Title of Invention

ETHER SUBSTITUTED IMIDAZOPYRIDINES

Abstract

Imidazopyridine compounds that contain an ether or thioether functionality at the l-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases. Methods of preparing the compounds and intermediates useful in the preparation of the compounds are also disclosed.

Full Text

ETHER SUBSTITUTED EVflDAZOPYRIDINES Field This invention relates to imidazopyridine compounds that have ether or thioether substitution at tbe 1 -portion, and that may contain additional functionality. The invention also provides pharmaceutical corapositiouB containing these compounds and methods of inducing cytokine biosynthesis by administration of the compounds. Despite these recent discoveries of compouode that are useful as immune response modifiers, there is a continuing need for compounds that have the ability to modulate the immune response, by induction of cytokine biosynthesis or other mechanisms. Summary In one aspect, the invention provides imidazwpyridine compounds that have ether substitution at the 1-position. These compounds have the general formula (la): wherein X, V?, and The various R variables are as defined herein, hi other aspects, the invention provides pharmaceutical compositions containing the compounds and methods of using the compounds to achieve a therapeutic effect, Such effects include the induction of cytokine biosynthesis, the induction of interferon biosynthesis, treatment of viral conditions and treatment of neoplastic conditions, m other aspects, the invention additionally provides methods of making the compounds and intermediate compounds useful in their syntheait. Many of the compounds of the invention have an ether linkage at the 1-position of the compounds, The compounds may include additional substitution that occurs after the initial ether linkage, such as aryl, heteroaryl, hetarocyclyi, amido, sulfonamide, urea, and the like. An additional set of compounds provided by the invention contain a thioether linkage at the 1-position; these thioether compounds may also have additional substitution after the initial thioether linkage, including alkyl, aryl heteroaryl, and heterocyclyl- Detailed Description Several classes of ether and thioether substituted imidazopyridine compounds ore disclosed herein. Although each has a different type of substitution at the 1 -position of the compound, many of the substituents at the other positions of the imidazopyridine core can be independently selected from the same group of radicals. Therefore, the following system is used to describe some embodiments of the invention: different classes of compounds are each described by a different general structure of Formula la, such as lb, I-l, 1-2, and so on. Corresponding different Ri substituents for those compounds will be similarly identified as Ri.i, Ru, and so on. The other substituents, which havotlie same definitions for each* class of compounds, will have common designations such as X, Y, Z, Rz, R3, R4, Rs, and so on. If the same variable appears twice in a particular substituent or compound, such as in " - NfRsy, men each instance of the variable can be independently selected from the permitted values for the variable. -alkyl; -aryl; -heteroaryl; -heterocyclyl; -alkenyl; -Rs-aryl; -Rj~ heteroaryl; and -Rs-heterocyclyl; each Kj is independently hydrogen, Ci-jo alkyl, or Cj-io alkenyl; Rj is alkylene, alkenylene, or alkynylene, which may be interrupted by one ar more -O- groups; Ri U =0 or =S; R8 is a bond, alkylene, alkenylene, or alkynylene, which may be interrupted by one or more -0- groups; Rp is hydrogen, CLIO alkyl, or arylalkyl; or Rp can join together with any carbon atom of Ri to form a ring of the formula - Ri: is C3.7 aDcylene which is straight chain or branched, wherein the branching does not prevent formation of the ring; and Rx, Ry and Rz are independently selected from hydrogen and non-interfering substitutents; or a pharmaceutically acceptable salt thereof, wherein the compound or salt of Formula la induces the biosynthesis of one or more cytokines. wherein: Xis -CHIR5)-. -CH(Rs).alkylen^, -CH(R5)-aIkenylene-, or CH(R5)-allcylene-Y-alkylene-; -Ri-N(R9)-C(R7)-N(Ri O-Q-Rr-dkyl; -K*-N(R9)-C(R7)—N(RU)-Q—RHwteroaryl; -&-NCR,)- Ccyclyl; -Rr^(Rs>-C(R7)^N(Rn)H; -ftlkanyl; -aryl; -&-wyl; -hetoroaiyl; -heterocyclyl; -Re-hotoroaryl; and -Rfi-heterocyclyl; Ri_* is selected from: -alky!: -flryl; -bsteraaryl; -beterocyclyl; -aflcrayl; -Rr-aryl; -Rf-hetraroaryl; and -Rj-hetorocyclyl; Ra is selected from the group consisting of -Hydrogen; -aJtyl; -alkenyl; -aryl; -hsteroaryl; -heterocyclyl; -alkylene-Y-alkyl; -aJkylene-Y- fllkenyl; -aJkylene-Y-aryl; and *alkyl or aBtenyl substituted by one ormore eubstituents selected from the group consisting of; -OH; -halogen; -C{0)-CMoaUcyl; -CfOj-O-d-io alkyl; -NV, ' -aryl; -hfiteroBryl; -heterocyclyl; -C(0)-aryl; and -C(0)-heteroaryl; Yis-0-or-S(0)o.:-; Z is-N(R5K -0-, or -&-; Q is a bond, -C(OK or -SOj-; A represents the atoms necessary to provide a 5- or 6-membered heterocyclic or heteroaromatic ring that contains up to three hcteroatcras; R] and R4 are independently selected from the group consisting of hydrogen, CMD alkyl, Cj-10 alfcenyi, CMO alkynyl, CM0 aflcoxy, Cuo aJkyl&io, amino, alkylamino, diattylamino, halogen, and nitre; each Rs is independently hydrogen, CI-IO alkyl, or CMO alkenyl; Re is alkyiene, alkenylene, or alkynylene, ■which may be interrupted by one or more -0- groups; R7 is =0 or =S; Rg is B bond, alkyiene, alkenylene, or alkynylene, which may be interrupted by one or more-O- groups; Re is hydrogen, CMo alkyl, or arylalfcyl; or Re can join together with any carbon atom of R* to form a ring of the formula -heterocyclyl; -C(0)-aryl; and -C(0>hetBroaryl; Y«-0-or-S(OVr; R3 and R4 are independently solected from the group consisting of hydrogen, d-10 alfcyi, d-10 alkenyl, d-io alkynyl, d-10 aQancy, d-10 allcylthio, amino, alkylamino, diaBcylaminot halogen, and nitro; each R3 is independently hydrogen, d-10 «ttyi»0r c2-!ff *lka«»yl; R R?i8=OorH5; Rs is a bond, alkyiene, alkeayiene, or aScynyiene, which may be interrupted by one or more -0- groups; . R» is hydrogen, d-10 &&yl, or uylalkyl; or Rj, can join together with any carbon atom of Re to form a ring of the formula Ru is Ci.7 alfcylene which is straight chain or branched, wherein the branching does not prevent formation of the ring; or a pharmaceuticaUy acceptable salt thereof wherein: X is -CH(R5h -CH(Rs>8Jkj'Jene-, -CHfRshOkmyim^, or CH(&)-aBcyIene-Y-alkyIene-; Ri.2 is selected from the group consisting of: -R -R6-N(Rs)-SOr-Rg-alkenyl; -Rf-N(R9>-SOr-Rr-aryl; -Rf-N(Rs)-SCVRHwto»aryl; -Rr-N(R9>-SOr-Rr-l»eterocyclyl; -R«-N(R!,)-SOj-Ri0i -Ri-N(R»>SOs-N(Rs>lU-alken>1; -Ri-NtRsJ-SCh-NfRsVRraryl; -Rs-N(Kj>)-S02-N(Rs>lirlieteroflO']; -R«-N(Rp)-SO:-N(R5)-S»-heterocyclyl; and -R*-N(R9)-SOi-NH2; R2 is selected from the group consisting of -hydrogen; -alkyl; -alkenyl; -aryl; -heteroaryl; •beterocyclyl; -alkylene-Y-alkyl; -alkylene-Y- alkenyl; -alkyiene-Y-aryi; and - alkyl or alkenyl substituted by one or more substmiente selected from the group consisting of: -OH; -halogen; -C(0)-Cuo alkyl; -C(0)-0-Cuo alkyl; -N3; ' -aryl; -heteroaryl; -heterocyclyl; ' -C(0)-Bryl; and -C(0)-heteroaryl; Y is -O- or -S(0)o-j-i Rj and R* are independently selected from the group consisting of hydrogen, CMO alkyl, CJOO alkenyl, CMO alkynyl, Q„m alkoxy, Cuo alkylthio, amino, alkylamino, dialkylaniino, halogen, andnitro; each Rj is independently hydrogen, CMO alkyl, or C2.10 alkcnyl; Rfi is alkylene, alkenylenc, or alkyaylene, which may be interrupted by one or more -O- groups; Ra is a bond, alkylene, alkenylene, or aUcynylene, Much may be interrupted by one or more -O- groups; Rs is hydrogen, CMO alkyl. or arylalkyl; or R9 can join together with any carbon does not prevent formation of the ring; or s pharmaceutical!}' acceptable salt thereof. wherein: Xis -CHCRs)-, -CH(Rs)-alkytoM-, -CH(Rs)-alkBQylen Ri.j is selected from flie group consisting o£ .RJp-N(R9)-CCR7)-N(R3)-Q-Rir«lkyl; -Rr-NCReh C(R7)-N(Rj)-Q-R«-alkflnyl; -lU-NGU)- C(R7)-M(R3>-Q-Rff-aryl; -Re-N(Rs)- CfRiJ-NCRsy-Q-Rg-heteroaryl; -Re-NCRs)- C(R7>-N(Rs)-Q-Rrneterooyslyi; -JU-N(R -hettrowyl; -hetamoyclyl; -alkylene-Y-alkyl; -alkylate-Y^alkenyl; •*Jkylene-Y-aryl; end - alkyl or alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(R5)2; ■C(0)-Culclalkyl; .C(OHK,.w alkyl; -N3; -aiyl; -heteroaryl; -heteroeyclyl; -C(0)-aryl; and -C(0)-heteroaryl; Yis-0-or-S(0)w-; Q is a bond, -C(0)-, or -SO2-; A. represents the atoms necessary to provide a 5 - or 6- membered heterocyclic or hetsro aromatic ring that contains up to three heteroatoms; R3 and & are independently selected from the group consisting of hydrogen, CLIO alky!, C2.10 alkenyl, CMO alkynyl, C[.l0 alkoxy, CMO allcylthio, amino, alkylamino, dialkylamino, halogen, and nitro; each JL5 is independently hydrogen, C\.\a alfcyl, or C2.10 alkenyl; R* IB alkylcne, alkenylans, or alkynylsns, which maybe interrupted by one or more -O- groups; eachR7is»Oors=S; Ri IE a bond, alkylate, alkcnylene, or alkynylene, which may be interrupted by one or more -0- groups; R? is hydrogen, Cwo alky], or arylalkyl; or R? can join together with any carbon wherein: X is -CHptsK -CHCR-sValkylene-, -CH(Rs)-alkBiiyIene-J or CH(lLs)-alkyIene-y-alkyiene-; Ru is selected from the group consisting of: -alkcnyl; -aryl; and R2 is selected from the group consisting of: -hydrogen; -aUcyl; -alkenyl; -aryl; -heteroaryl; -heterocyclyl; -alkylene-Y-alkyl; -alkylene-Y-alkenyl; -aJkytene-Y-aryli and - alky] or alkenyl substituted by one or more subrtitueots selected from the group consisting of: -OH; -halogen; -N(R5)2; -C(0)-C!.io alkyi; -C(0)-0-C|-io alkyi; -N3; -aryl; -hetefoaryl; -heterocyclyl; -C(0)-aryl; and -C(OH>eteroaryl; Yis-O-or-S(0)n-; R3 and R* are independently selected from the group consisting of hydrogen, CUD alkyi, CMO alkenyl, CMO alkynyl, C,.tc alkoxy, CMO alkylthio, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, CHO alkyi, or CMO alkenyl; and Rs IB alkylene, alkenylene, or alkynylone, which may be interrupted by one or more -0- groups; or a pharmaoeuticaliy acceptable salt thereof. wherein: f X ie -CH(RS)-, -CH(Rs>(Jkylene-, -CH{R.5)-alkenylene-, or CH(R3>aUcylene-Y-aIkylene-; Rj.s is selected from the group consisting of: -heteroaryl; -heterocyclyl; -Re- heteroaryl; and -Ri-hetarotyclyl; Ra is selected from the group consisting of: -hydrogen; -alkyl; -alkcnyt; -aryl; -heteroaryl; -hetorocyclyl; -alkylene-Y-alkyl; -alkylen&-Y- alkenyl; -alkyiene-Y-aryl; and - alkyl or alkenyl substituted by one or more subatituents selected from the group consisting of: -OH; -halogen; -C(0)-C[.io alkyl; -C(0)-0-C)jD alkyl; -N3; -aryl; -beteroaryl; -heterocyciyl; -C(0)-aryl; and -CCO)-lieteroaryl; Y is ~0- or -S(OXw-; R3 and R* afe independently selected from the group consisting of hydrogen, CJ-JO alkyl, CMD alkenyl, CWo alkynyl, d-io aUcoxy, CMO alkyltbio, amino, alkylaroino, dialkylamino, halogen, and nitio; each E-5 is independently hydrogen, Ci-io alkyl, or C2-10 alkenyl; and Re is alkylene, alkenylene, or alkynylene, which may be interrupted by one or more -O- groups; or a phaimflceutically acceptable salt thereof. Compounds of Formula 1-6 Another embodiment includes thioether compounds represented by Formula (1-6)-. ■wherein: X is ~CH{KsK -CHCRjJ-ttlfcylene-, -CH(R5)-aikenyIene-, or CH^-alkyieiw-Y-alkytae-; Ri-i is selected from the group consisting of; -alkyl; -aryl; -heteroaryl; -heteroeyclyl; -aflcenyl; -Rc-aryl; -Re- heteroaryl; -Re-heterocyelyl; Rj is selected from the group consisting of: -hydro gee; -afcyl; -alkenyl; -aryl; -heteroaryl; -hoterocyclyl; -alkylene-Y-elkyl; - alkylene-Y- alkenyl; -aflcylene-Y-aryl; and - alkyl or alkenyl substituted by one or more subetitufints selected from the group consisting of; -OH; -halogen; -N(Rs)i; -C(0)-C,.ioalkyi; -C(O>O-CM0 alkyl; -Nj; -aryl; -heteroaryl; -heteroeyclyl; -C(0>aryl; and -C(0)-heteroaryl; Yis-O-or-S(0Vr; Ru and JU are independently selected from lhe group consisting of hydrogen, Ci-m alkyl, CMO alkenyl, C2.io alkynyl, C\.\z alkoxy, CHO alkylthio, amino, alkylamino, dialkylamino, halogen, and nitto; each Rs is independently hydrogen, Ci-io alkyl, or Ca-to alkenyl; and Re is alkylene, alkenylene, or alkynylene, which may be interrupted by one or more -O— atoms; or a pharmacentically acceptable salt thereof. Intermediate Compounds Another aspect of the invention includes intermediate compounds of Formulas II, IV. V, LVITJ, UX-f, LIX-2, IIX-3, LK-4, UX-5, LXXVUI, LXXDC. LXXX-4, and LXXX-5. In one embodiment, a class of intermediate compounds is represented by Formula H: wherein X is -CH(RsK -CHtR^aJkylene-, .CH(Rs>alkenylene-, or CH(Rj)-atkylene-Y-alkylane-; Ri is selected from the group consisting of: -hydrogen; -alkyl; -alkenyl; -aryl; -heteroaryl; -heterocyclyl; -alfcylttie-Y-alkyl; -alfcylene-Y- alksnyl; -alkylene-Y-aryl; and -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N0U)a; r -C(0)-CM()alkyl; -C(0)-0-CMO alkyl; -N3; -aryt-, -heteroaryl; -heterocyclyl; -C(0)-aryi; and -C(0)-heteroaryl; Yis^O-or-S(0)o.2-; Rs and R4 are independently selected from the group consisting of hydrogen, CMO alkyl, Cs-to alkenyl, CMO alkynyl, CMO alkoxy, CMO alkylthio, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, CMO alkyl, or C2.10 alkenyl; R$ is allcylene, alkenylene, or alkynylene, which mey be interrupted by one or more -O— atomsi and Ro is hydrogen, CMO alkyl, or arylaJkyl; or R9 can join together with any carbon wherein; X is -CH(Rj)-, -CH(Kj)-ailcylBne-, -CHfRsJ-alkenylene-, or C3i(Rs)-alkylcnc-y-8llcy1eiie-; Ku is selected from the group consisting of: -alkyl; -aryl; -heteroaryl; -hfrterocyclyl; -alkenyl; -Re-aiyl; -R$- heteroaryl; -Re-lieterocyclyl; R2 is selected from the group consisting of; -hydrogen; -alkyl; -aQcenyl; -Hryl; -heteroaryl; -hetorocyclyl; -aOcylene-Y-alkyl; - alkyene-Y- alkenyl; -alkylene-Y-aryi; and - alkyl or alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(Rs)j; -C(0)-CM[1alkyl; -C(0)-0-CMO alkyl; f -N* -aryl; -heteroaryl; -hetorocyclyl; -C(0)-aryl; and -C(0)-heteroaryl; Yifi-0-or-S(0)o.2s R3 and R4 are independently selected from the group consisting of hydrogen, CH0 alkyl, C3.l0 alkenyl C3.10 alkynyl, C|.|0 alkoxy, CMo alkylthio, amino, allcylamino, dialkylamino, halogen, and nitro; each Rj is independently hydrogen, CUB alkyl, or C2.10 alkenyl; and R« is alkylene, alkcnylene, or alkynylene, which may be interrupted by one or more -0— atoms; or a phatmaceutically acceptable Bait thereof. R.2 is selected from the group consisting of: -hydrogen; -alkyl; -alkenyl; -aryl; . -heteroaryl; -lieterocyclyl; -alkylene-Y-Alkyl; - aJky\eoe-Y- alkenyl; -alkylene-Y-aiyl; and - alkyl or alkenyl substituted by one or more substituents selected from the group consisting of: wherein ; X is -CH(Rj)-, -CH(R5)-alkylenc-, -CH(R.5)-alkenyleine-, or ' CtI(R5)-Bl!iyIene-Y-alkylcaie-; Ra iE selected from the group consisting of: -hydrogen; -alkyl; -alkoiyt; -aryl; -hateroaryl; -heterocyolyl; -alkylene-Y-alkyl; -alkyien&-Y- alksnyl; -alkylene-Y-aryl; aDd -alkyl or alkenyl Bubatituted by one or more Buhatituents selected from the group consisting of: -OH; -halogen; -C(O>Ci.i0 alkyl; -C(O)-O-CM0 alkyl; -hydrogen; -alfcyl; -alkenyl; -aryl; -Jieieroaryl; -heterocyclyl; -aHcylene-Y-alkyl; -atkylane-Y- alkenyl; -alkylene-Y-aryi; and - fllkyl or alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(R,)a; -C(0)-CMo &lkyl; -C(O)-O-CH0alkyl; -Nj; -aryl; -heteroaryl; 1 -heterocyclyl; -C(0)-aryl; and -C[0>neteroaryl; Yis-0-or-S(0)o.i-; Z is-N(Rs>-, -0-, or -S~; Q is a bond, -CO-, or -SOj-; A represents the atoms necessary to provide a S- or 6-mcmbered hstorocynlic or heteroaromatic ring that contains up to three heteroatoms; Rj and R4 are independently selected from the group consisting of hydrogen, Ci.10 alkyl, CMO alkenyl, C3.iC allcynyl, CMO alkoxy, CMO alkylthio, amino, alkylmrino, dialkylamino, halogen, and nitro; each Rj is independently hydrogen, CMO alkyl, or CMO alkenyl; B* is alkylefte, alkenyJeno, or alkynylene, which may be interrupted by one or more-O-groups; Rjis-Oor=S; . Rg is a bond, alfcylene, alkenylene, or aflcynyleric, which may be interrupted by one or more -O- groups; R9 is hydrogen, CMO alkyl, or arylalkyl; or Re can join together with any carbon does not prevent formation of the ring; or a pharmaceutically acceptable Bait thereof. Ri-5 is selected from the group consisting of: -beteroaryl; -beterocyclyl; -Re-heteroaryl; and -R$-heterocyclyl; R: is selected from the group consisting of: -hydrogen; -alkyl; -sUcemyl; -aryl; -heteroaryl; -beterocyclyl; -alkylene-Y-alkyl, -alkylcne-Y- alkenyl; -aJkylene-Y-aryl; and R3 and R4 are independently selected fiam the group consisting of hydrogen, C].10 aJkyl, Ca-io alksayl, C2.