (I) can be prepared by reacting protected alcohol (VII) with an amide forming agent such as, for example, (Rn-)20 or Rjj-X or Rjj-OH (IX) to produce .alcohol (IA) . Alcohol (IA) then has the nitrogen protecting group removed to produce the corresponding compounds of formula (I). Compounds of formula (X) can be prepared by further N-protecting alcohol (VII) to form the diprotected alcohol (XB). Diprotected alcohol (XB) is reacted with an amide forming agent such as, for example, (Rn-)20 or RN-X or RN-OH (IX) to produce compound (XA). Compound (XA) then has the nitrogen protecting groups removed to produce the corresponding compounds of formula (X). One skilled in the art will appreciate that these are all known reactions in organic chemistry. A chemist s.>illed in the art, knowing the chemical structure of the compounds (AA) , (I) and (X) of the invention would be able to prepare them by known methods from known starting materials without any additional information. The explanation below therefore is not necessary but. is deemed helpful to those skilled in the art who desire to make the compounds of the invention. The backbone of the intermediate (VII) , from which the compounds of formula (AA), (I) and (X) can be readily prepared, can be considered a hydroxyethylcLmine moiety, - NH-CH(R)-CH(OH)-. Such backbones can be prepared by methods disclosed in the literature and known to those skilled in the art. For example, J. Med. Chem., 36, 288- 291 (1993), Tetrahedron Letters, 28, 5569-5572 (1987), J. Med. Chem., 38, 581-584 (1995) and Tetrahedron Letters, 38, 619-620 (1997) and WO 02/02506 all disclose processes to prepare hydroxyethylamine type compounds and/or their intermediates. SCHEME A sets forth a general method used in the invention to prepare the appropriately substituted amines I and X. The compounds of the invention are prepared by starting with the corresponding amino acid (A) . The amino acids (A) are known to those skilled in the art or can be readily prepared by methods known to those skilled in the art. The compounds of the invention have at least two chiral centers, which give 2 sets of diastereomers, each of which is racemic for a total of at least four stereoisomers. While biologically active end products result from all stereoisomeres, the (S,R) configuration is preferred. The first of these chiral centers (the carbon carrying R.x) derives from the amino acid starting material (A) . It is preferred to commercially obtain or produce the desired enantiomer rather than produce an enantiomerically impure mixture and then have to separate out the desired enantiomer. Thus it is preferred to start the process with enantiomerically pure (S) -amino acid (A) of the same configuration as that of the desired X product. In Scheme A, the protection of free amine (A) to produce the (S)-protected amino acid (II) is depicted. Amino protecting groups are known to those skilled in the art, as discussed below. See for example, "Protecting Groups in Organic Synthesis", John Wiley and sons, New York, N.Y., 1981, Chapter 7,- "Protecting Groups in Organic Chemistry", Plenum Press, New York, N.Y., 1973, Chapter 2. The function of the amino protecting group is to protect the free amino functionality (-NH2) during subsequent reactions on the (S)-amino acid (A) which would not proceed either because the amino group would react and be functionalized in a way that is inconsistent with its need to be free for subsequent reactions or the free amino group would interfere in the reaction. When the amino protecting group is no longer needed, it is removed by methods known to those skilled in the art. By definition the amino protecting group must be readily removable as is known to those skilled in the art by methods known to those skilled in the art. Suitable amino PROTECTING GROUPS are discussed below. The (S)-protected amino acid (II) is transformed to the corresponding (S)-protected compound (III) by two different methods depending on nature of R2 and R3. R2 and R3 can be the same or different. It is preferred that R2 and R3 both be -H. If R2 and R3 are not the same, an additional chiral or stereogenic center is added to the molecule. To produce compounds of formula (III) where R2 and R3 are both -H, the (S)-protected arnino acid (II) is reacted with diazomethane, as is known to those skilled in the art, followed by reaction with a compound of the formula H-Xx to produce the (S) -protected compound. (Ill). Xi includes -Cl, -Br, -I, -O-tosylate, - O-mesylate, -O-nosylate and -O-brosylate. It is preferred that -Xi be -Br or -Cl. Suitable reaction conditions include running the reaction in ¦ inert solvents, such as but not limited to ether, tetrahydrofuran and the like. The reactions from the (S)-protected amino acid (II) to the (S)-protected compound (III) are carried out for a period of time between 10 minutes and 1 day and at temperatures ranging from about -78° to about 20-25°. • It is preferred to conduct the reactions for a period of time between 1-4 hours and at temperatures between -30° to -10°. This process adds one methylene group. Alternatively, the (S)-protected compounds of formula (III) can be prepared by first converting the (S) -protected amino acid (II) to a corresponding methyl or ethyl ester, according to methods established in the art, followed by treatment with a reagent of formula Xx- C(R2) (R3)-Xi and a strong metal base. The base serves to affect a halogen-metal exchange, where the -Xi undergoing exchange is a halogen selected from chlorine, bromine or iodine. The nucleophilic addition to the ester derivative gives directly the (S)-protected compound (III). Suitable bases include, but are not limited to the alkyllithiums including, for example, sec- butyllithium, n-butyllithium, and t-butyllithium. The reactions are preferably conducted at low temperature, such as -78°. Suitable reaction conditions include running the reaction in inert solvents, such as but not limited to, ether, tetrahydrofuran and the like. Where R2 and R3 are both hydrogen, then examples of Xi-C(R2) (R3) -Xx include dibromomethane, diiodomethane, chloroiodomethane, bromoiodomethane and bromochloromethane. One skilled in the art. knows the preferred conditions required to conduct this reaction. Furthermore, if R2 and/or R3 are not -H, then by the addition of -C(R2) (R3) -Xi to esters of the (S)-protected amino acid (II) to produce the (S) - protected compound (III), an additional chiral center will be incorporated into the product, provided that R2 and R3 are' not the same. The (S)-protected compound (III) is then reduced by means known to those skilled in the art for reduction of a ketone to the corresponding secondary alcohol affording the corresponding alcohol (IV) . The means and reaction conditions for reducing the (S)-protected compound (III) to the corresponding alcohol (IV) include, for example, sodium borohydride, lithium borohydride, borane, diisobutylaluminum hydride, and lithium aluminium hydride. Sodium borohydride is the preferred reducing agent. The reductions are carried out for a period of time between 1 hour and 3 days at temperatures ranging from -78° to elevated temperature up to the reflux point of the solvent employed. It is preferred to conduct the reduction between -78° and 0°. If borane is used, it may be employed as a complex, for example, borane-methyl sulfide complex, borane-piperidine complex, or bora.ne- tetrahydrofuran complex. The preferred combination of reducing agents and reaction conditions needed are known to those skilled in the art, see for example, Larock, R.C. in Comprehensive Organic Transformations, VCH Publishers, 1989. The reduction of the (S)-protected compound (III) to the corresponding alcohol (IV) produces the second chiral center (third chiral center if R2 and R3 are not the same). The reduction of the (S)-protected compound (III) produces a mixture of enantiomers at the second center, {S, R/S)-alcohol (IV). This enantiomeric mixture is then separated by means known to those skilled in the art such as selective low-temperature recrystallization or chromat©graphic separation, for example by HPLC, employing commercially available chiral columns. The enantiomer that is used in the remainder of the process of SCHEME A is the (S,S) -alcohol (IV) since this enantiomer will give the desired (S,R)-substituted compound I or X. The (S, S)-alcohol (IV) is transformed to the corresponding epoxide (V) by means known to those skilled in the art. The stereochemistry of the (S)-(IV) center is maintained in forming the epoxide (V) . A preferred means is by reaction with base, for example, but not limited to, hydroxide ion generated from sodium hydroxide, potassium hydroxide, lithium hydroxide and the like. Reaction conditions include the use of C]_-Cg alcohol solvents; ethanol is preferred. A common co- solvent, such as for example, ethyl acetate may also be employed. Reactions are conducted at. temperatures ranging from -45° up to the reflux temperature of the alcohol employed; preferred temperature ranges are between -20° and 40°. An alternative, and preferable process for preparing the epoxide (V) when Ri is 3,5-dif luorokenzyl, is set forth in SCHEME D. The first step of the process is to protect the free amino group of the (S) -amino acid (A) with an amino protecting group, PROTECTING GROUP, as previously discussed to produce the (S)-protected amino acid (II). In the alternative process, the (S)-protected arnino acid (A) is transformed to the corresponding (S) - protected ester (XVII) in one of a number of ways. One method involves the use of lithium hydroxide. Using lithium hydroxide, the (S)-protected amino acid (A) and the lithium hydroxide are mixed and cooled to from about -20° to about 10°. Next a methylating agent, selected from the group consisting of dimethylsulfate, methyl iodide and methyl triflate, is added. It is more preferred that the methylating agent is dimethylsulfcite. This is followed by heating to from about 20° to about 50°. Alternatively, the (S)-protected amino acid (A) is contacted with a weak base such as bicarbonate or preferably carbonate. This is followed by addition of the methylating agent. Heat is not necessary but car. be used to facilitate the reaction. The carbonate method is known to those skilled in the art. For those (S)- protected esters (XVII) where Z± is not methyl, one skilled in the art knowing the chemical structure would know how to prepare the desired compounds from known starting materials. In one known method the (S)- protected amino acid (A) is contacted with an activating agent, such as DCC, followed by addition of the appropriate alcohol, Zi-OH. This method is operable when Zi is Ci-C4 alkyl (optionally substituted) , -CH2-CH=CH;: or phenyl (optionally substituted). SCHEME E sets forth an alternative process for1 the preparation of the ester (II). In the process of SCHEME E, the aldehyde (XX), which is known to those skilled in the art, is reacted with the phosphorous compound (XXI) , where X3 is a good leaving group, to produce the olefin (XXII). The phosphorous compounds (XXI) are known to those skilled in the art. It is preferred that X3 is Ci- C3 alkyl; it is more preferred that X3 is Ci alkyl. The aldehyde (XX) and the phosphate (XXI) are combined in an organic solvent then cooled to about 0°. A base such as DBU or TMG is added and the contents of the reaction mixture are warmed to about 20-25° and stirred until the reaction is complete. Once the reaction is complete, it is preferred to separate the E- and Z-olefin isomers (XXII). The separation is done by methods known to those skilled in the art, such as by silica gel chromatography. Next the olefin (XXII) is hydrogenated with a suitable hydrogenation catalyst to obtain the desired ester (II). Some hydrogenation reactions will give racemic ester (II) . The desired stereochemistry of the ester (II) is (S)-, and therefore it is preferable to use the Z-olefin (XXII) with a hydrogenation catalyst. I- is preferred that the hydrogenation catalyst is a compound of the formula [Rh(diene)L]+X" where Rh is rhodium; where diene is cyclootediene and nonbornadiene; where L is DIPMAP, MeDuPhos, EtDuPhos. Binaphane, f- Binaphane, Me-KetalPhos, Me-f-KetalPhos, BINAP, DIOP, BPPFA, BPPM, CHIRAPHOS, PROPHOS, NORPHOS, CYCLOPHOS, BDPP, DEGPHOS, PNNP and where X" is C1O4', BF4", CF3-SO3", Cl", Br", PF6" and SbF6". It is preferred that the hydrogenation catalyst be either DIPMAP or EtDuPhos. Suitable solvents include polar solvents such as alcohols, preferably C1-C5 alcohols and THF, more preferably methanol, ethanol, isopropanol and THF. The chiral hydrogenation is performed in a temperature range of from about -20° to about reflux. It is preferred that the reaction be performed in the temperature range from about 0° to about room temperature (25°) . The chiral hydrogenation is performed under a pressure of from about one atmosphere to about 100 psig; it is more preferred that the chiral hydrogenation be performed under a pressure of from about 10 psig to about 40 psig. The (S)-protected ester (II) is then transformed to the corresponding (S)-protected ketone (III; by reaction with a slight excess of a compound of the formula CH2C1X2 where X2 is -Br and -I in one of two different ways. In one process, no exogenous nucleophile is used. That process requires (1) the presence of three or more equivalents of strong base which has a pKb of greater than about 30 followed by (2) adding acid. The other process requires (1) the presence of about 2 to about 2.5 equivalents of strong base which has a pKb of greater than about 30, (2) contacting the mixture of step (1) with about 1 to about 1.5 equivalents of an exogenous nucleophile and (3) adding acid. Suitable strong bases are those which has a pKb of greater than about 30. It is preferred that the strong base be selected from the group consisting of LDA, LiHMDS and KHMDS; it is nore preferred that the strong base be LDA. Suitable acids are those, which have a pka of less than about 10. It is preferred the acid be selected from the group consisting of acetic, sulfuric, hydrochloric, citric, phosphoric and benzoic acids; it is more preferred that the acid be acetic acid. The preferred solvent for the process is THF. The reaction can be performed in the temperature range from about -80° to about -50°; it is preferred to perform the reaction in the temperature range of from about -75° to about -65°. Suitable nucleophiles include alkyl lithium, aryl lithium, alkyl-Grignard and aryl-Grignsird reagents. It is preferred that the nucleophile be selected from the group consisting of phenyl lithium, n-butyl lithium, methyl magnesium bromide, methyl magnesium chloride, phenyl magnesium bromide, phenyl magnesium chloride; it is more preferred that the nucleophile be n-butyl lithium. The (S)-protected ketone (III) is then reduced to the corresponding (S)-alcohol (IV) by means known to those skilled in the art for reduction of a ketone to the corresponding secondary alcohol. The means and reaction conditions for reducing the (S)-protected compound (III) to the corresponding alcohol (IV) include, for example, sodium borohydride, lithium borohydride, borane, diisobutylaluminum hydride, zinc borohydride and lithium aluminium hydride. Sodium borohydride is the preferred reducing agent. The reductions are carried out for . a period of time between about 1 hour and about 3 days at temperatures ranging from about -78° to elevated temperature up to the reflux point of the solvent employed. It is preferred to conduct the reduction between about -78° and about 0°. If borane is used, it may be employed as a complex, for example, borane-methyl sulfide complex, borane-piperidine complex, or borane- tetrahydrofuran complex. The preferred combination of reducing agents and reaction conditions needed are known to those skilled in the art, see for example, Larock, R.C. in Comprehensive Organic Transformations, VCH Publishers, 1989. The reduction of the (S)-protected compound (III) to the corresponding alcohol (IV) produces a second chiral center. The reduction of the (S) - protected compound (III) produces a mixture of diastereomers at the second center, (S, R/S)-alcohol (IV). This diastereomeric mixture is then separated by means known to those skilled in the art such as selective low-temperature recrystallization or chromatographic Separation, most preferably by recrystallization or by employing commercially available chiral columns. The diastereomer that is used in the remainder of the process of SCHEME A is the (S,S)-alcohol (IV) since this stereochemistry will give the desired epoxide (V). The alcohol (IV) is transformed to the corresponding epoxide (V) by means known to those skilled in the art. The stereochemistry of the (S)-(IV) center is maintained in forming the epoxide (V) . A preferred means is by reaction with base, for example, but not limited to, hydroxide ion generated from sodium hydroxide, potassium hydroxide, lithium hydroxide and the like. Reaction conditions include the use of C^-Cg alcohol solvents; ethanol is preferred. A common co-solvent, such as for example, ethyl acetate may also be employed. Reactions are conducted at temperatures ranging from about -45° up to the reflux temperature of the alcohol employed; preferred temperature ranges are between about -20° and about 40°. The epoxide (V) is then reacted with the appropriately substituted C-terminal amine, RC-NH2 (VI) by means known to those skilled in the art which opens the epoxide to produce the desired corresponding enantiomerically pure (S,R)-protected alcohol (VII). The substituted C-terminal amines, RC-NH2 (VI) of this invention are commercially available or cire known to those skilled in the art and can be readily prepared from known compounds. It is preferred that when Re is phenyl, it is substituted in the 3-position or 3,5-positions. Suitable reaction conditions for opening the epoxide (V) include running the reaction in a wide range of common and inert solvents. C^-Cg alcohol solvents sire preferred and isopropyl alcohol most preferred. The reactions can be run at temperatures ranging from 20-25° up to the reflux temperature of the alcohol employed. The preferred temperature range for conducting the reaction is between 50° up to the reflux temperature of the alcohol employed. When the substituted C-terminal amine (VI) is a l-amino-3,5-cis-dimethyl cyclohexyldicarboxylate it is preferably prepared as follows. To dimethyl-5-isophthalate in acetic acid and methanol, is added rhodium in alumina in a high-pressure bottle. The bottle is saturated with hydrogen at 55 psi and shaken for one week of time. The mixture is then filtered through a thick layer of celite cake and rinsed with methanol three times, the solvents are removed under reduced pressure (with heat) to give a concentrate. The concentrate is triturated with ether and filtered again to give the desired C-terminal amine (VI). When the substituted C-terminal amine (VI) is l-amino-3,5-cis- dimethoxy cyclohexane it is preferably following the general procedure above and making non-critical variations but starting with 3,5-dimethoxyaniline. When the substituted C-terminal amine . (VI) is an aminomethyl group where the substituent on the methyl group is an aryl group, for example NH2-CH2-aryl, is not commercially available it is preferably prepared as follows. A suitable starting material is the (appropriately substituted) aralkyl compound. The first step is bromination of the alkyl substituent via methods known to those skilled in the art, see for example R.C. Larock in Comprehensive Organic Transformations, VCH Publishers, 1989, p. 313. Next the alkyl halide is reacted with azide to produce the aryl-(alkyl)-azide. Last the azide is reduced to the corresponding amine by hydrogen/catalyst to give the C-terminal amine (VI) of formula NH2-CH2-Rc-aryi. SCHEME B discloses an alternative process for production of the enantiomerically pure (S,R)-protected alcohol (VII) from the (S)-protected compound (III). In the alternative process, the (S)-protected compound (III) is first reacted with the appropriately substituted C- terminal amine RC-NH2 (VI) using the preferred conditions described above to produce the corresponding (S) - protected ketone (XI) which is then reduced using the preferred conditions described above to produce the corresponding (S,R)-protected alcohol (VII). SCHEME C discloses another alternative