[0 alkynyl, CMO altaay, C,.iD allylihio, amino, alkyiamino, dialkylamino, halogen, and nitra; each R5 is independently hydrogen, Cj.tc aftyl or Cj.to aUcenyl; compound of Formula XH, In step (4) of Reaction Scheme I, a 3-njtro-2-phenaxypyridine of Formula Xm is chlorinated using conventional chlorinating agents to provide a 3-nitn>-2-phenoxypyridine of Formula XIV. Preferably, the reaction is carried out by combining a compound of Formula XIH with thionyl chloride in a suitable solvent such as dichlororoethane and heating. Io step (7) of Reaction Scheme I, B 4-phBnoxy-l^jmidazo[4,5-{:]pyridkLc of Formula XVI is reacted with a compound of Formula RwSNa to provide a 2-phenoxy- \B-iraidazo[4,5-c]pyridine of Formula HI. Preferably, a thiol of the Formula Rj-fiSH is reacted with sodium hydride in a suitable solvent such as KN-dimethylfbrmamids to generate the anion, which is then reacted with a compound of Formula XVI. pbannacsuticall}' acceptable salt thereof can be isolated using conventional methods. ID step (11) of Reaction Scheme I, a 4-phenoxy-lif-imidazo[4,5-clpyridin-4-aiiiine of Formula XLIII is aminated as in atep (8) to provide a lW-imidazo[4t5-e]pyridiri-4-amine of Formula XVTII which is B subgenus of Formula 1-6. The product or a pharmaceutieally acceptable salt thereof can be isolated using conventional methods. I Some embodiments of the invention including compounds of Formula 1-1,1-2,1-3, and intermediate compounds can be prepared according to Reaction Scheme TI where KM, In step (5) of Reaction Scheme II, a 2Adxcbloro-3-nitropyridine of Fonnula XI (see Reaction Scheme I) is reacted with an amine of Formula XXIV to provide a 2-chloro-3-nitropyridine of Formula XXV. The reaction can be carried out by adding an amine of Formula XXfV to a solution of a compound of Fonnula XI in a suitable solvent such as N^-dimelhylfonnarnide in the presenc& of a base such as triethylamins. Alternatively, step (8) can be carried out by (i) reacting the diamine of Formula XXVII with an acyl halide of Formula RaC(0)Cl or R:C(0)Br and then (H) cyclizing. hi part (i), the acyl halide is added to a solution of the diamine in a suitable solvent such as pyridine. The reaction can be carried out at ambient temperature. In part (ii), the product of part (i) is heated in pyridine in the presence of pyridine hydrochloride. Ureas and thioureas of Formula 1-3 can be prepared from l#-imidazo[4,5-c]pyridin-4-amines ofFormulaHimng conventional methods. For example, a compound of Formula II can be reacted with an iaocyanatc of Formula R,N=C=0. The reaction can be carried out by adding the isooyanateto a solution of B compound of Formula II in a suitable solvent such as chloroform, optionally in the presence of a base such as trietbylaraine, at ambient temperature. Alternatively, ft compound of Formula II can be reactftd with a thioisocyanate of Fonnula RiN=C=S, a sulfonyl iaocyanate of Formula R»S(02)N=C=0 or a carbamoyl chloride of Formula R»NC(0)Cl. The product or a pharmaceutieally acceptable salt thereof can be isolated using conventional methods. presence of B conventional heterogeneous catalyst such as 10% palladium on carbon. The hydrogsnation reaction is conveniently carried out in a Pan- vessel in a solvent such as methanol. Finally, the resulting tert-butyt l-fhetsToarylpropoxyiethyicarbamatss can be dsprotccted to provide 2-(heteroarylpropoxy)ethylamines under conditions described above. In step (2) of Reaction Scheme HI, a2-cWoro-3-mtropyridtne of Formula XXK-4 or XXDC-5 is reacted with sodium phenoxide to provide a 3-ratro-2-phenoxypyricIine of Formula XXX-4 or XXX-5. Phenol is reacted with sodium hydride in a suitable solvent such as diglyme {bis(2-methaxyethyl) ether) to form the phenoxide. The phenoxide is solvent such as pyridine. The reaction can be carried out at ambient temperature, In part (ii), the product of part (i) is heated in pyridine in the presence of pyridine hydrochloride. The product can be isolated tram the reaction mixture using conventional methods. In step (5) of Reaction Scheme HI, a 4-phenoxy-lff-imidazo[4,5-(:]pyridine of Formula XXXH-4 or XXXII-S ia aminated to provide a 1H-imidazo[4,S^]pyridin-4-amine of Formula 1-4 oi 1-5. The reaction can be carried out by combining a compound of rormula XXXII-4 or XXXH-5 with ammonium acetate and heating (140 -160°C). Optionally, the reaction can be carried out in a pressure vessel. The product or a pharmaceutically acceptable salt thereof can be isolated using conventional methods. In Reaction Scheme m, when K.H,5 is &M the products of steps (1M5) are of the Formulas XXDt-4,fXXX-4, XXXI-4, XXXII-4, and 1-4, respectively. likewise, when R|. «, sis R,.j the products of stepB (l)-(5) are of the Formulas XXDC-5, XXX-5, XXXI-5, XXXTJ-5, and 1-5. Some embodiments of the invention including compounds of Formula I-1 and intermediate compounds can be prepared according to Reaction Scheme IV where Alternatively, step (3) can be carried out by (i) reacting the diamine of Formula XXXIV with an acyl halide of Formula R2C(0)C1 or R2C(0)Br and then (ii) cydiring. In part (i), the acyl halide is added lo a solution of the diamine in a suitable solvent such as pyridine. The reaction can be carried out at ambient temperature. In part (ii), the product Formula XXXH-4 is arainated to provide a l#-imidazo[4,5-c]p>ridra-4-ainine of Formula 1-4. The reaction can be earned out by combining a compound of Formula XXXH-4 with ammonium acetate and heating f 140 -160°C). Optionally, the reaction can bo carried out in a pressure vessel. The product or a pharmaoeutically acceptable salt thereof can be isolated using conventional methods. In step (1J of Reaction Scheme V\ the allcyne bond of a 4-phsn.oxy-lH-imidazo[4,5-c]pyridine of Formula XXXVII, which is a subgenus of Formula XXXE-4 or XXXJI-5, is reduced to form a 4-phenoxy-lH-irflidaza[4,5-c]pyridine of Formula XXXVIH, which is also a subgenus of Formula XXXE4 or XXXII-5. Preferably, the reduction is carried out using a conventional heterogeneous catalyst such as platinum oxide, platinum on carbon, or palladium on carbon, The reaction can conveniently be heterogeneous catalyst such as platinum on carbon or palladium OE carbon. Tlie reaction can be conveniently carried out on a Parr apparatus in a suitable solvent such as toluene, Alternatively in step (1), NijB can be generated in aitu from sodium borohydride andNiClj in the presence of methanol. A compound ofFormulaXXK-4 can be added to the resulting reducing agent solution to effect reduction of the nitro group. When a compound of Formula XXK-4 contains an alkenyl, alkynyl, alkenylsne or alkynylsne phenoxide is then reacted at an elevated temperaturt with a compound of Formula XLH. The product can be isolated from the reaction mixture using conventional methods. JJI stop (4) of Reaction Scheme VI, B 4-pbenoxy-li?-imidazo[4,5-c)pyridinc of Formula XXXEE-4 is aminated to provide a lif-irrud^zo[4,5-c]pyridin-4--arnine of Formula 1 14. The reaction can be carried out by combining a compound of Formula XXXH-4 wife ammonium acetate and heating (140 - 160°Q. Optionally, the reaction can be carried out in a pressure vessel. The product or a pharmaceutically acceptable salt thereof can be isolated using conventional methods. imidazo[4,5-c]pyridinyl)flcetamide of Formula Via provides a (7-substituted)-(4-amino-I/f-imio!azo[4,5-c]pyridmyI)acetamide of Formula XLIV, The bmmination reaction car be carried out by treating the acetamide of Formula Via in a solution of acetic acid with bromine and potassium acetate at ambient temperature, The direct nitration reaction can be carried out "by treating the acetamide of Formula Via witb one equivalent of nitric acid in the presence of excoas acetic acid and boating the reaction, optionally, at reflux. The product can be isolated using conventional methods. In step (2) of Reaction Scheme VII, a(7-Bubstituted)-(4-amino-li?-imidazo[4,5-c]pyridinyl)acetamide of Formula XLIV is bydrolyzed under acidic conditions to pruvide clpyridin-4-amines of Formula Ila using conventional methods. For example, a compound of Formula Da can be reacted with an isocyanate of Formula £,^=€=0, where Rj is Rg-alkyl, Rg-aUcotiyl, R*-aryt, Rrhetaroaryl or Rj-haterocyclyl. The reaction can bo carried out by adding the isocyanate to a solution of a cornpound of Formula HE in a (suitable solvent such as chloroform, optionally in the presence of abase such as triethylamine, at ambient temperature. Alternatively, a compound of Formula Ila can be reacted with a thioisocyanate of Formula R«N™C=S, a sulfonyl isocyanate of Formula R»S(0j)N=O0 or carbamoyl chloride of Formula RjNQpJCl. The product or & pharmacciiTicalfy cceptable salt thereof can be isolated using conventional methods. product can b& isolated from the reaction mixture using conventional methods. In step (4) of Reaction Scheme VIH, a tetrazob[l,5-a]pyridine-7,8-diamine of Formula XLK is reacted with a carboxylic add or an equivalent thereof to provide a 7J-J-imidazo[4,5-c]tetrazolotl,5-a]pyridipe of Formula L. Suitable equivalents to a carboxytfc In stftp (7) of Reaction Scheme VHI a 7H-imidazo[4^-c]tetrazolo[)^-n]pyriilinc of Formula LH is reacted with triphGnyiphosphine to form an JV-triphenylphoaphinyl compound af Formula LIU. The reaction with triphenylphosphjne can be mn in a suitable solvent such as toluone or 1,2-dichlorobenzene wider an atmosphere of nitrogen with heating, for example at the reflux temperature. ojpyridine of Formula LII with hydrogen in the presence of an catalyst and an acid. The reaction can be conveniently run in a Pan apparatus 'with a suitable catalyst, Buch as platinum IV oxide, and a suitable acid, such as trifluoroaeetie acid or concentrated hydrochloric acid. The product cm be isolated from the reaction mixture using conventional methods. Some embodiments of the invention including compounds of Formula XVIIIa and intermediate compounds can be prepared according to Reaction Scheme IX where Ra, E-3, R4, and X are as defined above, R' and R" art independently hydrogen or CJ.IQ alkyl, and Etie ethyl, In step (1) of Reaction Scheme IX a 7if-imidazo[4.5-c]tetrazolo[l,5-a]pyridino of Formula LHa, which is a subgenus of Formula LH, is hydrolyzed to provide a 1H-imidazo[4,5-c]tetrazo]D[l,5-fl]pyridine of Formula IHb. The reaction can be carried out under conventional saponification conditions by treating the ester with aqueous sodium hydroxide in a suitable solvent or solvent mixture such as tetranydrofuraD/hiethanoi. The Alternatively, steps (4) and (5) of Reaction Scheme DC can be omitted, aftd the tetrazoto ring cm be reductivcly removed from a 7H-imidaza[4,5-e|tetra7.olo[l,$-c]pyridine amide of Formula IHc to provide a l#-imidazo[4,5-c}pyridin^-amiue of Formuia XVIHa. The reaction can be canied out by reacting the 7tf-itmdazo[4,5-cjtetrazoloD ,5-a]pyridine amide of Formula LUc with hydrogen in the presence of an In step (I) of Reaction Scheme X a 2-chJoro-3-mtropyridine of Formula XXV is reacted with BE alkali metal azide to provide an 8-nitrotetrazolo[l,S-n]pyridine of Formula LV. The reaction can be earned out as described in step (I) of Reaction Scheme VIH The prodtict can be isolated from the reaction mixture using conventional methods. methods. In another example, a 7^f-imidn2o[4,5-c]fetnizolo[I,5-a]pyritiin5 of Formula LATH is reacted with p. chloroattcaawulfonyl chloride of formula CJ-Ru-SfG^Cl to provide a subgenus of compounds of Formula LK-2 wherein RQ and R]Q join to form a ring having the structure diazabicyclo[5.4.0]uiidecene-7 (DBU) at ambient temperature. If the intermediate chloroslkaaamide is isolated, the reaction with DBU can be carried out m a suitable solvent such as N-dimethylformarnide. The product can be isolated using conventional methods. in the presence of an catalyst and an acid, The reaction can be conveniently run in a Pan apparatus with a suitable catalyst, such as platinum IV oxide, and a suitable acid, such as trifiuoroacetic acid or concentrated hydrochloric acid. The product can be isolated from the reaction mixture using conventional methods. Some embodiments of the invention including compounds of Formula 1-4,1-5, and intermediate compounds can be prepared-according to Reaction Scheme XI where Ru.5 (RM andE.1.5), R2, R3, Ri, and X are as defined above. In step (1) of REaction Scheme XI, a 2-chloro-3-nitropyridine of Formula XXIX-4 or XXIX-5 is reacted with an alkali metal azide to provide an 8-mtrotstrazoto[l,5-a]pyridrae of Formula LXH-4 or LXU-5. The reaction can be carried out as described in catalyst and an acid. The reaction can be conveniently run in a Parr apparatus with a suitable catalyst, such as platinum IV oxide, and a suitable acid, such as trichloroacetic acid or concentrated hydrochloric acid. The product can be isolated from the reaction mixture using conventional methods. dichlaromethane in the presence of pyridine and catalytic 4-dimethylaminopyridine (DMAP). The product can be isolated from the reaction mixture using conventional methods. In step (2) of Reaction Scheme XH, a a-ehloro-3-nitropyridine of Formula LXVI is reacted with an alkali metal azide to provide an 8-nitrotetrazalo[t ,5-o]pyridine of Formula i out by coupling a heteroarylbromid*, for example, 5-bromopyrimidiiic, or heterocyclylbromide with tic alkyae group of a 7#-imidazo(4,5-c]tetrazoIo[l,5-.ctfryridiiis of Formula LKXI, The coupling reaction can proceed through a palladium complex, generated from a palladium catalyst, for example ajpyridioe of Formula LVC-5 with hydrogen in the presence of an catalyst and w acid. The reaction can be conveniently run in a Parr apparatus with a suitable catalyst, such as platinum TV oxide, and a suitable acid, such as trifluoroacetic acid or concentrated hydrochloric acid. The product can be isolated from the reaction mixture using conventional methods. Some embodiments of the invention including compounds of Formulas LXXVH-1, LXXVII-2, LXXVH-3, and intermediate compounds can be prepared according to in step (5) of Reaction Scheme XIH, the nifro group of a compound of Formula LXXHI is reduced to provide a pyridine-7,8-diainiiie of Formula LXXTV. The reaction can be carried out by the addition of podium borohydride and nickel chloride to a solution of a compound of Formula LXXHI in a suitable solvent or solvent mixture such as mcthanol/dichloromethane at ambient temperature. The product can be isolated from the reaction mixture using conventional methods. hi step (6) of Reaction Scheme XE, s pyridine-7,8-diatmne of Formula LXXTV reads with a carboxylic acid or an equivalent thereof to provide an imida7,o[4,5-e]pyridinfi of Formula LXXV. The reaction can be carried out BE described in stsp (4) of Reaction Scheme VilL In step (7) of Reaction Scheme XHL an imidazo[4,5-c]pyridine of Formula LXXV is deprotected under acidic conditions to provide a lH-iroida2o[4,5-c]pyridiii-4--aniitie of Formula LXXVL The reaction can be carried out by diaaolving an imidazo[4,5-c]pyridin.e of Formula LXXV in trifluoroacetic acid and stirring at ambient temperature. Optionally, the reaction coo be carried out in a suitable solvent such as dichlMomethafle. In step (8) of Reaction Scheme XIII, a lH-imidazo[4,5-c]pyridui-4-amine of Formula LXXV1 is converted to a lH-imidazo[4)5-c]pyridin-4-arnine of Formula LXXVH-1,2,3, which is a subgenus of Formula 1-1,1-2, and 1-2, using conventional methods. The reaction can be carried out as described in step (11) of Reaction Scheme II. It is understood that one skilled in the art will select the appropriate reaction schemes and steps therein to prepare a compound described in the various aspects and cmbcdimentB of the invention to avoid or minimize undesired or conflicting reactions. For example, when Rj is chloro a reaction scheme which does not involve a tetrazolo intermediate can be selected. Reduction of a nitro group at R3 or IU can be avoided by placement on the pyridine ring after reduction of the nitro group al Ihc 3-poeUion of the pyridine ring. When an alkanyl, alkynyl, alkenylene, or alkynylene group is present, reduction of the nitro group at the 3-poshion of the pyridine ring can be carried out by using the N12B reduction without reducing the alkenyl, alkynyl, alkenylene, or afliynylene group. When removing & tetrazolo ring in the presence of a readily reducible group such as an alkenyl or heteroaryl group, the formation of an W-triphenylphosphinyl compound followed by hydrolysis can he used in place of the reductive removal to preserve, for example, the alkenyl or heteroaryi group. The term "non-interfering substituenls" refers to R*. RY» and Rz groups which do not prevent a compound of Formula h from inducing the biosynthesis of one or more cytokines, Illustrative hon-interfering Rx groups include those described above for Rj. Illustrative non-interfering Ry and Rz groups include those described above for R3 and R4. As used herein, the terms "alkyl", "alkenyl", "aDcynyl" and the prefix "alk-" are inclusive of both straight chain and branched chain groups and of cyclic groups, i.e. cycloptkyl and cycloalkenyl. Unless otherwise specified, these groups contain from 1 to 20 carbon atoms, with alkenyl groups containing from 2 to 20 carbon atoms, and alkynyl groups containing from 2 to 20 carbon atoms. Preferred groups have n total of up to 10 carbon atoms, for example, up to 8 carbon atomB, up to 6 carbon atoms, and up to 4 carbon atoms. Cyclic groups can bo monocyclic or polycyclic and preferably have from 3 to 10 ring carbon atoms. Exemplary cyclic groups include cyclopropyl, cyclopropylmethyl, cyclopcntyl, cyclohexyl, adamantyf, and substituted and unsubstituted norbomyl and norboraenyl. Unless otherwise specified, "alkylene", "alkenylene", and "alkynylene" are the divalent forms of "alkyl", "alkenyl", and "alkynyl" defined above. The term "haloalkyl" is inclusive of groups that are substituted by one or more halogen atoms, including perfluorinated groups. This is also true of groups that include the prefix "halo-". Examples of suitable haloalkyl groups are chloromethyl, trifluorometbyl, and the like. The term "aryl" as used herein includes carbocyclic aromatic rings or ring systems. Examples of aryl groups include phenyl, naphthyl, biphenyl, fluorenyl and indsnyl. The term "heteroaryl" includes aromatic rings or ring systems that contain at least nne ring heteroatom (e.g., O, S, N). Suitable heteroaryl groups include furyl, thienyl, pyridyl, quinolinyl, isoquinolinyl, indolyl, isoindolyl, triazolyl, pyrroiyl, terrazolyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, benzofiiranyl, benzothiophenyl, carbazolyl, benzoxazolyl, pyrimidinyl, benzjmidazolyl, quinoxalmy], benzothiazolyl, naphthyridinyl, jsoxazolyl, isothiazoly), purwyl, qainazolmyl, and so on. "Hetorocyclyl" includes non-aromatic rings or ring syBtcms that contain at least one ring hetftroatom (e.g., 0, S, N) and includes all of flic fully saturated and partially unsaturated derivatives of the above mentioned heteroaryl groups, Exemplary heterocyclic groups include pyrrolidinyl, tetrahydrofuranyl, morpholinyl, thiomorpholinyl, piperidmyl, piporazinyl, thiazolidinyl, imidazolidmyl, isothiazolidinyl, and the like. The aryl hoteroaryl, and hotcrooyclyl groups can be unsubstituted or substituted by one or more; mbstituents independently selected from the group consisting of alkyl, alkoxy, methylonedtoxy, etnylenedioxy, allcylthio, haloalkyl, haloatkoxy, baloalkylthio, halogen, nitro, hydroxy, mercapto, cyano, carboxy, formyl, aryl, aryloxy, aryhbio, arylalkoxy, arylalkylthio, heteroaryl, hcteroaryloxy, heteroaryWiio, heteroarylalkoxy, hoteroarylalkyltbio, amino, aEcylamino, diatkylamino, heterocyclyl, heterocycloalkyl, alkylcarbonyl, Hlkenylcarbonyl, alkoxycarbonyl, haloalkylcarbonyl, haloalkoxycarbonyl, alkylthiocarbonyl, arylcarbonyl, beteroarylearbonyl, hetarocyclylcarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, arylthiocarbonyl, heteroarylthiocarbnnyl, alkanoyloxy, alkonoylthio, alkanoylamino, aroyloxy, aroylthio, aroylamino, alkylaminosulfonyl, alkylsulfbnyl, arylsulfonyl, heteroarylsulfonyl, aryldiazinyl, alkylsulfonylamino, arylsulfonylaminc, arylalkylmlfonylamiiio, alkylcarbonylamino, alkenylcarbonylamino, arylcarbonylamino, arylalkylcarbonylamino, heteroaryl carbonylamino, heteroarylalkycarbonylamino, alkylsulfonylamiiio, alkenylsulfbnylamino, arylsulfonylamino, arylalkylsulfonylamino, heteroarylsulfonylamino, heteroarylalkylBulfonylamino, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, arylalkylaminocarboriyl, alkenylamiuocarbonyl, heteroarylaminocarbonyl, heteroarylalkylaminocarbonyl, alkylaminocarbonylamino, alkenylaminocarbonylamino, aiylammocartonylamino, arylalkylaminocarbonylarninojheteroarylanmocaAonylarnino, heteroarylalkylaminooarbonylamino and, in the case of heterocyclyl, oxo. If any other groups are identified as being "substituted" or "optionally substituted", then those groups can also be substituted by one or more of the above enumerated substituents. The invention is inclusive of the compounds described herein in any of their pharmaceutically acceptable forma, including isomers (e.g., diastereomers and enantiomere), salts, solvates, polymorphs, and the like, h particular, if a compound is optically active, the invention specifically includes each of the compound's enantiomers as well as racemic mixtures of the enantiomers, i rlpyridiii-4-ainiDe; 2-eaoxyniethyU6,7-d]methyl-I-[2-(4-phenyIbut-ynyIoKy)ethyIi-1ff-imidazo[4,5- c]pyridm-4-ainine; and 2-oaioxym ethyl-6,7-d!me&yl-l-[2-(4-phenyIbx;toxy)(rthyll-lH-imida2o[4,5-c)pyridm-4- amine; or phaimaceutically acceptable salts thereof Cytokines whose production may be induced by the admrnisttation of compounds according to dit invention ganwally include iDicrfemn-a (TFN-a) andor tujnar necrosis ffictor-a Cn-tz) as well as cBrtain jnterleiddnB (IL), includjng tL-l, IL-6, IH 0 and H 12, and a variety of afhar cytokjnes. Among oftier effects, ttese and otiier cytokines can inhibit vims production and tumor cedl grow&, making tlie compounds UBefid in the iTBatraent of viral diseases and tumors. Accordingly, the invention providcE a me&od of inducing cytokine biosynthesis in an animal compming sdministerii an ective amount of a Doaund or componition of the invention to the animal. and B cells to produce an amount of one or more cytokinse auch as, for example, IFN-a, TNF-a, IL-I, IL-6, IL-10 and IL-IJ that is increased ovw the background level of such cytokines. The precise amount will vary according to factors known in the art but is expected to be a dose of about 100 nftTcg to about SO mg/kg, preferably about 10 g/kg to ahout 5 mg/kg. The invention also ppovidss a msthod of Ireatitig a viral infecdon in an animal and a method of treating a neoplastic disease in an animal comprising Hdminifltoring an ofTeotive amount of a compoirod or composition of file invention to the animal. An amount effective to treat or inhibit aviral infection is an amount that will cause a reduction in one or more of &e mamfsetationB of viral infaetion, such as viral loEionfi, viral load, rate of vinu prodviotion, and mortality as compared to untreated control animals. TJie preciaa wnount wilJ vary according to fectore known in tfie art but is e:q)ected tobeadoseofabout 100 ngiQcg to aboiit SO mg/kg, preferably about 10 tig/leg to about 5 Dig/kg. An amaunt of e comgotmd cSocdve to aest a nwpUutic condition is an amount that wi]I cause a reduction in tomor size or in number of tumor feci. A gain, the preoise amount will vary according to bctois known in ait but is expected to be s dose of about 100 ng to about 50 mg/kg, prefieabJy about 10 g/kg to about 5 mg/k. The inventioJi is fiuthK- describai by the fbllowinB exampies, which are provided for iUuslratiDn only and are not intended to be limitjog In any way. PanD 5>dim5liiyl-2-phBnoxy-N-(2-ph8iioxyethyl)pyridine.3,4-diaminft Anhydrous toluene (100 ml), 5% platinum on carbon (Pt/C) (1.5 g), and 2,:i-diine[hyl-5-Eitro-6-phmoxy-N-(2-phsnoxyethyl)pyriditi-4-amine (2.97 g) &om Part C were piaccd ill a Parr hydrogen ation flask at a hycirogcn pressure of 3-,5 kPa for 4 hours with Bhaking. Additional 5% Pt/C (1.5 g) was added and the reaction was allowed to hydroxide. The basic byer was washed with DCM and the conAined organic layers were dried with magnesium sulfiite and coDcentrated mider reduced pressure. The resulting oil was passed through a silica gel column using 95/5 dichloromethane/metbanol as the eluant The product -wtis recrystallizcd from isopropyl alcohol, and the resulting white solid was dried under vacuum to provide 6,7-dimetiiyI-l-{2-pfaMiDxyothyl)-lfl-iniida2o[4,5-c]pyridiD-4-aniine, m.p. 197.0 -199.0 "C. Analysis: Calculated for Ci«HtBN40; %C. 68.06; %H, 6.43; VoN* 19.84 Found: %C. 67,85; %H, 6.33; %N. 19.74. Parte 2,6,7-trimethvl-4-phQTuixy. l.(2-phenQy7ethylVlfr-iimda2Qt4,5-clpyddmt A flolution of sodium phenoxide WHB prepared by adding phenol {0.60 g) in portions over a period of 1 hour to a chilled solution of 2-inethoxyetiiylcfiier(diglyme) (40 ml) and sodium hydride (60% in oil) (0.27 g). Aftw 1 hoiji, 4-chloro-2,6.7-triTtielhyl-l-C2-phBnoxyBthyl)-lH-iinidazo[4,5-e}pyridiae (1.91 g) from Part B was added to Iho sodium phenoxide solution and the resulting dark brown mixture was heated to reflux for 7 days. At this time, the reaction was 80% conlGte. Remaining sodium hydride was queached by die addition of methanol (5 ml), and the sotvents were then removed under reduced pressure. The oil was dissolved in eOiyl acetate, waabsd with water and brine, dried with magnesium sulfate, and conoenfrated under reduced pressure. The resulting brown solid was run ough a silica gsl column using 80/20 ethyl acetate/hexane as &e etuant. NMR analysii oftht dried salid indicated sufficient purity for carrying the product Triethylamine (1 -93 ml), anhydrous ofluraol (35 ml), and N.{2-chlom-5,6-dimethyl-4-i;C2-pheno)cyethyl)flmmo]pyTidin-3-yl}peintammido (1.32 g) from Part A wore combinfid and heated to reflux for 24 houis. The reaction stalled, so the mixture wsfi cooled and tiie solvent was removed under reduced pressure. Pyridine (75 ml) and an equivalent of pyridine HCl waK added and the reaction mixture was heated to reflux for 16 hours. TLC analysis indicated that the reaction was complete. The reaction was allowed to cool and the solvent was removed under reduced pressure. The resulting product was (solved in c&iyl acetate and washed 4 times with water {150 ml each) to remove the pyridine HCI. The organic layer was dried with magnesium sul&te and the solvent was removed under reduced pressure. NMR analyeie of the dried brown solid indicated sufficient purity ibr use of the product in the next step. Parte 2-ijTityl-6,7-dinietb)'l-4--ph«TOX)'-]-(2-phraioxyethyJ)-l-imidaz£>[4,5-i?]pyridbe 2-MeJboxyelhj ether (diglyme) (1.50 ml) and sodium hydride (60% in oil) (0.12 g) were corobiDed and cooled to 0 °C. Phmol (0.27 g) waB added slowly in portioDs over i hour to allow for DontroHed release of hydrogen gBS. 2-Buty!-4-cbloro-6,7-dimEAy]-3-(2-phonoxyethyl)-l/f-iinidazof4,5-£:]pyrid!M (0.96 g) fitom Part B was tbesn added and tiie reaction mixture beoame daA brown. Ths reaction mixtuie was heated to reflux for 5 days,«(which time HPLC analysis indicated die iwiction was complete. The reaction mixture was cooled and washed with water. TTie mhrtore was filtered and the resultrng solid was dried under vacuum at 60 *C overnight. NMR analyaia of the product indicated BufBcicnt purity for use of the product in the next step. PanD 2-huty] 6,7-dimetiiyl-1 -(2-phenQxye1iiyl> lH-imidazo[4,5-clpyridin-4-amine A sealed tube containing aramonium acetate (7.S g) and 2-butyl-6,7-dimethyl-4-phenoxy-l-(2-phsiioxyethyl)-lH-iniidazo[4,5-c]pyridine (0.75 g) from Part C was heated in an oil bath to 150 "C for 48 hours. The reaction reached 70% completion and was allowed to cool to room temperature. The reaction mixture was then dissolved in ethyl acetate and washed with a saturated aqueous solution of sodium bicarbonate. The organic layer was dried with magnesium sulfate and concentrated under reduced pressure. The product was passed through a silica gel column using 10/90 me&anol/etiiyl acetate as tlie eluant. To remove inQJurities, the product was recrystallized twice from acetonitrile with cfiarooai. The resulting white crystals wgre crushed and dried to yield 2-butyl-6,7-dimethyM-(2-phcnoxyethyI)-Ii!r-imidazo[4,5-c]pyridin-4-amine,m.p. 130.0- i32.0°C. Anaiysifi; Caioulated fer CioKiAO: %C, 70,98; %% 7.74; %N, 16.55 Found; %C, 70,80; %H, 7,43; %N, 16.56, I 2-(b8ii2yloxy)ethylamine HCl The product from Part A (45.4 g, 180.6 nimol), 2.2 M hydrochloric acid in ethano! (200 mL), and 10% aqueous hfliracliloric acid (20 mL) were combined and etiired for 62 hoyrs. ThcTeactionwasdatemiinedtobecompletebyTLC aiidHPLCanalyais, The valatilss were rsmoved under reduced pressure, and the resulting BDlifls were rscrytallized from etliy] acetate. T'he resulting white fluffy crystals ware filtsred off, rinsed wifli dieihyl ether, and dried for 1 hour to provide 27.4 g of white solids. NMR analysis confirmed the hydrochloride salt of 2-(benzyloxy)ethylainiTif5, which was used in Ihc next step. tranfifflT was compiete after 15 miniUeE, and Ihe rcsuifing orange solution was heated to about 150 "C for 4.5 hours when the reacUon was determbed to be essentially complete by tlPLC. The resulting reaction solution was cxmccntrated under reduced presaurej and the resulting dark oil wm dissolved in tthyl acetate. The ethy acetate solution was wased with ammonium chloride (1 x), 1 K potassium hydroxide {3 x), and brine (2 %). The potassium hydroxide fractions were combined and extracted with diohloromethane (4 x). The organic fractions were combined, dried witii inagnesiBm sulfate, and concejitrated amide, and TLC (with l/I hexane/ethyl acetate) and HPLC analysis iTidicated no Etarting matMial or olher by-products present. The resulting reaction salutioc was heated lo reflux {- 90 °C) for about ] 0 hours, HPLC analysis of the resulting reaction solution indicated about 4% of the amide remaining along -w-ith the desired product. The reaction soJution was cooled to ronm temperature and coucentrarad under reduced pressure. The resulting oil was triturated with hexane/diethyl ether, and the resulting solid was filtered off ami dried to provide 4,33 g of pure product. A second crop Soxn the hexane/dietby! ether was lecovsred to provide an additional 0.3157 g of desired product. PartG 1 -I2-(BeaizyiffKy)otliyI] -2-(eliioxyoietiiyI)-6,7-dime&j4- lH--iimdazo[4,5--i?5pyridin-4- amine 2-(Etboxymethyl)-1 -l2'(bwzyloxy)9yl]-6,7-dimothyl-4-phanoxy- IK-imidM»J4,5-c]pyridbe (4.33 g, 10.03 tomOl) waa placed in & s reaction flaak, and then anuxiomum uwtato (45 g) was added. Tbe Q* was sul«d wifti a ton stirw cap and heated to 156 "C for 44 hours. The reaction was deteimined to be complete by HFLC analysis, and the desired product's molecular weight ns confumed by LCMS, The reaultii\g solution was basified with 1N potafiaium hydroxide to a pH of about U. The basic solution was extracted with (liddoromethane (5 x), and the organic layers w&e combined, washed with water {3 x) and brine (3 x), dried witii magnesium sulfate, filtered, and concentrated imder reduced pressure. The resulting oil was triturated with diethyl Bflier. After &o resulting aolida were filtered off and dried, they were r«irystalli2ed from ediyl acetate/iHethyl ether and again dried. KMR analysis or the recrystallized solids indicated impurities. 'I'hc rccrystallized solids were dissolved in ethanol. Hydrochloric acid (10 mL, 1 N) v/aa added lo UID ethanol solution, and the resulting salt was nUortid ufT and diflfiolved in water. The resnlting aqueous solution was basified with 1N potassium hydroxide to a pH of about 14 and extracted wifb dichloioniethane (4 x). The organic layers were combined, washed with water (2 x) and brine (3 x), dried with magnesium sulfate, filtered, and eoncentcated undot reduced pressure to a white solid. Tlu wlute solid was dried to provide 1.4285 gofl-[2-(benzyloxy)Bti]yl]-2-(eihoxyinethyl)-6,7-dimDthyl-l/r-inudazo[4,5-c]pyridiD-4-8mine, m.p. 107.3-108.2 "C. Analysis: Calculated for CaoHaNA: %C, 67.77; %H, 7,39; %N. 15.81; Pound: %C, 67.88; %H, 7.44; %N, 15.79. Hmm (300 MHz, DMS0-d6) 8 7,22-?.31 (m. 3H), 7.14 (dd, J - 9.4,1.9Hz, 2H), 5.81 (s, 2H), 4.67 (8,2H), 4.57 (t, J = 5.6 Hz, 2H), 4.42 (s, 2H), 3.76 (t, J = 5.6 Hz, 2H), 3.47 ((I, J = 7.2 Hz, 2H), 2.34 (a, 3H), 2.30 (6,3H), 1.12 (t, J « 7.2 Hz, 3H) l-[2-(beti2y]oxy)ethy]]-2,5,7-triinethyl-li?-in3idazo[4,5-c]p>TiiMn-4-amiiie K[3-(Ben2ylDxy)rtb}]-2,5,7-trimeith>-4-ph(3M3ty-l/?-iniida2ot4,5-c]pyridiiw (5.113 g, 33.195 mmol) from Part A and amniDniuin aceiate (51 g) were combined in & dried glass pressure flask under nitrogen. The flask was sealed and hcBted to 150 "C for 46 hours. The reaction was complete, and thft resulting solution was cooled and basified to apH of about 12 with 1N potassium hydroxide. The basic solution was extracted with dichloromethune (3 x), and the organic layers were combined, waslied with water (3 x) and brine (3 x). dried with magnesium sulfate, filtered, and concentrated mider reduced pressure. The resulting oil was triturated wilh dietiiyl ether, and the resulting solids were red off, NMR analysis of the ftoUdaindicafedrcflidual phenol. TTie solids were iolved in ethyl acetate. The athj acetate solution was washed with 1 N poiassiam Iroxide (4 x), water (3 %) and brinft (3 x), dried with magnesium aulfeie, filtered, and icentrated undH- reduced preaBure- The reaiUins oil was diluted wilh dietbyl elher, and fif seveiBl hours the resiiltiTig crystfdB were fiftered off and rinBcd wife diethyl ether. le resulting solids, which by NMR analysis were &w of &e idicnol. were dried at 60 °C r 17 hours under high vacunni to provide 215 g of l-P-(bflOZ)dmty)Bthyi]-2,6,7- imBthyl-lH-itmdfl2o[4,5 Jialysis; Calculated fw CgHaNiO; %C. 69.65; %H, 7.14; %N, 18,05; Pound: %C, was dissolved in etbyl acelate. The ethyl acetate solution was washed with brine (3 x), dried with magneBiTim aul&to, filtered, and comsentratcd under reduced pressure. The resulting tan solids wars triturated wifli disfliyl sfher, 0lEarcd ofEl and dried to provids 6.5S62 £ of pure product fby NMR and LCVMS), which wsfi used in &e next step. PaitB 1 -t2-(benzyloxy)ethyl]-6,7-dimothyl-2-propyl- li?-itaida2o[4,5-c]pyridiD-4-amine l-[2-{Seniyloxiethyl]-6j7-diinetiiyl-4henoxy-2-prop54-lif-iiiudazo[4,S-cjpyridine (6.6 g, 15-8 nmiol) and Bnmomiim acetate (66 g) were ctHublned in a dried gluB preasure fla under nitrogen with stirring. The ftask was vealed with a teflon screw c and heated to 156 °C for 44 hours. The rcaottoit ms complete as detennined by HPLC and LC/MS/aad the resulting strfution waa cooled and basified to a pH of about M wi 1N potassium hydroxide. The basic solution was extracted with dtchloramefhane (5 x), and the organic Isyete were combined, waehed with 1K potasmum hydroxide (3 x), water (I x) and brine (3 x), dried with mapiesium sulfete. filtered, and concentrated under reduced preBsurc, The reBulting irsiduo was tritarated with ethyl acetate/dicthyl ether, and the resulting solids were filtered off and dried. NME, analysis of the solids indicated impurities. The solids were recrystallized from iaopropyl alcohol and dried, Impurities were found in the resulting solids (3.29S2 g), which were them recrystallizod feim ethyl acerata'hEaane and agaJB dried. The resulting solids (2.4076 g), still with impurities, werre dissolved in ethanol, and the resulting eolution was treated with 1 M hydrochloric acid in diethyl cfiior (10 mL). The resulting hydrochloride salt was filtered off, diaaolved iu water, and the aqueous solution was basified with IN potassium hydroxide to a pH of about 14. The rwulting aqueous mixture was extracted with dichloromethanc (5 x), and the combined organic layers were washed with water (3 x) and brine (3 x), dried with magnesium Hul&te, filtered, and concentrated under reduced pressure. The resulting white solid was dried to ptnvide 1.5999 g of I-[2-(bear50Ky)eQij'J]-6,7-dimcthyl-2-propyj-l/A imida2Dl4,5-c}pyridifr4-amine, m.p. 99.5-100.0 "C. AnslysiB; Calculated for CjoHjeNdO: %C, 70.98; %H, 7.74; %N, 16.55; Found: %C, 70.79; VoH, 7.71; %N, 16.80. 'H MMH (300 MHz, DMSO-da) 5 7,24-7,31 (m, 3H), 7.14 (dd, J = 9,4,2.3 Hz, 2H), 5.60 (s, 2H), 4.46 (t, J = 5.6 Hz, 2H). 4,41 (s, 2H), 3.71 (t, J = 5.3 Hz, 2H). 2.78 (t, J = 7.5 Hz, 2H), 2.32 (s, 3H), 2.29 (s, 3H), 1.76 (sextet, J = 7.5 Hz, 2H), 0.95 (t, J = 7.2 H?., 3H) a slightly cloudy oil (7.22 g). 3-Braino-I -phanjipropyne was coafinncd by NME analyBis. PartB I-[C2-Oiioro-5,6-cfimetbyI- 5-mtropyridm-4-yt)ainino]etIian-2-oI 2,4-Diohloro-5,6-dimethy]-3-EiTrDpyridmc (60 g. 271.4 mmol), anhydrous K-dimethylformamide (900 mL), BthflnoJomme (19.6 mL, 325.S mraol), and anhy;!/ i.nis tricthylamine (45,4 mL, 325.8 mmol) were combiDcd with stirring under nitrogen. The reaction inixture wia held at 40 "C for 17 hours when TLC and HPr:C monitoring adiested complete reaction witii no stiating iiiateriaJ prMsnt. The reeuUmg reaction oixture was cancBntratcd under reduced preaaure, the resulting yellowish orange solids vore triturated with water (3x1 L), filtsred of and dried by diBSolving Ihe solidi; In nethaaol/diethyl sther, followed by remova! of the solvents under reduced preisr.ijre. The waiting solids -wen slurried in diethyl etiior, followed by removal of the diefo>1 o&er mder reduced presBure. After rqieating the slurrying and solvent removal several tjmefi, thfc rBHulting solid was dried at 85 "C for 16 hours under high vacuum to provide 55.2 g of yellow BoHd, which \\'as carried on to the next st. NMR analysis confirmed l-[(2-diloKi-5,6-dinicthyI-3itropyridin-4-yl)amino]efcan-3-o]. Parte l-[(2,3-Diniethyl-5-nitro-6-pheaKiKypyridin-4-yI)araino]ettian-2-ol A sohition of phenol (94 g, 998.9 tamol) in diglyme (200 tnL) was added slowly over 45 minuteE to a solution of sodium hydride (38.06 g, 951.5 mmol, 60% in mineral oil) in diglyme (100 mL) cooled to 4 "C with an ice bath. Hydrogen gas evolved, and the temperature increased to a maximum of 34 °C, hut was immediately reduced by slowing the rale of phenol addition. After addition was complete, the reaction mixture was stirred for 1 hour. About 200 mL of the rosultuagdear eotution was removed and set aaide. The ice bflJh was removed, and l-[C2-chlDro-5,6-dimethyl-3-nitropyridin-4-yl)amino]Btb!m-2-o] (55.2 g, 224.69 mmol) dissolved in diglyme (400 mL) was added to the clear reaction solution under nitrogen. The flask fiom which ttic starting material was transferred was rinsed with diglyme (2 x 100 mL), and the rinflingB were added to the resulting reaction mixture. This reaetian ciixture was heated to HO " for 4 hours under a fkiw of nimeo, and then the resulting reaction mixture was concraitrated imder reduced pressure. The resulting oil was cooled to about 5 'C for 2 days, triturated w bexane, and passed through B silica gal column uaing 8/2 hexane/stiiyl acetate, thn 7/3 hexanc/ethyl acetate, and ending with 6/4 hexane ethyl acetate over 3 days. A first IQ.5 g fraction of impure product and a second 3.9 % fraction of pure product were isolated. The first fraction (9.6510 g) was dissolved in ethyl acetats/liexane and the product allowed to crystallize. The crystals were filtered off and dried to provide 9.6510 g of product, which was combined with the previous 3.9 g of pure product and carried on to the next step. rtD C2,3-E)irr)s&y)-5-mtrr>-6-pbenoxjT3)ddJD-4~y!)ainJDD3e&-2-}d Acetate l-[(2,3-Dimethyl-5-mtro-6-phe]ioxypyridin-4-yl)Eiinino]fltiian-2-o] (13.55 g, 44.67 tnol), anhydrous dichloromefiiaae (150 mL), pyridine (21.7 mL), and methylamintyridine (0.11 g) ware combined, and them acrtic BulQed was added ider nitrogeti. The rcBulting Bohition was Btirred at mom tcraperfttare for 30 minutes, be reaction was complete, and the reaction Bolution was coocentrsted under reduceid traaiue. The resultiiig oil was dissoived in dichioromedume, and the dichlDromeAane lution was washed with 4% sodium bioarboaate (3 x), water (3 x), and brine (3 x), dried /ith magnesium sulfate, filtered, and concentrated under reduced pressure, The resulting 'cllow solid was triturated witfi diethyl ether, and the solids were filtered offand dried to irovide 11.5 g of product The l-[(2,3-Diracthyl-5-mtro-6-phCTQxypyridin-4-irI)anuno]etii-2-yI acetate structure was confirmed by NMR and its moiecular weight was ponfinnedbyLC/MS. PartE l-[(3-Ainino-5,6-diin ethyl-2-pheao7cypyri din-4-yI)amino]eaj-2-yl Acetate l-[(2,3-Dimothyl-5-nitro-6-pheBoxypyridin-4-yl)ammo]eth-2-yl acetate (11,S g, 33.30 mrool) was combined with 5% platinum on carbon (S.O g) in B Parr flarfc. Toluene was added to the flask (120 niL) and the resulting mixture was pressurized with hydrogen atSIOkPaaf roomtemperaturefor I.hours. The reaction was complete as determined by LC/MS and HPLC, The resulting reaction mixtore was filtered through Celitef" filter agent, and the filter cake was rinsed with more toluene. The volfttiles were removed under reduced pressure, and die resulting oil was oarried on to the next st, PartF l-[2,6,7-Trimeth5-4-phenoxy-lir-imidazo[4,5-cJpyridin-I-yI]eth-2-yi Acetate l-[;(3-Aiiiino-5,5-dunetiiyl-2-phenoxypyridin-4.yI)BminD]eth-2-yl acetate (10.5 g, 33.29 nunol), toluene (100 mL), pyridine hydrochloride (0.077 g, 0.6659 mmol), and triethy! oithoacetate (9.1 mL, 49.94 nrniDl) were combined wi& stirring and the resulting mixture was heated to a gentle reflux (about 95 "C) for 1.5 hours. The reaction was complete. The resulting reactioii mixture was concentrated under reduced pressure to white solids, which were dissolved in ethyl acetate. The efliyl acetate Bohtion was wsshed wilh water (3 x) and brine (2 x), dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting solid was triturated with diethyl ethn, Qllercd off, and dried at 60 °C overnight to provide 11.1 g of pure product, i\iuch was carried on to the nc7:t step. Parte 1 -I2,6,7-Trimethyl-pheinoxy-l/J-imida2o[4,5-c]pyridin-l -yl]eftian-2-ol l-[2,6J-TriinethyMhenoxy-Iii-imida2o[4,5-r]pyridiii-l-yl]cth-2-yi acetate (11.1 g» 33.0 mmol}, mothmol (250 mL), and potasuum cariioiiate (1.14 g, 8.2S nunol) were combined with ettmng and heated to 45 "C tmder mtrngfia. The reaction was complsto aAer 30 minutes, and flie reaction mixture was concenttatcd under reduced pressure to a solid, which was dissolved in dichlorometbane. Tlie resulting solution was subjected to flash dvnmatography using 9/1 dicMoromethmie/methanol, A white solid was isolated and dried to provide 9.1 g of product. PartH l-[2,6,7-Triinettiyl-4-phenoxy-lJ:f-imidazo[4,5-c]pyridin-l->d]eth-2-yJ(3-Phenylprop-2-ynyl) Ether Sodium hydride (0.82 g, 20.48 mmol, 60% io raineral oil) and anhydrous N,N-dimetiijlfoiBiamide (20 mL) were combined and stJired for 5 mmutes imdcr nitrogen. A solution of l-i;2,6,7-trJmethyl-4-phenoxy-lH-imidazo[4,5-c]pyridin-l-yl]ethan-2-oI (5.8 e> 19.50 mmol) from Part G in N J-dimethylformaraide (30 mL) was ttien. added to the sodium hydride over 5 minutes. After stirring the resulting reaction solution for 10 minutes ai room temperature, HSDlutionof3-bromo-l-phenylpropyne(4.18g, 21.45 mmol) from Part A in N,N-dimetiiylformamide (15 mL) was added to the reaction solution, and the resulting reaction mixture was stiired for A hours and 10 minutes. Sodium hydride (0.10 g, 60 % in mineral oil) and then 3-brorao-l-phcnylpropync (1 g) were added to the reaction mixture, and after stirring for 30 minutes, HPLC monitoring of the reaction mixture indicated about 7% starting material remMning. The reaction mixture was concentrated under reduced pressure, and the resulting oil was dissolved in dichlorometiiane. The dichloromcthane solution was wasiied with saturated ammonium chloride (3 x), water (3 x), and brine (3 x), dried with magnesium sulfate, filtered, and concentrated under reduced pressure to a brown solid, wliich was triturated with diethyl ether, The resulting solid was filtered off, and a second crop was collected from the mother liquor. The combined solids were passed through a coluimi of eilica (120 'j;. 