process for production of enantiomerically pure (S,R)-protected alcohol (VII) but this time from the epoxide (V). In the process of SCHEME C, the epoxide (V) is reacted with azide to produce the corresponding enantiomerically pure (S,R)-protected azide (XII). Conditions to conduct the azide mediated epoxide opening are known to those skilled in the art, see for example, J. March, Advanced Organic Chemistry, 3rd Edition, John Wiley & Sons Publishers, 1985, p. 380. Next, the (S,R)-protected azide (XII) is reduced to the corresponding protected amine (XIII) by methods known to those skilled in the art. Preferred reducing conditions to reduce the (S,R)-protected azide (XII) in the presence of a t-butoxycarbonyl N-protecting group include catalytic hydrogenation, the conditions for which are known to those skilled in the art. Alternative reducing conditions which may be used to avoid N- deprotection with protecting groups other than t- butoxycarbonyl are known to those skilled in the art, see for example, R.C. Larock in Comprehensive Organic Transformations, VCH Publishers, 1989, p. 409. Last, the (S,R)-amine (XIII) is transformed to the corresponding protected alcohol (VII) by nitrogen alkylation with a compound of the formula Rc-X3. X3 is an appropriate leaving group, such as but not limited to, -Cl, -Br, -I, -O-mesylate, -O-tosylate, O-triflate, etc. X3 may also be an aldehyde; the corresponding coupling with (XIII) via the known reductive amination procedure gives the protected (S,R)-alcohol (VII). In the formation of compounds of foirmula (I) , the protected alcohol (VII) is reacted with an appropriately substituted amide forming agent (IX) such as, for example, an anhydride, acyl halide, or acid of the formulas (Rn)2O or RHX or RnOH (IX) respectively, by means known to those skilled in the art to produce the corresponding (S,R)-substituted amine (IA). Nitrogen acylation conditions for reaction of the alcohol (VII) with an amide forming agent (IX) to produce the corresponding compound (IA) are known to those skilled in the art and can be found, for example, in R.c. Larocx in Comprehensive Organic Transformations, VCH Publishers, 1989, p. 981, 979, and 972. The (S, R)-protected amne (IA) is deprotected to the corresponding compounds (I) by means known to those skilled in the art for removal of amine protecting group. Suitable means for removal of the amine protecting group depend on the nature of the protecting group. Those skilled in the art, knowing the nature of a specific protecting group, know which reagent is preferable for its removal. For example, it is preferred to remove the preferred protecting group, BOC, by dissolving the (S,R)-protected amine (IA) in a trifluoroacetic acid/dichloromethane (1/1) mixture. When complete, the solvents are removed under reduced pressure to give the corresponding (S,R)-amine (I) (as the corresponding salt, i.e. trifluoroacetic acid salt) which is used without further purification. However, if desired, the (S,R)-amine (I) can be purified further by means known to those skilled in the art, such as for example,, recrystallization. Further, if the non-salt form is desired that also can be obtained by means known to those skilled in the art, such as for example, preparing the free base amine via treatment of the salt with mild basic conditions. Additional BOC deprotection conditions and deprotection conditions for other protecting groups can be found in T.W. Green and P.G.M. Wuts in "Protective Groups in Organic Chemistry, John Wiley and -Sons, 1991, p. 309. Suitable chemically suitable salts include trifluoroacetate, and the anion of mineral acids such as chloride, sulfate, phosphate; preferred is trifluoroacetate. In the formation of compounds of formula (X) , alcohol (VII) is further protected as described above to form the diprotectred compound (XB). Compound (XB) is then reacted with an appropriately substituted e.mide forming agent (IX) to form compound (XA) , as described above for compound (IA). Deprotection of (XA) to compunds ' (X) is conducted as described for the transformation of compound (IA) to compounds (I). The protection of amines is conducted, where appropriate, by methods known to those skilled in the art. Amino protecting groups are known to those skilled in the art. See for example, "Protecting Groups in Organic Synthesis", John Wiley and sons, New York, K.Y., 1981, Chapter 7; "Protecting Groups in Organic Chemistry", Plenum Press, New York, N.Y., 1973, Chapter 2. When the amino protecting group is no longer needed, it is removed by methods known to those skilled in the art. By definition the amino protecting group must be readily removable. A variety of suitable methodologies are known to those skilled in the art; see also T.W. Green and P.G.M. Wuts in "Protective Groups in Organic Chemistry, John Wiley and Sons, 1991. Suitable amino protecting groups include t-butoxycarbonyl, benzyl- oxycarbonyl, formyl, trityl, phthalimido, trichloro- acetyl, chloroacetyl, bromoacetyl, iodoacetyl, 4- phenylbenzyloxycarbonyl, 2-methylbenzyloxycarbonyl, 4 - ethoxybenzyloxycarbonyl, 4-fluorobenzyloxycarbonyl, 4- chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, 2- chlorobenzyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 3-bromobenzyloxycarbonyl, 4- nitrobenzyloxycarbonyl, 4-cyanobenzyloxycarbonyl, 2-(4- xenyl)isopropoxycarbonyl, 1,1-diphenyleth-l- yloxycarbonyl, 1,1-diphenylprop-l-yloxycarbonyl, 2- phenylprop-2-yloxycarbonyl, 2-(p-toluyl)prop-2-yloxy- carbonyl, cyclopentanyloxycarbonyl, 1-methylcyclo- pentanyloxycarbonyl, cyclohexanyloxycarbonyl, 1-methyl- cyclohexanyloxycabonyl, 2-methylcyclohexanyloxycarbonyl, 2-(4-toluylsulfonyl)ethoxycarbonyl, 2-(methylsulfonyl)- ethoxycarbonyl, 2 -(triphenylphosphino)ethoxycarbonyl, fluorenylmethoxycarbonyl, 2-(trimethylsilyl)ethoxy- carbonyl, allyloxycarbonyl, 1-(trimethylsilylmethyl)prop- 1-enyloxycarbonyl, 5-benzisoxalylmethoxycarbonyl, 4- acetoxybenzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2 -ethynyl-2-propoxycarbonyl, cyclopropylme thoxycarbonyl, 4-(decyloxyl)benzyloxycarbonyl, isobrornyloxycarbonyl, 1- piperidyloxycarbonyl, 9-fluoroenylmethyl carbonate, -CH- CH=CH2 and phenyl-C(=N-)-H. It is preferred that the protecting group be t- butoxycarbonyl (BOC) and/or benzyloxycarbonyl (CBZ) , it is more preferred that the protecting group be t- butoxycarbonyl. One skilled in the art will recognize suitable methods of introducing a t-butoxycarbonyl or benzyloxycarbonyl protecting group and may additionally consult T.W. Green and P.G.M. Wuts in "Protective Groups in Organic Chemistry, John Wiley and Sons, 1991 for guidance. The compounds of the invention may contain geometric or optical isomers as well as tautomers. Thus, the invention includes all tautomers and pure geometric isomers, such as the E. and Z geometric iscmers, as well as mixtures thereof. Further, the invention includes pure enantiomers and ¦diastereomers as well as mixtures thereof, including racemic mixtures. The individual geometric isomers, enantiomers or diastereomers may be prepared or isolated by methods known to those skilled in the art, including but not limited to¦ chiral chromatography; preparing diastereomers, separating the diastereomers and converting the diastereomers into enantiomers through the use of a chiral resolving agent. Compounds of the invention with designated stereochemistry can be included in mixtures, including racemic mixtures, with other enantiomers, diastereomers, geometric isomers or tautomers. In a preferred aspect, compounds of the invention with (S, R, R) , (S, S, S) , or (S, R, S) stereochemistry are typically present in these mixtures in excess of 50 percent. Preferably, compounds of the invention with designated stereochemistry are present in these mixtures in excess of 80 percent. More preferably, compounds of the invention with designated stereochemistry are present in these mixtures in excess of 90 percent. Even more preferably, compounds of the invention with designated stereochemistry are present in these mixtures in excess of 99 percent. The invention encompasses pharmaceutically acceptable salts of the compounds of formula (AA), (I) and (X) . Pharmaceutically acceptable salts are preferred over the corresponding amines of formula (AA), (I) or (X) since they produce compounds which are more water soluble, stable and/or more crystalline. Pharmaceutically acceptable salts are any salt which retains the activity of the parent compound and does not impart any deleterious or undesirable €>ffect on the subject to whom it is administered and in the context in which it is administered. Pharmaceutically acceptable salts include salts of both inorganic and organic acids. The preferred pharmaceutically acceptable salts include salts of the following acids acetic, aspartic, benzenesulfonic, benzoic, bicarbonic, bisulfuric, bitartaric, butyric, calcium edetate, camsylic, carbonic, chlorobenzoic, citric, edetic, edisylic, estolic, esyl, esylic, formic, fumaric, gluceptic, gluconic, glutamic, glycollylarsanilic, hexamic, hexylresorcinoic, hydrabamic, hydrobromic, hydrochloric, hydroiodic, hydroxynaphthoic, isethionic, lactic, lactobionic, maleic, malic, malonic, mandelic, methanesulfonic, methylnitric, methylsulfuric, mucic, muconic, napsylic, nitric, oxalic, p-nitromethanesulfonic, pamoic, pantothenic, phosphoric, monohydrogen phosphoric, dihydrogen phosphoric, phthalic, polygalactouronic, propionic, salicylic, stearic, succinic, succinic, sulfamic? sulfanilic, sulfonic, sulfuric, tannic, tartaric, teoclic and toluenesulfonic. For other acceptable salts, see Int. J. Pharm., 33, 201-217 (198S) and J. Pharm. Sci., 66(1), 1, (1977). The invention provides compounds, compositions, kits, and methods for inhibiting beta-secretase enzyme activity and A beta peptide production. Inhibition of beta-secretase enzyme activity halts or reduces the production of A beta from APP and reduces or eliminates the formation of beta-amyloid deposits in the brain. Methods of the Invention The compounds of the invention, and pharmaceutically acceptable salts thereof, are useful for treating humans or animals suffering from a condition characterized by a pathological form of beta-amyloid peptide, such as beta- amyloid plagues, and for helping to prevent or delay the onset of such a condition. As used herein, the term "treating" means that the compounds of the invention can be used in humans with at least a'tentative diagnosis of disease. The compoundiS of the invention will delay or slow the progression of the disease thereby giving the individual a more useful life span. The term "preventing" means that the compounds of the invention are useful when administered to a patient who has not been diagnosed as possibly having the disease at the time of administration, but who would normally be expected to develop the disease or be at increased risk for the disease. The compounds of the invention will slow the development of disease symptoms, delay the onset of the disease, or prevent the individual from developing the disease at all. Preventing also includes administration of the compounds of the invention to those individuals thought to be predisposed to the disease due to age, familial history, genetic ' or chromosomal abnormalities, and/or due to the presence of one or more biological markers for the disease, such as a known genetic mutation of APP or APP cleavage products in brain tissues or fluids. In treating or preventing the above diseases, the compounds of the invention are administered in a therapeutically effective amount. The therapeutically effective amount will vary depending on the particular compound used and the route of administration, as is known to those skilled in the art. In treating a patient displaying any of the diagnosed above conditions a physician may administer a compound of the invention immediately and continue administration indefinitely, as needed. In treating patients who are not diagnosed as having Alzheimer's disease, but who are believed to be at substantial risk for Alzheimer's disease, the physician should preferably start treatment when the patient first experiences early pre-Alzheimer's symptoms such as, memory or cognitive problems associated with aging. In addition, there are some patients who may be determined to be at risk for developing Alzheimer's through the detection of a genetic marker such as APOE4 or other biological indicators that are predictive for Alzheimer's disease. In these situations, even though the patient does not have symptoms of the disease, administration of the compounds of the invention may be started before symptoms appear, and treatment may be continued indefinitely to prevent or. delay the onset of the disease. Dosage Forms and Amounts The compounds of the invention can be administered orally, parenterally, (IV, IM, depo-IM, SQ, and depo SQ), sublingually, intranasally (inhalation), intrathecally, topically, or rectally. Dosage forms known to those of skill in the art are suitable for delivery of the compounds of the invention. Compositions are provided that contain therapeutically effective amounts of the compounds of the invention. The compounds are preferably formulated into suitable pharmaceutical preparations such as tablets, capsules, or elixirs for oral administration or in sterile solutions or suspensions for parenteral administration. Typically the compounds described above are formulated into pharmaceutical compositions using techniques and procedures well known in the art. About 1 to 500 mg of a compound or mixture of compounds of the invention or a physiologically acceptable salt or ester is compounded with a physiologically acceptable vehicle, carrier, excipient, binder, preservative, stabilizer, flavor, etc., in a unit dosage form as called for by accepted pharmaceutical practice. The amount of active substance in those compositions or preparations is such that a suitable dosage in the range indicated is obtained. The compositions are preferably formulated in a unit dosage form, each dosage containing from about 2 to about 100 mg, more preferably about 10 to about 30 mg of the active ingredient. The term nunit dosage from" refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient. To prepare compositions, one or more compounds of the invention are mixed with a suitable pharmaceutically acceptable carrier. Upon mixing or addition of the compound(s) , the resulting mixture may be a solution, suspension, emulsion, or the like. Liposomal suspensions may also be suitable as pharmaceutically acceptable carriers. These may be prepared according to methods known to those skilled, in the art. The form of the resulting mixture depends upon a number of factors, including the intended mode of administration and the solubility of the compound in the selected carrier or vehicle. The effective concentration is sufficient for lessening or ameliorating at least one symptom of the disease, disorder, or condition treated and may be empirically determined. Pharmaceutical carriers or vehicles suitable for administration of the compounds provided herein include any such carriers known to those skilled in the art to be suitable for the particular mode of administration. In addition, the active materials can also be mixed with other active materials that do not impair the desired action, or with materials that supplement the desired action, or have another action. The compounds may be formulated as the sole pharmaceutically active ingredient in the composition or may be combined with other active ingredients. Where the compounds exhibit insufficient solubility, methods for solubilizing may be used. Such methods are known and include, but are not limited to, using cosolvents such as dimethylsulfoxide (DMSO), using surfactants such as Tween®, and dissolution in aqueous sodium bicarbonate. Derivatives of the compounds, such as salts or prodrugs may also be used in formulating effective pharmaceutical compositions. The concentration of the compound is effective for delivery of an amount upon administration that lessens or ameliorates at least one symptom of the disorder for which the compound is administered. Typically, the compositions are formulated for single dosage administration. The compounds of the invention may be prepared with carriers that protect them against rapid elimination from the body, such as time-release formulations or coatings. Such carriers include controlled release formulations, such as, but not limited to, microencapsulated delivery systems. The active compound is included in the pharmaceutically acceptable carrier in an amount sufficient to exert a therapeutically useful effect in the absence of undesirable side effects 0:1 the patient treated. The therapeutically effective concentration may be determined empirically by testing the compounds in known in vitro and in vivo model systems for the treated disorder. The compounds and compositions of the invention can be enclosed in multiple or single dose containers. The enclosed compounds and compositions can be provided in kits, for example, including component parts that can be assembled for use. For example, a compound inhibitor in lyophilized form and a suitable diluent may be provided as separated components for combination prior to use. A kit may include a compound inhibitor and a second therapeutic agent for co-administration. The inhibitor and second therapeutic agent may be provided as separate component parts. A kit may include a plurality of containers, each container holding one or more unit dose of the compound of the invention. The containers are preferably adapted for the desired mode of administration, including, but not limited to tablets, gel capsules, sustained-release capsules, and the like for oral administration; depot products, pre-filled syringes, ampoules, vials, and the like for parenteral administration; and patches, medipads, creams, and the like for topical administration. The concentration of active compound in the drug composition will depend on absorption, inactivation, and excretion rates of the active compound, the dosage schedule, and amount administered as well as other factors known to those of skill in the art. The active ingredient may be administered at once, or may be divided into a number of smaller doses to be administered at intervals of time. It is imderstood that the precise dosage and duration of treatment is a function of the disease being treated and may be determined empirically using known testing protocoLs or by extrapolation from in vivo or in vitro test data. It is to be noted that concentrations and dosage values may also vary with the severity of the condition to be alleviated. It is to be further understood that for any particular subject, specific dosage regimens should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions, and that the concentration ranges set forth herein are exemplary only and are not intended to limit the scope or practice of the claimed compositions. If oral administration is desired, the compound should be provided in a composition that protects it from the acidic environment of the stomach. For example, the composition can be formulated in an enteric coating that maintains its integrity in the stomach and releases the active compound in the intestine. The composition may also be formulated in combination with an antacid or other such ingredient. Oral compositions will generally include an inert diluent or an edible carrier and may be compressed into tablets pr enclosed in gelatin capsules. For the purpose of oral therapeutic administration, the active compound or compounds can be incorporated with excipients and used in the form of tablets, capsules, or troches. Pharmaceutically compatible binding agents and adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches, and the like can contain any of the following ingredients or compounds of a similar nature: a binder such as, but not limited to, gum tragacanth, acacia, corn starch, or gelatin; an excipient such as microcrystalline cellulose, starch, or lactose; a disintegrating agent such as, but not limited to, alginic acid and corn starch; a lubricant such as, but not limited to, magnesium stearate; a gildant, such as, but not limited to, colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; and a flavoring agent such as peppermint, methyl salicylate, or fruit flavoring. When the dosage unit form is a