40 x 200 mm) using 95/5 ethyl acetate/dichloroinethane. A white solid (5.4 g) was isolaied and cairied □□ to tlic next step. HPLC analysis indicated the presence of about 9% starting imtKial in the white solid. Parti 2,6,7-Trimeftiyl-l-{2-[(3-phBn5p-2-ynyI)oxy]sfliyl}-lif-inudazo[4,5-s]p)'ridin-4- Etmine l-i;2,6,7-Trimoth>4'4-phcnoxy-lff-injidazo[4,5-c]pyridiii-l-yl]eth-2-yl(3-pbooylprop-2-ynyI) ethra'(5.4 g, 13.122 nimo])Jrani Part Hand ammonium acetate (54 g) were combined in a glass jmssm vessel The venel was sealed with a teflon screw cap, Had the reaction mixture was heated to 150 "C for 45 hours. The reaction was essentifllly complete, and the resulting reaction sohition was cooled with an ice bath, acidiiied to a pH of 1 with 10% hydrochloric acid, and washed with dichloromethane (3 x 500 mL). The combined organic portions were washed wifli 10% hydrochloric acid (4 x). The acidic aqueous portioos wore combined, basified wifli potassium hydroxide pellets to a pH of 14. The resulting brown solids wore filtered off and recryatallizcd from methnnol, A first crop of 0.6 E was collected for use in Example 5, and a second crap was collected and found to contain about 2% of the 4-hydroxy confound by NMR analjis. The second crop was returned to the mother liquor, and dichloromethane was added until all solids were dissolved. IM Hydrochloric acid in diethyl ether (20 mL) was added to the resulting solution, and the solids at formed were filtered of and dissolved in water, which was basiiied to a pH of 14 with potassimu hydroxide pellets. The resulting solution was washed with dichloromethane (3 x). The organic portions were combined, washed with water (2 x) and brine (2 x), dried with magnesium sulfate, filtered, and concentrated under reducedpresfiure. TheresultingwhiteBolidCl.S g) was dissolvediodicliloromefhane (150 mL), and IM hydrochloric acid in diethyl ether (5.3 mL) was added to the resulting solution, The acidified solution was concentrated under reduced pressure. The resultine solids were dissolved in water, and this aqueous solution was filtered to remove an oily sludge. The filtrate was baaified with a few drops of 20% potassium hydroxide and then IN potassium hydroxide to a pH of 13, The fine white precipitate that formed was fihered oS; rinsed with disthyl etlior, and dried under vacuum for 18 hours to provide 1.8064 g of 2,6,7-trimethyH-{2-[(3-phenylprop-2-ynyl)oxy]cthyl)-Ifl'-imidazD[4,5-c3pyridiii-4-amine,m,p. IBe.S-lSV.S-C, lesulting mixture under a nitrogen purge, and then the mixture was placed under hydrogen at a proaaurs of 310 kPs for 4 houis. The resultine reaction mixture was filtered tlirough a layer of Celite" filter agent, and the fiittale was concentraied under reduced pressure to a clear oil, The oil was diasolved in 5% methanol in diethyl ether {- 50 mL), and IM hydrochloric acid in diethyl ether (1.7 mL) was added to the resulting solution. Volatiles were removed under reduced pressure, and the resulting solids were dissolved in water. The aqueous solution was stiired for 10 minutes when the product oiled out of solution. The aqueous portion was washed with dichloromethane (3 x). The combined organic porlionE were washed with water (2 x) and brine (3 x), dried with magnesium sulfate, filtered, and concentrated to a glassy oil imrifir reduced preesure. The oil was triturated withdiodiyl other. The solids that formed after 10 minutes of stirring were filtered off and dried for 18 hours to provide 0.31 B5 gof2,6,7-trimethyl-l-[2-(3-phenylpropox'y)cthyl]-l.ff-;jnidiizo[4,5-f:Jpyridin-4-amine,ra.p. HS.3-119.0'C. Sodium hydride (0.41 g, 10.24n«nol, 60% inmineral oil) and anhydrous N,N-dimethylFormamide (10 mL) were combined and stirred for 5 minutes under nitrogen. A solution of l-[2,6J-trimethyl-4-phenoxy-lH-iimdazo[4,5-c]pyridin-l-yl]otlian-2-ol (2-9 g, 9.752 nrmol) from Part G of Example 7 in.NJ-dimethylfonnajmde(15 mL) was then added to the sodium hydride over 5 minutes. After stirring the resulting reaction solution for lOminutsE at room temperatur6,aBoIution of cinnamyl bromide (2.U g, 10.73 mmtil) in N,N-dimethylformamide (15 ml.) waE added to the reaction solution, and the rssulting reaction mixture was stirred for 4 Iiours and 10 minutss. Sodium hydride (O.IO g, 60 % in mineral oil) and tiien cirmamy! bromide (0.1 g) were added to the reaction mixture, and after stirring for 30 minutcB, HPLC monitoring of the reaction mixture indicated about 9% starting material remaining. The reaction mixture was concentrated under reduced pressure, and the resulting oil was dissolved in diobloromelbaue. The dichloromethaitf aoluiion was washed with saturated ammonium chloride (3 x), water (3 x), and brine {3 x), dried with magnesiinn sulfate, filtered, and concentrated under reduced pressrure to a white solid, which contained about 6% starting material by HPLC anaJysJB. Ths white solid was passed through a column of ailica (120 g, 40 x 200 mm) using 95/5 ethyl acolate/dichloromethane. The Isolated product was triturated with diethyl e&er, filtered off, and dried to provide 2.9 g of product with no startisg material. HUB was earned on to die next step. PartB 2,6,7-Trimeithyl-l-(2-{[(2E)-3-phenyIprop-2-enyI]oxy)ethyl)-lH-imidazo[4,5-£]pyridin-4-amine l-l;2,6,7-Trimcthyl-4-phenoxy-l/f-imidazo[4,5-c]pyridin-I-yl]eth-2-yl[(2E)-3-pheQy)rop-2-Dnyl] ether (2.9 g, 7.013 mmol) IromPart A and ammonium acetate (54 g) ware Combined in a glass pressure vesael The vessel was scaled witb a teflon screw cap, and the reaction mixture was heated ta 1 SO *C for 45 hours. The reaction was complete, and the resulting reaction Eolution was cooled with an ice bath, basified to a pH of about 13 with IN potassium hydroxide, and washed with dichloromethane (4 x 500 niL). The combined organic portions were washed wilii water (3 x) and brine (3 x), dried with magnesium sulfate, filtered, and concentrated under reduced pressure to a white solid. The resulting white solid was slowly passed through a column containing 200 g silica that had been heated with 1% dieibyi ether in dichloromethane using 9S dichlorometbane/methanol, Two crops of product were isolated from the cluted solution, and both were recrystallized fim isopropyl alcohol. The resulting white powdei' was dried under vacuum for IS hours to provide 0.7479 g of 2,6,7-trimethyUl-(2-{[(2E)-3-phenylprop-2-enyl]oxy) efeyl)-l//-imida2o[4,5-c]pyridin-4-aadne, m.p. 143.7-144.8 "C. Analysis: Calculated for CwFIiNO: %C. 71.40; %H, 7.19; Y,M, 16.65; Found: %C, 71.36; %H, 7.10; %N. 16.74. 'E NMR (300 MHz, DMSO-d} 6 7.30-733 (m, 4H), 7.20-7:25 (m, IH), 6.37 (d, J = 16.2 Hz, IH), 6.20 (dt, J = 16.2, 5.3 Hz, IH). 5.62 (s, 2H), 4,46 (I, J = 5.3 Hz, 2H), 4.05 fdd. J = 6.2,1.2Hz, 2H), 3.74 (t, J= 5.3Hz.2H), 2.51 (s, 3H), 2.36 (s, 3H), 2.28 (s, 3tl) 2,5-dimrthyI-5-nitro-6-phmoxy-N-[2 2.Methoxysthyl ethor (diglyme) (50 ml) and sodium hydride (60% in oil) (5.77 g) were combined. Under a nitrogen atmosphere, s. solution of phenol (13.58 g) and diglyme (250 ml) was added slowly over 10 minutes to allow for controlled gas evolution, 2-chloro-5,6-dimethy!-3-nitro-N-r2-(3-pyridin-3-ylpTDpoxy)ethyl]pyridiii-4-amine (35.1 g) from Part A was then added and the reaction mixture 'was heated to 90 "C, Afler 1.25 hours, the reaction mixture clouded and the terrperature was iDcrcased to 110 'C. After an additional 3.75 hours, HPLC and TIX; analysiE indicated ttie reaction was complotc. The reaction mixture was coolcid and the Bolvent was removed under reduced prcaaure. The resulting oil was dissolved in ethyl acetate and washed onco with 20% potassium hydroxide, once with IN potassium hydroxidei, 3 times with waterj and 3 times wift brine. The combined organic layors were dried with magnesium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatogrhy over siUca, eluting with 90/10 ethyl acstateybexane, The fractions containing purified product were concentrated under reduced pressure and dried undw vacuum at 70 'C ovsniit. >MR silica "using 95/5 ethyl acetate/mBthanol as the duant The jMXJduct was dried and then triturated with diefliy] eer to yield s white solid that was dried under vacuum at 80 "C ovemiL NMR analyaie of the dried solid indicated apure product. PartE 2,6,7-trinisthyl-l-p-(3-pyridiii-3-ylpn5)oxy)eiiyI]-liif-iinidazo[4,5-]pyridin-4-aaiiiie Under a nitrogtai fltmosphere, 2,6,7-trJmethyI-4-ph«io3:y-l-[2-(3-pyridin-3-ylprop£»ty)dhyl]-lfl'-iniidazo[4,5-c]pyridinB (4 g) from Part D and ammonium acetaie (40 g) were heated in a sealed tube to 1 SO "C. After 46.S hoars, NMR analysis indicated that only 7% of the starting materia) remained. The reactioQ mixture was cooled to ambient temperature, diluted wlih ethyl acetate, and washed 3 times with IN potasfiium hydroxide and once m& water. Tlie organic layeis were dried v/iHi magnesimn sul&te and atmoephorc, this product was cDmbined with enhydrous pyridine (100 ml) and pyridine HCl (0.08 g) and itic reaction mixture was cooled to 0 "C to an ice bath. Etiioxyacetyl chloride wae added drtqjwise to the reaction mixture over 5 minutes, which induced the formation of a precitate and changed the color of the solution from clear to pale yellow. Aiier 30 minutes, TLC and HPLC analysis indicated the reaction was complete. The reaction mixture was gently heated to reflux (100 °C) for 17.5 hours under 8 niti-ogen atmosphere. The mixture was allowed to cool and wag then concentrated under reduced pressure, Tlic oil was dissolved in eliiyJ iicetM& and washed once with saturated potassium cartionate, 3 times with water, and 5 times with brine. The brownish red organic layer was purified by column chromatography over silica using ethyl acetate is the eluant. The resulting oil was triturated with diethyl etlier and dried to yield a white solid. NMR and LC/MS analysis indicated sufficient purity for use ofihe product in the next step. PartB 2-(otho3C)metbyi)-6J-dimethyI-l-[2-(3-pyridm-3-ylpropoxy)efliyI]-lff-inuda2o[4,5- c]pyridin-4-Mnine Under a. nitrogen atmosphere, 2-(6thoxymcftyI)-6,7-dimctliyl-4-plienoxy-l-[2-(3-pyridiTi-3-ylpropoxy)Btiiyl]-lif-iimdazo[4i5-c]pyridme (4.6 g) from Part A and ammomum acetate (46 g) were heated in a sealed tube to ISO "C. ASLCT 65 hours, NMR anuljis indicated that the inaction was complete. The reaction mixture was couli to aoxbient SC. The resulting tan precipitate was isolated by filtration, dissolved in dichloromefliane (-3 L) and fitteired to remove some black solids. The filtrate was washed with 10% Sodium carbonate and brine, drieid over niagneBium Bulfete and then concentrated under reduced pressure to provide 272 g of a light tan solid. This solid was recrystalltzed from heptane (2.5 mL/g) to provide 248 g of 2,4-diohloro-5,6-dimcthyl-3-ratrDpyridmo as large amber rods. PaitB A solution of 5-amino-l -pentanol (28.03 g, 271,4 mmol) m N,N-diraothylfbrmamide (200 mL) was added over a period of 45 minutos to a solution of 2,4-dichloro-5,6-dimethyl-3-nitropyriduie (60.01 g, 271.4 rnmol) mNI-dimethylformoKiide. The reaction was stirred ovemigiit and then the NrN-diqie(hylformamide was removed by vacuum distillation. The residue was dissolved in ethyl acetate (500 mL), washed wifii water (4 x 75 mL), dried over magnesium sulfate and then concentrated under reduced prftBBuie. The crude product was dissolved m hot etliyl acetate (400 inL). Hexane was added until a clear solution was obtained then the mixture was allowed to cool to ambient temperatuTB. Tlie resulting precipitate was isolated by filtration and washed with cold hexEinc to provide 26. 87 g of 5-[(2-chloro-5,6-diinetfiyl-3-nitropyridin-4-yI)amiiio"JpentaE-l-ol as a solid. An additional 4.41 g was isolated from the iiltratB. bicarbonate (2 X 100 mL) and brine (1 x 100 mL), dried over magnesium sulfate and then concentrated under reduced pressure to provide 30.96 g of -(5-chloropcntyI)-2,3- diraethyl-5-mtcQ-6-phetioxypyridin-4-ainine. PartE A solution afA-(5-ciiloropentyl)-2,5-diinethyi-5-nitro-6-phenaxypyridm-4-ami)ie (30.86 g, BSmmoI) in toluene (200 mL) Was added to aPsir vessel contaiuing a mixture of niL). The pH was adjuBtod to >13 with 15% sodium hydroside and then the ■mixture was sxtractpd with chlorofonc (2 x 100 mL). The combined cKiracts were dried over magnesium sulfate aiui then concentrated under reduced pressure. The residue was purified on deactivatod silica gsl (triethylamine) cluting with IVo methanol in oblorofonn and dien recrystallized from ethyl aoatate/hexanes to provide I.0S9 g of 2,6,7-triracthyI-l- Part A Benzenethiol (2.42 niL, 23,6 mmol) was added diopwise to a suBpcnfiion of sodium hydride (0.944 g of 60%, 23,6 ramoi) in anhydrouB N,N-dimBthylfonnamide (50 mL) and fftiired until a clear solution was obtained. A solution of I-{5-chIoropcaityI)-2,6,7-triinethyl-4-phcnoxy-lff-imidazo[4,S-c]pyridine (6.5 g, 18.2 mmol) in anhydrous N,N-dinieliiylformamidB (50 mL) was added dropwiBc. Tlie reaction mixture was stirred at aiDbient temperature for 1 hours, then it was quenched with water and extracted with ethy] acetate (300 mL), The extract was washed wifii water (5 x 75 mL), dried over magnesium sulfate and then concentrated under reduced pressure to provide 7.20 g of 2,6,7-trimethyl-4-phenoxy" 1 -[5 -(phenylthio)pentyl}-lJ-imidazo[4,5-c]pyridine. Parte Mnmomnra acatatc (25 g) and 2,6,7-tiimfi8iyl-4-phenoxy- J -[5-(phenylthio)pentyl]-lH'imidazo[4,5-c]pyridine (2.50 g, 5.80 mmol) were combined and hofltt-d ai leOC in a sealed tube for 2 days. The reaction mixture was cooled to ambient tenerature and diluted with water (100 mL). Sodium hydroxide (15%) was added and tlie mixture was extracted with chlorofomi (2 x 150 mL). The combined extracts were dried over magnesium sulfate and tiien concentratEd under reduced pressure. The residue Part A Under a nitrogen atmosphere, a aolution of 2-(2-ammofittioxy)ethanol (27.8 mL, 277 mmol) in tctrahydrofitran (1 SO mL) was cooled to 0°C. Sodium hydroxide (140 mL of 2N) was added, A solution of di-rert-butyl dicarbonatc (60.27 g, 277 mmol) in tetrahydrofiiran (ISO mL) was added dropwiso over a poriod of 1 hour with rapid stirring. The reaction waa allowed to warm to ambioit tenrpcrature and stir ovcxnight. The tetiflbydrofuran was removed under reduced pressure. ThepH of the resulting Blurry was adjusted to-3 by adding sulfuric acid(150mLof IM). The mixture was extracted with ethyl acetate (fi x 100 mL). The combined extraote were washed with water (2 x 100 mL) and brine (1 x 100 mL), dried overmagnesimnaulfete and then concentrated under reduced pressure to provide 48.53 g of rert-butyl 2-(2-hydroxysthoxy)ethylt:arbamate as a colorisBB ail. Parts Under a mtrogsn atmosphere, a solution of fert-butyl 2-(2-hydroxyethoxy)BThylcart)amate (4E.53 g, 236 mmol) m anhydrous dichloromethanc (1 L) was cooled to CC. Triethylamine (49.4 mL, 354 mmol)) was added. Methanesulfonyl Parte Sodium BZide (16.8 g, 259 iomol) was added Co a solution of Z-iZ-Kten-butoxycarbonyl)amh»o]cfi)oxy)cthyl mettanesulfonate (66.9 g, 236 nunol) in N,N-dimcthylfbrmamide (400 mL). The reaction was heated at 90'C for 1,5 hours. Ths reaction mixture was allowed to cool to ambient temperature, diluted with cold water (500 roL) and then extracted witii diettiyl ether (4 x 300 mL). The combined extracts were waahed with water (4 x 100 mL) and brine (1 x 200 mL), dried over magnegium sulfite .and then concentrated under reduced pressure to provide 52 g of tert-butyl 2-(2-a2idoethoxy)ethy!caibamate. PartD A solution of rert-butyl 2-(2-azidoethoxy)cthylcarbamatc (52 g. 226 mmol) in methanol (500 mL) was added to a Parr vessel containing 10% palladium on carbon (4 g) which had been wetted with toluaie (30 mL). Hie mixture was placed under hydrogen pressure (30 pai; 2.0 X 10* Pa). After 18.5 hours analysis by thin layer chromatognhy indicated that the reaction was not complete. Catal) (0.5 g) was added and the hydrogenation was contmued for an additional 4 hours. The reaction mixture was filtered through a layer of Celite© filter aid and a glass wool filter pad. The filter cake was rinsed with a mixture of isopropanol and meliianol. The filtrate was concentrated under reduced presBure to provide tert-bntyl 2-(2-aminoethoxy)e&ylcarbamate. PartE A mixture of 2,4-dihydroxy-5,6-dimethyl-3-nihopyridine (245 g, 1.33 mol) and phosphorous oxychloride (2.2 L) vis heated at SS'C ovemit The bulk of ttie phosphorous oxychloride (1.75 L) was removed under reduced pressure to provide a blaclc oil. The oil was poured into water (2.5 L) and the mixture was cooled in an ice bath to S'C, The resultmg tan precipitate was isolated by filhon, dissolved in dichloromethane (~3 L) and filtered to remove some black solids. The filteate was washed with 10% chlorids (20.10 mL, 260 ramQ]) wag added dropwiae over eperiodof 10 nunutes. The reaction was allowed to warm to ambient tanpBrature and stir ovemi. The reaction was quendiBd with saturated sodhnD hicaibooBte ablution (500 mL). The organic layer was waahfid with watw (3 x 500 mL) sad brine (1 x 500 mL), dried over sodium sulfate and then concentrated under reduced pressure to provide 66,9 g of 2~ {2-[{tBn-butaxycBrbonyl)ammo]ethoxy|ethyl methanesulfonatc as abrown oil. Parte Sodium BZide (16.8 g, 259 iomol) was added Co a solution of Z-iZ-Kten-butoxycarbonyl)amii»o]cfi«)xy>cthyl mettanesulfonate (66.9 g, 236 nunol) in N,N-dimcthylfbrmamide (400 mL). The reaction was heated at 90'C for 1,5 hours. Ths reaction mixture was allowed to cool to ambient temperature, diluted with cold water (500 roL) and then extracted witii diettiyl ether (4 x 300 mL). The combined extracts were waahed with water (4 x 100 mL) and brine (1 x 200 mL), dried over magnegium sulfite .and then concentrated under reduced pressure to provide 52 g of tert-butyl 2-(2-a2idoethoxy)ethy!caibamate. PartD A Bolution of fert-butyl 2-(2-azidoethoxy)cthylcarbamatc (52 g. 226 mmol) in methanol (500 mL) was added to a Parr vessel containing 10% palladium on carbon (4 g) which had been wetted with tolnaie (30 mL). Hie mixture was placed under hydrogen pressure (30 pai; 2.0 X 10* Pa). After 18.5 hours analysis by thin layer chromatognhy indicated that the reaction was not complete. Catal) (0.5 g) was added and the hydrogenation wee contmued for an additional 4 hours. The reaction mixture was filtered through a layer of Celite© filter aid and a glass wool filter pad. The filter cake was rinsed with a mixture of isopropanol and methanol. The filtrate was concentrated under reduced presBure to provide tert-bntyl 2-(2-aminoethoxy)e&ylcarbamate. PartE A mixture of 2,4-dihydroxy-5,6-dimethyl-3-nihopyridine (245 g, 1.33 mol) and phosphorous oxychloride (2.2 L) vis heated at SS'C ovemit The bulk of ttie phosphorous oxychloride (1.75 L) was removed under reduced pressure to provide a blaclc oil. The oil was poured into water (2.5 L) and the mixture was cooled in an ice bath to S'C, The resultmg tan precipitate was isolated by filtratioQ, dissolved in dichloromethane (~3 L) and filtered to remove some black solids. The filteate was washed with 10% sodium carbonate and brins, dried over mnosium sulfete and ttien concentrated under reduced pressure to provide 272 g of a light tan solid. Tide solid was recryatallized from heptane (2.5 mL/g) to provide 248 g of 2,4-dichloro-5,5-dimethyl-3-i]itrop>Tidiiie as large amber rods. PartF A tmxture of ammomum acetate (100 g) and fcrt-butyl 2-i;2-,6,7-trini5thyt-4-phonoxy4H-iinidazD[4,5-c]pyridiD-l-yl)eaioxy]ethylcaibamate{9.85 g) was heated at leO'C for 18.5 hours. The reaction mixture was diluted wifli water (100 mL), jnade basic (pH 13) with 15% Bodium hydroxide (160 mL), saturated wifli sodium chloride d then extracted with chlcrofarm (9 x 100 mL), The combined extracts wra-c dried over magneHium sulfate and then conoentrfllsd uuder reduced pressure. AnaJysis by high perfbrmance liquid chrDinatography and NMR. showed fcat the rasidue coutaiaed about 13%DfK-{2-[2,6,7-triinethy)-4-phenxoy-l-iniidazD[4,5-e]pyridiD-l-yl)cthoxy]ethyI}acetaniide. The residue was combined with Hmmonium acetate (73 g) in a pressure vessel and heated at ISCC for 20 botzrs. The reaction was woriccd up as before. Residual ammontum acetate was removed by sublimation (high vacuum at 35°C) to provide 7.36 g of K-{2.r4-amino-2,6J-trimo&yi-I-tniidazo{4,5-c]pyridin-I-.'liflftirtwiethvU acotamide. ParlK N-{2-[4-anuno-2,S,7--trimEith>'J-l/f-iniidflzo|;4,5-c]pyridin-l-}'J)«hoxy]elhyJ>acctamide (7.3'6 g), concentrated hydrodilDric acid {45 EQL) and absolute s&iaaol (100 wL) were oomhined end heated at 90°C. AAet 26.5 hoars adiMaml ctHWentrated hydrochJoric acid (2 mL) was added. The reaction was etoppd after 20 boure and concentrated under nsduced pressure, In ontor to remove cKoess faydrochloric acid, the residue wis twice diluted with edianol (100 mL) and concHitratcd under reduced proHure. The residue was dissolved in water (100 inL) and waed with chloroform (3 x 50 mL). The aqueous layer was adjuated to pH S12with 15% Bodiuni hydroxide, In the eKflmplBB bsbw the oon>oundB were purified either by preparative bi perfomiflnce liquid chromatography (Mettiod A) or by flash chromatography (Method B). In Method A the compounds were purified by preparative hi performance liquid chromatogTHphy using a Waters FraetiDn Lynx automated pmiScation system. The prep 1 Using the method of Examples 17 - 32, tmu-2-phenylcycIopropylcarbonyl chloride was reacted with l-[2-(2-ammoeaioxy)eQiyl]-2,6,7-trimdhyl4-u cjpyridii>4-amine to provide the desired conund. The product was punfied using Method B. The ofaBcrvod accurate mass was 408.2392. Exaiiq)leB34-50 The compounds in the table below were prepared using ttic following method. The iqjpropriBte sulfony! chloride (1.1 eq.) was added to a test tube c Using tile method of Examples 34 - 50, D-(+)-10-camphorsulfbnyl chloride was reacted with l-[2 Using the mefliod of Examples 34 ~ 50,4MJimBthylamuiowob«izene-4'-sulfonyl chloride was reacted with l-[2-(2-aiiunoctiioxy)othyl]-2,6,7-triinethyI-lif-imidazo[4,5-c:]pyndtn-4-Binme to provide the desired compound. The product was purified using MothodA. The observed BccuratemaaB was 551.2551. Exanke 54 - 68 The compounds in the table below were prepared using the foUowiag method. The appropriate isocyanate (1.1 eq.) was added to a test tube containing a solution of l-[2-(2-amiiioothoxy)etIiyI]-2,6,7-trimcthyl-l.Sr-imida20[4,5-c]pyridm-4-amine (25 mg) in chloroform (5 niL). The test tube was capped, vortexed and then placed on a shaker at ambient temperature overnight (-18 hours). The solvenf was removed by vacuum contrifugation. The table below shows the structure of die free base (compounds purified by Method A were iBolated as trifluoroacet&te salts), the observed sccurats mass and the purificsation method that W&B used for that particular compound. Using the method of ExampleB 54 - 6S, tranfi-2-phEmylcycloprcipy] isocyanats was reacted wilii l-[2-(2-ammoethoxy)BfliyI]-2,6J-trimethyl-lii/'-iniida2o[4,5-c]pyridm-4- Using OK method of Bougies 54 - 68, N-methyl-N-f hencaxbamoyl chloride was reacted with l-[2-(2-amimettioxy)Bttiyl]-2,6,7-trimethyl-lff-iinidazo[4,5-c]pyridm-4-amino to provide the draired compound. The product was purified using Method A. TTie observed accurate mass waa 397.2343. Examples 72-76 The compounds in fee table below were prepared using fl« following me&od The appiDpriate iaothiocyanate (1.1 eq.) was added to a test tube conbuning a solution of I-[2-(2-arainoerthoxy)ethj]-2,6,7-trimoth>4-lfl-imidazo[4,5-c]pyridin-4-Hmine(25 mg) in chlorofomi (S xdL). The test tube was ciQsped, vortexed and then placed on a shaker at ambient temperature overnight (-18 hours). The solvent was removed by vacuum centrifugation. The tabic below shows the structure of the free base (compounds purified by Method A were isolated as trifluoToacetate salts), the observed accurate mass and the purification method that was used for that particular compound. Under a nitrogen atmosphere, metbane sulibnic Bubydride (550 mg) was tidded to a soluticmof l-[2-(2-ammodtooxy)ethyl]-2,6J-trimeth5-liif-iinidflZo[4,5-c]pyridLii-4-amine (757 mg, 2.875 mmol), tristhylamine {S20 piL) and chloroform (11 mL). The reaction mixture was allowed to stir at ambient temperature &r about 3 hours. The reaction mixture was diluted witii chlorofonn (20 mL) and washed with aaturated sodium bicarfaonate solution (10 mL). The organic layer was dried over magnoBium sulfate and solutions were washed wi& water (2 i) and brine (3 x), dried over mfignaeium sulfate, nltercd, and concentrated under reduced prcraure. Ion concantrafion, a wliite precipitate formed, and the organic solution was washed again with water (3 x !00 roL). The combined waehinge were extracted with chloroform (3 x 50 mL). The combined organic soIutionB were washed with brine (3 x 50 mL), driad over magnesium sulfate, filtered, and Under t nitrogsn atmosphere, diglyme (20 mL) was added to sodium hydride (0.548 g, 13.7 mmol), which is available as a 60% dispersion in mineral oil, and the mixture was cooled to 0 'C, A solution of phenol (135 g, 14,4 raraoT) in diglyme (20 mL) was added, and the addition flask wae rinsed with additional diglymc (2x5 mL), which was added to the reaction flaek. The reaction became homogaioous and was atirred for 30 ; bicarbonate (3 x), and Hie comhmei aqaeoos washings were extracted with cWorofonn (3 x). The combined organic soluticinK ware driod over sodium sulfate, filtered, and conoentrated under reducsd pressure to provide a white powder. The powder was dried for three days under vaouiUE at room temperature to provide 4,01 g of//-{4-[2-(bonzylo>:y)ethyIainino]-6-methyI-2-phenoxypyridiii-3-y!}-2-e&oxyac6tamide as a whits i BoUd. PartH Ammonium acotate (25 g, 0.32 mol) and l-[2-(benzyloxy)aJhyl]-2-(Bflioxymftthyl)-6-m6th5-4-phettoxy-li?-imidazo[4,5-c]pyridine (2.5 gj 6,0 mmol) were heated at 150 "C in. a sealed tube for 22 hours. Tbo resulting solution was adjusted to pH 14 with ihs I additiOQ of 20% sodium hydroxide, and water (50 mL) was added. The mixture was atinwl fiir several boars to provide a yellow precipitate, which was isolated by filtration. The precipitate (1.75 g) was recryatalBzed from a 50:50 mixture of hexaneiethyl acotate (29 mUz), and the crystals were isolated by filtration and dried mider vacuum for 23 hours at 60 "C to provide 1.05 g of l-[2-(b8nzylo?cy)sIhy]J-2-(othox3m«thyI)-6-methyI- Under a nitrogen atrndsphere, anhydrous triethylamine t45.5 mL, 326 mraa!) and 3-liromopyridme (12.9 mL, 138 nunol) were added to a solution of/ert-butyl 2-(prop-2-yBylQxy)cthylcartamate (26.0 g, 125 mmol) in anhydrous DMF (400 mL), and tiie reaction was heated at 80 "C. Dichlorobis(triphcinylphoBphine)pBUBdiiuii (II) (1.76 g, 2.51 mmol) and coppsr (I) iodide (0.96 g, 5.02 mmol) ware then added, and the reaction was heated at 80 "C for one hour. The volatiles were removed under reduced preasyre, and the residual black oil was dissolved in ethyl acetate (500 mL). The eolution was washed with dilute aqueous sodium bicarbonate (1 x 200 mL) and brine (2 x 100 mL), dried over chlorofoim (S x 100 mL). The combined extracts woro washed with brine (2 x 100 mL), dried over magnesium suUate, iiltered, and conccnttated under reduced pressure to provide adaAoil(S.5 g). The basic solution was then extracted with chloroform for six hcmra using a contiDUous extractor. The extracts were coDCsntrated under reduced pressure to provide a yellow oil (1 g). The oils were combined and purified by distillation (108-110 "C at 2.1 X 10' Pa) to yield 7.74 g of 2-[3-(pyridin-3-yl)propoxy]Bthylanune as a pale yellow oil. PartE Undst & nitrogen purge, 5% pldtinuin on cariion (2.0 g), toluene (5 mL), and 2-propano!(SjiiL)w*» added tuft Parr vessel. Aaohtion of(6-methyl-3-mtTe-2- phBnoxypyridm-4-yl)-{2-[3-(pyridm-3-yl)propoxy]c&yl)amme(5.71 g, 14,0rainol)iD toluene (45 mL) was then added. The vsasol was placed under hydrogen pressure (49 psi. 3.4 X 10* Pa) for three hours. An analysis by liquid chroraatography/mass spectrometry indicated the presence of starting material, and additional 5% platinum on carbon (0,1 g) Ammoniian acetate (27.0 g, 0.350 mol) and 2-(ethoxymetiiyl)-6-methy]-4- phflnoxy-l-{2-[3-(pyridm-3-yl)propoxy]etiiyl}-lJif-imiiiazoI4,5-c]pyridme (2.72 g, 6.09 mmol) -WBTB heated at 155 *C in a scaled tube for 21.5 hours. The solution was allowod to cool to room tenqjerature and adjusted to pH N with the addition of 1 N Bodium hydroxide, The Bolutionwaa extracted with dichloromothane (3 x). The combined HrtTBcts ware washed with water (3 x) and brinD (3 x), dried over sodium sulfate, filtered, and concentrated under reduced preasure to provide 2.19 g an amber-cobred oil. The crade oil was purified by column ohromatography on ailica gd (200 g, cluting wi& 89:11 ethyl acctats:mcthaiK>I) to provide 0.SS8 gof an oil. The oil was dissolved in2-propanol tietted with a 1.0 M flolutkm of bydrochloric acid in diethyl ether (4.64 niL), and the resulting aalt was lecrystallized from l-ptop&nol. The aalt was treated with aquwus temperature. The volatilcs were romoved under reduced pressure, end the nsidue was disBolved in ethyl acetate (100 mL). The solution was washed with saturated aqueous ammonium chloride (! x 50 mL), 1 N patassium hydroxide (2 x 50 mL), and brine (2 x 50 mL), and then dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide an oil. The oil was dried for three days under high vacuum at room temperature to provide 4.7 g of (2,3-dimeyl-5-nitro-6-phenoxypyridiri-4-yI)-{2-[3-(l ,3-thiazoi-2-yI)propoxy]ethyl}amin6 as an oil. PartD 7.89 mmol) wers heated at ISO 'C in a sealed tube for 29.5 hours. The resulting solution was allowed to cool, and ttiB pH was adjusted to 14 with Qie addition of 1 N potassium hydroxide. The solution was atiired for one hour and was (haa extracted with ethyl acetate (1 X 200 mL). The extract was washed with 1N potaasium hydroxide (3 x 50 mL) and brine (3 x 50 niL), dried over magneaium sulfate, filtered, and concentrated under reduced pressure to provide a brown solid. The solid was triturated with diethyl eflier, isolated by filtration, and purified by column chromatogry on silica gel (1 OOg, eluting with 96:4 dichloromeflianeOTflthanol) to provide an oil, which was triturated with hexane to form a solid (0.60 g). The solid was dissolved in ethyl acetate, filtered through a 4 fun syringe filter, and concentrated under reduced pressure to provide a solid. The solid was triturated with hejcane, isolated by filtration, and dried to provide 0.446 g of 2-(ethoxymBthyl)-6,7- yI)propoxy]oQiyl}pyridinc-3,4>diamine is described in Example 82, parts A through D, Under a nitrogen atmosphere, a solution of S.e-dimethyl-phenoxy-W4- {2-[3-(l ,3-thiazol-2-yI)prc?poxyJeQ]yl}pyridine-3,4-diaiiiine (2.9 g, 7.3 mmol), pyridine hydrochloride (0.017 g, 0.145 mmol), and triethylotthofonnate (1.8 mL, 11 mmol) in toluene (75 mL) was heated at reflux for 30 minutes. The volati'Iee were removed under reduced pressure, and the residue was dissolved in dichloromethane. The resulting solution was washed with saturated aqueous sodium bicarbonate (2 x 20 mL) and brine (2 x 50 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide an oil- The oil was triturated with diethyl ether to form a solid that was isolated by filtration, to provide 2.15 g of 67imothyM-pheiiCKy-I'{2-[3-(13-thia2ol-2-yl)propoxy]ethyl}-lff-imidazo[4,5-c]pryridine as an off-white powder. provide a yollow oil [63-2 g). The oil was purified by distillation (1Q3-105 DC at 63 Pa) to yield 47.5 g of 2-(pyridin-4-ylmcthoxy)ethyIamine as a colorless oil. PartC Under a nitrogen atmosphere, triethylamine (7.4 mL, 53 mmol) was added to a solution of 2,4-dichbro-5,6-diineliiyl-3-nitcopyridine (9.78 g, 44.2 mmol) in anhydrous DMF (200 mL). 2-(Tyridm-4-yhnothoxy)ethylaraine (6.8 g, 45 mmol) was added, and the reaction was stirred at room temperature for 17,5 hours. The reaction solution was slowly added to water (1.8 L) and stirred for two hours to form a precipitate, which was isolated Under a nitrogen atmosphere, pyridine hydrochloride (0,013 g, 0.11 mmol) and triBthylorthofbrmate (1.4 mL, 8.2 mmol) were added to a solution of 5,6-dimethyl-2-phmoxy-V,-[2-(pyridm-4-yhneaoKy)ethyl]pyridineO,4-diaminB (1.99 g, 5.46 mmol) in Ammonium acetate (15 g, 0,19 mol) and 6,7-dimBlhyl-4-phcnoxy-l-[2-(pyridiD-4-ylmertM>xy)dfayl]-li?-imidizo[4,5-clpyridiiie (1.52 g, 4.06 mnn]) were heated at 155 °C in a sealed tube fei 23.5 hours. The solution was allowed to cool to room temperature and adjusted to pH 14 with the addition of 1N sodium hydroxide. The solution was extracted with diehloTomethane, and the combined extracts were washed with aqueous sodium bicarbonate (1 x), water (1 x), and brine (2 x), dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide an orange solid. The solid was recrystalHzed from acetonitrile and then from 2-propacol to yield 0,407 g of a white solid, which was further purified by column chromatography on silica gel (treated with diethylamine, eluting with 95:5 dichbromethaneimothanol}. The product was washed with water, isolated by filtration, end dried ID provide 0.247 g of 6,7-dimeuryl-l-[2» (pyridm-4-yhnethOTy)emyl]-lif-hiudazo[4,5-c]pyridiiHV-amiM as a white powder, mp 195-196 °C. 'HNMR(300 MHz,DMSO) 6 8.45 (d, J- 5.6HL, 2H), 7.93 (6,1H), 7.14(d, J~6.2Hz, 2H), 5.75 (s, 2H), 4,56 (t, /=■ 5.3 Hz, 2H), 4.51 (s, 2H), 3.7? (t, J- 5.3 Hz, 2H), 2.35 (s, 3H),2.30(s,3H); MS (APCI) m/z 298 (M 4 H)+; Anal. Calcd for CfHisNsO: C, 64.63; H, 6.44; N, 23.55; Found: C, 64.42; H, 6.64; N, 23.31. Under a nitrogen atmosphere, tetrahydrofuran (THF) (150 niL) was cooled to 0 °C. Sodium, hydride (9.30 g, 233 mmol), available as a 60% dispersion in mineral oil, was added with stirring. A solution of phenol (21.1 g, 225 mmol) in THF (80 mL) was added dropwiBP over a period of one hour. A solution of 5-(2-chloro-5,6-duiiethy]-5-mtropyridin-4-ylamino)pentaD-l-ol (44.5 g, 155 mmol) in THF (80 mL) was then added dropwiae over a period of 40 minutes. The reaction was allowed to warm to room temperature and heated at reflux overnight. An analysis by thin layer chromatography (TLC) indicated that the reaction was incomplete. Additional reagent was prepared as described above by adding phenol (7-1 g, 75 mmol) to sodium hydride (3.2 g, 80 mmol) in A solution of sodium dithionite (90.5 g, 520 rmnol), available as approximately 8S% pure sodium hydrosulfite, in water (200 mL) was added to a solution of (5-chloropentyI)-(2-dimethyl-5-nitn>6-pheaoxy-pyridinyl)amine (37.8 g, 104 nnnol) in ethanol (575 raL), and the mixture was stirred rapidly for five hours. The mixture did not became homogeneous, and additional ethanol (200 mL) was added. The mixture remained heterogeneous and was separated into two batches. A solution of sodium dithionite (40 g, 230 mmol) in water (150 mL) was partitioned evenly between the two batches, and the reactions were stirred for an additional hour. An analysis by TLC indicated that the reactions were complete. A white solid was removed from the reaction Under e nitrogen atmosphere, a solution of 4-chlorobenzenethiol (868 nig, 6,00 ramol) in DMF (5 mL) was added to a mixture of sodium hydride (60% dispersion, 240 mg, 6.00 mmol) in DMF (15 mL); the reaction became homogeneous and was stirred for 15 minutes. Solid l-(5-cblorop«jtyl}-e,7'imemyI-pheiioxy-2-propyl-ljy-imidaxo[4I5-c]pyridine (1.93 g, 5.00 mmol) was added in small amounts, and the reaction was stirred for 1.5 hours. Water (25 mL) was added, and the resulting solution was extracted with ethyl acetate (3 x 50 mL). The combined extracts were washed with water (5 x 30 mL) and brine (2 x 10 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a colorless oil, which crystallized overnight. The solid was dried for three hours under high vacuum to provide 2.58 g of 1 -[5-(4- crude product was purified by column chromatography on silica gal (eluting with 94:5:1 dichloromethaneiniethariolitristhylaaiine) to provide £ product that was impure as determined by HPLC analysis. A second purification by column chromatography on silica gel (eluting with 96:3:1 dicbtoromethane:methsnol:triethylmnine) also resulted in impure material. The solid was recrystallized from acetonitrile, and the crystals were isolated by filtration, washed with cold acetonitrile and ethyl acetate, dried under high vacuum to provide 0.53 g of l-[54-chlorobenzraesul&nyl)pontyl3-6,7-dimeQiyl-2-propyl-lff- imidazo[4,5-e]pyridin-4-anrbic as white needles, inp 147.0-149.0 °C. NMRPOO MHz, CDCI3) 8 7.83 (d, J- 8.6,2H), 7.55 (d, J= 8.6,2H), 4.S2 (brs,2H), determined by nuclear magnetic resonance (NMR) spectroscopy analysis. The solid was dissolved in hot 2-propanol and treated with one equivalent of a 1 M solution of hydrochloric acid in diethyl ether, Chloroform and water were added, and the aqueous layer was extracted with chloroform (3 x). The combined organic solutions were dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide & solid, The solid was stirred with 2-propanoJ, isolated by filtration, washed with cold 2-propanol, and dried under high vacuum. The solid was men dissolved in dichlorometriane (loo mL), and the resulting solution was washed with 1 M sodium hydroxide (2 x 40 mL). The basic solution was extracted with dichloromemane (2 x 30 mL), and the combined extracts were Ammonium acetate (15 g, 0.20 mol) and 6,7-dimBthyl-4-«a»xy-2-propyl-l-[5-(pyridine--sionyOpeiOH-imidazoS-cJjyridine (1.54 g, 3.13 mmol) were heated at 160 "Ciiia waled tube for 16 bona. The solution was allowed to cool to room temperature and partitioned between chloroform (30 raL) and 1 M sodium hydroxide (30 mL), The aqueous solution was men extracted with chloroform (3 x 30 mL). The combined organic solutions were washed, dried, filtered, and concentrated as described in Example 85 to provide 1.47 g of an off-white foam. The crude product was recrystallized from acetanitrilfi to provide 672 mg of 6,7-lmiethyl-2-propyl-l-[5-(pyridme-2-siilfbnyl)pentyl]-lff-iniida2o[4l5]pyridmamme as a white powder, mp 143.0-144.5 added (18 g, 0.23 rool), and the reaction was continued overnight at 160 "C. The solution was allowed to cool to room temperature and partitioned between chloroform (100 mL) and 1 M sodium hydroxide (75 mL), Following the work-up, the crude product (1.37 g) was purified by column chromatography on silica gel (eluting with 97:3:0.1 dichloromdhaneimethanohammoruiim hydroxide) and then recrystallized from acetonitrile to provide 0.715 g of l-[5-(bonzeoeaulfon:yl)pentyl]-6,7-dimethyl-2-propyI-li?