capsule, it can contain, in addition to material of the above type, a liquid carrier such as a fatty oil. In addition, dosage unit forms can contain various other materials, which modify the physical form of the dosage unit, for example, coatings of sugar and other enteric agents. The compounds can also be administered as a component of an elixir, suspension, syrup, wafer, chewing gum or the like. A syrup may contain, in addition to the active compounds, sucrose as a sweetening agent and certain preservatives, dyes and colorings, and flavors. The active materials can also be mixed with other active materials that do not impair the desired action, or with materials that supplement the desired action. Solutions or suspensions used for parenteral, intradermal, subcutaneous, or topical application can include any of the following components: a sterile diluent such as water for injection, saline solution, fixed oil, a naturally occurring vegetable oil such as sesame oil, coconut oil, peanut oil, cottonseed oil, and the like, or a synthetic fatty vehicle such as ethyl oleate, and the like, polyethylene glycol, glycerine, propylene glycol, or other synthetic solvent; antimicrobial agents such as benzyl alcohol and methyl parabens; antioxidants such as ascorbic acid and sodium bisulfite; chelating agents such as ethylenediatninetetraacetic acid (EDTA); buffers such as acetates, citrates, and phosphates; and agents for the adjustment of tonicity such as sodium chloride and dextrose. Parenteral preparations can be enclosed in ampoules, disposable syringes, or multiple dose vials made of glass, plastic, or other suitable material. Buffers, preservatives, antioxidants, and the like can be incorporated as required. Where administered intravenously, suitable carriers include physiological saline, phosphate buffered saline (PBS), and solutions containing thickening and solubilizing agents such as glucose, polyethylene glycol, polypropyleneglycol, and mixtures thereof. Liposomal suspensions including tissue-targeted liposomes may also be suitable as pharmaceutically acceptable carriers. These may be prepared according to methods known for example, as described in U.S. Patent Mo. 4,522,811. The active compounds may be prepared with carriers that protect the compound against rapid elimination from the body, such as time-release formulations or coatings. Such carriers include controlled release formulations, such as, but not limited to, implants and microencapsulated delivery systems, and biodegradable, biocompatible polymers such as collagen, sthylene vinyl acetate, polyanhydrides, polyglycolic acid, polyorthoesters, polylactic acid, and the like. Methods for preparation of such formulations are known to those skilled in the art. The compounds of the invention can be administered orally, parenterally (IV, IM, depo-IM, SQ, and depo-;3Q) , sublingually, intranasally (inhalation), intrathecally, topically, or rectally. Dosage forms known to those skilled in the art are suitable for delivery of the compounds of the invention. Compounds of the invention may be administered enterally or parenterally. When administered orally, compounds of the invention can be administered in usual dosage forms for oral administration as is well known to those skilled in the art. These dosage forms include the usual solid unit dosage forms of tablets and capsules as well as liquid dosage forms such as solutions, suspensions, and elixirs. When the solid dosage forms are used, it is preferred that they be of the sustained release type so that the compounds of the invention need to be administered only once or twice daily. The oral dosage forms are administered to the patient 1, 2, 3, or 4 times daily. It is preferred that the compounds of the invention be administered either three or fewer times, more preferably once or twice daily. Hence, it is preferred that the compounds of the invention be administered in oral dosage form. It is preferred that whatever oral dosage form is used, that it be designed so aB to protect the compounds of the invention from the acidic environment of the stomach. Enteric coated tablets are well known to those skilled in the art. In addition, capsules filled with small spheres each coated to protect from the acidic stomach, are also well known to those skilled in the art. When administered orally, an administered amount therapeutically effective to inhibit beta-secretase activity, to inhibit A beta production, to inhibit A beta deposition, or to treat or prevent AD is from about 0.1 mg/day to about 1,000 mg/day. It is preferred that the oral dosage is from about 1 mg/day to about 100 mg/day. It is more preferred that the oral dosage is from about 5 mg/day to about 50 mg/day. It is understood that while a patient may be started at one dose, that dose may be varied over time as the patient's condition changes. Compounds of the invention may also be advantageously delivered in a nano crystal dispersion formulation. Preparation of such formulations is described, for example, in U.S. Patent 5,145,684. Nano crystalline dispersions of HIV protease inhibitors and their method of use are described in U.S. Patent No. 6,045,829. The nano crystalline formulations typically afford greater bioavailability of drug compounds. The compounds of the invention can be administered parenterally, for example, by IV, IM, depo-IM, SC, or depo-SC. ' When administered parenterally, a therapeutically effective amount of about 0.5 to about 100 mg/day, preferably from about 5 to about 50 mg daily should be delivered. When a depot formulation is used for injection once a month or once every two weeks, the dose should be about 0.5 mg/day to about 50 mg/day, or a monthly dose of from about 15 mg to about 1,500 mg. In part because of the forgetfulness of the patients with Alzheimer's disease, it is preferred that the parenteral dosage form be a depo formulation. The compounds of the invention can be administered sublingually. When given sublingually, the compounds of the invention should be given one to four times daily in the amounts described above for IM administration. The compounds of the invention can be administered intranasally. When given by this route, the appropriate dosage forms are a nasal spray or dry powder, as is known to those skilled in the art. The dosage of the compounds of the invention for intranasal administration is the amount described above for IM administration. The compounds of the invention can be administered intrathecally. When given by this route the appropriate dosage form can be a parenteral dosage form as is known to those skilled in the art. The dosage of the compounds of the invention for intrathecal administration is the amount described above for IM administration. The compounds of the invention can be administered topically. When given by this route, the appropriate dosage form is a cream, ointment, or patch. Because of the amount of the compounds of the invention to be administered, the patch is preferred. When administered topically, the dosage is from about 0.5 mg/day to about 200 mg/day. Because the amount that can be delivered by a patch is limited, two or more patches may be used. The number and size of the patch is not important, what is important is that a therapeutically effective amount of the compounds of the invention be delivered as is known to those skilled in the art.- The compounds of the invention can be administered rectally by suppository as is known to those skilled in the art. When administered by suppository, the therapeutically effective amount is from about 0.5 mg to about 500 tng. The compounds of the invention can be administered by implants as is known to those skilled in the art. When administering a compound of the invention by implant, the therapeutically effective amount is the amount described above for depot administration. Given a particular compound of the invention and a desired dosage form, one skilled in the art would know how to prepare and administer the appropriate dosage form. The compounds of the invention are used in the same manner, by the same routes of administration, using the same pharmaceutical dosage forms, and at the same dosing schedule as described above, for preventing disease: or treating patients with MCI (mild cognitive impairment) and preventing or delaying the onset of Alzheimer's disease in those who would progress from MCI to AD, for treating or preventing Down's syndrome, for treating humans who have Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, for treating cerebral amyloid angiopathy and preventing its potential consequences, i;e. single and recurrent lobar hemorrhages, for treating other degenerative dementias, including dementias of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, and diffuse Lewy body type of Alzheimer's disease. The compounds of the invention can be used in combination, with each other or with other therapeutic agents or approaches used to treat or prevent the conditions listed above. Such agents or approaches include: acetylcholine esterase inhibitors such as tacrine (tetrahydroaminoacridine, marketed as COGNEX®), donepezil hydrochloride, (marketed as Aricept® and rivastigmine (marketed as Exelon®); gatnma-secretase inhibitors; anti-inflammatory agents such as cyclooxygenase II inhibitors; anti-oxidants such as Vitamin E and ginkolides; immunological approaches, such as, for example, immunization with A beta peptide or administration of anti-A beta peptide antibodies? statins; and direct or indirect neurotropic agents such as Cerebrolysin®, AIT-082 (Erailieu, 2000, Arch. Neuxol. 57:454), and other neurotropic agents of the future. In addition, the compounds of formula (AA) , (I) or (X) can also be used with inhibitors of P-glycoprotein (P-gp) . P-gp inhibitors and the use of such compounds are known to those skilled in the art. See for example, Cancer Research, 53, 4595-4602 (1993), Clin. Cancer Res., 2, 7-12 (1996), Cancer Research, 56, 4171-4179 (1996), International Publications WO99/64001 and WO01/10387. The important thing is that the blood level of the P-gp inhibitor be such that it exerts its effect in inhibiting P-gp from decreasing brain blood levels of the compounds of formula (A) . To that end the P-gp inhibitor and the compounds of formula (A) can be administered at the same time, by the same or different route of administration, or at different times. The important thing is not the time of administration but having an effective blood level of the P-gp inhibitor. Suitable P-gp inhibitors include cyclosporin A, verapamil, tamoxifen, quinidine, Vitamin E-TGPS, ritonavir, megestrol acetate, progesterone, rapamycin, 10,ll-methanodibenzosuberane, phenothiazines, acridine derivatives such as GF120918, FK506, VX-710, LY335979, PSC-833, GF-102,918 and other steroids. It is to be understood that additional agents will be found that have the same function and therefore achieve the same outcome; such compounds are also considered to be useful. The P-gp inhibitors can be administered orally, parenterally, (IV, IM, IM-depo, SQ, SQ-depo), topically, sublingually, rectally, intranasally, intrathecally and by implant. The therapeutically effective amount of the P-gp inhibitors is from about 0.1 to about 300 mg/kg/day, preferably about 0.1 to about 150 mg/kg daily. It is understood that while a patient may be started on one dose, that dose may have to be varied over time as the patient's condition changes. When administered orally, the P-gp inhibitors can be administered in usual dosage forms for oral administration as is known to those skilled in the art. These dosage forms include the usual solid unit dosage forms of tablets and capsules as well as liquid dosage forms such as solutions, suspensions and elixirs. When the solid dosage forms are used, it is preferred that they be of the sustained release type so that the P-gp inhibitors need to be administered only once or twice daily. The oral dosage forms are administered to the patient one thru four times daily. It is preferred that the P-gp inhibitors be administered either three or fewer times a day, more preferably once or twice daily. Hence, it is preferred that the P-gp inhibitors be administered in solid dosage form and further it is preferred that the solid dosage form be a sustained release form which permits once or twice daily dosing. It is preferred that what ever dosage form is used, that it be designed so as to protect the P-gp inhibitors from the acidic environment of the stomach. Enteric coated tablets are well known to those skilled in the art. In addition, capsules filled with small spheres each coated to protect from the acidic stomach, are also well known to those skilled in the art. In addition, the P-gp inhibitors can be administered parenterally. When administered parenterally they can be administered IV, IM, depo-IM, SQ or depo-SQ. The P-gp inhibitors can be given sublingually. Vlhen given sublingually, the P-gp inhibitors should be given one thru four times daily in the same amount as for IM administration. The P-gp inhibitors can be given intranasally. When given by this route of administration, the appropriate dosage forms are a nasal spray or dry powder as is known to those skilled in the art. The dosage of the P-gp inhibitors for intranasal administration is the same as for IM administration. The P-gp inhibitors can be given intrathecally. When given by this route of administration the appropriate dosage form can be a parenteral dosage form as is known to those skilled in the art. The P-gp inhibitors can be given topically. When given by this route of administration, the appropriate dosage form is a cream, ointment or patch. Because of the amount of the P-gp inhibitors needed to be administered the patch is preferred. However, the amount that can be delivered by a patch is limited. Therefore, two or more patches may be required. The number and size of the patch is not important, what is important is that a therapeutically effective amount of the P-gp inhibitors be delivered as is known to those skilled in the art. The P-gp inhibitors can be administered rectally by suppository as is known to those skilled in the art. The P-gp inhibitors can be administered by implants as is known to those skilled in the art. There is nothing novel about the route of administration nor the dosage forms for administering the P-gp inhibitors. Given a particular P-gp inhibitor, and a desired dosage form, one skilled in the art would know how to prepare the appropriate dosage form for the P-gp inhibitor. It should be apparent to one skilled in the art that the exact dosage and frequency of administration will depend on the particular compounds of the invention administered, the particular condition being treated, the severity of the condition being treated, the age, weight, general physical condition of the particular patient, and other medication the individual may be taking as is well known to administering physicians who are skilled in this art. Inhibition of APP Cleavage The compounds of the invention inhibit cleavage of APP between Met595 and Asp596 numbered for the APP695 isoform, or a mutant thereof, or at a corresponding site of a different isoform, such as APP751 or APP770, or a mutant thereof (sometimes referred to as the "beta secretase site") . While not wishing to be bound by a particular theory, inhibition of beta-secretase activity is thought to inhibit production of beta amyloid peptide (A beta). Inhibitory activity is demonstrated in one of a variety of inhibition assays, whereby cleavage of an APP substrate in the presence of a beta-secretase enzyme is analyzed in the presence of the inhibitory compound, under conditions normally sufficient to result in cleavage at the beta-secretase cleavage site. Reduction of APP cleavage at the beta-secretase cleavage site compared with an untreated or inactive control is correlated with inhibitory activity. Assay systems that can be used to demonstrate efficacy of the compound inhibitors of the invention are known. Representative assay systems are described, for example, in U.S. Patents No. 5,942,400, 5,744,346, as well as in the Examples below. The enzymatic activity of beta-secretase and the production of A beta can be analyzed in vitro or in vivo, using natural, mutated, and/or, synthetic APP substrates, natural, mutated, and/or synthetic enzyme, and the test compound. The analysis may involve primary or secondary cells expressing native, mutant, and/or synthetic APP and enzyme, animal models expressing native APP and enzyme, or may utilize transgenic animal models expressing the substrate and enzyme. Detection of enzymatic activity can be by analysis of one or more of the cleavage products, for example, by immunoassay, fluorometric or chromogenic assay, HPLC, or other means of detection. Inhibitory compounds are determined as those having the ability to decrease the amount of beta-secretase cleavage product produced in comparison to a control, where beta- secretase mediated cleavage in the reaction system is observed and measured in the absence of inhibitory compounds. Beta-Secretase Various forms of beta-secretase enzyme are known, and are available and useful for assay of enzyme activity and inhibition of enzyme activity. These include native, recombinant, and synthetic forms of the enzyme. Human beta-secretase is known as Beta Site APP Cleaving Enzyme (BACE), Asp2, and memapsin 2, and has been characterized, for example, in U.S. Patent No. 5,744,346 and published PCT patent applications WO98/22597, WO00/03819, WO01/23533, and WO00/17369, as well as in literature publications (Hussain et al., 1999, Mol. Cell. Neurosci. 14:419-427; Vassar et al., 1999, Science 286:735-741; Yan et al., 1999, .Nature 402:533-537; Sinha et al. , 1999, Nature 40:537-540; and Lin et al., 2000, PNAS USA 97:1456-1460). Synthetic forms of the enzyme have also been described (W098/22597 and WOOO/17369). Beta- secretase can be extracted and purified from human brain tissue and can be produced in cells, for example mammalian cells expressing recombinant enzyme. Preferred rearranged compounds are effective to inhibit about 50% of beta-secretase enzymatic activity at a concentration of less than 50 micromolar, preferably at a concentration of 10 micromolar or less, more preferably 1 micromolar or less, and most preferably 10 nanomolar or less. APP Substrate Assays that demonstrate inhibition of beta- secretase-mediated cleavage of APP can utilize any of the known forms of APP, including the 695 amino acid "normal" isotype described by Kang et al., 1987, .Nature 325:733-6, the 770 amino acid isotype described by Kitaguchi et. al., 1981, Nature 331:530-532, and variants such as the Swedish Mutation (KM670-1NL) (APP-SW) , the London Mutation (V7176F), and others. See, for example, U.S. Patent No. 5,766,846 and also Hardy, 1992, Nature Genet. 1:233-234, for a review of known variant mutations. Additional useful substrates include the dibasic amino acid modification, APP-KK disclosed, for example, in WO 00/17369, fragments of APP, and synthetic peptides containing the beta-secretase cleavage site, wild type (WT) or mutated form, e.g., SW, as described, for example, in U.S. Patent No 5,942,400 and WO00/03819. The APP substrate contains the beta-secretase cleavage site of APP (KM-DA or NL-DA) for example, a complete APP peptide or variant, an APP fragment, a .recombinant or synthetic APP, or a fusion peptide. Preferably, the fusion peptide includes the beta- secretase cleavage site fused to a peptide having a moiety useful for enzymatic assay, for example, having isolation and/or detection properties. A useful moiety may be an antigenic epitope for antibody binding, a label or other detection moiety, a binding substrate, and the like. Antibodies Products characteristic of APP cleavage can be measured by immunoassay using various antibodies/ as described, for example, in Pirttila et al., 1999, Neuro. Lett. 249:21-4, and in U.S. Patent No. 5,612,486. Useful antibodies to detect' A beta include, for example, the monoclonal antibody 6E10 (Senetek, St. Louis, MO) that specifically recognizes an epitope on amino acids 1-16 of the A beta peptide; antibodies 162 and 154 (New York State Institute for Basic Research, Staten Island, NY) that are specific for human A beta 1-40 and 1-42, respectively; and antibodies that recognize the junction region of beta-amyloid peptide, the site between residues 16 and 17, as described in U.S. Patent No. 5,593,846. ' Antibodies raised against a synthetic peptide of residues 591 to 596 of APP and SW192 antibody raised against 590- 596 of the Swedish mutation are also useful in immunoassay of APP and its cleavage products, as described in U.S. Patent Nos. 5,604,102 and 5,721,130. Assay Systems Assays for determining APP cleavage at the beta- secretase cleavage site are well known in the art. Exemplary assays, are described, for example, in U.S. Patent Nos. 5,744,346 and 5,942,400, and described in the Examples below. Cell Free Assays Exemplary assays that can be used to demonstrate the inhibitory activity of the compounds of the invention are described, for example, in WO00/17369, WO 00/03819, and U.S. Patents No. 5,942,400 and 5,744,346. Such assays can be performed in cell-free incubations or in cellular incubations using cells expressing a beta-secretase and an APP substrate having a beta-secretase cleavage site. An APP substrate containing the beta-secretase cleavage site of APP, for example, a complete APP or variant, an APP fragment, or a recombinant or synthetic APP substrate containing the atnino acid sequence: KM-DA or NL-DA, is incubated in the presence of beta-secretase enzyme, a fragment thereof, or a synthetic or recombinant polypeptide variant having beta-secretase activity and effective to cleave the beta-secretase cleavage site of APP, under incubatdon conditions suitable for the cleavage activity of the enzyme. Suitable substrates optionally include derivatives that may be fusion proteins or peptides that contain the substrate peptide and a modification useful to facilitate the purification or detection of the peptide or its beta-secretase cleavage products. Useful modifications include the insertion ' of a known antigenic epitope for antibody binding; the linking of a label or detectable moiety, the linking of a binding substrate, and the like. Suitable incubation conditions for a cell-free in vitro assay include, for example: approximately 200 nanomolar to 10 micromolar substrate, approximately 10 to 200 picomolar enzyme, and approximately 0.1 nanomolar to 10 micromolar inhibitor compound, in aqueous solution, at an approximate pH of 4 -7, at approximately 37 degrees C, for a time period of approximately 10 minutes to 3 hours. These incubation conditions are exemplary only, and can be varied as required for the particular assay components and/or desired measurement system. Optimization of the incubation conditions for the particular assay components should account for the specific beta-secretase enzyme used and its pH optimum, any additional enzymes and/or markers that might be used in the assay, and the like. Such optimization is routine and will not require undue experimentation. One useful assay utilizes a fusion peptide having maltose binding protein (MBP) fused to the C-terminal 125 amino acids of APP-SW. The MBP portion is captured on an assay substrate by anti-MBP capture antibody. Incuba~ion of the captured fusion protein in the presence of beta- secretase results in cleavage of the substrate at the beta-secretase cleavage site. Analysis of the cleavage activity can be, for example, by immunoassay of cleavage products. One such immunoassay detects a unique epitope exposed at the carboxy terminus of the cleaved fusion protein, for example, using the antibody SW192. 17his assay is described, for example, in U.S. Patent No 5,942,400. Cellular Assay Numerous cell-based assays can be used to analyze beta-secretase activity and/or processing of APP to release A beta. Contact of an APP substrate with a beta- secretase enzyme within the cell and in the presence or absence of a compound inhibitor of the invention can be used to demonstrate beta-secretase inhibitory activity of the compound. Preferably, assay in the presence of a useful inhibitory compound provides at least about 30%, most preferably at least about 50% inhibition of the enzymatic activity, as compared with a non-inhibited control. In one embodiment, cells that naturally express beta-secretase are used. Alternatively, cells are modified to express a recombinant beta-secretase or synthetic variant enzyme as discussed above. The APP substrate may be added to the culture medium and is preferably expressed in the cells. Cells that naturally express APP, variant or mutant forms of APP, or cells transformed to express an isoform of APP, mutant or variant APP, recombinant or synthetic APP, APP fragment, or synthetic APP peptide or fusion protein containing the beta-secretase APP cleavage site can be used, provided that the expressed APP is permitted to contact the enzyme and enzymatic cleavage activity can be analyzed. Human cell lines that normally process A beta from APP provide a useful means to assay inhibitory activities of the compounds of the invention. Production and release of A beta and/or other cleavage products into the culture medium can be measured, for example by immunoassay, such as Western blot or enzyme-linked immunoassay (EIA) such as by ELISA. Cells expressing an APP substrate and an active beta-secretase can be incubated in the presence of a compound inhibitor to demonstrate inhibition of enzymatic activity as compared with a control. Activity of beta- secretase can be measured by analysis of one or more cleavage products of the APP substrate. For example, inhibition of beta-secretase activity against the substrate APP would be expected to. decrease release of specific beta-secretase induced APP cleavage products such as A beta. Although both neural and non-neural cells process and release A beta, levels of endogenous beta-secretase activity are low and often difficult to detect by EIA. The use of cell types known to have enhanced beta- secretase activity, enhanced processing of APP to A beta, and/or enhanced production of A beta are therefore preferred. For example, transfection of cells with the Swedish Mutant form of APP (APP-SW); with APP-KK; or with APP-SW-KK provides cells having enhanced beta-secretase amount of CTF99 fragments of APP in the cell lysates is reduced as compared with the control. The cleavage products of APP can be analyzed, for example, by immune reactions with specific antibodies, as discussed above. Preferred cells for analysis of ' beta-secretase activity include primary human neuronal cells, primary transgenic animal neuronal cells where the transgene is APP, and other cells such as those of a stable 293 cell line expressing APP, for example, APP-SW. In vivo Assays: Animal Models Various animal models can be used to analyze besta- secretase activity and /or processing of AP? to release A beta, as described above. For example, transgenic animals expressing APP substrate and beta-secretase enzyme can be used to demonstrate inhibitory activity of the compounds of the invention. Certain transgenic animal models have been described, for example, in U.S. Patent NOS.: 5,877,399; 5,612,486; 5,3 87,742; 5,720,936; 5,850,003; 5,877,015,, and 5, 811, 633, and in Ganes et al., 1995, Nature 373:523. Preferred are animals that exhibit characteristics associated with the pathophysiology of AD. Administration of the compound inhibitors of the invention to the transgenic mice described herein provides an alternative method for activity and producing amounts of A beta that can be readily measured. In such assays, for example, the cells expressing APP and beta-secretase are incubated in a culture medium under conditions suitable for beta-secretase enzymatic activity at its cleavage site on the APP substrate. On exposure of the cells to the compound inhibitor, the amount of A beta released into the medium and/or the amount of CTF99 fragments of APP in the cell lysates is reduced as compared with the control. The cleavage products of APP can be analyzed, for example, by immune reactions with specific antibodies, as discussed above. Preferred cells for analysis of beta-secretase activity include primary human neuronal cells, primary transgenic animal neuronal cells where the transgene is APP, and other cells such as those of a stable 293 cell line expressing APP, for example, APP-SW. In vivo Assays: Animal Models Various animal models can be used to analyze beta- secretase activity and /or processing of APP to release A beta, as described above. For example, transgenic animals expressing APP substrate and beta-secretase enzyme can be used to demonstrate inhibitory activity of the compounds of the invention. Certain transgenic animal models have been described, for example, in U.S. Patent Nos.: 5,877,399; 5,612,486; 5,387,742; 5,720,936; 5,850,003; 5,877,015,, and 5,811,633, and in Ganes et al., 1995, Nature 373:523. Preferred are animals that exhibit characteristics associated with the pathophysiology of AD. Administration of the compound inhibitors of the invention to the transgenic mice described herein provides an alternative method for demonstrating the inhibitory activity of the compounds. Administration of the compounds in a phairmaceutically effective carrier and via an administrative route that reaches the target tissue in an appropriate therapeutic amount is also preferred. Inhibition of beta-secretase mediated cleavage of APP at the beta-secretase cleavage site and of A ieta release can be analyzed in these animals by measure of cleavage fragments in the animal's body fluids such as cerebral fluid or tissues. Analysis of brain tissues for A beta deposits or plaques is preferred. On contacting an APP substrate with a beta-secretase enzyme in the presence of an inhibitory compound of the invention and under conditions sufficient to permit enzymatic mediated cleavage of APP and/or release of A beta from the substrate, the compounds of the invention are effective to reduce beta-secretase-mediated cleavage of APP at the beta-secretase cleavage site and/or effective to reduce released amounts of A beta. Where such contacting is the administration of the inhibitory compounds of the invention to an animal model, for example, as described above, the compounds are effective to reduce A beta deposition in brain tissues of the animal, and to reduce the number and/or size of beta amyloid plagues. Where such administration is to a human subject, the compounds are effective to inhibit or slow the progression of disease characterized by enhanced amounts of A beta, to slow the progression of AD in the, and/or to prevent onset or development of AD in a patient at risk for the disease. Unless defined otherwise, all scientific and technical terms used herein have the same meaning as commonly understood by one of skill in the art to which this invention belongs. All patents and publications referred to herein are hereby incorporated by reference for all purposes. Definitions The definitions and explanations below are for the terms as used throughout this entire document including both the specification and the claims. It should be noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to a composition containing "a compound" includes a mixture of two or more compounds. It should also be noted that the term "or" is generally employed in its sense including "and/or" unless the content cleeirly dictates otherwise. The symbol "-" in general represents a bond between two atoms in the chain. Thus CH3-O-CH2-CH(Ri) -CH3 represents a 2-substituted-1-methoxypropane compound. In addition, the symbol "-" represents the point of attachment of the substituent to a compound. Thus for example aryl(Ci-Cs)alkyl- indicates an alkylaryl group, such as benzyl, attached to the compound at the alkyl moiety. Where multiple substituents are indicated as being attached to a structure, it is to be understood that the substituents can be the same or different. Thus for example "Rm optionally substituted with 1, 2 or 3 Rg groups" indicates that Rm is substituted with 1, 2, or 3 Rq groups where the Rq groups can be the same or different. APP, amyloid precursor protein, is defined as any APP polypeptide, including APP variants, mutations, and isoforms, for example, as disclosed in U.S. Patent No. 5,766,846. A beta, amyloid beta peptide, is defined as any peptide resulting from beta-secretase mediated cleavage of APP, including peptides of 39, 40, 41, 42, and 43 amino acids, and extending from the beta-secretase cleavage site to amino acids 39, 40, 41, 42, or 43. Beta-secretase (BACE1, Asp2, Memapsin 2) is an aspartyl protease that mediates cleavage of APP at the amino-terminal edge of A beta. Human beta-secretase is described, for example, in WO00/17369. Pharmaceutically acceptable refers to those properties and/or substances that are acceptable to the patient from a pharmacological/toxicological point of view and to the manufacturing pharmaceutical chemist from a physical/chemical point of view regarding composition, formulation, stability and patient acceptance. A therapeutically effective amount is defined as an amount effective to reduce or lessen at least one symptom of the disease being treated or to reduce or delay onset of one or more clinical markers or symptoms of the disease. By "alkyl" and wCi-Cg alkyl" in the present invention is meant straight or branched chain alkyl groups having 1-6 carbon atoms, such as, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, 2- pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl. It is understood that in cases where an alkyl chain of a substituent (e.g. of an alkyl, alkoxy or alkenyl group) is shorter or longer than 6 carbons, it will be so indicated in the second WC" as, for example, "C1-C10" indicates a maximum of 10 carbons. By "alkoxy" and "Cx-C6 alkoxy" in the present invention is meant straight or branched chain alkyl groups having 1-6 carbon atoms, attached through at least one divalent oxygen atom, such as, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert- butoxy, pentoxy, isopentoxy, neopentoxy, hexoxy, and 3- methylpentoxy. By the term "halogen" in the present invention is meant fluorine, bromine, chlorine, and iodine. "Alkenyl" and WC2-C6 alkenyl" means straight and branched hydrocarbon radicals having from 2 to 6 carbon atoms and from one to three double bonds and includes, for example, ethenyl, propenyl, l-but-3-enyl, l-pent-3- enyl, l-hex-5-enyl and the like. "Alkynyl" and "C2-C6 alkynyl" means straight and branched hydrocarbon radicals having from 2 to 6 carbon atoms and one or two triple bonds and includes ethynyl, propynyl, butynyl, pentyn-2-yl and the like. As used herein, the term "cycloalkyl" refers to saturated carbocyclic radicals having three to twelve carbon atoms. The cycloalkyl can be monocyclic, or a polycyclic fused system. Examples of such radicals include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. The cycloalkyl groups herein are unsubstituted or, as specified, substituted in one or more substitutable positions with various groups. For example, such cycloalkyl groups may be optionally substituted with. Ca-Cg alkyl, C1-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (Ci-C6) alkylamino, di(Ci-Cs) alkylamino, C2-C6alkenyl, C2-Csalkynyl, Cx-Cg haloalkyl, Ci-Cs haloalkoxy, amino (Ci-C6) alkyl, mono(C1- Cs) alkylamino (d-C6) alkyl or di (d-C6) alkylamino (d- Cs) alkyl. By "aryl" is meant an aromatic carbocyclic group having a single ring (e.g., phenyl) , multiple rings (e.g., biphenyl), or multiple condensed rings in which at least one is aromatic, (e.g., 1,2,3,4-tetrahydronaphthyl, naphthyl), which is optionally mono-, di-, or trisubstituted. Preferred aryl .groups of the present invention are phenyl, 1-naphthyl, 2-naphthyl, indanyl, indenyl, dihydronaphthyl, tetralinyl or 6,7,8,9- tetrahydro-5H-benzo[ajcycloheptenyl. The aryl groups herein are unsubstituted or, as specified, substituted in one or more substitutable positions with various groups. For example, such aryl groups may be optionally substituted with, for example, d-Cs alkyl, Ci-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(d~ Ce)alkylamino, di (d-C6) alkylamino, C2-Csalkenyl, C2- Cgalkynyl, d~C6 haloalkyl, d~Ce haloalkoxy, amino(Ci- C6) alkyl, mono (Cx-Cs) alkylamino (d-Cs) alkyl, di (d- C6) alkylamino (d-C6) alkyl, -COOH, -C(=O)O(d-C6 alkyl), -C(=O)NH2, -C(=0)N(mono- or di-d-Cs alkyl), -S (d-C6 alkyl), -SO2(d-Cs alkyl), -O-C(=O) (d-Cs alkyl), -NH- C(=O)-(d-Cs alkyl), -N(d-C6 alkyl) -C(=0) - (d-C6 alkyl), - NH-SOa-(d-C6 alkyl), -N(d-Cs alkyl) -S02- (d-C6 alkyl), - NH-C(=O)NH2, -NH-C(=0)N(mono- or di-d~Cs alkyl), -NH(d- C6 alkyl)-C(=O)-NH2 or -NH(d-C6 alkyl)-C(=0)-N-(mono- or di-d-Cs alkyl) . By "heteroaryl" is meant one or more aromatic ring systems of 5-, 6-, or 7-membered rings which includes fused ring systems of 9-11 atoms containing at least one and up to four heteroatoms selected from nitrogen, oxygen, or sulfur. Preferred heteroaryl groups of the present invention include pyridinyl, pyrimidinyl, guinolinyl, benzothienyl, indolyl, indolinyl, pryidazinyl, pyrazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, itnidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furanyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochrotnanyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromonyl, chromanonyl, pyridinyl-N-oxide, tetrahydroquinolinyl, dihydroguinolinyl, dihydroguinolinonyl, dihydroisoquinolinonyl, dihydrocoumarinyl, dihydroisocouraarinyl, isoindolinonyl, benzodioxanyl, benzoxazolinonyl, pyrrolyl N-oxide,, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, guinolinyl N- oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N- oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N- oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N- oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N- oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, benzothiopyranyl S,S- dioxide. The heteroaryl groups herein are unsubstituted or, as specified, substituted in one or more substitutable positions with various groups. For example, such heteroaryl groups may be optionally substituted with Ci-C6 alkyl, Ci-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(Ci-Cs)alkylamino, di (Cx-CsJalkylamino, C2-Csalkenyl, C2-CGalkynyl, Ci-C6 haloalkyl, d-C^ haloalkoxy, amino (Ci-C6) alkyl, mono(d~ C6)alkylamino(C1-C6) alkyl or di (C1-Cs)alkylamino (Ci- C6) alkyl, -COOH, -C(=O)O(Ci-C6 alkyl), -C(=0)NH2, C(=0)N(mono- or di-Ci-Cs alkyl), -S(Ci-C6 alkyl), -SO2(Ci-Cs alkyl), -O-C(=O) (Cx-Cs alkyl), -NH-C (=0)- (CS-C6 alkyl), - N(Ci-C6 alkyl) -C(=O)-(Ci-C6 alkyl), -NH-SO2-(d-C6 alkyl), - N(Ci-C6 alkyl)-S02-(Ci-Cg alkyl), -NH-C (=0)NH2, -NH- C(=0)N(mono- or di-d-C6 alkyl), -NH(C1-C6 alkyl)-C(==0) - NH2 or -NHCd-Cg alkyl)-C (=0)-M-(mono- or di-Ci-C6 alkyl). By "heterocycle", "heterocycloalkyl" or "heterocyclyl" is meant one or more carbocyclic ring systems of 3-, 4-, 5-, 6-, or 7-membered rings which includes fused ring systems of 9-11 atoms containing at least one and up to four heteroatoms selected from nitrogen, oxygen, or sulfur. Preferred heterocycles of the present invention include morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, tiiiomorpholinyl S,S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S,S-dioxide, oxazolidinonyl, dihydropyrazolyl, dihydropyrrolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, ' dihydrofuryl, dihydropyranyl, azepanyl, diazepanyl, tetrahydrothienyl S-oxide, tetrahydrothienyl S,S-dioxide and homothiomorpholinyl S- oxide. The heterocycle groups herein maybe unsubstituted or, as specified, substituted in one or more substitutable positions with various groups. For example, such heterocycle groups may be optionally substituted with C^-Cg alkyl, Cj.-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (Ci-Cg) alkylamino, di (Ci-CE) alkylamino, C2-C6alkenyl, C2-Csalkynyl, Cx-Ce haloalkyl, C!