-inadazo[4»5}pyridiD-4-amine at a white powder, nm 134.0-136.0 °C with a phase 4-[(2ChlorD"5f6-diffl6tey3-iutrop}ddia-4-yl)flmin£>3butaa-l -ol (20.00 g, 93.07 mmol) and additional dioxans (-30 mL) ware added. The reaction mixture was heated at reflux for 3 hours and then allowed to stand at ambient temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was diluted with water (200 mL) and then extracted with ethyl acetate (300 mL). The extract was washed with water (2 x 100 mL) then with brine, driad over magnesium sulfate, filtered and then concentrated under reduced pressure to provide an oil. The oil was purified by flash PartE The oil from Part D was combined with toluene (90 mL), trimethyl orthobutyrate (6.04 mL, 148 mmol), and pyridine hydrochloride (0.9 g). The reaction mixture was heated at reflux for 30 minutes; frimetby] orthobutyrate (1 mL) was added and the reaction mixture was heated at reflux tor 1.5 hr and then allowed to cool to ambient temperature, The reaction mixture was diluted with ethyl acetate, washed sequentially with water and e white solid. PartH Ammonium acetate (45.24 g) and l-[4-(mdbesulfonyl)butyl]-67-dimethyl-4-pbanQxy-2-propyl-lif-imidazo[4,5-c]pyridine (3.77 g, 9.07 mmol) were combined and heated at 160 °C for about 19 hours. The reaction mixture was allowed to stand at ambient temperature for 2 days. The reaction mixture was partitioned between dichloromethane (300 mL) and water. The layers were separated The aqueous layer was made basic with 5% sodium hydroxide and then extracted with dichloromethane (2 x 100 mL). The combined organics were washed with aqueous 5% sodium hydroxide, dried over sodium sulfate, filtered and then concentrated under reduced pressure to provide a white solid. Thia material wtirecryataUzed from acetamitrito to pro TbiB material was further purified by flash chromatography (silica gel, during sequentially with 1 % methanol m dichloromethane coatauung .0.1 % ammonium hydroxide, 2 % methanol in dichloromethane containing 0.1 % ammonium hydroxide, 4 % methanol in d!icWottnuethane containing 0.1 %ammoniuin hydroxide and 10% methanol in mchtoromethane containing 0.1 % amraonium hydroxide) to provide a white solid. This Thionyl chloride (2.86 mL, 39.2 mmol) was added to a chilled (0 °C) solution of 3-[(2(3-dimeth)4-S-nim3-6-phcinoxy[>yridin-4-yl)amino]propaii-l-ol (11.3 g, 35.6 mmol) in dichloramethans (\ 70 mL). The reaction mixture was atirred at ambient temperature for 0.5 hr and thm heated at reflux for 0.5 hr. The reaction mixture was allowed to cool to ambient temperature. A precipitate was isolated by filtration and then dried under vacuum PartG Using the general method of Sample K9 Part G, 6,7-dimethyi-I-[3-(mofcyl1hio)prapyI]-plimoxy-2-propyl-lH-imida2of4f5-c]pyridine (3.41 g, 9.23 mmol) was oxidized to provide 2.39 g of l-[3-(mothanesulfonyl)pTopyl]-6J-dimothyl-4-phenoxy-2-propyl-lH-imidazo[4,5-cjpyiidbie as a white solid. PartH Using the general method of Example 89 Part A, 6-ammohexan-l-ol (15.91 g, 135.7 mmol) was reacted with 214-dichloiD-5J6-dimothyl-3-nitropyridme (30 g, 136 mmol) to provide 14.79 g of 6[(2-chloro-5,6-dimcthyl-3-nitiyridm-4.yr)amino]hcxan-l-ol HE a yellow solid. PattB Using the general method of Example 90 Part B, 6-[(2-chloro-5J6-dimethy]-3-nitropyridin-4-yl)amino]hexan-l-ol (14,00 g, 46.39 mmol) was reacted with sodium Uiring the general method of Example 89 Part E, the material froni Part D was reacted with trimethyl orthobutyrate (4.86 mL, 30.3 mmol) and purified to provide 2.4 g of H6-chlorohexyl>6J-draethylphmoxy-2- as an off- white solid. PartF Ufling the general method of Example 89 Part F, l-(6-chlorohexyl)-6,7-dimethyl-4-pheiwxy-2-propyl-lff-imidazo[4,5-c]pyridinfi (2.0 g, 5,0 mmol) was reacted with sodium PartC Under a nitrogen atmosphere, a solution of potassium carbonate (28.46 g, 205.9 mmol) and sodium dithionite (32.26 g, 185.3 mmol) in water (100 mL) was added dropwise to a solution of the material from Part B (13. B g, 42 mmol) and dioctyl vioiogen (1,17 g, 2,06 mmol) in dichloromethane (275 mL) and water (35 mL). The addition funnel was rinsed wife additional water (37 mL), which was added to the reaction. The reaction was heated at reflux for three hours. The aqueous layer was extracted with dichloromethane (3 x 50 mL), and the combined organic solutions were dried over sodium sodium hydroxide (100 mL) and solid Bodium hydroxide until the solution axhibitod a pH of 14. The solution was extracted with chloroform (3 x 80 mL), and the combined extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide 1.8 g of the crude product as a white foam. The crude product was purified by column chromatography on silica gel (eluting with 98:2 chlorofornrmethanol) and recrystallized fiom ethyl acetate:hoxane. The solid wns triturated with ethyl acetate and dried at 70 °C in a vacuum oven overnight to provido 0.57 g of l-[5-(4- Example 93-96 The general methods described in Example 92 wore used for Examples 93-96. The reagent selected in lieu of 4-chlorobenzenethial in Part E of Example 92 is shown in the table below for Examples 93-96, The oxidation products from Part E were purified by trituration with ethyl acetate. A description of the isolation of the final compounds, obtained after Part F, follows. The etude product was purified by flash chromatography on silica g©J (eluting with 98:2 cMorofbrmirnethanol) to yield a colorless oil that was reerystallized from acetoniriile. After the product was dried under reduced pressure, 0.72S g of the product was obtained as a white powder, mp 130.5-132.0 °C. Examples 97-99 The general methods described in Example 92 were used for Examples 97-99. ID Part K 3-amino-l-propanol was used in lieu of 5-amino-l-pontanol. The purification in Part D was carried out by column chromatography on silica gel (suiting with 95:5 chlorofotm:m6thanol) followed by trituration with ethyl acetate;hexane. The thio] selected in Part E of Example 92 is shown in the table below for Examples 97-99, The oxidation products from Part E were purified by trituration with ethyl acetate. Example 97 l-[3 4-amine The crude product was trituratBd with ethyl acetate and dried at 60 °C under high vacuum for three days to provide 1.037 g of fee desired product as a white powder, mp 186.5-188.0 °C. Example 98 6,7-Dmiethyl-2-propyl-l -[3-(pjTJdine-2-snlfDnyl)pmpyl]-I ff-imidazo[4>chdtn-4- aroins The crude product was rscrystaUized from acetonitrile and Oven, purified by column chromatography on a Biotage Horizon1" Higb-Perforaiance Flash Chromatography instrument A second recrvstaUiiation from acetonitrile provided 0.1 SO g of the desired product u a off-white powder, mp 172.0-173.5 "C. !HNMR(300 MHz, CDClj) 6 8.69 (ddd, J-4.7,1-7,1.0,1H), 8.09 (ddd, J« 7.8,1.2, 1.0,1H), 7,98 (ddd, J= 7.8,7.8,1.7,1H), 7.57 (ddd, J-7.8,4.7,1.1,1H), 4.83 (br s, 2H), 4.42 (dd, J* 7.9,7.9,2H), 3.49 (dd, J- 7.3,7.3,2H), 2.77 (dd, /= 7.7,7.7,2H), 2.42 (s, 3H), 2.38 (a, 3H), 2.29-2.17 (m, 2H), 1.92-1.78 (m, 2H), 1.06 (t, J= 7.4,3H); MS (APCI) m6 388 (M +H)4; Anal. Calcd for CISHJJNSOJS: C, 58.89; H, 6.503; N, 18.07; Found; C, 58.51; H, 6,37; N, 17.80. Example 99 4-[3-(4-Amino-6,7-dimethyl-2ropyl-limida20[4,5]pyridin-l *yl)propane-l -sulfonyl]benzoic acid ethyl ester Ethyl-4-mercaptobenzoate was prepared by treating 4-mercaptobenzQic acid (1.50 g, 9.73 mmol) with ethanol (97 mL) in the presence of catalytic concentrated sulfuric acid under a nitrogen atmosphere. The reaction was heated at reflux for three hours. The volume of the reaction was reduced to 10 mL under reduced pressure and then partitioned between water (100 mL) and ethyl acetate (100 mL), The aqueous layer was extracted with ethyl acetate (3K 100 mL), and the combined organic solutions were washed with water (75 mL) and saturated aqueous sodium bicarbonate (2 x 75 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide an oil. The oil was dissolved in dichloromethane (100 mL), and the resulting solution was extracted with saturated aqueous Hodium carbonate (3 x 100 mL). The combined extracts were washed with dichloromefliane (3 % 50 mL) and then treated with concentrated hydrochloric acid to adjust to pH 7. The solution was then extracted with dichloromethane (3 x 100 mL), and the combined extracts were washed with water (50 mL), dried over pressure, and the residual solid was dissolved in water (60 znL). The solution was washed with dicbJaromethane (2 x 20 mL) and ethyl acetate £20 mL) and then treated with concentrated hydrochloric acid to adjust to pH S. A precipitate formed, which was isolated by filtration and dried overnight in a vacuum oven at 60 "C. The material was treated with 1 M hydrochloric acid in diethyl ether, and then the solvent was removed under reduced pressure. The resulting white solid was recryBtallized from efhanol, and the crystals were diaolved in a mixture of 1N hydrochloric acid and methanol with gentle heating. The solution was concentrated under reduced pressure, and the resulting solid was dried at 80 "C under high vacuum to provide 240 mg of 4-[34-arnirio-6f7- 2-propyl-lff-iimda»[4,5-c]pyrfdin-l-yl)pT acid hydrochloride as a white powder, mp >250 °C. lHKMR (300 MHz, DMSO-rfs) 6 8.18 (d, ./=■ 8.6,2H), 8.03 (d, J= 8.6,2H), 7.79 (br s, 2H), 4.41(dd, J" 7.7,7.7,2H), 3.65 (dd, J- 7.3,7.3,2H), 2.79 (dd, /« 7.7, 7.7,2H), 2.41 (B, 3H), 2.29 (s, 3H), 2.034.91 (m, 2H), 1.81-1.69 (m, 2H), 0.96 (t, J» 7.5,3H); MS (APCI) m/z 431 (M + H - HC1)+; Anal. CalcdforCuHtfCINS: C, 52.01;H, 5.92;N, 11.56; Found: C, 51.62;H, 5.86; N, 11.41. two hours and become homogeneous. The solvents were removed under reduced pressure, and tho residual white solid was dissolved in water (50 mL). The solution was washed with ethyl acetate (3 x 10 mL) and then adjusted to pH 4 with the addition of concentrated hydrochloric acid. A white solid precipitated, which was isolated by filtration, washsd with water, and dried for three hours in a vacuum oven at 60 °C to provide 2.26 g of 4-[3-(S,6-&Tay\-i-pKppyi-lHAaMa[]XtsOB2ah[\ ,5-a]pyridin-7 ■ yl)propane-l -Bulfonyl]beazoic acid as a white solid. Pert A The general method described m Port A of Example 80 was followed using 2-(2-aminoethoxy)ethanol (46.0 mL, 458 mmol) in lieu of etiuuiolamine to prepare 90,0 g of rert-butyl 2-C2-hydroxyethoxy)ethylcarbamatB as a colorless oil. PartB Under a nitrogen atmosphere, a solution of rert-butyl 2-(2-hydroxyethoxy)ethylcarbamate (89.0g, 434 mmol) in dichloromethane (1,5 L) was cooled to 0 »C; triethylamine (90.7 mL, 650 mmol) was added dropwiae. Methanesulfonyl chloride (36.9 mL, All mmol) was then added over a period of 45 minutes. A precipitate framed, and the reaction became yellow. The reaction was allowed to warm to room temperature and stirred overnight. Saturated aqueous sodium bicarbonate (750 mL) was added. The organic layer was then sequentially washed with water (3 x 500 mL) and brine (250 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 119.2 g of 2-{2-[(«rt-butoxycarbonytyamino}elhoxy}e£hyl methanesulfbnate as a light orange oil. Parte Under a nitrogen atmosphere, sodium azide (29.8 g, 458 mmol) was added to a solution of 2-{2-[(ferf-butoxycBjbonyl)armno]emoxy}ethyl metbanesulfonate (118 g, 416 mmol) in DMF, and the reaction was heated at 90 °C for six hours. The reaction was allowed to cool to room temperature overnight, and then the solvent was removed under reduced pressure. Water (1 L) was added, and the remitting solution was extracted with diethyl ether (4 % 500 roL). The combined extracts were washed with water (1 x 250 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to yield 93.0 g of/art-butyl 2-(2-azidoeiBrjxy)erhylcarbflmate as a coloriess oiL PartD Under a nitrogen purge, 10% palladium on carbon (9,2 g) was added to a solution of «rt-butyl 2-(2-aridoefeoxy)otb.ylcarbamate (92.0 g, 399 mmol) in toluene (900 mL) in a pressure vesae!- The vessel was placed under hydrogen pressure (30 pgi, 2.0 it 10s Pa), and for the first 20 minutes, the hydrogen was replaced every five minutes and brought to a pressure of (20 psi, 1.4 x10s Pa). The reaction was mahtfahwd raider hydrogen pressure (20pa, 1.4 x 10s Pa) overnight. Th» reaction mixture was filtered through a layer of CELTTE filter aid, and thefiltor cake was washed with etbsnot. The filtrate was ooncentrated under reduced pressure to yield 77.4 g of terf-butyl 2-(2- Under a nitrogen purge, 5% platinum on carbon (2.5 g) was added to a Parr vessel containing a solution of terr-bvtyl 2-{2-[(2-chloro-5,6-dinieQiyI-8-nitrotetrazolo[l,5-c]pyridlr>7-yI)ammo]e1haxy}emylcarbamate (25.0 g, 63.2 mmol) in toluene (500 mL). The vessel was placed under hydrogen pressure (30 psi, 2.0 x 10* Pa) for four hours, and then 2-propanol (50 mL) was added. The reaction mixture was filtered through a layer of CELTTE filter aid, and the filter cake was washed with 2-propanol (500 mL) and ethanol (500 mL). The filtrate was concentrated under reduced pleasure to yield 22.9 % often* butyl 2-{2-[(8-ammo-5,6-dim«th>4t«ra2olo[l,5-o]pyrid1n-7-yl)anrino]emoxy}emykarbamite as a brown oil. PartH The general method described in Part E of Example 85 was used to convert tert-butyl 2-{2-[(8-ajmo-5,6-diinethyhrazolo[l,5wi]pyridin-7' yl)ammo]ethoxy}ethylcarbamate (22.8 g, 62.4 mmol) to terf-butyl 2-{2-[(8-ethyI-S,6-dmiemyl-7/f-iraidazot4,5-c]tetraazolo[ l,5-fl]pyridm-7-yl)]emoxy} cthylcarbamate, Triethylorthopropionato (13.2 mL, 65.5 mmol) was used in lieu of trimethylorthobutyrate. The crude product was obtained as a light brown solid (20.2 g), which was stirred with water (500 mL) for 15 minutes, isolated by filtration, and dried overnight in a vacuum oven at B0 °C» to provide the desired product, mp 186-188 °C, which was used without further purification. Parti A solution of trifluoToacetic acid (188 mL, 2.44 mol) in dichloromefhane (300 mL) was cooled tD 0 °C. A solution of retf-butyl 2-(2-[(8-ethyl-5,6-dimethyl-7ff-iraidaBo[4,5-c]tetrazob[l,5-clpyridin-7-yl)]ethoxy}ethylcarbamate (19.7 g, 48.8 mmol) in dichloromethane (300 mL) was then slowly added over a period of 30 minutes, and the reaction was stirred overnight The volatiles were removed under reduced pressure, and the residual brown oil was stirred with 2-propanol (300 mL) to form a white salt, which was isolated by filtration and dried in a vacuum at 80 *C. The salt was dissolved in water (200 mL), and solid sodium carbonate was added to adjust to pH 12, The solution was extracted with chloroform overnight with a continuous extractor. The extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 11.5 gof2-[2 Examples 103 and 104 2-[2H8-Eft>d-5,6Hefcyl-7iif-iniidazo[4,5-c]tBtrazolo[l,5-a]pyridiii-7-y])ethoxy]ethytamine was obtained as described inParts A through I of Example 102. Under a nitrogen atmosphere, a solution of 2-[2-(B-ethyl-5,6-dunHthyl-7H-miiiia2o[4,5-c]tetraazolo[l,5-a]pyridin-7~yl)ethoxy]ethylarnine (1 equivalent) and in dichlororoethane was cooled to 0 8C; triethylamine (1.1 equivalents) was added. The acid chloride (LI equivalents) selected from the table below was then added dropwise, and the solution was allowed to warm to room temperature and stirred for several hours. The reaction was washed with 5% aqueous sodium hydroxide (200 mL), and (he aqueous layer was extracted with dichloromethane (2x200 mL). The combined tetanic solutions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a white solid, which was treated using the genera! method described ia Part F of Example 92 and purified as described below. 2-[2-(8-Bthyl-5,6-dimethyl-7/r-iniidBzo[4-e]tetiBii2olo[ 1,5-a]pyridin-7-yl)othoxy]cthylamine (2.00 g, 6.59 ramol) waa obtained as described in Parts A through I of Example 102 and treated using the method of Part J of Example 102 with 3-chloropropaneBulfbnyl chloride (0.88 mL, 7.25 mmol) used in lieu of methanesulfonyl chloride. The crude product was purified by column chromatography on silica gel (100 mL, eluting with 95:5 dichloromethane methanol) to provide an amber oil, which was triturated with diethyl ether, The product was isolated by filtration to provide 2.62 g of 3-chlOTO-AK2-[2-(8-emyI-5,61imethyl-7#-i yl)afooxy]dhyl}propane-l-sulfonarmde as a white solid, m. p. 126-129 °C. PartB Under a nitrogen atmosphere, l,8-diazabicyclo[S.4.0]undecene-7 (4.2 niL, 28 mmol) was added to a solution of 3-chloro-Ar-{2-t2-(8-athyl-5,6-dimethy!-7i?- mp 157-159 BC. 'H NMR (300 MHz, CDC13) 6 4.86 (B, 2H), 4.44 (t, /= 5.4 Hz, 2H), 3.74 (I, J- 5,4,2H), 3.57-3.51 (m, 2H), 3.13-3.08 (m, 2H), 3.04-2.97 (m, 2H), 2.89 (q, J= 7.S, 2H), 2.87 (t, J = 6.8,2H), 2.44 (s, 3H), 2.42 (s, 3H), 2.19-2.08 (m, 2H), 1.41 (t, J= 7.5, 3H); MS (APCI) m£ 382 (M + H)+; Anal. Calcd for Ci7HarNjCfeS«0.50 HzO: C, 5279; H, 7.23; N, 17.93. Found: C, 52.54; H, 7.49; N, 18.02, high vacuum to provide 0,54 g of N-{2-t2-2-cfliyI-6J7-dimethyl-li/-imidazo[4,5-c]pyridin-l-yl)athoxy]ethyl}-A',-bein2oylureaaBawhitesolid,mp lg5-187°C. 'HNMR (300 MHi, CDC13) B 8,98 (br s, 1H), 8.87 (br t, 1H), 7.93-7.87 (m, 2H), 7.63-7.56 (m, IH), 7,52-7.44 (m, 2H)! 4.84 (s, 2H), 4.45 (t, J= 5.8 Hz, 2H), 3.76 (t, J= 5,8,2H), 3.57-3.46 (m, 4H), 2.91 (q( J" 7.5,2H), 142 (s, 6H), 1.41 (t, J- 7.5,3H); MS (APO) m£425 (M + H)+; Anal, Calcd for CMH:gN6O3»0.25 H20: C, 61.59; H, 6.70; N, 19.59. Found: C, 61.25; H, 6.90; N, 19.72. c]pyridin-4-amine (1.45 g, 5.23 mmol), obtained as described in Part A of Example 107, was treated with benzenesuUbnyl iaocyanate (0.70 mL, 5.2 mmol) using a modification of the method described in Example 105. The crude reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluting with 79.5:19.5:1 dicMoromeumeimothanoLtridhylairiuie) to provide a white solid. The8oUd(1.05g)wasstmwith90:10dicbJoromethane:meflianol(4Oa5L), isolated by filtration, and recrystallized from DMF(IOIBL) to provide 0.41 gofN-[({2-{2-(4-arnmo-2-etbyl,7-dimethyl4ff-imidazo[4,5-c]pyridiD-l -yl)ethoxy)emyl}amir»)carboiiyl]beoBnesulfonaniide as a white solid, mp 201-203 °C. MS (ESI) mh 461 (M + H)+. removed under reduced pressure. The residual oil was treated with aqueous hydrochloric acid (50 mL of 1 M) and stirred for 30 minutes; a white precipitate farmed. The solution was then washed with dichtoromelhane (3x2 mL), treated with 1 N aqueous potassium hydroxide to adjust to pH U, and cooled to near 0 °C. The product precipitated and was isolated by filtration, washed with diethyl ether, and dried under reduced pressure. The resulting solid was washed with water, isolated by filtration, washed with diethyl ether, end recrystalHzed from toluene, The solid was dissolved in methanol, and the Eolation was concentrated under reduced pressure. This was repeated three times before the solid was finally triturated with diethyl ether and isolated by filtration to provide 2.17 g of 2- (etboxymeu\yl)-6,7-dimeftyl4-[2-(pyridinyiniethoxy)eQiyI]- l#-umdazQ[4,5-e]pyriduv 4-amine as small tan crystal*, mp 143-145 °C. 