-Cs haloalkoxy, amino (C^Cg) alkyl, monofCi- Cs) alkylamino (Cx-Cg) alkyl, di (^-Ce) alkylamino (.C^-Ce) alkyl or =0. All patents and publications referred to herein are hereby incorporated by reference for all purposes. Structures were named using Name Pro IUPAC Naming Software, version 5.09, available from Advanced Chemical Development, Inc., 90 Adelaide Street West, Toronto, Ontario, M5H 3V9, Canada. The present invention may be better understood with reference to the following examples. These examples are intended to be representative of specific embodiments of the invention, and are not intended as limiting the scope of the invention. CHEMISTRY EXAMPLES The following detailed examples describe how to prepare the various compounds and/or perform the various processes of the invention and are to be construed as merely illustrative, and not limitations of the preceding disclosure in any way whatsoever. Those skilled in the art will promptly recognize appropriate variations from the procedures both as to reactants and as to reaction conditions and techniques. PREPARATION 1 tert-Butyl (IS)-3-bromo-l-(3,5- difluorobenzyl)-2-oxopropylcarbamate (III) N-methyl-morpholine (5.83 Ml, 53 mmole, 1.05 eg.) is added to [23)-2- [ (tert-butoxycarbonyl)amino]-3-(3,5- difluorophenyl)propanoic acid (II, 15 g, 50 mmole) in THF (100 mL) and the reaction is cooled to -78°. Isobutyl chloroformate (6.87 mL, 53 mmole, 1.05 eq.) is added rapidly. The cold bath is then removed and the mixture stirred for 1 hr. The reaction was monitored by TLC to insure completion of the reaction and the mixture is then filtered and washed with dry THF (50 ml) and kept cold in the filtered flask at -20°. In a ice-salt bath is placed a 50 0 ml graduate cylinder containing ether (200 mL) and aqueous potassium hydroxide (40%, 60 ml) . 1-methyl-3-nitro-1- nitrosoguanidine (5.6 g, 106 mmole, 2.1 eq.) is added slowly with stirring and temperature kept below zero degree. The mixture turned yellow and the bubbling lasted for 10 minutes. The stirring is stopped and without mixing the layers, the top diazomethane ethereal layer is transferred with non-ground tip pipette into the stirred mixed anhydride mixture at -20°. The reaction is monitored by TLC (ethyl acetate/hexane, 50/50; Rf = 0.69). After 1 hour nitrogen is then bubbled into the mixture. The solvent is removed under reduced pressure (with heat) and the mixture is partitioned between ether and water. The phases are separated, the organic phase is washed with bicarbonate, saline, dried over anhydrous sodium sulfate, filtered, and solvent removed under reduced pressure (with heat). The residue is dissolved in ether (100 mL) and hydrobromous acid (48%, 15 mL, 135 mmole, 2.7 eq,) is added at -20°, the cold bath is removed and the mixture is stirred for another half hour. The reaction is monitored by TLC (ethyl acetate/hexane, 50/50; Rf = 0.88]. The mixture is partitioned between ether and water, washed with bicarbonate, saline, dried over anhydrous sodium sulfate, filtered, and the solvent removed. The residue is recrystallized from ethanol to give the title compound, TLC (ethyl acetate/hexane, 50/50) Rf = 0.88; MS (MH+) = 379.3 PREPARATION 2 tert-Butyl (IS, 2S)-3-bromo-l-(3,5- difluorobenzyl)-2-hydroxypropylcarbamate (IV) Sodium borohydride (1.32 g, 34.9 mmole, 1.1 eq.) is added to tert-Butyl (IS)-3-bromo-l-(3,5-difluorobenzyl) - 2-oxopropylcarbamate (III, PREPARATION 1, 12 g, 31.75 mmole) dissolved in absolute alcohol (500 mL) -78°. The reaction mixture is stirred for 3 0 minutes and monitored by TLC (ethyl acetate/hexane, 20/80; Rf = 0.2). The mixture is quenched with water (10 mL) and the solvent removed under reduced pressure with heat (not exceeding 30°) to dryness. The solid is partitioned between dichloromethane and water, washed with saline, dried over anhydrous sodium sulfate. The solvent is removed under reduced pressure to give the title compound, TLC (ethyl acetate/hexane, 20/80) Rf = 0.2; MS (MH+) = 381.2 PREPARATION 3 tert-Butyl (IS) -2-(3,5-difluorophenyl)-1- [(2S)-oxiranyl]ethylcarbamate (V) tert-Butyl (IS, 2S)-3-bromo-l-(3,5-difluorobenzyl)- 2-hydroxypropylcarbamate (IV, PREPARATION 2) is dissolved in absolute alcohol (150 mL) and ethyl acetate (100 mL) and potassium hydroxide (2.3 g, 34.9 mmole, l.leg.) in ethyl alcohol (85%, 5mL) is added at -20°. The cold bath is then removed and the mixture stirred for 30 minutes. The reaction is monitored by TLC (ethyl acetate/hexane, 20/80) . When the reaction is complete, it is diluted with dichloromethane and extracted, washed with water, saline, dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. The crude material is purified by flash chromatography on silica gel to give the title compound, TLC (ethyl acetate/hexane, 20/80) Rf = 0.3; MS (MH+) = 300.4. PREPARATION 4: tert-Butyl (IS, 2R) -1- (3,5-di.f luorobenzyl) - 2-hydroxy-3-[(3-(triflurormethyl) benzyl)amino]- propylcarbamate tert-Butyl (IS)-2-(3,5-difluorophenyl)-1-[(2S) - oxiranyl] ethylcarbamate (PREPARATION 3, 8.5 g, 28.4 mmole) is mixed with isopropanol (145 ml) . The reaction flask is charged with 3-(trifluoromethyDbenzylamine. The reaction mixture is heated to reflux for 3 hours, HPLC analysis indicates complete disappearance of the epoxide. The reaction mixture is concentrated under reduced pressure and the residue is partitioned between ethyl acetate and aqueous hydrochloric acid. The orgamic phase is separated and washed with aqueous hydrochloric acid, bicarbonate, and saline then dried over sodium sulfate. Concentration under reduced pressure and recrystallization from hot hexane gives the title compound, MS (MH+) 475. PREPARATION 5: tert-Butyl (IS,2R)-1-(3,5- difluorobenzyl)-2-hydroxy-3-{(tert-butyloxy)carbonyl-3- {(trifluoromethyl)benzyl}amino}propylcarbamate To a solution of tert-butyl (1S,2R)-1-(3,5- difluorobenzyl)-2-hydroxy-3-[(3-(triflurortnethyl)benzyl)- amino]propylcarbamate (PREPARATION 4, 6.2 g, 13.1 mmole) in THF (70 ml) at 0° is added di-tert-butyl pyrocarbonate (6.3 g, 28.9 mmole). The reaction mixture is stirred at 20-25° for 18 hours. The reaction mixture is diluted with diethyl ether and washed with bicarbonate, 0.5 M citric acid, and saline then dried over sodium sulfate and concentrated to give the title compound, MS (MNa+) 597. PREPARATION 6: 3-iodo-5-(methoxycarbonyl)benzoic acid To an ice-cold, stirred solution of commercially available 3-amino-5-(methoxycarbonyl)benzole acid (5.19 g, 26.59 mmol) in 2 N hydrochloric acid (156 tnL) was added a solution of sodium nitrite (1.84 g, 26.67 mmol) in water (10.8 mL) . This mixture was then added dropwise to an ice-cold, stirred solution of potassium iodide (8.84 g, 53.25 mmol) in water (26.2 mL) . After stirring for 35 min, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with 5% aqueous sodium thiosulfate, and saturated sodium chloride, dried (sodium sulfate), and concentrated under reduced pressure. Purification by flash column chromatography (silica, .50:50:2 hexanes/ethyl acetate/acetic acid) afforded the title compound (4.48 g, 55% yield) as an off-white solid. ESI-MS (m/z) : 305 [M + H] + . PREPARATION 7: 3-[(dipropylamino)carbonyl]-5- (1,3-oxazol-2-yl)benzoic acid To a -70 °C solution of oxazole (4.0 g, 58 mmol} in tetrahydrofuran (100 mL) was added n-butyllithium (1.6 M in hexanes, 40 mL, 64 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 166 mL, 166 mmol) was added and the reaction mixture was warmed to 0 °C for 1 h. To this mixture was added 3-iodo-5-(methoxycarbonyl)benzoic acid (PREPARATION 6, 21.4 g, 55 mmol) and palladium (0) tetrakis (triphenylphosphine) (2.7 g, 2.34 mmol). The reaction mixture was heated at reflux for 1 h. The reaction mixture was diluted with ethyl acetate (300 mL), washed with water, and saturated sodium chloride. The organic layer was dried (sodium sulfate) and concentrated under reduced pressure. Purification by silica gel plug (10-33% ethyl acetate/hexanes) provided an oxazole (17.7 g, 97%) as a light yellow solid: XU NMR (300 MHz, CDC13) 5 8.73 (t, J= 2 Hz, 1H) , 8.24 (t, J= 2 Hz, 1H) , 8.11 (t, iT = 2 Hz, 1H), 7.77 (d, J = 1 Hz, 1H), 7.28 (d, J = 1 Hz, 1H) , 3.97 (s, 3H) , 3.49 (m, 2H) , 3.19 (m, 2H) , 1.71 (m, 2H), 1.57 (m, 2H), 1.01 (m, 3H), 0.76 (m, 3H). To a stirred solution of the ester from step 1 (17.7 g, 53.6 mmol) in tetrahydrofuran (50 mL) , methanol (25 mL), and water (25 mL) was added lithium hydroxide monohydrate (6.92 g, 165 mtnol). The reaction mixture was stirred at room temperature for 2 h, and then concentrated under reduced pressure. The residue was partitioned between water (100 mL) and diethyl ether (100 mL) . The aqueous layer was acidified to pH 4-5 with hydrochloric acid and extracted with ethyl acetate (3 x 200 mL) . The combined organic layers were washed with saturated sodium chloride, dried (sodium sulfate), and concentrated under reduced pressure to one-half its original volume. The resulting precipitate was collected by filtration and washed with hexanes to provide the title compound (15.5 g, 91%) as an off-white solid: mp 131-133 °C; XH NMR (300 MHz, CD3OD) 5 8.72 (s, 1H) , 8.22 (s, 1H) , 8.10 (s, 1H) , 8.06 (d, J = 1 Hz, 1H) , 7.36 (d, J = 1 Hz, 1H) , 3.52 (m, 2H) , 3.25 (m, 2H) , 1.76 (m, 2H) , 1.62 (m, 2H) , 1.02 (tn, 3H) , 0.76 (m, 3H) ; APCI MS m/z 317 [M + H]+. PREPARATION 8: (1R,2S)-2-amino-3-(3,5-difluorophenyl) -1- ({[3-(trifluoromethyl)benzyl] amino}methyl)propyl 3- [(dipropylamino)carbonyl]-5-(l,3-oxazol-2-yl)benzoate dihydrochloride To a solution of tert-butyl (1S,2R)-1-(3,5- difluorobenzyl)-2-hydroxy-3-{(tert-butyloxy)carbonyl-3- {(trifluoromethyl)benzyl}amino}propylcarbamate (PREPARATION 5, 594 mg, 1.0 mmole) in DMF (2 mL) is added 3- [ (dipropylaraino)carbonyl]-5-{1,3-oxazol-2-yl)benzoic acid (PREPARATION 7, 316 mg, 1.0 mmole), l-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (210 mg, 1.1 mmole}, and 4-(dimethylamino)pyridine (146 mg, 1.2 mmole). After -36 hours, the reaction mixture is diluted with ethyl acetate and washed with bicarbonate (2X) and brine (4X) then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate is purified on silica gel by flash chromatography using a gradient solvent of ethyl acetate/hexane (20/80 to 50/50) to give butoxycarbonyl)amino] -1-({(tert-butoxycarbonyl) [3- (trifluoromethyl)benzyl]amino}methyl)-3-(3,5- difluorophenyl)propyl 3- [ (dipropylamino)carbonyl]-5-(1,3- oxazol-2-yl)benzoate, MS (MNa+) 895. (1R,2S)-2-[(tert-butoxycarbonyl)amino]-1-({(tert- butoxycarbonyl) [3-(trifluoromethyl)benzyl]amino}methyl)- 3- (3,5-difluorophenyDpropyl 3- [ (dipropylamino) carbonyl] - 5- (l,3-oxazol-2-yl)benzoate (482 mg, 0.55 mmole) is dissolved in hydrochloric acid/dioxane (4N, 3 ml) is stirred for 1 hour at 20-25°. The solvent is then removed under reduced pressure to give the title compound, MS (MH+) 673. PREPARATION 9: N~l— [ (2R, 3S) -3-amino-4- (3 , 5- difluorophenyl)-2-hydroxybutyl] -5-(1,3-oxazol-2-yl)- N~3~,N~3—dipropyl-N~l—[3-(trifluoromethyl)benzyl]- isophthalamide hydrochloride To a solution of tert-butyl (1S,2R)-1-(3,5- dif luorobenzyl) -2-hydroxy-3-[(3- (trifluorormethyl)benzyl)amino]propylcarbamate (PREPARATION 4, 393 mg, 0.83 mmole) in DMF (2 mL) is added 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2- yDbenzoic acid (PREPARATION 7, 262 mg, 0.83 mmole), 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (175 mg, 0.91 mmole), and 4-(dimethylamino)pyridine (122 mg, 1.0 mmole). After -18 hours, the reaction mixture is diluted with ethyl acetate and washed with bicarbonate (2X) and brine (4X) then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate is purified on silica gel by flash chrotnatography using a gradient solvent of ethyl acetate/hexane (50/50 to 70/30) to give tert-butyl (lS,2R)-l-(3,5-difluorobenzyl)-3-{[3- [ (dipropylamino) carbonyl] -5- (1, 3-oxazol-2-yl)benzoyl] [3- (trifluoromethyl)benzyl]amino}-2-hydroxypropylcarbamate, MS (MH+) 773. tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-3-{ [3- [(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoyl] [3- (trifluoromethyl)benzyl]amino}-2-hydroxypropylcarbamat» (226 mg, 0.29 mmole) is dissolved in hydrochloric acid/dioxane (4N, 2 ml) is stirred for 20 minutes at 20- 25°. The solvent is then removed under reduced pressure and the crude material purified by reverse phase ' HPLC using a gradient aolvent of acetonitrile/water with 0.5% trifluoroacetic acid. The trifluoroacetic acid salt obtained is converted to the hydrochloric salt by treatment with HCl in methanol (1.25 M, 5 mL) . Concentration under reduced pressure gives the title compound, MS (MH+) 673. The following compounds are prepared essentially according to the procedures described in the schemes, charts, examples and preparations set forth herein. REARRANGEMENT EXAMPLES The following examples illustrate the acyl group migration that takes place with compounds of the invention. These examples are for illustration purposes, and are not intended to limit the scope of the invention. General Procedure: A compound of formula (I) OR (X) (5 mg) is dissolved in DMSO-d6 (50 0 |iL) and either pH 4 buffer solution (500 nL, potassium hydrogen phthalate buffer) or pH 7 buffer solution (500 uL, sodium and potassium phosphate buffer) is added. The sample is then heated to 40°C. The 0-acyl or N-acyl to N-terminal N-acyl migration is monitored by observing the change in chemical shift for the aromatic fluorines using 19F-NMR. (Fluorine shifts associated with the desired migration were confirmed by spiking with authentic analogue). The sample is analyzed by 19F-NMR at approxiamately 0, 1.5, 3, 24, 48, and 144 hours. The amount of O-acyl pro-drug, N- acyl pro-drug, and desired migration product at each time point are assigned by integrating the corresponding NMR signal. N-l~-[(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2- hydroxybutyl]-5-(1,3-oxazol-2-yl)-N~3-,N-3—dipropyl- N~l—[3-(trifluoromethyl)benzyl]isophthalamide hydrochloride (PREPARATION 7, 5 mg) is dissolved in DMSO- d6 (500 uL) and pH 4 buffer solution (500 nL, potassium hydrogen phthalate buffer) is added. The sample is then heated to 40°C. The N-acyl to N-terminal N-acyl migration is monitored by observing the change in chemical shift for the aromatic fluorines using 19F-NMR. (Fluorine shifts for the desired migration product in the presence of buffer was confirmed by spiking with authentic migration product, N1-((IS,2R)-1-(3,5- difluorobenzyl)-2-hydroxy-3-{[3- (trifluoromethyl)benzyl]amino}propyl)-5-(1, 3-oxazol-2- yl) -N3,N3-dipropylisophthalamide.) NMR data is collected at 0, 1, 3, 25, 48, 96, and 144 hours. The amount of N- acyl pro-drug and desired migration product present at each time point is assigned by integrating the corresponding NMR signal. No migration to O-acyl pro- drug was observed using this method and was confirmed by spiking with authentic compound. The following examples illustrate the solution acyl group migration of compounds of the formulae (I) and (X) as observed by 19F NMR spectroscopy. Data were collected as described in Example 1, above. EXAMPLE 2: Rearrangement of (1R,2S)-2-amino-3-(3,5- difluorophenyl)-1-({ [1-(3- ethynylphenyl)cyclopropyl]amino}methyl)propyl 3- [(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate (22) . BIOLOGY EXAMPLES Example A Enzyme Inhibition Assay The rearranged compounds of the invention are analyzed for inhibitory activity by use of the MBP-C125 assay. This assay determines the relative inhibition of beta-secretase cleavage of a model APP substrate, MBP- C125SW, by the compounds assayed as compared with an untreated control. A detailed description of the assay parameters can be found, for example, in U.S. Patent No. 5,942,400. Briefly, the substrate is a fusion peptide formed of maltose binding protein (MBP) and the carboxy terminal 125 amino acids of APP-SW, the Swedish mutation. Th*, jbeta-secretase enzyme is derived from human brain tissue as described in Sinha et al, 1999, Nature 40:537- 540) or recombinantly produced as the full-length enzyme (amino acids 1-501), and can be prepared, for example, from 293 cells expressing the recombinant cDNA, as described in WO00/47618. Inhibition of the enzyme is analyzed, for example, by immunoassay of the enzyme's cleavage products. One exemplary ELISA uses an anti-MBP capture antibody that, is deposited on precoated and blocked 96-well high binding plates, followed by incubation with diluted enzyme reaction supernatant, incubation with a specific reporter antibody, for example, biotinylated anti-SW192 reporter antibody, and further incubation with streptavidin/alkaline phosphatase. In the assay, cleavage of the intact MBP-C125SW fusion protein results in the generation of a truncated amino-terminal fragment, exposing a new SW-192 antibody-positive epitope at the carboxy terminus. Detection is effected by a fluorescent substrate signal on cleavage by the phosphatase. ELISA only detects cleavage following Leu 596 at the substrate's APP-SW 751 mutation site. Specific Assay Procedure: Compounds are diluted in a 1:1 dilution series to a six-point concentration curve (two wells per concentration) in one 96-plate row per compound tested. Each of the test compounds is prepared in DMSO to make up a 10 millimolar stock solution. The stock solution is serially diluted in DMSO to obtain a final compound concentration of 200 micromolar at the high point of a 6- point dilution curve. Ten (10) microliters of each dilution is added to each of two wells on row C of a corresponding V-bottom plate to which 190 microliters of 52 millimolar NaOAc, 7.9% DMSO, pH 4.5 are pre-added. The NaOAc diluted compound plate is spun down to pellet precipitant and 20 microliters/well is transferred to a corresponding flat-bottom plate to which 30 microliters of ice-cold enzyme-substrate mixture (2.5 microliters MBP-C125SW substrate, 0.03 microliters enzyme and 24.5 microliters ice cold 0.09% TX100 per 30 microliters} is added. The final reaction mixture of 200 micromolar compound at the highest curve point is in 5% DMSO, 20 millimolar NaOAc, 0.0S% TX100, at pH 4.5. Warming the plates to 37 degrees C starts the enzyme reaction. After 90 minutes at 3 7 degrees C, 200 microliters/well cold specimen diluent is added to stop the reaction and 20 microliters/well was transferred to a corresponding anti-MBP antibody coated ELISA plate for capture, containing 80 microliters/well specimen diluent. This reaction is incubated overnight at 4 degrees C and the ELISA is developed the next day after a 2 hour incubation with anti-192SW antibody, followed by Streptavidin-AP conjugate and fluorescent substrate. The signal is read on a fluorescent plate reader. . Relative compound inhibition potency is determined by calculating the concentration of compound that showed a fifty percent reduction in detected signal (IC50) compared to the enzyme reaction signal in the control wells with no added compound. In this assay, preferred compounds of the invention exhibit an IC50 of less than 50 micromolar. Example B Cell Free Inhibition Assay Utilizing a Synthetic APP Substrate 341 >- A synthetic APP substrate that can be cleaved by beta-secretase and having N-terminal biotin and made fluorescent by the covalent attachment of Oregon green at the Cys residue is used to assay beta-secretase activity in the presence or absence of the inhibitory compounds of the invention. Useful substrates include the following: Biotin-SEVNL-DAEFRC[oregon green]KK [SEQ ID NO: 1] Biotin-SEVKM-DAEPRC[oregon green]KK [SEQ ID NO: 2] Biotin-GLNIKTEEISEISY-EVEFRC[oregon green]KK [SEQ ID NO: 3] Biotin-ADRGLTTRPGSGLTNIKTEEISEVNL-DAEFRC [Oregon green] KK [SEQ ID NO:4] Biotin-FVNQHLCoxGSHLVEALY-LVCoxGERGFFYTPKAC[oregon green] KK [SEQ ID NO: 5] The enzyme (0.1 nanotnolar) and test compounds (0.001 100 micromolar) are incubated in pre-blocked, low affinity, black plates (384 well) at 37 degrees for 30 minutes. The reaction is initiated by addition of 150 millimolar substrate to a final volume of 3 0 microliter per well. The final assay conditions are: 0.001 - 100 micromolar compound inhibitor; 0.1 molar sodium acetate (pH 4.5); 150 nanomolar substrate; 0.1 nanomolar soluble beta-secretase; 0.001% Tween 20, and 2% DMSO. The assay mixture is incubated for 3 hours at 37 degrees C, and the reaction is terminated by the addition of a saturating concentration of immunopure streptavidin. After incubation with streptavidin at room temperature for 15 minutes, fluorescence polarization is measured, for example, using a LJL Acqurest (Ex485 nm/ Em530 nm) . The activity of the beta-secretase enzyme is detected by cJbaii^pfes in the fluorescence polarization that occur when the substrate is cleaved by the enzyme. Incubation in the presence or absence of compound inhibitor demonstrates specific inhibition of beta-secretase enzymatic cleavage of its synthetic APP substrate. In this assay, preferred compounds of the invention exhibit an IC50 of less than 50 micromolar. Example C Beta-Secretase Inhibition; P26-P4'SW Assay Synthetic substrates containing the beta-secretase cleavage site of APP are used to assay beta-secretase activity, using the methods described, for example, in published PCT application WO00/47618. The P26-P4'SW substrate is a peptide of the sequence: (biotin)CGGADRGLTTRPGSGLTNIKTEEISEVNLDAEF [SEQ ID NO: 6] The P26-P1 standard has the sequence: (biotin)CGGADRGLTTRPGSGLTNIKTEEISEVNL [SEQ ID NO: 7] . Briefly, the biotin-coupled synthetic substrates are incubated at a concentration of from about 0 to about 200 micromolar in this assay. When testing inhibitory compounds, a substrate concentration of about 1.0 micromolar is preferred. Test compounds diluted in DMSO are added to the reaction mixture, with a final DMSO concentration of 5%. Controls also contain a final DMSO concentration of 5%. The concentration of beta secretase enzyme in the reaction is varied, to give product concentrations with the linear range of the ELISA assay, about 125 to 2000 picomolar, after dilution. The reaction mixture also includes 20 millimolar sodium acetate, pH 4.5, 0.06% Triton X100, and is ipcu.ba.ted at 37 degrees C for about 1 to 3 hcurs. Samples are then diluted in assay buffer (for example, 145.4 nanomolar sodium chloride, 9.51 millimolar sodium phosphate, 7.7 millimolar sodium azide, 0.05% Triton X405, 6g/liter bovine serum albumin, pH 7.4) to quench the reaction, then diluted further for immunoassay of the cleavage products. Cleavage products can be assayed by ELISA. Diluted samples and standards are incubated in assay plates coated with capture antibody, for example, SW192, for about 24 hours at 4 degrees C. After washing in TTBS buffer (150 millimolar sodium chloride, 25 millimolar Tris, 0.05% Tween 20, pH 7.5), the samples are incubated with streptavidin-AP according to the manufacturer's instructions. After a one hour incubation at room temperature, the samples are washed in TTBS and incubated with fluorescent substrate solution A (31.2 g/liter 2- amino-2-methyl-l-propanol, 30 mg/liter, pH 9.5). Reaction with streptavidin-alkaline phosphate permits detection by fluorescence. Compounds that are effective inhibitors of beta-secretase activity demonstrate reduced cleavage of the substrate as compared to a control. Example D Assays using Synthetic Oligopeptide-Substrates Synthetic oligopeptides are prepared that incorporate the known cleavage site of beta-secretase, and optionally detectable tags, such as fluorescent or chromogenic moieties. Examples of such peptides, as well as their production and detection methods are described in U.S. Patent No: 5,942,400, herein incorporated by reference. Cleavage products can be detected using high performance liquid chromatography, or fluorescent or oMtunogenic detection methods appropriate to the peptide to be detected, according to methods well known in the art. By way of example, one such peptide has the sequence SEVNL-DAEF [SEQ ID NO: 8] , and the cleavage site is between residues 5 and 6. Another preferred substrate has the sequence ADRGLTTRPGSGLTNIKTEEISEVNL-DAEF [SEQ ID NO: 9] , and the cleavage site is between residues 26 and 27. These synthetic APP substrates are incubated in the presence of beta-secretase under conditions sufficient to result in beta-secretase mediated cleavage of the substrate. Comparison of the cleavage results in the presence of the compound inhibitor to control results provides a measure of the compound's inhibitory activity. Example E Inhibition of Beta-Secretase Activity - Cellular Assay J I An exemplary assay for the analysis of inhibition of beta-secretase activity utilizes the human embryonic kidney cell line HEKp293 (ATCC Accession No. CRL-1573) transfected with APP751 containing the naturally occurring double mutation Lys651Met52 to Asn651Leu652 (numbered for APP75L), commonly called the Swedish mutation and shown to overproduce A beta (Citron et al., 1992, Nature 360:672-674), as described in U.S. Patent NO. 5,604,102. The cells are incubated in the presence/absence of the inhibitory compound (diluted in DMSO) at the desired concentration, generally up to 10 micrograms/ml. At the end of the treatment period, conditioned media is analyzed for beta-secretase activity, for example, by alWklysis of cleavage fragments. A beta can be analyzed by immunoassay, using specific detection antibodies. The enzymatic activity is measured in the presence and absence of the compound inhibitors to demonstrate specific inhibition of beta-secretase mediated cleavage of APP substrate. Example F Inhibition of Beta-Secretase in Animal Models of AD Various animal models can be used to screen for inhibition of beta-secretase activity. Examples of animal models useful in the invention include, but are not limited to, mouse, guinea pig, dog, and the like. The animals used can be wild type, transgenic, or knockout models. In addition, mammalian models can express mutations in APP, such as APP695-SW and the like described herein. Examples of transgenic non-human mammalian models are described in U.S. Patent Nos. 5,604,102, 5,912,410 and 5,811,633. PDAPP mice, prepared as described in Games et al. , 1995, Nature 373:523-527 are useful to analyze in vivo suppression of A beta release in the presence of putative inhibitory compounds. As described in U.S. Patent No. 6,191,166, 4 month old PDAPP mice are administered compound formulated in vehicle, such as corn oil. The mice are dosed with compound (1-30 mg/ml; preferably 1- 10 mg/ml). After time, e.g., 3-10 hours, the animals are sacrificed, and brains removed for analysis. Transgenic animals are administered an amount of the compound inhibitor formulated in a carrier suitable for the chosen mode of administration. Control animals are untreated, treated with vehicle, or treated with an inactive compound. Administration can be acute, i.e., single dose or multiple doses in one day, or ca:n be chronic, i.e., dosing is repeated daily for a period of days. Beginning at time " 0, brain tissue or cerebral fluid is obtained from selected animals and analyzed for the presence of APP cleavage peptides, including A beta, for example, by immunoassay using specific antibodies for A beta detection. At the end of the test period, animals are sacrificed and brain tissue or cerebral fluid is analyzed for the presence of A beta and/or beta-amyloid plaques. The tissue is also analyzed for necrosis. Animals administered the compound inhibitors of the invention are expected to demonstrate reduced A beta in brain tissues or cerebral fluids and reduced beta amyloid plaques. in brain tissue, as compared with non- treated controls. Example 6 Inhibition of A Beta Production in Human Patients Patients suffering from Alzheimer's Disease (AD) demonstrate an increased amount of A beta in the brain. AD patients are administered an amount of the compound inhibitor formulated in a carrier suitable for the chosen mode of administration. Administration is repeated daily for the duration of the test period. Beginning on day 0, cognitive and memory tests are performed, for example, once per month. Patients administered the compound inhibitors are expected to demonstrate slowing or stabilization of disease progression as analyzed by changes in one or more of the following disease parameters: A beta present in CSF or plasma; brain or hippocampal volume; A beta deposits in the brain; amyloid plague in the brain; and secies for cognitive and memory function, as compared with control, non-treated patients. Example H Prevention of A Beta Production in Patients at Risk for AD Patients predisposed or at risk for developing AD are identified either by recognition of a familial inheritance pattern, for example, presence of the Swedish Mutation, and/or by monitoring diagnostic parameters. Patients identified as predisposed or at risk for developing AD are administered an amount of the compound inhibitor formulated in a carrier suitable for the chosen mode of administration. Administration is repeated daily for the duration of the test period. Beginning on day 0, cognitive and memory tests are performed, for example, once per month. Patients administered the compound inhibitors are expected to demonstrate slowing or stabilization of disease progression as analyzed by changes in one or more of the following disease parameters: A beta present in CSF or plasma; brain or hippocampal volume; amyloid plaque in the brain; and scores for cognitive and memory function, as compared with control, non-treated patients. The invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention. The invention has been described with reference to various specific and preferred embodiments and techniques. However,1 it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention. WE CLAIM :- 1. A compound of formula: or a pharmaceutically acceptable salt thereof, wherein one of RN and Rs' is hydrogen and the other is -C (=O} - (CRR') 0_6R-100 -C(=O) - (CRR') -O-R'100, -C (=O)- {CRR')1-6-S-R' -100, -C {-=O) - (CRR'-).1-6-C (=O)-R100, -C (=O) - (CRR' ) 1-6- SO7-R10n, -C(=O)-(CRR')1-5-NR100-R'100, or wherein R, is selected from the group consisting of H; NH2; -NH- (CH2}h6-R4_ 1,- -NHR3; -NR5OC(O)R5; C,-C4 alkyl-NHC (O) R5; - (CH?) o-4Re; -O-C1- C4 alkanoyi; OH; C6-C10 aryloxy optionally substituted with 1, 2, or 3 groups that are independently, halogen, C1-C4 alkyl, -CO7Hr -C(O)-C1-C4 alkoxy, or C1-C4 alkoxy; C1-C6 alkoxy; ary] C1-C4 alkoxy; -NR50CO2R51; -C1-C4 alkyl-NR50CO2R5; -C=N; -CF3; -CF2-CF3; -C=CH; -CH2-CH=CH2;- - (CH2) 1-4-R4-1;-(CH2)- 4-NH-R4-1; -O-(CHy,}n6-R4-1; -S- (CH2) n5-R4-1; - (CH2) 0_4-NHC (O)- (CH2} 0-5-R52; — (CH2) 0-2-R53- (CH2} n-4-R54; wherein n6 is 0, 1, 2, or 3; n7 is 0, 1, 2, or 3; R4-1 is selected from the group consisting of -SO2- (C1-C8 alkyl), -SO-(C1-C4 alkyl), -S-{C1-C8 alkyl) , -S-CO-(C1-C5 alkyl) , -SO2-NR4_2R4_3; -CO-Ca-C2 alkyl; -CO-NR4-3R,1-4; R4_2 and R4_:: are independently H, C1-C3 alkyl, or C3-C5 cycloalkyl; R4_4 is alkyl, arylalkyl, alkanoyi, or arylalkanoyl; R4-6 is-H or C1-C6 alkyl; R5 is selected from the group consisting of C3-C7 cycloalkyl; C1-C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, -NR6R7, C1-C4 alkoxy, C5-C6 heterocycloalkyl, C5-C6 heteroaryl, C6-C10 aryl, C3-C7 cycloalkyl C1-C4 alkyl, -S-C1-C4 alkyl, -SO2- C1-C4 alkyl, -CO2H, -CONR6R7/ -CO2-C1-C4, alkyl, C6-C10 aryloxy; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, C1-C4 haloalkyl, or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groups- that are independently C1-C4, alkyl, C1-C4 alkoxy, halogen, or C2-C4 alkanoyl; aryl optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, OH, C1-C4, alkyl, C1-C4 alkoxy, or C1-C4 haloaikyl; and -NR5R7; wherein R6 and R7 are independently selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkanoyl, phenyl, -SO2-C1-C4 alkyl, phenyl C1-C4 alkyl; R8 is selected from the group consisting of -SO2-heteroaryl, -SO2-aryl, -SO2-heterocycloalkyl, -SO2C1-C10 alkyl, C(O) NHR9, heterocycloalkyl, -S-C1-C6 alkyl, -S-C2-C4 alkanoyl, wherein R9 is aryl C1-C4 alkyl, C1-C4 alkyl, or H; R50 is H or C1-C6 alkyl; R51 is selected from the group consisting of aryl C1-C4 alkyl; C1-C4 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, heteroaryl, -NR6R7 -C(O)NR6R7, C1-C4 cycloalkyl, or -C1- C4 alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups that are independently C1-C4,; alkyl, C1-C4 alkoxy, halogen, C2-C4 alkanoyl, aryl C1-C4 alkyl, and - S02 C3.-C4 alkyl; alkenyl; alkynyl; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently OH, C1-C4 alkyl, Ci-C4 alkoxy, halogen, NH2, NH{C1-C6 alkyl} or N(C1-C6 alkyl) (C1-C6 alkyl); heteroarylalkyl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, NH2, NH(C1-C4 alkyl) or N(C1-C4 alkyl) (C1-C6 alkyl); aryl; heterocycloalkyl; C3-C8 cycloalkyl; and cycloalkylalkyl; wherein the aryl; heterocycloalkyl, C3-C8 cycloalkyl,- and cycloalkylaikyl groups are optionally substituted with 1, 2, 3, 4 or 5 groups that -are independently halogen, CN, NO2, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkanoyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxy, C1-C6 hydroxyalkyl, C1-C6 alkoxy C1-C6 alkyl, C1-C6 thioalkoxy, Ci~C6 thioalkoxy Ci-C6 alkyl, or C1-C6 alkoxy C1-C6 alkoxy; R&2 is heterocycloalkyl,. heteroaryl, ary]., cycloalkyl, S (O)-0-2-C1-C6 alkyl, CO2H, -C(O)NH2, -C (O) NH (alkyl) , -C (O)N (alkyl) (alkyl) , -CO2-alkyl, -NHS (O) 0-2-C1-C6 alkyl, -N(alkyr}S(O)o-2-C1-C6 alkyl, -S (O} O-2-heteroaryl, -S(O)C- 2-aryl, -NH(arylalkyl), -N(alkyl)(arylalkyl), thioalkoxy, or alkoxy, each, of which is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkyl, alkoxy, thioalkoxy, halogen, haloalkyl, haloalkoxy, alkanoyl, NO2, CN, alkoxycarbonyl, or aminocarbonyl; R5.-, is absent, -O-, -C(O)-, -NH-, -N (alkyl)-, -NH-S (O) 0_2-, - N (alkyl)-S{G)0-2-, -S (O)0_2-NH-, -S (0) 0_2- N (alkyl) -, -NH- C(S)-, or -N(alkyl)-C(S)-; R54 is heteroaryl, aryl, arylalkyl, heterocycloalkyl, CO2-H, - CO2-alkyl, -C(O)NH(alkyl), -C(O)N(alkyl) (alkyl), -C(O)NH2, C1-C8 alkyl, OH, aryloxy, alkoxy, arylalkoxy, NH2, NH (alkyl), N (alkyl) (alkyl), or -Cr-C6 alkyl-CO2- Ci-C6 alkyl, each of which is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkyl, alkoxy, CO2H, -C02-alkyl, thioalkoxy, halogen, haloalkyl, haloalkoxy, hydroxyalkyl, alkanoyl, N02, CN, alkoxycarbonyl, or aminocarbonyl; X is selected from the group consisting of -C!-C6 alkylidenyl optionally optionally substituted with 1, 2, or 3 methyl groups; and -NR4_6-; or R4 and R4_6 combine to form -(CH2)ni0-, wherein n10 is 1, 2, 3, or 4; Z is selected from the group consisting of a bond; S02; SO; S; and C(0); Y is selected from the group consisting of K; C-L-Ct haioalkyl; C5- C6 heterocycloalkyl; C6-C10 aryl; OH; -N (Y^ (Y2) ; d-dc alkyl optionally substituted with i thru 3 substituents which can be' the same or different and are selected from the group consisting of halogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy; C3-C8 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from Ci-C3 alkyl, and halogen; alkoxy; . aryl optionally . substituted with halogen, aikyi, alkoxy, CN or N02; arylalkyl optionally substituted with halogen, alkyl, alkoxy, CN or N02; wherein Yi and Y2 are the same or. different and are H; d~dc alkyl optionally substituted with i, 2, or 3 substituents selected from the group consisting of halogen, C1-C4 alkoxy, C3-C8 cycloalkyl, and OH; C2-C6 alkenyl; C2-C6 alkanoyl;- phenyl; -SO2-Ci-C4 alkyl; phenyl CL-C4 alkyl; or C3-C8 cycloalkyl C1-C4 alkyl; or Yi, - Y2 "and the ¦ nitrogen" to which they are attached form a ring selected from the group consisting of piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently Ci-C6 alkyl, d-C6 alkoxy, C-t-Cs alkoxy C3- C6 alkyl, or halogen; R-, is -{CH2)i-2-S.{O)0-2-{C1-C6 alkyl), or . d-Cao alkyl -substituted with 1, 2, or 3 groups independently selected from halogen, OH, =O, -SH, -CsN, -CF3, -C1-C3 alkoxy, amino, mono- or dialkylamino, -N(R)C(O)R'-, -0C(=0) -amino and -0C (==0)-mono- or dialkylamino, or C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -CsN, -CF3, C1-C3 alkoxy, amino, and mono- or dialkylamino, or aryl, heteroaryl, heterocyclyl, -Ci-C6 alkyl-aryl, -Ci-C6 aikyl-heteroaryl, or -Ci~C6 alkyl-heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, -OH, -SH, -C=N, -NR1O5R'1O5, -CO2R, -N(R)COR', or -N(R)SO2R', -C (=0) - (C:-C4) alkyl,- -SOz-amino, -SO?- mono or dialkylamino, -C(=0)-amino, -C(=0)-mono or dialkylamino, -SO2-(C1-C4) alkyl, or -Ci-Ce alkoxy optionally substituted with 1, 2, or 3 groups which are independently a halogen, or C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -Q=N, -CF3, C1-C3 alkoxy, amino, -C2-C6 alkyl and mono- or dialkylamino, or Ci-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -CsN, -CF3, -C1-C3 alkoxy, amino, mono- or dialkylamino and -Ci-C3 alkyl, or C2-Cic alkenyl or C2-Ci0 alkynyl each of which is optionally substituted with 1, 2, or 3 groups .. independently selected from halogen, -OH, -SH, -C^N, -CF3, C1-C3 alkoxy, amino, Cj-Cg alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further ... ..substituted with oxo; R and R' independently are hydrogen or Cj-Cin alkyl; R2 is selected from the group consisting of H; Ci-C6 alkyl, optionally substituted with 1, 2, or 3 substituents that are independently .selected, from, .the .. .group .consisting of C1-C3 alkyl, halogen, -OH, -SH, -C=N, -CF3, C1-C3 alkoxy, and -NRj_ 3Ri-b; wherein Ra_3 and Ri_b are- -H or Ci~C6 alkyl; -(CH2)0-4-aryl; - (CH2) 0-4-heteroaryl; C2-C6 alkenyl; C2-C6 alkynyl; -CONRN_2RN_3; -SO2NRN_2RN_3; -CO2H; and -C02- (Q-C4 alkyl); R3 is selected from the group consisting of H; Ci-Cs alkyl, ......optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of Cx-Cs alkyi, halogen, -OH, -SH, -G=N, -CF3, C!-C3 alkoxy, and -NR-,. aRi_b; -(CH2)0_4-aryl; - (CH2) 0-4-heteroaryl; C2-Cl} alkenyl; C2-C6 alkynyl; -CO-NRN_2RN_3; -SO2-NRN_2RN_3; -CO2H; and -CO-0-(d-Q alkyl); or R2, R3 and the carbon to which they are attached form a carbocycle of three thru seven carbon atoms, wherein one carbon atom is optionally replaced by a group selected from-O-, -S-, -S02-, or -NRN_2-; Rc is selected from the group consisting of Ci-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R20s, -OC=ONR235R24o,- -S (=0)0-2 (Ci- C6 alkyl), -SH, -NR235C=ONR235R24G/ -C=ONR235R24o, and -S (=O)2NR235R240; -(CH2)0-3-(C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, - CO2H, and -CO2-(Ci-Q alkyl); - (CR245R250) o-t-aryl; - (CR245R250) o-i" heteroaryi; - {CR24SR250) 0-4-heterocycloalkyl; - (CR245R250) 0-4- aryl-heteroaryl; - (CR2$sR2so) 0-4-aryl-heterocycloalkyl; - {CR24SR25o) o-^raryl-aryl; - {CR945R250) 0-4-heteroaryl-aryl; - (CR245R250) 0-4-heteroaryl-heterocycloalkyl; - (CR245R25o)o-4- heteroaryl-heteroaryl; - {CR24bR25o) 0-4-heterocycloalkyl- heteroaryl; - (CR^^Rsso) C-4-heteracycloalkyl-heterocycloalkyl; - {CR245R250) 0_4-heterocycloalkyl-aryl; -{C (R255) {R260) J1-3-CO-N- (^255)2; -CH(aryl)2; -CH (heteroaryl) 2; -CH (heterccycloalkyl) 2; -CH(aryl)(heteroaryl); cyclopentyl, cyclohexyl, or cycioheptyl ring fused to aryl, heteroaryl, or heterocycloalkyi wherein one carbon of the cyclopentyl, cyclohexyl, or cycioheptyl is optionally replaced with NH, NR215, 0, or S{=0)o-2, and wherein the cyclopentyl, cyclohexyl, or cycioheptyl group can be optionally substituted with 1 or 2 groups that are independently R205 or =0; -CONR235R24o; -S02-(Ci-C* alkyl); C2-Cib alkenyl optionally substituted with 1, 2, or 3 R205 groups; C2-C10 alkynyl optionally substituted with 1, 2, or 3 R205 groups; -(CH2)0-s- CH { (CH2) 0-6-OH) - (CH:) s-i-aryl; - (CH2) 0-i-CHRc-6- (CH2) 0-1- heteroaryl; -CH(-aryl or -heteroaryl)-C0-0(d-C4 alkyl); - CH(-CH2-OH>-CH(OH>-phenyl-NO2; (Ci-C6 alkyl) -0- (Ci-C6 alkyl)- OH; -CH2-NH-CH2-CH(-O-CH2-CH3)2; .ind -(CH2)0-6- C(=NR235) (NR235R240) ; wherein each aryl.is optionally substituted with 1, 2,. or 3 R200; ea-Ch heteroaryl is optionally substituted with 1, 2, 3, or 4 R200 '• each heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R210; R200 at each occurrence is independently selected from the group consisting of Ci-C6 alkyi optionally substituted with 1, 2, or 3 R205 groups; OH; -NO2; halogen; -CO2H; ¦ C=N; .-(CH2)0-!-CO-NR22oR225; - (CH2) D_«-CO-(Ci-C12 alkyl); - (CH2) 0-4-CO- (C2-C12 alkenyl) ; - (CH2) 0-4-CO- (C2-Ci2 alkynyl); - (CH2) 0-4-CO- (C3-C7 cycloalkyl) ; - (CH2) 0-4-CO- aryl; - (CH2) 0_4-CO-heteroaryl; -{CH?)0-^-CO- heterocycloalkyl;- (CH2) o-!-C02R215; - (CH2> 0-4-S02-NR22oR225; -{CH2)0-4-SO-{C1-C8 alkyl); - (CH2) 0_4-SO2-(C^C^ alkyl); - (CH2)0- CO2R215; -{Cfi2)0-4-N{H or R215) -CO-N {R215) 2; - (CH2) 0_,-N-CS- N(R2i5)2; -(CH2)0-i-N(-H or R215)-CO-R220; - (CH2) o-4-NR22oR225; -{CH2)0-4-O-CO-{C,-C6 alkyl); " - {CH2) 0.4-O-P (O) ~ (ORZi0) 2; - (CH2) 0-4-O-CO-N (R215) 2. - (CH2) 0-4-O-CS-N (R215) ?; - (CH2) 0-4-O- (R215)2; -(CH2}0_,-O-{R2-,5)2-COOH; - (CH2) 0-,-S- (R215) ¦>; {CH2)c-4-O-(Ci-C6 alkyl optionally substituted with 1, 2, 3, or 5 -F) ; C3-C7 cycloalkyl; C2-C6 alkenyl optionally substituted with 1 or 2 R205 groups; C2-C6 alkynyl optionally substituted with 1 or 2 R2G5 groups; -(CH2)0_ 4-N(H or R215)-SO2-R270; and -(CH2)0-«- C^-C-j cycloalkyl; wherein each aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R20b, R2io °-r Cy-C& alkyl substituted with 1, 2, or 3 groups that are independently R205 or R2i0; wherein each heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R2i0; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or Ci-C6 alkyl substituted with 1, 2, or 3 groups that are independently R?.o5 or R2]0; R?-j3 at each occurrence is independently selected from the group consisting of Cn-C6 alkyl, halogen, -OH, -O- phenyl, -SH, -C=N, -CF3, C^-Ce alkoxy, NH2, NH(Ci~C6 alkyi), and N-(C!