'H NMR (300 MHz, DMSO) 8 8.45 (d, J= 6.2 Hz, 2H), 7.11 (d, J- 5.6 Hz, 2H), 5.80 (s, 2H), 4.69 (s, 2H), 4.61 (t, J- 5.6 Hz, 2H), 4,48 (s, 2H), 3.80 (t, J = 5.6 Hz, 2H), 3.48 {q, J - 6.9 Hz, 2H), 2.37 (s, 3H), 2.31 (a, 3H), 1.10 (t, J- 6.9 Hz, 3H); MS(APCI)m£356(M + H)+; Anal. Calcd for CipHuNjOj: C, 64.20; H, 7.09; N, 19.70; Found: C, 63.93; H, 7.43; N, 19.76. {pyrid»4-ytaiethoxy)ethyi;]tetrazolon (6.0 g, 19 ramol), prepared as described in Parts A and B of Example 109, was treated with triethylorthoacetate (3.7 mL, 20 mmol) in lieu of trimethylorthobutyrate. The crude product was triturated with diethyl ether and isolated by filtration to provide 6.07 g of 5,6,8-trmiethyl-7-[2-(pyridm4-ylmethoxy)ethyl]JH-mndBzo[4,5-c]tetra2ob[l,5-cjpyridine as a brown solid. PartB The general method of Part D of Example 109 was used to convert 5,6,8-trimethyl- 7-[2-(pyridin-ybMthoxy)ethyI]-7#- (4.44 g, 13.0 mmol) to 2.1E g of 2,6,7-trimemyl4-[2-(pyridin-4-ylmethoxy)ethyl]-lunidazo[4,5-c]pyridin-4-aniine, which was obtained as a white solid, mp 208-210 °C. Using a modification of the method described in Part A of Example 65,2-(2- was prepared. Ethanolarunte was used in lieu of 5-anuno-l-pentanol, and the reaction was heated at 60 °C for six hours. PartB Pyridine (1.0 mL, 12 mmol) and 4-dimethylaminopyridine (DMAP) (0.005 g, 0.04 mmol) was added to & solution of 22-cUoro-5t6-dime1iiyl-3*nitropyridin-4-ylatnino)athanol (0.50 g, 2.0 mmol) in anhydrous dichloromethane (4.5 mL). Under a nitrogen atmosphere, acetic anhydride (0.8 mL, 8 mmol) was added, and the yellow solution was stirred at room temperature for 1.3 hours. The volatile? were removed under reduced pressure, and the residual yellow oil was dissolved in dichloromethane. The solution was washed with aqueous sodium bicarbonate, water, and brine, and then dried over sodium BUlfate, filtered, and concentrated under reduced pressure to provide 0.55 g of acetic acid 2-(2-chloro-5,6-dimemyi-3-nitropyrid4-ylamino)emyl ester as a yellow solid. PartG The method described in Part A of Example 81 was followed. 2-(8-Ethoxymefliyl-S,6-dimethyl-7i7-irQidBZo[4,5-c]tetrazolo[l,5-a]pyridin-7-yl)e1hanol (4.98 g, 16,S mraol) was used in lieu terr-butyl 2-hydroxyethylcarbamate. 8-Ethoxymethyl-5,6-dimcthyl-7-(2- prop-2-jiijdoxyethy[>7if-imiiiiizo[4,5-c]tBtraz(>lotl15-a]pyiidine (5.5 g), containing some minor impurities, was obtained RB a white solid. PartH The method described in Part B of Example 81 was followed. S-Ethoxymsthyl-5,6- Undo: a nitrogen purge, 2-(etiioxymotbyl),7-limethyl-l-{2-[(3-p)nteudin-5-ylprop-2-ynyI)oxy]ethyl}-l-iniidazo[4f5-c]pyridiii-4-amine (0.69 g, 1.8 mmmol), prepared as described in Example 111, 10% palladium on carbon (0.1 g), and methanol (10 mL) were added to a Parr vessel. The vessel was placed under hydrogen pressure (50 psi, 3.4 x 10s Pa) for 2.5 hours. The reaction mixture was filtered tiirough a layer of CELTTE filter aid, and the filter cake was rinsed with methanol (200 mL). The filtrate was concentrated under reduced pressure to yield an oil, which was triturated with diethyl other then recrystallized from toluene (3 mL). The crystals were dried for 24 hours at 94 °C and men dissolved in methanol. The solution was concentrated to provide an oil that was triturated with diethyl ether and dried under reduced pressure to provide 0.202 g of 2-(ettttxymemyl)-6,7-dmiefoyl-l-[2-(3-p)TiOT Solid potassium acetate (0.62 g, 6.32 tnmol) was added to a solution of Ar-{2-[2-(4- aniiiio-2-]m>pyl-liy-ffiiidazo[4,5-*]pyri (1,8 g, 5.27 mmol) in acetic acid (32 mL). After the potassium acetate had dissolved bromine (1.26 g, 7.91 mmol) was added dropwise. The reaction was stirred at ambient temperature for 40 minutes at which time analysis by mis layer chromatography indicated that the reaction was complete. Excess bromine was quenched by the addition of saturated aqueous sodium bisulfite (~ 1 mL). The pH of the reaction mixture was adjusted to pH 7 by the addition of saturated aqueous sodium bicarbonate (100 mL) followed by the addition of solid sodium bicarbonate. The reaction mixture was extracted with dichloromethane (2 x 100 mL). The combined extracts were washed sequentially with water, saturated aqueous sodium bicarbonate (100 mL) and brine (100 mL), dried over sodium sulfate, filtered and men concentrated under reduced pressure to provide a brown gooey solid. This material was purified by chromatography (silica gel eluting with 95:5 Part A Using the general method of Example 113, fert-butyl2-[2-(4-amino-2-propyl-l-imidazo[4,5-c]pyridin~l-yl)othoxy]ctliylcaibaniate (0.9 g, 2,48 mmol) was brominated to provide 0.85 g of fetf-butyl 2-[24-amim>-7-bromo-2-prDpyl-lff-imida2o[4,5-c]pyridiii-l-yljethflxylethylcarbamatc as a brown foam. PartB Hydrochloric acid (1.8 mL of 4.25 M in ethanol) was added to a solution of the material from Part A in ethanol (10 mL). The reaction was heated at reflux for 1 hour and than concentrated under reduced pressure to provide a brown foam. The foam was recrystallized from ethyl acetate (13 mL) to provide 0.4 g of l-[2-(2-aminoethoxy)othyI]-7-bromo-2-|nx)pyl-lH-inudazo[4,5-c]pyridm4-ainiiie as brown rock-necdiea, mp 114 -117 "C. Anal. Calcd for CnHafirNjO: C, 45.62; H, 5.8?; N. 20.46. Found: C, 45.90; H, 5.58; N, 20.15. Triethylamine (0.07 g, 0.66 mmol) WEB added to a solution of l-[2-(2- aminoetho:)orayl]-7-bromc-2-prcpyl-Uf-imid (0,15 g( 0,44 mmol) is dichlororaethaae ( 2 mL). 4-Chlorobeiwoyl chloride (0.0° g, 0.53 mmol) was added dropwise to the reaction mixture, The reaction mixture was stirred at ambient temperature for 10 minutes at which time analysis by thin layer chromatography indicated that the reaction was complete. The reaction mixture was partitioned between dicbJoromethane (30 mL) and saturated aqueous sodium bicarbonate (20 mL). The layers were separated. The organic layer was washed sequentially with saturated aqueous ammonium chloride (20 mL) and brine (20 mL), dried over sodium sulfate, filtered and then concentrated under reduced pressure to provide 0.23 g of a clear, glassy solid. The crude material was purified by chromatography (silica gel eluting with 95:5 DiohlorobisttriphonylphosphinejslladiumCn) (0,25 g, 0.36 mmpl) and copper (I) iodide (0.14 g, 0.71 mmol) were added to a suspension containing N-{2-[2-(4-araino-7-bromo-2-pmpyI-lif-imidazo[4,5-c]pyridin4-yl)ethoxy]ethyl}methanBfonamide (1.5 g, 3.57 mmol), triethylamine (2 mL, 14 mmol), hexyne (1.23 mL, 10.7 mmol) and acetomtrile (18 mL). The reaction was heated to reflux and the progress was monitored by high performance liquid chromatography, After 2.5 hours hexyne (1 aq.), dichlDrohia(triphenylpbDsphinfi)panadiiim(II) (0.1 eq) and copper (I) iodide (0.2 eq) were added. After an additional hoar dichbrobiB(triphenylphosphine)palladium(ir) (0,1 eq) and copper (I) iodide (02 eq) were added. After a total reaction time of 5.5 or the reaction mixture was allowed to cool to ambient temperature and thai it was concentrated under reduced pressure to provide a dark oil. Hie oil was partitioned between dichloromethane (200 mL) and saturated aqueous ammonium chloride (100 mL), The organic layer was separated, washed with brine (100 mL), dried over sodium sulfate, filtered and then concentrated under reduced pressure to provide a dad: sludge. This material was purified by chromatography (silica gel ending with 95:5 djchloromethanermemano]) to provide 1.0 g of a brown oil which was found to be a 85:15 mixture of product and starting material. The oil was combined with triethytanine (1.5 eq), hexyne (I eq.), acetonitrite (5 mL), dicbioittbis(triphenyh)bnBpnine)pBlls4ium(II) (0,1 eq), and copper (I) iodide (0.2 eq) and then heated at reflux for 2 hr. The reaction mixture was allowed to cool to ambient temperature and then stirred for 20 hr. The reaction mixture was concentrated under reduced pressure to provide a dark oil. The oil was purified by chromatography (silica gel eluting with 95:5 dichloromemane:methanoI) to provide N- {2-[24-amin6-7-hex-l-ynyl-2-propyl-IH-inudBzo.S-cpyridin-l-yOedioxylethylJmethaiwsul&naraide as a colorless oil. 'HNMR (300 MHz, DMSO-4tf) 5 7.68 (bs, 1H), 6.99 (t, J - 6.0 Hz, 1H), 6.30 (bs, 2H), 4.55 (t, J= 5.7 Hz, 2H), 3.74 (t, J= 5.7 Hz, 2H), 3.41 (t, J= 5.7 Hz, 2H), 3.03 (q, J= 5.9 Hz, 2H), 2.86-2.81 (m,5H),2.46(m,2H),1.83(Bextet,7-7.5Hz,2H), 1.59-l.40(m, 4H), 1.00 (t. /- 7.5 Hz, 3H), 0.93 (t, /- 7.2 Hz, 3H); I MS (APCI) m/z 422 (M + H)+. inadezo[4]pyridin-l-yi)etiiozy]cttiyl}methanBsulfbnaniide (-0.5 g) was added to the vessel followed by the addition of methanol (-10 mL). The vessel was placed on a shaker and placed under hydrogen pressure (50 psi, 3.4X lO'Pa). After 20 hours the reaction mixture was filtered through a layer of CELITB filter agent to remove the catalyst and the filter cake was washed with methanol (-100 mL), The filtrate was concentrated under reduced pressure. The residue was purified by chromatography (silica gel during with i 95:5 dicbloromethanennethanol) to provide M{2-[2-(4-anuno-7-hexyl-2-propyl--ltf- iimdizo[4,5)pvridm-l-yl)emaxy}Brayl}mem as a clear oil. lH NMR (300 MHz, DMSO-4,) 8 7.38 (s, 1H), 6.97 ft J= 6.0 Hz, IB), 6.00 (bs, 2H), 4.35 (t, J- 5.7 Hz, 2H), 3.68 (t, J= 5.7 Hz, 2H), 3.37 (m, 2H), 3.00 (q, J~ 5.9 Hz, 2H), 2.84 (t, J= 7.5 Hz, 2H), 2.82 (s, 3H), 2.72 (t, /= 7.5 Hz, 2H), 1.81 (sextet, /- 7.5 Hz, 2H), 1.55-1.50 (m, 2H), 1.37-1.28 (m, 2H), 1.01 (t,J~ 7.5 Hz, 3H), 0.89-0.84 (m, 3H); MS (APCI) m/z 426 (M+H)+. i The general methods described in Example 101 were followed with the following modifications. To one-third of the crude solution of 4-[3-(5,6-dimethyl-8-propyl-7-irmdzo[4,5-c]tetrazolo[l,5-fl]pyridin-7-yl)propane-l-sulfbnyl]benzo chloride m dichloromethane, described in Part B of Example 101, was added butylamme (0,49 mL, 4.9 mmol) io lieu of morpholine, and the reaction was stirred overnight. Additional butylamine (0.5 mL) was added, and the reaction was stirred for two hours, Dichloromethane (100 roL) was added to the reaction mixture, and the resulting solution was washed with saturated aqueous sodium carbonate (3 x 25 mL), water (3 x 25 mL), 10% by volume acetic acid in water (3 x 30 mL), and water (30 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was dried for three hours in a vacuum oven at 100 °C and then triturated with ethyl acetate to provide a solid that was isolated by filtration and dried for throe hours in a vacuum oven at 90 °C. Ar-Butyl[3-(5,6Hiimethyl-8-propyi-7i?-imidazo[4,5-c]tetrazob yI)propaEe-l-Bulfbayl]benzaraide (830 mg, 1.62 mmol) was treated as described in Part C of Example 101. The crude product was purified by column chromatography on silica gel (elutug sequentially with chloroform and 90:10 chlorofbrnnrjeihanol) to provide the product as an oil, which was recryatallized from ethyl acetatehexanc with a few drops of methanol to yield crystals. The crystals were isolated by filtration, washed with hexanes, and dried in a vacuum oven at SO °C to provide 0.18 g of 4-[34-anuno-6,7-dimemyl-2- propyl-l/f-bnidazo[4,53pyridm-1-yl) powder, mp 147.0-149.0 °C. 'H NMR (300 MHz, CDCh) 8 7.83-7.75 (m, 4H), 6.71-6.63 (m, 1H), 4.83 (br B, 2H), 4.35 (dd, /= 7.2,7.2,2H), 3.50 (quart, J- 7.2,2H), 3.05 (dd, J- 7.5,7.5,2H), 2.74 (dd, /= 7.7,7.7,2H), 2.35 (s, 3H), 2.28 (s, 3H), 2.13 (quint, J= 7.4,2H), 1.84 (sextet, J= 7.6, 2H), 1.73-1.62 (m, 2H), 1.46 (sextet, J= 7.3, 2H), 1.05 (t, /- 7.3,3H), 0.99 (t, /- 7.3, 3H); MS (APCI) m/z 486 (M + H)+; Anal. Calcd for CzsHssNAS: C, 61.83; H, 7.264; N, 14.42; Found; C, 61.50; H, 7.2; N, 14.06. The general methods described in Example 101 were used with the following modifications. To one-third of the crude solution of 4-[3-(5,6-dimethyl-8-propyl-7//- iniidazo[415]tetra7oIo[I-fl]pyiidin-7-yI)propme-I'ilfonyI3bBiizoyi chloride in diclilorometbane, described in Part B of Example 101, was added tf-methylbutylamine (0.5B3 mL, 4.92 mmol) in lieu of moipholine, and the reaction was stirred overnight. Additional tf-methyl burylamins (0.5 mL) was added, and fee reaction was stirred for two hours. The crude product was recrystallized from ethyl acetateihexane, and the crystals wars dried for three hours in a vacuum oven at 90 °C. Ar-Buty]-4-[3-(5,odimethyI-8-pnyI-7ff-imidam[4,5]tetrazolo[l benzamide (770 rag, 1,46 mmot) was treated as described in Part C of Example 101. The crude product was recrystaltized from ethyl acetate:hexane with a couple drops of methanol to provide crystals, which wore isolated by filtration, washed with hexane, and dried for four hours under high vacuum at 50 "C to provide 0.56 g of 4-[3-(4-amino-6,7-dimethyl-2-propyl- lff-irmdazo[4,5-c]pyridin-l -yl)propane-l -sultbnyl]-W-bnryl--inethylbonzarnide as a white powder, mp 127.0-129.0 °C. *H NMR (300 MHz, COCh) 8 7.95 (d, J- 8.4,2H), 7.58 (d, J= 8,4,2H), 4.92 (br s, 2H), 4.42 (dd, J" 7.8,7.8,2H), 3.55 (dd, J = 7.8,7.8,1H), 3.21 - 3.05 (m, 4.5 H), 2,90 (B, 1.5 H), 2.77 (dd, J - 7,7,7.7,2H), 2.43 (s, 3H), 2.39 (s, 3H), 2.23 (quint, J - 7.6, 2H), 1.93-1.36 (rn, 5H), 1.15 (quart, J= 7.5, 1H), 1.07 (t, .7-7.4,3H), 0.99 (U-7.0,1.5H), 0.81 (U= 7.4,1.5H); MS(APCI)m/z500(M+H)+; Anal. Caled for CMHJNSOJS: C, 62.50; H, 7.464; N, 14.02; Found: C, 62.26; H, 7.78; N, 13.87. Under a nitrogen atmosphere, propanenitrile (120 mL, 1.7 mmol) was added dropwise to raalonyl dichloride (100 g, 0.709 mmol), and the reaction was stiired for 24 hoars at room temperature during which time e precipitate formed. Dioxane (300 mL) was added to the reaction mixture, and (he precipitate was isolated by filtration and washed with dioxane (100 mL) to provide a tan solid. The solid was dissolved in a mixture of dioxane (75 mL) and methanol (30 mL) with heating. The methanol waa removed under reduced pressure, and a white precipitate formed, which was isolated by filtration and washed with dioxane. The solid was dried overnight in a vacuum oven at 80 "C to provide 13.0 g of 6 A solution of 6oTohycVoxy-5-me3yriojn-2(lW)-one hydrochloride hydrate (67,0 g, 0.313 mmol) in concentrated sulfuric acid (335 mL) was cooled to -0 °C; nitric acid (19.6 mL of 16 M) was added dropwise over a period often minutes. The reaction was stirred for 20 minutes and then poured slowly into 2.5 L of ice water. A yellow precipitate formed, which was isolated by filtration and dried overnight in a vacuum oven at 60 eC to provide 39.7 g of 6hlom4ydroxy-5-methyl-3-nitropyridin-2(Ltf)-one as a yellow solid. PartC A solution of 6hloro-4-hydR-5-memyl-3-mtropyridb-2(l/)-one (10.9 g, 53.4 mmol) in dichloromethane (380 mL) was cooled to 0 °C. Triethylarnine (22.3 mL, 160 mmol) was added, and the solution was stirred for ten minutes. TrifJuoromemanesulfDnic anhydride (18.0 mL, 107 mmol) was then added dropwise over a period of five minutes, and the solution was stirred for 1.5 hours at 0 °C. A solution of ferf-butyl 2-(2-aminoethoxy)ethylcarbamate (12.0 g, 58.8 mmol), prepared as described in Parts A through D of Example 102, in a small amount of dichloromethanc was then added over a period of five minutes, and the reaction was allowed to warm to room temperature slowly and stirred overnight. The solution was then washed with water (2x150 mL) and brine (150 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gei (eluting sequentially with 80:20 hexanes: ethyl acetate and 50:50 hexiinesiethyl acetate) to provide a yellow oil, which was dissolved in diethyl ether and concentrated under reduced pressure to provide 16.5 g of triflumsmethsMsulftnic acid 4-[(2-{2-((tert- butoxycaibonyI)ammo]Bthoxy}emyl)aruizw]-6" as a solid PartD A solution of trifluoromeOMmesiilfojuc acid 4~[(2-{2-[(tert- butoxyc«bmyI)aminD]etlK>xy)emyI)an ester (14.3 g, 27.4 mmol), Wi(4-mBraoxybeiizyl)anm» (7-00 E. 27,4 mmol), and triefiiylamine (3.82 mL, 27.4 mmol) in toluene (250 mL) wn heated at 90 "C for two hours and then allowed to cool to room temperature overnight Diethyl ether (300 mL) was added, and the solution was washed with water (200 mL) and brine (200 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified twice by column chromatography on silica gel (eluting sequentially with 80:20 hexanes:ethyl acetate and 70:30 hexanos:ethyl acetate) to provide 8.73 g of {2-[2-(2-[bis{4-raethoxybeiizyl} anu]-6-ch1oro-S-memyl-3,-nitropyridin-4-ylamino)ethoxy]emyl)carbamic acid tert-butyl ester. PartE Under a nitrogen atmosphere, sodium borohydride (0.76 g, 20.0 mmol) was added in two portions to a solution of nickel (IT) chloride hydrate (1.57 g, 6.62 mmol) in methanol (160 mL), and the mixture was stirred at room temperature for 15 minutes. A solution of {2-[2 ylanmio)ethoxy3ethyl)caibamic acid fert-butyl ester (8.37 g, 13.3 mmol) in methanol (10 mL) and dichlorometbane (10 mL) was then added, and the addition tunnel was rinsed with a mixture of methanol (10 mL) anddichloromBthane(lOmL), The reaction was stirred for two hours, during which time additional sodium borohydride was added three times (0.5 g, 0.5, g and 1.0 g). Water (200 mL) was then added, and the methanol was removed under reduced pressure. The remaining solution was extracted with diethyl ether (700 mL, 300 mL), and the combined extracts were washed with water (200 mL) and brine (200 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to product the crude product contaminated with water. Toluene (300 mL) was added and men removed by distillation to provide [2 PartF The material from Part E was treated using (he general method described in Part E of Example 85 with the following modification. Pyridmiump-toliwnesulfbnate (0.1 equivalent) was used in lieu of pyridine hydrochloride. The crude product was purified by column chromatography on silica gel (elutwg sequentially with 60:20 hexanearethyl acetate and 70:30 hexancsiethyl acetate) to provide 5 g of [2 Trifluoroacotic add (40 mL) was added to [2-(2- {4-fbis-(4-memoxybenzyl)ainino]-6.chlorc-7- ylJethoxy)cthyl]carbainic acid tot-butyl ester (1 g, 14 mmol). The reaction was swirled until it became homogeneous and was allowed to stand at room temperature overnight The reaction was concentrated under reduced pressure, and dichloromethane was added and removed under reduced pressure (5 x 40 mL) to provide a white solid. The solid was triturated in chloroform, isolated by filtration, and dried under reduced pressure with heating. The solid was dissolved in concentrated hydrochloric acid (5 mL) and stirred for three hours. Aqueous sodium hydroxide was then added. A white solid formed, which was isolated by filtration, washed with water and diethyl ether, and dried for five hours under high vacuum at 70 °C to provide 0,144 g of l-[2-(2-aminoetbDxy)ethyI]-6-chloro-7. methyl4-propyl-lff-imidjizo[4,5-c]pyridm4-amxnB as a white solid, mp 158.0-161.0 °C. 