-C6 aikyl) (Ci-C6 alkyl); R2ic at each occurrence is independently selected from the group consisting of Q-Ce alkyl optionally substituted with 1, 2, or 3 R205 groups; C2-Cc alkenyl optionally substituted with 1, 2, or 3 R205 groups; C2-C6 alkynyl optionally substituted with 1, 2, or 3 R2os groups; halogen; Ci-Cg alkoxy; Ci~C6 haloalkoxy; -NR22oR22!>' OH; CsN; C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R205 groups; -CO-{Ci-C4 alkyl); _SO2-NR235R240; -CO- NR235R240; ~S02-(C1-C4 alkyl); and =0; wherein R215 at each occurrence is independently selected from the group consisting of Ci-Cs alkyl, - (CH2) 0-2- (aryl) , C2-Cfi alkenyl, C2-C6 alkynyl, C3_C7 cycloalkyl, and -(CH?)n-?- (heteroaryl) , - (CH2) 0_2- (heterocycloalkyl) ; wherein the aryl group at each occurrence is optionally substituted with i, 2, or 3 groups that are independently R205 or R2io; wherein, the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R2io; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R2i0; R220 and R225 at' each occurrence are independently selected from the group consisting of -H, -C:-C6 alkyl, hydroxy Ci-C6 alkyl, amino C-.-C6 alkyl; halo Ci-C6 alkyl; -C3-C7 cycloalkyl, - (d-C2 alkyl) - (C3-C7 cycloalkyl), -(C!-C« alkyl)-O-{Ci-C3 alkyl), -C2-C6 alkenyl, -C2-C6 alkynyl, -C1-C6 alkyl chain with one double bond and one triple bond, -aryl, -heteroaryl, and -heterocycloalkyl; wherein. . the -aryl ,group. -at . each occurrence is optionally substituted with 1, 2, or 3 R270 groups, wherein R270 at each occurrence is independently R205, Ci-C6 alkyl optionally substituted with 1, 2, or 3 R205 groups; Cz- C5 alkenyl optionally substituted with 1, 2, or 3 R205 groups; C2-C6 alkynyl optionally substituted with 1, 2, or 3 R205 groups; halogen; Ci-C6 alkoxy; Ci-C6 haloalkoxy; NR235R240; OH; C=N; C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R205 groups; - OXCi-C^ alkyl); -S02-NR235R24o; -CO-NR235R240; -S02- (Cj-CU alkyl); and =0; wherein the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R205 groups; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R205 groups; R235 and R240 at each occurrence are independently H, or Ci-C6 alkyl; R245 and R250 at each occurrence are independently selected from the group consisting of H, C1-C4 alkyl, C1-C4 hydroxyalkyl, C;L-Cs alkoxy, C-,-C,; . haloalkoxy, -(CH2)0_4- C3-.C7 cycloalkyl, C2-C6 . alkenyl, C2-C6 alkynyl, aryl Ci- C4 alkyl,. heteroaryl C-j-CU alkyl, and phenyl; or R245 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms, optionally ..where one carbon atom is replaced by a heteroatom selected from the group consisting of -O-, — S-, -SO2-, and -NR220-; R255 and R26o at each occurrence are independently selected from the gxoup.consisting of H; Ci-C6 alkyl optionally substituted with 1, 2,. or 3 .R30s groups; C2-C6 alkenyl optionally substituted with i, 2, or 3 R235 groups; C2- C6 alkynyl optionally substituted with 1, 2, or 3 R2os groups; - (CH2)i-2-S (0)0-2-(Ci-C6 alkyl); - (CH2) 0-4-C3-C-, cycloalkyl optionally substituted with 1, 2, or 3 R20s groups; - (Ci-C4 alkyl)-aryl; - {C2.-C4 alkyl)-heteroaryl; -{G1-C4 alkyl)-heterocycloalkyl; -aryl; -heteroaryl; -heterocycloalkyl; _(CH2) 1-4-R26D- (CH2) 0_4-aryl; -(CH2) 1-4- R265-(CH2)0_,,-heteroaryl; and; - (CH2) i-4-R26s- (CH2)0-4- heterocycloalkyl; wherein R265 at each occurrence is independently -O-, -S- or - NfCr-Ce alkyl)-; each aryl or phenyl is optionally substituted with 1, 2, or 3 groups that are independently R2o5r R210/ or Ci-C6 aikyl substituted with i, 2, or 3 groups that are independently R205 or R2io; each heteroaryl is optionally substituted with 1, 2, 3, or 4 R?ooa each heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R2i0; R100 and R'100 independently represent aryl, heteroaryl, heterocyclyl, -aryl-W-aryl, -aryl-W-heteroaryl, -aryl-W- heterocyclyl, -heteroaryl-W-aryl, -heteroaryl-W-heteroaryl, -heteroaryl-W- heterocyclyl, -heterocyclyl-W-aryl, -heterocyclyl-W-heteroaryl, -heterocyclyl-W-heterocyclyl, - CR [ (CH2) o-2-0-R150] - (C'A2) 0-2-aryl, -CH [. (CH2) 0-2-O-R150J - heterocyclyl or -CH[ (CH2) 0-2-O-R150] - (CH2) 0-2-heteroaryl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from -OR, -N02, Ci-C6 alkyl, halogen, -CsN, -OCF3, -CF3, -(CH2)0-4- O-P(=O) {OR) {OR') , -{CH2)o-4-CO-NR105R'io5/ -{CH2)0-4-O- (CH2)0-4-CONR1o2R3o2/, -(CH2)o-«-CO-(Ci-C12 alkyl), -{CH2)O_4- CO-{C2-Ci2 alkenyl), . - (CH2) cm-CO-{C2-C12 alkynyl) , -{CH2)o- (CH2)0_4-Ri20/ -(CH2)o- R120, -(CH2)c- Riso, -{CH2)o-4-S02-NR105R'io5/ - (CH2) 0-4-SO-(Ct-Cs alkyl), -(CHzJo^-SCVfCi-Ciz alkyl), - (CH2) 0_4-SO2- (CH2) 0-4~ (C3-C7 cycloalkyl), - {CH2) 0-4-N{Ri50) -CO-O-R150/ ~ (CH2) 0.4-N {R150) - CO-N (R150) 2/ - (CH2) 0-4-N (R150) -CS-N (R150) 2, ~ (CH2) 0-4~N {R150) - CO-Rics, -(CH2)o-4-NRio5R'ios/ -{CH2)0-4-Ri40/ - (CH2) 0-4-O-CO- (Ci-Cs alkyl), - (CH2) 0-4-O-P (0) - (O-R110) 2, - (CH2) 0-4-0-CO- N{R150)2, -{CH2)0-4-O-CS-N{R150)2, - (CH2) 0-4-O-(Ri5o) , -(CH2)o-s-0-Ri5o'-COOH, - (CH2) 0-4-S-(Ri5o) • ~ (CH2) 0-4~N (R150) - SO2-R105, ~{CH2)o-4- C3-C7 cycloalkyl, (C:-C30) alkenyl, and (C2-Cio) alkynyl, or R100 is Cjl-Cio alkyl substituted with 1, 2, or 3 R115 groups, or R100 is -(Ci-C6 alkyl)-O-d-Cg alkyl) or -(Ci-C6 alkyl)-S-(Ci-C6 alkyl), each of which is optionally substituted with 1, 2, or 3 R115 groups, or R100 is C3-C8 cycloalkyl optionally substituted with 1, 2, or 3 R115 groups; W is -(CH2)0-4-, -0-, -S{O)0_2-, -N(R135)-, -CR{OH)- or -C{0)-; R102 and R1.02' independently are hydrogen, or ¦ C1-C10 aUcyl optionally substituted with.l, 2, or 3 groups that are independently halogen, aryl or -Ruo; R105 and R'105 independently represent -H, -Ri;o, -Ri20r C3-C7 cycloalkyl,. - {C!-C2 alkyl) - {C3-C7 cycloalkyl), - {d-C6 alkyl)- O-.(Ci-C3 alkyl),. C2-C6.alkenyl, C2-C6 alkynyl, or Ci~C6 alkyl chain with one double bond and one triple bond., or . .Ci-Cfi .alkyl .optionally ..substituted with -OH or -NH2; or, C-_-C6 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, or Rior, and R'105 together with the atom to which they are attached form a 3 to 7 membered carbocylic ring, where one member is optionally a heteratom selected from -O-, -S{O)0-2-# -N{Ri35)- , the ring being optionally substituted with 1, 2 or 3 independently selected Ri40 groups; R115 at each occurrence is independently halogen, -OH, -CO2R102, - Ci-C6 thioaikoxy, - -CO2-phenyl, -NR105R'135, -SO2- {Ci-Ce alkyl), -C(=O)R1S0, R180, -CONR105R'io5# -SO2NR105R' 105/ -NH-CO-(d-C6 alkyl), -NK-C{=O)-OH, -NH-C (=O) -OR,- -NH-C (=0) -O-phenyl, -O- C(=O)-{Ci-C6 alkyl), -0-C(=0)-amino, -0-C(=0)-mono- or dialkylamino, -0-C(=0)-phenyl, -0- (Ci-C6 alkyl)-C02H, -NH- SO2-{Ci-C6 alkyl>, Ci-C6 alkoxy or Ci-C6 haloalkoxy; R135 is Ci-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3_C7 cycloalkyl, - {CH2)0-2-(aryl) , - (CH2) Q-2- (heteroaryl) , or -(CH2)0-2- (heterocyclyl); R140 is heterocyclyl optionally substituted with 1, 2, 3, or 4 groups independently selected from Cx-C^, alkyl, Ci-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(Ci- C6)alkylamino, . .d±(C3-C6) alkylamino, C2-C6 alkenyl, C2-C6 alkynyl, Ci-C6 haloalkyl, Cj-Cs haloalkoxy, amino (Ci-C6) alkyl, mono (Ci-C6) alkylamino (Ci-C6) alkyl, di (Ci-C6) alkylamino (Cx- CG) alkyl, and =0; R145 is C:-C5 alkyl or CF3; Riso is hydrogen, C3-C7 cycloalkyl, -(Ci-C2 alkyl) - (C3-C7 cycloalkyl) , C2-C6 alkenyl, C2-C6 alkynyl, C,.-C6 alkyl with one double bond and one triple bond, -R110, -Ri2o» or Ci-C6 alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from -OH, -NH2/ Ci~C3 alkoxy, RiiOf and halogen; R150' is C3-C7 cycloalkyl, -(C:-C3 alkyl) - {C3-C7 cycloalkyl), C2-C6 alkenyl, C2-C6 alkynyl, Ci~C6 alkyl with one double bond and one triple bond, -Ruo, -R120/ or Cx-Cg .alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from -OH, -NH2, C:-C3 alkoxy, Ruo, and halogen; R155 is C3-C7 cycloalkyl, -(Ci-C2 alkyl) - (C3-C7 cycloalkyl), C2-C6 alkenyl,. C2-C6 ¦ alkynyl, Ci-C6 alkyl with one double bond and one triple bond, -Ruo, -R120/ or Ci~C6 alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from -OH, -NH2, Ci~C3 alkoxy, and halogen; Rise is selected from morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S- dioxide, pyrrolinyl and pyrrolidinyl, each of which is optionally substituted with 1, 2, 3, or 4 groups independently selected from Ci-Cfc alkyl, Ca-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(C2- Ce) alkylamino, di {Ci-C6) alkylamino, C2-C6 alkenyl, C2-C6 alkynyl,. Ci-C6 haloalJcyl, Ci~C6 haloalkoxy, amino (Ci-C6) alkyl, mono (Ci-C6) alkylamino (Ci-C6) alkyl, di (Ci-Ce) alkylamino (Ci- C6) alkyl, and =0; R110 is aryl optionally substituted with 1 or 2 Ri25 groups; R:2s at each occurrence is independently halogen, amino, mono- or dialkylamino, -OH, -C=N, -SO2-NH2, -SO2-NH-Ci-C6 alkyl, -S02- N(Ci-C6 alkyl)2, -S02- (C:-C4 alkyl), -CO-NH2, -CO-NH-CZ-CS alkyl, or -CO-N(Ci-C(. alkyl} 2, or C;.-Cs alkylr C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups, that are independently selected from Ci-C3 alkyl, halogen, -OH, -SH, -CsK/ -CF3; C-.-C3 alkoxy, amino, and mono- and diaikyiamino, or . Ci-C6 alkoxy optionally substituted with one, two or three of halogen; Ri2o is heteroaryl, which is optionally substituted with 1 or 2 R-,?r- groups; and R-:3n is heterocyciyl optionally .substituted with 1 or 2 R125 groups. 2. A compound as daimedJn:ciairni1 wherein RN is hydrogen: 3. A compound as claimed in claim -1 wherein RN' is hydrogen. 4. A compound as ciaimedin claim -1 wherein R-; is -Ci-Cf alkyl-aryl, -C-i-Cs alkyl-heteroaryl, or -Ci-Ce alkyl- heterccyclyl, where the--ring -portions of each are optionally substituted- with 1, 2, 3, or 4 ..groups independently selected from halogen, -OH, -SH, -C=N, - N02, -NRiosR'ios, -CO2R, -N(R)COR', or -N (R) SO2R' , -C (=0) - (Ci--C4) alkyl, —SO2-a7ninc, - ¦¦ -S02-mono ¦ or . dialkyiaiuino/ . -C (-0)-amino, ' ." -C(=O) -mono or -dialkylaminc, -3O2-(Ci-C4) ¦ alkyl, or Ct-Cg alkoxy- optionally .substituted, with" 1, 2, , or 3 groups "which" are" independently- selected from halogen, or C3-C7 cycioalkyl optionally substituted with 1, 2, or 3 ¦groups independently selected-from halogen, -OH, -SH, -C=M, -iCF3,.\ Ci-rCs alkoxy,-amino,. -Ci-C6 alkyl and mono- or dialkyiair.inO;. or C2-C10 alkyl optionally- substituted with 1, 2, or 3 ¦groups- independently ¦ -selected -from halogen, -OH, -SE,. -CsN, -CF3, -C1-C3 alkoxy, amino.. mono- or dialkylaminc a.nd. -C1-C3 alkyi, or Cp.-C-,.r, alkenyl or C2-C10 alkynyl each of which . is.. optionally substituted with -1, 2, or 3 groups independently selected from halogen, -OH, -SK, -G=N, -CFj, C1-C3 alkoxy," amino, C-l~C6 alkyl and mono- or dialkylamino;"and the heterocyclyl group is"optionally further substituted with oxo.. 5. A compound as claimed in claim 1 wherein R2 and R3 are independently selected from H or Ct-Cs alkyl optionally substituted with 1, 2, or 3 substituents. selected from the group consisting of' C1-C3 alkyl, halogen, -OK, -SH-> -CsN, -CF3/ C;-"C3 alkoxy, and -NRj-aRj-j,. 6. A compound as claimed in claim-1 wherein ¦ Rr is - (CR245R350) n-rf-aryl, cr - (CRoasR^so) n-heteroaryl, wherein aryl and heteroaryl are- optionally substituted- with 1, 2, or 3 R200 groups. 7. A compound as claimed in claim 2 wherein Rk1 is Y X R4 wherein Rj is- NH2; -Nfi-.{CII2)-n6-R*-i;---NHR3;¦ -NRseC Ca)R^; .or- -NR50CO2Rt.i; wherein n6. is 0,-1,2, or 3; n7. is 0, 1,2, or 3; R,i_-, is selected from the group consisting of -SO2-(C-..-Cs alkyl}, -SO-(Ci-Ca alkyl), -S-{Ci-C8 alkyl}, -S-CO- {Cx-Ce alkyl), -SO2-NR4..::R4-3; -CO-C1-C2 alkyl; -CO-NR4-3R4-4; R.5-2 and ?.«.3 -are independently H, ..Cy-H?, alkyl, or Q»-C6 CjV'C-LU'ClJ.TV^J. / R4-4 is alkyl, phenylalkyl, C2-C4 alkanoyl, or phenylalkanoyl; R5 is cyclopropyl; cyclobutyl; cyclopentyl; and cyclohexyl; wherein each cycloalkyl group is optionally substituted with one or two groups that are Ci~C6 alkyl, more preferably Ci-C2 aikyl, Ci-Ce alkoxy, more" preferably Ci-C2 alkoxy, CF3, OH, NH2, NH(d~C6 alkyl), N(d-C6 alkyl) (d-C6 alkyl), halogen, CN, or N02; or the cycloalkyl group is substituted with 1 or 2 groups that are independently CF3, Cl, F, methyl, ethyl or cyano; d~C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, -NR6R7j- d-d alkoxy, C5-C6 heterocycloalkyl, C5-C6 heteroaryl, phenyl, C3-C7 cycloalkyl, -S-d-C4 alkyl, -SO2-Ci-C4 alkyl, -CO2H, -CONR6R7, -CO2-C1-C4 alkyl, or phenyloxy; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, d~d haloalkyl, or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groups that are independently d~d alkyl, d~d alkoxy, halogen, or d~d alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, . OH, d~d alkyl, d-d alkoxy, or d~d haloalkyl; and -NR6R-,; wherein R6 and R7 are independently selected from the group consisting of H, C:.-Cs alkyl, C2-C6 alkanoyl, phenyl, -SO2-Ci-C4 alkyl, and phenyl Cx-C4 alkyl; R8 is selected from the group consisting of -S02-heteroaryl optionally substituted with 1 or 2 groups that are independently C:-C4 alkyl or halogen;, -SO2-aryl, -S02- ¦heterocycloalkyl, -C{O)NHR9/ heterocycloalkyl, -S-C2-C, _alkanoyl, wherein R5. is- phenyl C-^d alkyl, d-Ce alkyl,, or H; . R50 is H or d-C6 alkyl; Rs-i is -selected, from the.. group .consisting of phenyl d~C4 alkyl; d~C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, -NR6R7, -C(O)NR6R7, C3-C7 or -Gi.-C4 alkoxy; heterocycloalkyl optionally substituted with i or 2 groups that are independently d-C- alkyl, d-d alkoxy, halogen, C2-d alkanoyl, phenyl d~C4 alkyl, and -S02 d-C4 alkyl; heterocycloalkylalkyl optionally substituted with 1 or 2 groups that are independently Ci-C4 alkyl, C--C,. alkoxy, halogen, C2-C- alkanoyl, phenyl CT-Ca alkyl, and -S02 C^-Cc alkyl; alkenyl; alkynyl; heteroaryl optionally substituted with 1/ 2, or 3 groups that are independently OH, "Ci-C4 aikyl, Ci-C; alkoxy, halogen, NH2, NK(Ci-C6 alkyl) or N(Ct-C6 alkyl) (C!-C6 alkyl); heteroarylalkyl optionally substituted with- 1, 2, or 3 groups that are independently C-,.-C4 alkyl, CT-C4 alkoxy, halogen, NK2r NH(C1-C6 alkyl} or N(Cri-C6 alkyi) (C—C6 alkyl); phenyl; C3-C3 cycloalkyl, and cycloalkylalkyl, wherein the phenyl; C3-Cg -cycloalicyi, and cycloslkylalkyi groups -are optionally substituted with 1, 2,- 3, 4 or 5 groups that are independently halogen, CN, N02, Ci-C6 aikyl, Ci~C« alkoxy, C2-C6 alkanoyl, Ci-C0 haloalkyl, C:.--C5 haloalkoxy, . .. hydroxy, Ci-Cs hydroxyalkyl, Ci-C0 alkoxy Ci-C€ alkyl, C:-Ct thioalkoxy, Ci -Cfc thi.oalkoxy C,-Cfj aikyl, or C-.-C, alkoxy Ci-Cs alkoxy. 8. A compound as claimed in claims wherein RN is Z ^(CH2)rt7-CHC(O)- Y X R4 v;hereiri R4 is NH?; -NH-{CH25;ie-R,i-i; -NHRS; -NR50C(O)R6; or -NR53CO2R51; wherein n6 is 0, 1, 2, or 3; n7 z.z 0, 1, 2, or 3; R4-1 is selected -from the group consisting of -SO2-(Ci-Cs alkyl}, —SO-(Ci-C8 alkyi)-, -S- (C^-C?, alkyl) , -S-CO-(Ci-Cc alkyl) , -SO2-NR4_2R,,_3; -CO-Ci-C2 alkyl;. -CO-KR^^R^-a; R4_2 and Rt-s are independently H, C-^-.C^ alkyl, or C3-Ct; .cycloalkyl; Ri-4 is alkyl, phenylaikyl, C2-C4 alkanoyl, .or phenylalkanoyl; R5 is cyclopropyl; " cyciobutyl;.- cyciopentyl;. .and .cyclohexyl;- wherein each "cycloalkyl-group"is optionally "substituted with one or two groups that are Ci-C6 alkyl, more preferably Ci-C2 alkyl, Ci-C6 alkoxy, more preferably C!-C2 alkoxy, CF3, OH, NL2, NH(C!-C6 alkyl), N(d-C6 alkyl) (Ci-C6 alkyl), halogen, CN, or NO2; or the cycloalkyl group is substituted with 1 or 2 groups that are independently CF3, Cl, F, methyl, ethyl or cyano; Ci-C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, -NR6R7, C1-C4 alkoxy, C5-C6 heterocycloalkyl, C5-C6 heteroaryl, phenyl, C3-C7 cycloalkyl, -S-C1-C4 alkyl, -SO^-Cn-Cj alkyl, -CO2H, -CONR6R7, -CO2-C1-C4 alkyl,. or. . phenyloxy;. -heteroaryl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, C1-C4 haloalkyl, or OH; heterocycloalkyl optionally substituted with 1, 2, or 3 groups- • that-are independently C- halogen, or Cz-C4 alkanoyl; phenyl optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, OH,- Ci-O, alkyl, Ci-C4 alkoxy, or Ci-C4 haloalkyl; and -NR6R7; wherein RG and R7 are independently selected from the group consisting of H, C:-C6 alkyl, C2-C6 alkanoyl, phenyl, -SO2-C1-.C4 alkyl, and phenyl C1-C4 alkyl; Re is selected from the group consisting of -SO2-heteroaryl optionally substituted with 1 or 2 groups that are independently C!-C4 alkyl or halogen;, -SO2-aryl, -SO2- heterocycloalkyl, -C(0)NHRg, heterocycloalkyl, -S-C2-C4 alkanoyl, wherein R9 is phenyl w-C..; alkyl, Ci-C6 alkyl, or H; R50 is- H or Ct-C5 alkyl; R51 is selected from the group consisting of phenyl Ci~ C4 alkyl; C^-Cf, alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyaho, -NR6R7, -C{O)NR6R7, C3-C7 or -CS-Cj alkoxy; heterocycloalkyi .optionally..substituted v/ith 1 or 2 groups .that._are independently Ci-C4 alkyl, Ci-C4 alkoxy, halogen, C2-Ca alkanoyl, phenyl C:-C4 alkyl,-and -S02 Ci-C4 alkyl; heterocycloalkylalkyl optionally substituted with 1 or 2 groups that are independently C^C. alkyl, Ci-C* aikoxy, halogen, C2-C: alkanoyi, phenyl Cz-Q alkyl, and - S02 Cx-Ov alkyl; aikenyl; alkynyl; heteroaryl optionally substituted with 1, 2, or 3 groups that ... are . .independently OH, .-.Cv-Q alkyl, C,-C. alkoxy, halogen, NH2, NHfCN-Cg alkyl) or N(Ca-C6 aikyl} (Ci-C6 alkyl); heteroaryialkyl optionally substituted with 1, 2, or 3 groups that are independently C-.-C, alkyl, Ct-d alkoxy, halogen, NTK2/ NK(C--CS alkyl}- or N(C:~CS aikyl) (Cv-CE alkyl); phenyl; -C3-C8 ' cycioalkyl, and cycloallcyialkyi, ' wherein the phenyl; C-s-C., cycloalkyi, and ' cycloaikyiaikyi . ¦. groups are optionally substituted with 1, 2, 3, 4 or 5 groups' that arc" independently halogen, CN, KO2/ C!-C6 alkyl, C:-Ce alkoxy, CK-C« alJ'canoyl, C:-C6 "naloaikyi, t-Cg " haioaikoxy;"". hydroxy, C^-Cs hydroxyalkyl, C:-Cs alkoxy C:-Cfi aikyl, C:-C£ thioalkbxv, C,-G,; ¦•thibalicoxy C-L-Cs alkyl,' or C:--Cs .alkoxy C:-C6 alkoxy. 9. A compound as claimed in claim 2 wherein RK' is-C(=0)-phenyl, where the phenyl ring is optionally, substituted with 1 or 2 groups independently:selected from Ci-C6 alkyl, halogen,-. ¦-|GH2)u-«-CO-!«Rio5R'ib5/- -{CH2)'j^-0-CO- K (R:5o) z> ~ (CK2) c-i-W (R^c) -30=-Ric^ ~ (CH2) c-j-SO2-NRi05R' ios, C3-C7 cycioalkyl, {C;;—C;o) alkexiyl, - (,CH2) o-4~-R:.:"6/ ~(CK2)C_ «-R^2o, -(CH2)d-4-Ri3or or ¦ (Cj-Cao/aikynyl. 10. A compound as claimed in claim 3 wherein .Rs .. is-C.{.=O) -pher.yl, where -..the .pheayl.-.ring.. . i.s._ .optionally substituted- with I or 2 groups independently selected f rotr. C^.-Cq aikyl,- halog-en;'¦ - {G&},o-4-CO-NKinSR'res, -{CK2) 0-4-O-CC- N (-RiM5:;r --{CH2)c-4-'H{Ri5c)--SO?-Rioi,- -"{CH2> 0_^SG2-NEIO3R' j^r C--C7 cycloalkyl.. (Cn-C-) al-kenyl, ~{CK2}.>'.-R:r.u - (CKC) a_ 4-R120, -{CH2)6-«-Ri3C, or • (C2-e10)alkynyl. to aqueous media, wherein one of RN and RN' is hydrogen and the other is -C(=0)-(CRR')o-6Rioo, -C(=0)-(CRR')i.6-0-R'ioo, -C(=O)- (CRR')i.6-S-R'ioo, -C(=0)-(CRR')i-6-C(=0)-Rioo, -C (=0)-(CRR')1.6-S02-R10o,-C(=0)-(CRR')1.6-NR10o-R'ioo, or /Z^ /(CH2)n7^CHC(O)- Y X I R4 wherein R4 is selected from the group consisting of H; NH2; -NH-(CH2)ne-R4-i; -NHR8; -NR5oC(0)R5; C1-C4 alkyl-NHC(O)R5; -(CH2)o-4R8; -O- C1-C4 alkanoyl; OH; C6-Ci0 aryloxy optionally substituted with 1, 2, or 3 groups that are independently halogen, C1-C4 alkyl, -CO2H, -C(O)-d-C4 alkoxy, or d-C4 alkoxy; Ci-C6 alkoxy; aryl C1-C4 alkoxy; -NR50CO2R51; -C1-C4 alkyl-NR5oC02R5i; -C=N; -CF3; -CF2-CF3; -C=CH; -CH2-CH=CH2; -(CH2)i-4-R4-i;~(CH2)i-4- -NH-R4.1; -O-(CH2)n6-R4-i; -S-(CH2)n6-R4-i; -(CH2)o-4-NHC(0)- (CH2)o-6"R52; -(CH2)o-4-R53-(CH2)o-4-R54; wherein n6 is 0,1,2, or 3; n7is0, 1, 2, or 3; V« R4-1 is selected from the group consisting of -SO2- (Ci-C8 alkyl), -SO-(Ci-C8 alkyl), -S-(d-C8 alkyl), -S-CO-(d- C6 alkyl), -SO2-NR4-2R4-3; -CO-C1-C2 alkyl; -CO-NR4_ 3R4-4; R4-2 and R4-3 are independently H, C1-C3 alkyl, or C3-C6 cycloalkyl; R4-4 is alkyl, arylalkyl, alkanoyl, or arylalkanoyl; R4-6 is-H or Ci-C6 alkyl; R5 is selected from the group consisting of C3-C7 cycloalkyl; Ci-C6 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, -NR6R7, C1-C4 alkoxy, C5-C6 heterocycloalkyl, C5-C6 heteroaryl, C6-Ci0 aryl, C3-C7 cycloalkyl C1-C4 alkyl, -S-C1-C4 alkyl, -SO2-C1-C4 alkyl, -CO2H, -CONR6R7, -CO2-C1-C4 alkyl, C6-Ci0 aryloxy; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, C1-C4 haloalkyl, or OH: heterocycloalkyl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, or C2-C4 alkanoyl; aryl optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, OH, C1-C4 alkyl, C1-C4 alkoxy or C1-C4 haloalkyl; and -NR6R7; wherein R6 and R7 are independently selected from the group consisting of H, Ci-C6 alkyl, C2-C6 alkanoyl phenyl, -SO2-C1-C4 alkyl, phenyl C1-C4 alkyl; R8 is selected from the group consisting of -SO2-heteroaryl -SO2-aryl, -SO2-heterocycloalkyl, -SO2-C1-C10 alkyl, -C (O)NHRg, heterocycloalkyl, -S-Ci-Ce alkyl, -S-C2-C4 alkanoyl, wherein R9 is aryl C1-C4 alkyl, Ci-C6 alkyl, or H; R50 is H or Ci-C6 alkyl; R51 is selected from the group consisting of aryl C1-C4 alkyl; Ci-Ce alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, cyano, heteroaryl, -NR6R7, -C(O)NR6R7, C3-C7 cycloalkyl, or -C1-C4 alkoxy; heterocycloalkyl optionally substituted with 1 or 2 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, C2-C4 alkanoyl, aryl C1-C4 alkyl, and - SO2 C1-C4 alkyl; alkenyl; alkynyl; heteroaryl optionally substituted with 1, 2, or 3 groups that are independently OH, C1-C4 alkyl, Ci-C4 alkoxy, halogen, NH2, NH(Ci-C6 alkyl) or N(d-C6 alkyl)(Ci-C6 alkyl); heteroarylalkyl optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, Ci-C4 alkoxy, halogen, NH2, NH(d-C6 alkyl) or N(d-C6 alkyl)(Ci-C6 alkyl); aryl; heterocycloalkyl; C3-C8 cycloalkyl; and cycloalkylalkyl; wherein the aryl; heterocycloalkyl, C3-C8 cycloalkyl, and cycloalkylalkyl groups are optionally substituted with 1, 2, 3, 4 or 5 groups that are independently halogen, CN, NO2, C1- C6 alkyl, Ci-C6 alkoxy, C2-C6 alkanoyl, Ci-C6 haloalkyl, Ci-C6 haloalkoxy, hydroxy, C1-C6 hydroxyalkyl, Ci-C6 alkoxy Ci-C6 alkyl, C1-C6 thioalkoxy, d-C6 thioalkoxy Ci-C6 alkyl, or Ci-C6 alkoxy Ci-C6 alkoxy; R52 is heterocycloalkyl, heteroaryl, aryl, cycloalkyl, -S(O)0-2-Ci- C6 alkyl, CO2H, -C(O)NH2> -C(O)NH(alkyl), -C(O)N (alkyl)(alkyl), -CO2-alkyl, -NHS(O)0-2-Ci-C6 alkyl, -N (alkyl)S(0)o-2-Ci-C6 alkyl, -S(O)0-2-heteroaryl, -S(O)0-2- aryl, -NH(arylalkyl), -N(alkyl)(arylalkyl), thioalkoxy, or alkoxy, each of which is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkyl, alkoxy, thioalkoxy, halogen, haloalkyl, haloalkoxy, alkanoyl, NO2, CN, alkoxycarbonyl, or aminocarbonyl; R53 is absent, -O-, -C(O)-, -NH-, -N(alkyl)-, -NH-S(O)0-2-, -N (alkyl)-S(O)0-2-, -S(O)0-2-NH-, -S(O)M- N(alkyl)-, -NH-C (S)-, or -N(alkyl)-C(S)-; R54 is heteroaryl, aryl, arylalkyl, heterocycloalkyl, CO2H, - CO2-alkyl, -C(O)NH (alkyl), -C(O)N (alkyl) (alkyl), -C(O)NH2, Ci-C8 alkyl, OH, aryloxy, alkoxy, arylalkoxy, NH2, NH(alkyl), N(alkyl) (alkyl), or -Ci-C6 alkyl-CO2- Ci-C6 alkyl, each of which is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkyl, alkoxy, CO2H, -CO2-alkyl, thioalkoxy, halogen, haloalkyl, haloalkoxy, hydroxyalkyl, alkanoyl, NO2l CN, alkoxycarbonyl, or aminocarbonyl; X is selected from the group consisting of -Ci-C6 alkylidenyl optionally optionally substituted with 1, 2, or 3 methyl groups; and -NR4-6-; or R4 and R4-e combine to form -(CH2)nio-, wherein niois 1, 2, 3, or 4; Z is selected from the group consisting of a bond; SO2; SO; S; and C(O); Y is selected from the group consisting of H; C1-C4 haloalkyl; C5- C6 heterocycloalkyl; C6-Ci0 aryl; OH; -N(Yi)(Y2); C1-C10 alkyl optionally substituted with 1 thru 3 substituents which can be the same or different and are selected from the group consisting of halogen, hydroxy, alkoxy, thioalkoxy, and haloalkoxy; C3-C8 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from C1-C3 alkyl, and halogen; alkoxy; aryl optionally substituted with halogen, alkyl, alkoxy, CN or NO2; arylalkyl optionally substituted with halogen, alkyl, alkoxy, CN or NO2; wherein Y1 and Y2 are the same or different and are H; C1-C10 alkyl optionally substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, C1-C4 alkoxy, C3-C8 cycloalkyl, and OH; Cz-C6 alkenyl; C2-C6 alkanoyl; phenyl; -SO2-Ci-C4 alkyl; phenyl C1-C4 alkyl; or C3-C8 cycloalkyl C1-C4 alkyl; or Y1, Y2 and the nitrogen to which they are attached form a ring selected from the group consisting of piperazinyl, piperidinyl, morpholinyl, and pyrolidinyl, wherein each ring is optionally substituted with 1, 2, 3, or 4 groups that are independently C1-C6 alkyl, d-C6 alkoxy, C1-C6 alkoxy C1- C6 alkyl, or halogen; R1 is -(CH2)i-2-S(0)o-2-(Ci-C6 alkyl), or C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, =0, -SH, -CsN,-CF3,-Ci-C3alkoxy, amino, mono- or dialkylamino, -N(R)C(O)R'-, -OC(=O)-amino and -OC(=0)-mono- or dialkylamino, or C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, Ci-C3 alkoxy, amino, and mono- or dialkylamino, or aryl, heteroaryl, heterocyclyl, -Ci-C6 alkyl-aryl, -Ci-C6 alkyl- heteroaryl, or -Ci-C6 alkyl-heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen -OH, -SH, -C=N, -NRiO5R'io5, -CO2R, -N(R)COR', or -N (R)SO2R\ -C(=O)-(Ci-C4) alkyl, -SO2-amino, -SO2- mono or dialkylamino, -C(=O)-amino, -C(=O)-mono or dialkylamino, -SO2-(Ci-C4) alkyl, or -Ci-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently a halogen, or C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -CeeN, -CF3, C1-C3 alkoxy, amino -Ci-C6 alkyl and mono- or dialkylamino, or C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -CsN, -CF3, -C1-C3 alkoxy, amino, mono- or dialkylamino and -C1-C3 alkyl, or C2-Ci0 alkenyl or C2-Cio alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, -OH, -SH, -C=N, -CF3, C1-C3 alkoxy, amino, d-Ce alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo; R and R' independently are hydrogen or C1-C10 alkyl; R2 is selected from the group consisting of H; Ci-C6 alkyl, optionally substituted with 1, 2, or 3 substituents that are independently selected from the group consisting of C1-C3 alkyl, halogen, -OH, -SH, -ON, -CF3, C1-C3 alkoxy, and -NRl aRi-t>; wherein Ri-a and Ri-bare -H or Ci-C6 alkyl; -(CH2)o-4-aryl; -(CH2)o-4-heteroaryl; C2-C6 alkenyl; C2-C6 alkynyl; -CONRN-2Rn-3; -SO2NRN-2Rn-3; -CO2H; and -CO2-(Ci- C4 alkyl); R3 is selected from the group consisting of H; Ci-C6 alkyl, optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of C1-C3 alkyl, halogen, -OH, -SH, -C=N, -CF3, C1-C3 alkoxy, and -NRi-aRi-b; -(CH2)o-4-aryl; -(CH2) 0-4-heteroaryl; C2-C6 alkenyl; C2-C6 alkynyl; -CO-NRN-2Rn-3; -SO2-NRn.2Rn-3; -CO2H; and -CO-O-(Ci-C4 alkyl); or R2, R3 and the carbon to which they are attached form a carbocycle of three thru seven carbon atoms, wherein one carbon atom is optionally replaced by a group selected from-O-, -S-, -SO2-, or -NRN-2-; Re is selected from the group consisting of C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, -OC=ONR235R24o, -S(=O)0-2 (Ci-C6 alkyl), -SH, -NR235C=ONR235R24o, -C=ONR235R24o, and -S(=0)2NR235R24o; -(CH2)o-3-(C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, -CO2H, and -CO2-(Ci-C4 alkyl);-(CR245R25o)o-4-aryl;-(CR245R25o)o-4- heteroaryl; -(CR245R25o)o-4-heterocycloalkyl; -(CR245R2so)o-4- aryl-heteroaryl; -(CR245R25o)o-4-aryl-heterocycloalkyl; -(CR245R25o)o-4-aryl-aryl; -(CR245R25o)o-4-heteroaryl-aryl; - (CR245R25o)o-4-heteroaryl-heterocycloalkyl; -(CR24sR25o)o-4- heteroaryl-heteroaryl; -(CR245R25o)o-4-heterocycloalkyl- heteroaryl; -(CR245R25o)o-4-heterocycloalkyl-heterocycloalkyl; - (CR245R25o)(M-heterocycloalkyl-aryl; -[C(R255)(R26o)]i-3-CO-N- (R25s)2; -CH(aryl)2; -CH(heteroaryl)2; -CH(heterocycloalkyl)2; -CH (aryl) (heteroaryl); cyclopentyl, cyclohexyl, or cycloheptyl ring fused to aryl, heteroaryl, or heterocycloalkyl wherein one carbon of the cyclopentyl, cyclohexyl, or cycloheptyl is optionally replaced with NH, NR215, O, or S(=0)o-2, and wherein the cyclopentyl, cyclohexyl, or cycloheptyl group can be optionally substituted with 1 or 2 groups that are independently R205 or =0; -CO-NR235R240; -SO2-(Ci-C4 alkyl); C2-C10 alkenyl optionally substituted with 1, 2, or 3 R205 groups; C2-C10 alkynyl optionally substituted with 1, 2, or 3 R205 groups; -(CH2)o-i-CH((CH2)o-6-OH)-(CH2)o-i-aryl; -(CH2)o-i-CHRc-6-(CH2)o-i-heteroaryl; -CH(-aryl or-heteroaryl)- CO-O(Ci-C4 alkyl); -CH(-CH2-OH)-CH(OH)-phenyl-NO2; (C1- C6 alkyl)-O-(Ci-C6 alkyl)-OH; -CH2-NH-CH2-CH(-O-CH2-CH3)2; and -(CH2)o-6-C(=NR235)(NR235R24o); wherein each aryl is optionally substituted with 1, 2, or 3 R200; each heteroaryl is optionally substituted with 1, 2, 3, or 4 R200; each heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 R210; R200 at each occurrence is independently selected from the group consisting of Ci-C6 alkyl optionally substituted with 1, 2, or 3 R205 groups; OH; -N02; halogen; -CO2H; C=N;-(CH2)0-4-CO-NR22oR225;-(CH2)o-4-CO-(Ci-C12 alkyl); -(CH2)0-4-CO-(C2-Ci2 alkenyl); -(CH2)o-4-CO-(C2-Ci2 alkynyl); -(CH2)o-4-CO-(C3-C7 cycloalkyl); -(CH2)w-C0- aryl; -(CH2)(M-CO-heteroaryl; -(CH2)cm-C0- heterocycloalkyl;-(CH2)o-4-C02R2i5;-(CH2)o-4-S02-R22oR225; - (CH2)m-SO-(Ci-C8 alkyl); -(CH2)o-4-S02-(Ci-Ci2 alkyl); - (CH2)cm-SO2-(C3-C7 cycloalkyl); -(CH2)M-N(H or R215)- CO2R215;-(CH2) -N(R215)2;-(CH2)0^-N(-H orR2i5)-CO-R22o;-(CH2)o-4-NR220R225, -(CH2)m-O-CO-(C,-C6 alkyl);-(CH2)0-4-0-P(0)-(OR24o)2; -(CH2)o-4-0-CO-N(R215)2;-(CH2)o-4-0-CS-N(R215)2;-(CH2)o-4-0- (R2i5)2; -(CH2)o-4-0-(R2i5)2-COOH; -(CH2)04-S-(R215)2; - (CH2)o-4-0-(Ci-C6 alkyl optionally substituted with 1, 2, 3, or 5 -F); C3-C7 cycloalkyl; C2-C6 alkenyl optionally substituted with 1 or 2 R205 groups; C2-C6 alkynyl optionally substituted with 1 or 2 R205 groups; -(CH2)0. 4-N(H or R2i5)-S02-R22o; and -(CH2)o-4- C3-C7 cycloalkyl; wherein each aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205, R210 or C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R2i0; wherein each heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R210; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R2Os, R210, or Ci-Ce alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210; R205 at each occurrence is independently selected from the group consisting of Ci-C6 alkyl, halogen, -OH, -O- phenyl, -SH, -C=N, -CF3, Ci-C6 alkoxy, NH2, NH(Ci-C6 alkyl), and N-(d-C6 alkyl)(d-C6 alkyl); R2io at each occurrence is independently selected from the group consisting of Ci-C6 alkyl optionally substituted with 1, 2, or 3 R205 groups; C2-C6 alkenyl optionally substituted with 1, 2, or 3 R205 groups; C2-C6 alkynyl optionally substituted with 1, 2, or 3 R205 groups; halogen; Ci-Ce alkoxy; d-C6 haloalkoxy; -NR220R225; OH; C^N; C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R2o5groups;-CO-(Ci-C4 alkyl);.S02-NR235R24o; -CO- NR235R240; -SO2-(Ci-C4 alkyl); and =0; wherein R2i5 at each occurrence is independently selected from the group consisting of Ci-C6 alkyl, -(CH2)o-2-(aryl), C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, and -(CH2)o-2- (heteroaryl), -(CH2)o-2-(heterocycloalkyl); wherein the aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205 or R210; wherein the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R210; wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R210; R220 and R225 at each occurrence are independently selected from the group consisting of -H, -C1-C6 alkyl, hydroxy C1-C6 alkyl, amino C1-C6 alkyl; halo C1-C6 alkyl; -C3-C7 cycloalkyl, -(C1-C6 alkyl)-(C3-C7 cycloalkyl), -(C1-C6 alkyl)-O-(C1-C6 alkyl), -C2-C6 alkenyl, -C2-C6 alkynyl, -C1-C6 alkyl chain with one double bond and one triple bond, -aryl, -heteroaryl, and -heterocycloalkyl; wherein the aryl group at each occurrence is optionally substituted with 1, 2, or 3 R270 groups, wherein R270 at each occurrence is independently R205, C1-C6 alkyl optionally substituted with 1, 2, or 3 R205 groups; C2- C6 alkenyl optionally substituted with 1, 2, or 3 R2os groups; C2-C6 alkynyl optionally substituted with 1, 2, or 3 R205 groups; halogen; C1-C6 alkoxy; C1-C6 haloalkoxy; NR235R240; OH; C=N; C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R205 groups; -CO-(C1-C4 alkyl);-SO2-NR235R240;-CO-NR235R240;-S02-(C1-C4 alkyl); and =0; wherein the heterocycloalkyl group at each occurrence is optionally substituted with 1, 2, or 3 R2o5groups;wherein each heteroaryl group at each occurrence is optionally substituted with 1, 2, or 3 R205 groups; R235 and R240 at each occurrence are independently H, or C1-C6 alkyl; R245 and R250 at each occurrence are independently selected from the group consisting of H, C1-C1 alkyl, C,-C4 hydroxyalkyl, C1-C1 alkoxy, C1-C4 haloalkoxy, -(CH2)M- C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl C1- C4 alkyl, heteroaryl C1-C1 alkyl, and phenyl; or R245 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms, optionally where one carbon atom is replaced by a heteroatom selected from the group consisting of -O-, -S-, -SO2-, and -NR220-; R255 and R260 at each occurrence are independently selected from the group consisting of H; C1-C6 alkyl optionally substituted with 1, 2, or 3 R205 groups; C2-C6 alkenyl optionally substituted with 1, 2, or 3 R205 groups; C2- C6 alkynyl optionally substituted with 1, 2, or 3 R205 groups; -(CH2)1-2-S(O)0-2-(Ci-C6 alkyl); -(CH2)0-4 C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 R205 groups; -(C1-C4 alkyl)-aryl; -(C1-C4 alkyl)-heteroaryl; -(C1-C4 alkyl)-heterocycloalkyl; -aryl; -heteroaryl; -heterocycloalkyl; -(CH2)1-4-R265-(CH2)o-4-aryl; -(CH2)h- R265-(CH2)0-4-heteroaryl; and; -(CH2)i-4-R265-(CH2)o-4- heterocycloalkyl; wherein R265 at each occurrence is independently -O-, -S- or -N(C1-C6 alkyl)-; each aryl or phenyl is optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210; each heteroaryl is optionally substituted with 1, 2, 3, or 4 R200, each heterocycloalkyl is optionally substituted with 1,2, 3, or 4 R210 R100 and R'100 independently represent aryl, heteroaryl, heterocyclyl, -aryl-W-aryl, -aryl-W-heteroaryl, -aryl-W- heterocyclyl, -heteroaryl-W-aryl, -heteroaryl-W-heteroaryl, -heteroaryl-W- heterocyclyl, -heterocyclyl-W-aryl, -heterocyclyl-W-heteroaryl, -heterocyclyl-W-heterocyclyl, -CH [(CH2)o-2-0-Ri5o]-(CH2)o-2-aryl, -CH[(CH2)o-2-0-Ri5o]-(CH2)o-2- heterocyclyl or -CH[(CH2)o-2-0-Ri5o]-(CH2)a.2-heteroaryl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from -OR, -NO2, C1-C6 alkyl, halogen, -C=N, -OCF3, -CF3, -(CH2)0-4- O-P(=O)(OR)(OR'), -(CH2)0-4-CO-NR105R'105, -(CH2)M-O- (CH2)o-4-CONR102Rio2'.-(CH2)o-4-CO-(C1-C42 alkyl),-(CH2)0. 4-CO-(C2-Ci2 alkenyl), -(CH2)0-4-CO-(C2-Ci2 alkynyl), -(CH2)cm-CO-(CH2)o-4(C3-C7 cycloalkyl), -(CH2)o-4-R110, - (CH2)0-4 R120, -(CH2)o-4-R130, -(CH2)0-4-CO-R110, -(CH2)o-4-CO-R120,- (CH2)0-4-CO-R130, -(CH2)o-4-CO-R140, -(CH2)0^-CO-0-R15o, -(CH2)o-S02-NR105R'io5, -(CH^w-SO-Cd-Ca alkyl), -(CH2) o-4-S02.(C1-C42 alkyl), -(CH2)o^-S02-(CH2)0^-(C3-C7 cycloalkyl), -(CH2)o.4-N(R150)-CO-0-R150,-(CH2)0-4-N(R150)- CO-N(R150)2,-(CH2)0-4-N(R150)-CS-N(R15o)2,-(CH2)o^N(R15o)- CO-R105, -(CH2)o-4-NRiosR'iO5, -(CH2)o-4-Ri40,-(CH2)o-4-0-CO- (Ci-C6 alkyl), -(CH2)m-0-P(0)-(0-Riio)2, -(CH2)0-4-O-CO- N(R150)2> -(CH2)0-4-0-CS-N(R15o)2, -(CH2)o-4-0-(R150), -(CH2) SO2-R105, -(CH2)0-4- C3-C7 cycloalkyl, (C2-Cio)alkenyl, and (C2-Cio)alkynyl, or R100 is C1-C40 alkyl optionally substituted with 1, 2, or 3 Rn5 groups, or R100 is -(d-C6 alkyl)-O -C1- C6 alkyl) or -(Ci-C6 alkyl)- S- (d-C6 alkyl), each of which is optionally substituted with 1, 2, or 3 R115 groups, or R100 is C3-C8 cycloalkyl optionally substituted with 1, 2, or 3 Rn5 groups; W is -(CH2)o-4-, -O-, -S(O)0-2-, -N(Ri35)-, -CR(OH)- or -C(O)-; R102 and Ri02' independently are hydrogen, or C1-C40 alkyl optionally substituted with 1,2, or 3 groups that are independently halogen, aryl or -Rn0; R105 and R'105 independently represent -H, -Rno, -R120, C3-C7 cycloalkyl, - (C1-C2 alkyl)- (C3-C7 cycloalkyl), - (Ci-C6 alkyl)- O-(Ci-C3 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, or Ci-Ce alkyl chain with one double bond and one triple bond, or C1-C6 alkyl optionally substituted with -OH or -NH2; or, C1-C6 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, or R105 and R'105 together with the atom to which they are attached form a 3 to 7 membered carbocylic ring, where one member is optionally a heteratom selected from -O-, -S(O)0-2-, -N(Ri3s)-, the ring being optionally substituted with 1, 2 or 3 independently selected RMo groups; R115 at each occurrence is independently halogen, -OH, -CO2R102, - C1-C6thioalkoxy, -CO2-phenyl, -NR105R'135s, -SO2-(C1-C6 alkyl), -C(=0)R180, R180, -CONR105 R105, -SO2NR105R'105, -NH-CO-(C1-C6 alkyl), -NH-C(=O)-OH,-NH-C(=O)-OR, -NH-C(=O)-O-phenyl, -O- C(=O)-(C1-C6 alkyl), -O-C(=O)-amino, -0-C(=0)-mono- or dialkylamino, -O-C(=O)-phenyl, -O-(C1-C6 alkyl)-CO2H, -NH- SO2-(C1-C6 alkyl), C1-C6 alkoxy or d-C6 haloalkoxy; R135 is C1-C6 alkyl, C1-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, - (CH2)0-2-(aryl), -(CH2)0.2-(heteroaryl), or -(CH2)0.2- (heterocyclyl); R140 is heterocyclyl optionally substituted with 1, 2, 3, or 4 groups independently selected from C1-C6 alkyl,C1-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(C1-C6) alkylamino, di(C1-C6)alkylamino, C2-C6 alkenyl, C2-C6 alkynyl, C1- C6 haloalkyl, C1-C6 haloalkoxy, amino(C1-C6) alkyl, mono(C1-C6)alkylamino(Ci-C6)alkyl, di(C1-C6)alkylamino(Ci- C6)alkyl, and =0; R145 isC1-C6alkyl or CF3; R150 is hydrogen, C3 -C7 cycloalkyl, - (C1-C6 alkyl)- (C3-C7 cycloalkyl), C2 -C6 alkenyl, C2 -C6 alkynyl, C1-C6 alkyl with one double bond and one triple bond, -R110, -R120, or C1-C6 alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from -OH, -NH2, C1-C3 alkoxy, R110, and halogen; R150' is C3-C7 cycloalkyl, -(C1-C3 alkyl)-(C3-C7 cycloalkyl), C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl with one double bond and one triple bond, -Ruo, -R120, or C1-C6 alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from -OH, -NH2, C1-C3 alkoxy, R110, and halogen; R155 is C3-C7 cycloalkyl, -(C1-C2 alkyl)-(C3-C7 cycloalkyl), C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl with one double bond and one triple bond, -R110, -R120, or C1-C6 alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from -OH, -NH2, C1-C3 alkoxy, and halogen; R180 is selected from morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S- dioxide, pyrrolinyl and pyrrolidinyl, each of which is optionally substituted with 1, 2, 3, or 4 groups independently selected from C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(C1-C6) alkylamino, di(C1-C6)alkylamino, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, amino(C1-C6)alkyl, mono(C1-C6)alkylamino(C1-C6)alkyl, di(C1-C6)alkylamino(C1-C6) alkyl, and =0; R110 is aryl optionally substituted with 1 or 2 R125 groups; R125 at each occurrence is independently halogen, amino, mono- or dialkylamino, -OH, -C=N, -SO2-NH2, -SO2-NH-C1-C6 alkyl, -SO2-N(C1-C6 alkyl)2, -SO2-(C1-C4 alkyl), -CO-NH2, -CO-NH- C1-C6 alkyl, or -CO-N(C1-C6 alkyl)2, or C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups that are independently selected from C1-C3 alkyl, halogen, -OH, -SH, -C=N, -CF3, C1-C3 alkoxy, amino, and mono- and dialkylamino, or C1-C6 alkoxy optionally substituted with one, two or three of halogen; R120 is heteroaryl, which is optionally substituted with 1 or 2 R125 groups; and R130 is heterocyclyl optionally substituted with 1 or 2 R125 groups. 13. The method as claimed in claim 12 wherein the generation of the compound of formula (Y) occurs in vitro. 14. The method as claimed in claim 12 wherein the generation of the compound of formula (Y) occurs in vivo. 15. The method as claimed in claim 12 wherein the aqueous media has a pH of about 2 to about 10. 16. The method as claimed in claim 3 wherein the aqueous media has a pH of about 3 to about 7. 18. A pharmaceutical composition comprising a compound as claimed in any one of claims 1-11 or 17 and at least one physiologically acceptable carrier-or excipient 19. The pharmaceutical composition as claimed in claim 18 for the manufacture of a medicament. 20. The pharmaceutical composition as claimed in claim 18 for the manufacture of a medicament for use in the treatment or prevention of Alzheimer's disease, mild cognitive impairment Down's syndrome, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloid angiopathy, other degenerative dementias, dementias of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, or diffuse Lewy body type of Alzheimer's disease. The present invention relates to compounds of formula (I): useful in treating Alzheimer's disease and other similar diseases. Compounds of formula (I) include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of formula (I) are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

Documents:

441-kolnp-2005-granted-abstract.pdf

441-kolnp-2005-granted-assignment.pdf

441-kolnp-2005-granted-claims.pdf

441-kolnp-2005-granted-correspondence.pdf

441-kolnp-2005-granted-description (complete).pdf

441-kolnp-2005-granted-examination report.pdf

441-kolnp-2005-granted-form 1.pdf

441-kolnp-2005-granted-form 13.pdf

441-kolnp-2005-granted-form 18.pdf

441-kolnp-2005-granted-form 3.pdf

441-kolnp-2005-granted-form 5.pdf

441-kolnp-2005-granted-gpa.pdf

441-kolnp-2005-granted-reply to examination report.pdf

441-kolnp-2005-granted-specification.pdf