'E NMR (300 MHz, DMSO-d«) 6 6.15 (br s, 2H), 4.43 (t, J= 5.4,2H), 3.67 (t, J= 5.3, 2H), 3.27 (t, J- 5.7, 2H), 2.84-2.79 (m, 2H)r 2.54 (t, /« 5.7,2H), 2.47 (s, 3H), 1.86-1.74 (m, 2H), 1.19 (br a, 2H), 1.00 (t, /= 7.3,3H); MS (APCI) mh 312 (M + H)*; HEMS (ESI) calcd for CjNjOCl + H 312.1591, found 312.1588; Anal, calcd for CuNjOCl'OO: C, 53.31; H, 7.16; N, 22.20. Found: C, 53.34; H, 7.23; N, 22.02; The general methods described in Parte A and B of Example 111 were used to prepare acetic acid 2(2-ohloro-5J6-dinuyI-3-nitrop)ridiii-4-yl)smino]cthyI ester. Using die general method described in Part A of Example 92, acetic acid 2-[(2-chloro-5,6-dimothylO-nitropyridin-4-yl)amino)etbyl ester (64.0 g, 0.222 mmol) was converted to Hcedcacid2-[(5,6-dimetbyl-8-nitrotetrazolo[l]pyridin-7-yl)anu]e&yl ester. The crude product was triturated with diethyl ether and isolated by filtration to provide 60.0 g of the desired product as e yellow solid. PartB A Parr vessel was charged wife acetic acid 2-K5,6-Kbmeftyl-8-nitrotetrazolo[l,5-. a)pvridin-7-yl)ainino]ethyl ester (50.0 g, 170 mmol), 5% platinum on carbon (5.00 g), toluene (600 roL), and 2-propanol (50 mL) and purged with nitrogen. The vessel was then placed under hydrogen pressure (20 pa,) for 20 hours at room temperature. The reaction mixture was filtered through a layer of CSLTTE filter aid, and the filter cake was washed with 90:10 dichlOTomeJhane'.mftthanol. The filtrate was concentrated under reduced presHure to provide a dark gray Bolid, which was triturated with diethyl ether, isolated by filtration, and dried to provide 41.0 g of acetic acid 2-[(B-nmino-5,6-dunBthyltBtrazolo[ 1,5-a]pyhdin-7-yl)amino}ethyl eater as a light gray solid, PartC The general methods described in Parts G and H of Example 80 were used to convert acetic acid 2-[(8-Bnum ester (48.8 g, 185 mmol) to 56.5 g of acetic acid 2-C8-etboxymethyI-5,6-diniBthyl-7ff-imidazo[4,5-c]tBtra2olo[l-a]pyridin-7-yl)ethyl ester with the following modifications. In Pan H, one portion of pyridine hydrochloride (6,3 g, 54 mmol) was added, and the reaction was heated at reflux for 20 hours. After the work-up, the desired product was obtained as a tan solid, which was used without purification. PartD The general method described in Part F of Example 111 was used to convert acetic acid2-(le&oxymelhyl-5,fM}hna&iyl-7tf'ra eater (56.5 g, 170 mmol) to 2 The general method described in Part A of Example SI was followed, using 2-(S-etQ0xymethyI-5,6Huethyl-7/MmidaK g, 15.5 mmol) in lieu of *erf-butyl 2-hydroxyethylcarhamate and 3-bromo-l- phenylpropyne, prepared as described in Part A of Example 7, in lieu of propargyl bromide. The crude product was triturated with diethyl ether, isolated by filtration, and dried under reduced pressure to provide 5.93 g of 8-ethorymethyl-5,&-dimeuiyl-7-{2-[(3- phanylprup-2-ynyI)oxy]ethyl}-7#-iiiiM as a yellow solid. PartF The general method described in Part D of Example 109 was followed using 8-efcojcymetoyl-5,&ethyl-7-{2-[(3-phraylp c]tetrazolo[l,5-(i]pyridine (6.47 g, 16,0 mmol) as the starting material. The reaction with triphenylpho5phine(4.61 g, 17.6 mmol) required 41 hours, and the hydrolysis of the intermediate required lSboura. The cmde product (11.6 g) was dissolved in dicbloromethane and treated with a 1M solution of hydrochloric acid in diethyl ether (50 mL), The volanles were removed under reduced pressure, and the resulting solid was recrystallized from acetonitrile. The crystals were dissolved in water (20 mL), and the solution was adjusted to pH 14 with fee addition of 50% aqueous sodium hydroxide to provide a solid that was isolated by filtration. The solid was stirred wtih 1M aqueous potassium hydroxide for one hour, isolated by filtration, dried for three days under reduced pressure at 70 "C to provide 0.828 g of 2-othoxymethyl-6,7-dimethyl-I-{2-[(3- phIprop-2-ynyOoxy]e&yl}4-imida2o[4,5-c]pyridm-4-amirie as a white powder, mp 129-130 "C. 'H NMR (300 MHz, DMSO) 5 7.34-7.39 (m, 5H), 5,80 (s, 2H), 4.69 (s, 2H), 4.58 (t, J= 5.6 Hz, 2H), 4.37(s, 2H), 3.89 (t, J~ 5.6 Hz, 2H), 3.51 (q, /- 6.9 Hz, 2H), 2.39 fc, 3H)4 2.32 (s,3H), 1.13 (t,y* 7.2,3H); MS(APCI)«A379(M + H)+; Anal. Cakd for CnHafiNOi-O.lHaO: C, 69.49; H, 6.94; N, 14,73; Found: C, 69.25; H, 7.00; N, 14.65. The general method described in Example 112 was used to hydrogenate 2-ethoxymethyl-6,7-dime%M-{2-[(3-phmylp c]pytiditt-4-amine (1.17 g, 3.09 mmol), prepared as described in Example 122. The reaction was complete after 18 hours. The crude product, isolated as an oil, was dissolved with diethyl ether (20 mL) and treated with, a 1M solution of hydrochloric acid in diethyl other, The resulting salt was isolated by filtration, dried under reduced pressure, and recrystallized from ethyl acetate. The crystals, obtained in two crops, were dried for three hours under high vacuum at 60 °C to provide 0.777 g of 2-ethoxymethyl-6,7-dbriethyl-l-P-(3-phenylpropoxy)etbyl]-l/J-irnidazo[4,5-p]pyridin-4-aiBiae hydrochloride as a white powder, mpl2S-1306C, Part A 2-[2-(8-Ethyl-5,6-dimofliyl-7fl'-imidiBOt4,5-i;]telra2oIo[ 1,5-o]pyridin-7- yl)ethoxy]othylamine (2.0 g„ 6.6 mmol), obtained as described in Parts A through I of Example 102 was treated as described in Part J of Example 102 with 4-chlorobutyryl chloride (0.78 mL, 6.9 mmol) in lieu of methanesutfonyl chloride. The crude product was purified by column chromatography on silica gel (125 mL, elating with 90:10 dichloromeuWermethanoI) to provide 2,30 g of 4-chloo-#-{2-[28-emyI-5,6-&merhyl- 7#-urutfazo[4,5-c]tetraMlQ[l,5]pvridm-7-y09uTOxy]e& as a white solid, mp 149-151 °a PartB Under a nitrogen atmosphere, a mixture of sodium hydride (0.24 g, 6.1 mmol), 50% in mineral oil, and anhydrous DMF (10 mL) waB cooled to ~0 °C. A solution of 4-chIoro-W-{2-[2 yI)etfloxy]cthyl)butananiide (2.25 g, 5.52 mmol) in DMF (35 mL) was slowly added to the mixture, and the reaction was stirred for one hour. The volatiles were then removed under reduced pressure, and the residue was partitioned between water (100 mL) end dicbloromethane (100 mL). The aqueous layer was extracted with djchlorom ethane (2 x 100 mL), and the combined organic solutions were dried, filtered, and concentrated under reduced pressure to provide 1.94 gofa light orange solid, The solid was combined with crude product from a previous run (1.45 g) and purified by oolomn chromatography on silica gel (150 mL, eluting with 95 ;5 dkhloromBthaMimethanol) to provide 2.96 g of 1-{2-[2pynDhdm-2-one as a white solid, mp 141-143 *C. Parte 1- {2-[28-Ethyl-5>oetriyl-7H-imidazo[4,5-c]tBttazolotl ,5-a]pyridro-7- yl)e&oxy]etiiyl}pyrrolidm-2-one (2.86 g, 7.70 mmol) was treated using a modification of the general method described in Fart D of Example 109. 1-Dicblotobeozene was used as die solvent, and the reaction was heated at 130 °C for two days. The crude product was purified by column chromatography on silica gel (150 mL, eluting with 8030 dichloromethanemtethanol) to provide 2.03 g of a light brown oil, which solidified overnight The solid was recrystallized from acetonitrile (4.9 mL/g) twice and dried for two days in ft vacuum oven at 50 °C to provide 0.97 g of 1 - {2-[2-(4-amino-2-ethyl-6)7. dimemyl-limTid8Zo[4,5 mp 128-130 ftC. 'HNMR(3Q0 MHZ, CDCB) 8 4.84 (a, 2H),442 &J= 5,5 Hz, 2H), 3.71 (t, /= 5.5, 2H), 3.50-3.44 (m, 2H), 3.40-3.34 (m, 2H), 3.14-3.08 (m, 2H), 2.87 (q, J = 7.5,2H), 2.44 (s, 3H), 2.42 (s, 3H), 2.32-2.22 (m, 2H), 1.91-1.79 (m, 2H), 1.40 (t, J- 7.5, 3H); MS(APCI)m£346(M + H)*; Anal. Calcd for CNJOJ: C, 62.59; H, 7.88;N, 20.27. Found: C, 62.58; H, 8.16;N, 20.51, Example 125 #-{2-[2-(4-Amm6-cblaro-7-methyl-2-piopyl-lH- yl)ethoxy]emyl}ban2amide Under a nitrogen atmosphere, triemyJamine (3.0 mL, 12 mmol) was added to a mixture of l-[22-aminoatoxy)cfeyI].6hkro-7-m c]pyridin-4-amiBo bistrifluoroacetate (0.95 g, 1.76 mmol), the salt made from Part G of Example 121, in tetrahydrofuran (20 mL). Benzoyl chloride (0.3 mL) was added dropwise to the resulting solution, and the reaction was stirred at room temperature. A solution of 2% aqueous sodium carbonate (40 mL) was added, and the resulting mixture was stirred for 20 minutes and then extracted with diethyl ether (120 mL). A white solid precipitated from the diethyl ether and was isolated by filtration and washed with water (5 mL) and diethyl ether (30 mL). The solid was recrystallizcd from 2-propanol, isolated by filtration, and dried for 4,5 hours under high vacuum at 40 °C to provide 265 rug of N- {2-[2-(4-annho-6chloro-7-meftyl-2-pTcpyl-l/f-iniidB3o[4,5]pyridin-4-yl)ethoxy]ethyl Jbenzamidc as a white solid, mp 188,0-1 89.0 °C. 'HNMR(300 MHz, CDClj) 6 7.63 - 7.59 (m, 2H), 7.53-7.41 (m, 3H), 6,15 (br s, IH), 5.01 (br B, 2H), 4.45 (% J- 5.5,2H), 3.76 (t, /- 5.5,2H), 3.59-3.53 (m, 4H), 2.83-2.78 (m, 2H), 2.55 (s, 3H), 1.91-1.79 (m, 2H), 1.03 (t,/-7.3,3H); MS (APCQ m/z 416 (M + H)+; HRMS (ESI) ealcd for CjiHisNjOjCl + H 416.1853, found 416.1856; Anal, calcd for CaiHjsNACl: C, 60.64; H, 6.34; N, 16.84. Found: C, 60.61; H, 6.34; N, 16.74. Compounds of the invention have been found to induce cytokine biosynthesis when tested using the method described below. CYTOKINE INDUCTION IN HUMAN CELLS An in vitro human blood cell system is used to assess cytokine induction. Activity is based on the measurement of intorferon-a and tumor necrosis factor-a (IFN-a and TNF- a, respectively) secreted into culture media as described by Testennan et. al. In "Cytokine Induction by the Immunomodulfltore muquiraod and 5-27609", Journal of Leukocyte Biology, 58.355-372 (September, 1995). Blood Cell Preparation for Culture Whole blood from healthy human donors is collected by venipuncture into EDTA VKutainer tubes, Peripheral blood mononuclear cells (PBMC) are separated from whole blood by density gradient centrimgition using Hiatopaque4H077, Blood ie diluted 1:1 with Dulbecco's Phosphate Buffered Saline (DPBS) or Hank's Balanced Salts Solution (HBSS). The PBMC layer is collected and washed twice with DPBS or HBSS and retuspended at 4 x 106 cells/mL in RPMI complete. The PBMC suspension is added to 48 well fiat bottom sterile tissue culture plates (Costax, Cambridge, MA or Becton Dickinson Labware, Lincoln Park, NJ) containing an equal volume of RPMI complete media containing test compound. Compound Preparation The compounds are Bolubilized in dimethyl sulfoxide (DMSO). The DMSO concentration should not exceed a final concentration of 1% for addition to the culture wells. The compounds are generally tested at concentrations ranging from 30-0,014 uM. Incubation The solution of test compound is added at 60 uM to the first well containing RPMI complete and serial 3 fold dilutions are made in the wells. The PBMC suspension is then added to the wells in an equal volume, bringing the test compound concentrations to the desired range (30-0.014 uM). The final concentration of PBMC suspension is 2 x 106 cells/mL. The plates are covered with sterile plastic lids, mixed gently and then incubated for 18 to 24 hours at 37°C in a 5% carbon dioxide atmosphere. Separation Following incubation the plates are csnirifuged for 10 minutes at 1000 rpm (-200 x g) at 4°C. The cell-free culture supernatant is removed with a sterile polypropylene pipet and transferred to sterile polypropylene tubes, Samples are maintained at -30°C to -70°C until analysis, The wimples are analyzed for IFN-a by ELISA and for TNF-a by ELISA or 1GEN Assay. IFN-a and TFN-a Analysis by ELISA IFN-a concentration is determined by ELISA using a Human Multi-Species kit from PBL Biomedical Laboratories, New Brunswick, KT. Results are expressed in pg/mL. TNF-a concentration is determined using El-ISA Idts available from Biosource International, Camariuo, CA. Alternately, the TNF-ct concentration can be determined by Origen® M-Series Immunoassay and read on an K3EN M-8 analyzer from K3EN International, Gailhereburg, MD. The immunoassay us« a human TNF-a capture and detection antibody pair from Biosource International, CamariUo, CA. Results are expressed in pg/mL. The complete disclosures of the patents, patent documents, and publications cited herein are incorporated by reference in their entirety as if each were individually incorporated The present invention has been described with reference to several embodiments thereof The foregoing detailed description and examples have been provided for clarity of understanding only, and no unnecessary limitations are to be understood therefrom. It will be apparent to those skilled in the art that many changes can ' be made to the described embodiments without departing from the spirit and scope of the invention. Thus, the scope of the invention should not be limited to the exact details of the compositions and structures described herein, but ramer by the language of the claims that follow. We claim: 1. A compound of the Formula (la): wherein: X is -CH(R5, -CH(R5)- (C1-10)alkylene-, -CH(R5)- (C2-10)alkenylene-, or CH(R5)-(C i-i o)alkylene-Y-(C i -i o)alkylene-; Yis-O-,or-S(O)0-2-; -W-Ri is selected from -0-RM.5 and -S(O)0.2-Ri; RM.5 is selected from -R6-C(R7Z-R8-(C,.10)aIkyl; -R6-C(R7)-Z-R8-(CMo)alkenyl; -R6-C(R7)-Z-R8-aryl; -R6-C(R7)-Z-R8-heteroaryl; -R6-C(R7)-Z-Rg-heterocyclyl; -R6-C(R7)-Z-H; -R5-N(R9) -C(R7)-Rg-(CM0)alkyl; -R6-N(R9)-C(R7Rg-(C2-[o)alkenyl; -R6-N(R9) -C(R7R8-aryl; -R6-N(R9) -C(R7)-Rg-heteroaryl; -R6-N(R9) -C(R7)-R8-heterocyctyl; -R6-N(R9)-C(R7)-R10; -R6-N(R9)-S02-Rg-(C1.]o)alkyl; -R6-N (R9)-S02-R8-(C2.10)alkenyl; -Rs-N (R5)-S02-Rs-aryl; -R«-N (R9)-S02-R8-heteroaryl; -R6-N(R9)-S02-Rg-heterocyclyl; -R6-N(R9)-S02-RI0; -R6-N(R9)-S02-N(R5)-R8-(Ci.io)alkyl; -R6-N(R9)-S02-N(R5>RS-{C2-Io)alkenyl; -R6-N(R9)-S02-N(R5)-R8-aiyi; -R6-N(R9)-S02-N(R5)-R8-heteroary!; -R6-N(R9)-S02-N(R5)-Ra-heterocyclyI; -R6-N(R9)-S02-NH2; -R6-N(R9)-C(R7)-N(Rs)-Q-R8-(Ci.io)alkyl; -R6-N(R9)-C(R7)-N(R5)-Q-R8-(C2-io)alkenyl; -R6-N(R9)-C(R7)-N(Rs>Q-Rg-aryl; -R6-N(R9)-C(R7)-N(R5)-Q-R8-heteroaryl; -R6-N(R9)-C(R7)-N(R5)-Q-R8-heterocyclyl; -R6-N(R9)-C(R7)-N(R5)2; -R6-N(R9)-C(R7)-N(Rn)-Q-R8-(CMo)aIkyl; -R6-N(R9)-C(R7)-N(Rn)-Q-R8-(C2.10)alkenyl; -R6-N(R9)-C(R7)-N(R,i)-Q-R8-ary[; -R6-N(R9)-C(R7)-N(Rn)-Q-R8-heteroaryl; -R6-N(R9)-C(R7)-N(Rn)-Q-R8-heterocyclyl; -R6-N(R9)-C(R7)-N(Ru)H; -(C2-io)alkenyl; -aryl; -R6-aryl; -heteroaryl; -heterocyclyl; -Re- heteroaryl; and -Re-heterocyclyl; Z is-N(Rs)-, -0-, or -S-; Q is a bond, -CO-, or -S02-; A represents the atoms necessary to provide a 5- or 6-membered heterocyclic or heteroaromatic ring that contains up to three heteroatoms; Ri-6 is selected from: -(CM0)alkyl; -aryl; -heteroaryl; -heterocyclyl; -(C2-10)aIkenyl; -Re-aryl; -Re- heteroaryl; and -R-heterocyclyl; each R5 is independently hydrogen, CMO alkyl, or C2.10 alkenyl; Re is (C1-10)alkylene, (C2-10)alkenylene, or (C2-10)alkynylene, which may be interrupted by one or more -O- groups; R7 is =0 or =S; Rg is a bond, (C1-10)alkylene, (C2-10)alkenylene, or (C2-10)alkynylene, which may be interrupted by one or more -O groups; Rg is hydrogen, C1-10 alkyl, or aryl(C[.10)alkyl; or R9 can join together with any X is -CH(Rs)-, -CH(Rs)- (CoJalkylene-, -CH(R5)- (C2.10)alkenylene-, or CH(R5)-(C1.10)alkylene-Y-(C,.,o)alkylene-; -W-Ri is selected from -O-R1-1.5 and -S(O)0-2-Ri-6; R].i-5 is selected from -R6-C(R7)-Z-Rg-(CMo)alkyI; -R6-C(R7)-Z-R8-(C2.[o)alkenyl; -R6-C(R7)-Z-R8-aryl; -R6-C(R7)-Z-R8 -heteroaryl; -R6-C(R7)-Z-R8-heterocyclyl; -R6-C(R7)-Z-H; -R6-N(R9)-C(R7)-R8-(C1.10)alkyl; -R6-N(R9)-C(R7)-R8-(CMo)alkenyl; -R6-N(R9) -C(R7)-R8-aryl; -R6-N(R9) -C(R7)-Rg-heteroaryl; -Ri-N(R») -C(R7)-R8-heterocycly); -R6-N(R9) -C(R7)-Rio; -R6-N(R9)-SO2-Rr(CM0)alkyl; -R6-N(R9)-SO2-Rs-(C2.,0)alkenyl; -R6-N(R9)-S02-RB-aryl; -R6-N(R9)-S02-Rg-hetero aryl; -R6-N(R9)-S02-Rg-heterocyclyl; -R^-NCR^-SOz-Rio; -R6-N(R9)-SO2-N(Rs)-R8-(CM0)alkyl; -Rfi-NCRgJ-SOj-NCRjJ-Rs-CCMoJalkenyl; -R«-N -R6-N(R9)- S02-N(R5)-R8-heteroaryl; -R6-N(R9)-S02-N(Rs)-R8-heterocyclyl; -R^-NfRp)- SO2-NH2; -R6-N(R9)-C(R7)-N(R5)-Q-R8-(Cl.10)atkyl; -R6-N(R9)-C(R7)-N(R5)-Q-R8-(C2.,o)alkenyl; -R6-N(R9)-C(R7)-N(R5)-Q-R8-aryl; -R6-N(R9)-C(R7)-N(R5)-Q-R8-heteroaryl; -R6-N(R9)-C(R7)-N(R5)-Q-R8-heterocyclyl; -R6-N(R9)-C(R7)-N(R5)2; ^-NCR^-Ct^^NtRuJ-Q-Rg-td.ioialkyl; -R6-N(R9)-C(R7)-N(Rl,)-Q-R8-(C2.]o)aIkenyI; -R6-N(R,)-C(R7)-N(R] O-Q-Rs-aryl; -R6-N(R9)-C(R7)-N(R1i)-Q-R8-heteroaryl; -R6-N(R9)-C(R7)-N(Rn)-Q-R8-heterocyclyl; -R6-N(R9)-C(R7)-N(R„)H; -(C2-]o)alkenyl; -aryl; -Ri-aryl; -heteroaryi; -heterocyclyl; -Re- heteroaryi; and -Rs-heterocyclyl; Ri-6 is selected from: -(CM0)alkyl; -aryl; -heteroaryi; -heterocyclyl; -(C2-10)alkeny]; -R6-aryl; -Re- heteroaryi; and -Re-heterocyclyl; R2 is selected from the group consisting of: -hydrogen; -(CM0)alkyl; -(C2-10)alkenyl; -aryl; -heteroaryi; -heterocyclyl; ~(CM0)alky]ene-Y-(CM -(C1-10)alkylene-Y-(C2-10)alkenyl; -(C1.10)alkylene-Y-aryl; and - (C|.10)alkyl or (Cj.10Jalkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(R5)2; -C(O)-C,-10alkyl; -C(0)-0-CMO alkyl; N3; -aryl; -heteroaryl; -heterocyclyl; -C(0)-aryl; and -C(0)-heteroaryl; Yis-O- or-S(O)0-2-; Z is-N{R5)-, -0-, or -S-; Q is a bond, -C(0)-, or-S02-; A represents the atoms necessary to provide a 5- or 6-membered heterocyclic or heteroaromatic ring that contains up to three heteroatoms; R3 and R4 are independently selected from the group consisting of hydrogen, CMO alkyl, C2-10 alkenyl, C2-10 alkynyl, CMO alkoxy, C|.|o alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, CMO alkyl, or C2-10 alkenyl; Re is (C1.10)alkylene, (C2-10)aIkenyIene, or (C2.10)alkynylene, which may be interrupted by one or more -O- groups; R7 is O or =S; Rs is a bond, (Cj-to)alkylene, (C2-10)alkenylene, or {C2-jo)alkynylene, which may be interrupted by one or more -o- groups; R9 is hydrogen, CMO alkyl, or aryl(C1.i0)aIkyl; or R9 can join together with any X is -CH(R5, -CH(RS)- (CM0)alkylene-, -CH(R5)- (C2.fo)alkenyiene-, or CU(Rs (C i-10)alkylene- Y-(C i .\ 0)alkylene-; Ri-i selected from the group consisting of: -Rfi-CtRTj-Z-Rs-tC1oJalkyl; -R6-C(R7)-Z-Ra-(C2.]o)aIkenyI; -R6-C(R7)-Z-Rg-aryl; -R6-C(R7)-Z-Rg-heteroaryl; -R6-C(R7)-Z-R8-heterocyclyl; -R6-C(R7)-Z-H; -Rs N(R9) -QR-RHCMoJalkyl; -R6N(R9) -C(R7)-R8-(C2-10)alkenyl; -R6N(R9) -CtR-Rg-aryl; -Re N(Rg) -C(R7)-R8-heteroaryl; -R6N(Rg) -C(R7)-R8-heterocyclyl; and -RfiN(R8)-C(R7R10 Z is -N(R5h -O. or -S; R1is selected from the group consisting of: hydrogen; -(C,.,0)alkyl; -(C2-10)alkenyl; -aryl; -heteroaryl; -heterocyclyl; -(CMo)alkylene-Y-(C,.,o)alkyl; -(C1. 10)alky lene- Y-(C2-i 0)aJke ny 1; -(C1.10)alkylene-Y-aryl; and - (C1-10)alkyl or (Q.10)alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(R5)2; -C(O)-CM0 alkyl; -C(O)-O-CM0 alkyl; -N3; -aryl; -heteroaryl; -heterocyclyl; -C(0)-aryl; and -C(0)-heteroaryl; Yis-O- or-S(0)0.2-; Rs and R4 are independently selected from the group consisting of hydrogen, C1-10 alkyl, d-ic alkenyl, C2-10 alkynyl, Cj.10 alkoxy, C1-to alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, C1.10 alkyl, or C2.10 alkenyl; Re is (C,.10)alkylene, (C2-10)alkeny!ene, or (C2-10)a\kyny\ene, which may be interrupted by one or more - O - groups; R-i is =0 or =S; Rg is a bond, {C1.jo)alkylene, (C2-10)alkenylene, or (C2-10)alkynylene which may be interrupted by one or more - O - groups; R.9 is hydrogen, C1-10 alkyl, or aryl(C1-10)alkyl; or Rg can join together with any does not prevent format10n of the ring; or a pharmaceutically acceptable salt thereof. 4. The compound or salt as claimed in claim 3 wherein X is -CH(R5)-C,_5 alkylene-. 5. The compound or salt as claimed in claim 3 wherein R? is =0 and Rg is a bond. 6. The compound or salt as claimed in claim 3 wherein R9 is Cj.10 alkyl. 7. The compound or salt as claimed in claim 3 wherein RM is -R6-N(R9)-C(R?)-R8-(C,.,o)alkyl. 8. The compound or salt as claimed in claim 3 wherein R1-1 is -Rs-NCRg)-C(R7)-R8-aryl or -R6-N(R9)-C(R7)-R8-heteroaryl. 9. The compound or salt as claimed in claim 3 wherein RM is -R-6-N(R.9)-C(R?)-R10, and R9 and R10 join to form the ring. X is -CH(Rs)-, -CH(R5)- (CM0)alkylene-, -CH(R5)- (C2-10)alkenylene-, or CH(R5)-(CMO)alkylene-y-(C,.10)alky]ene-; R1-2 is selected from the group consisting of: -R6-N(R9)-SO2-R8-(C1.10)aIkyI; -R6-N(R9)-S02-R8-(C2-,o)alkenyl; -R6-N(RQ)-S02-R8-aryl; -R6-N(R9)-S02-R8-heteroaryl; -R6-N(R9)-S02-R8-heterocyclyl; -R6-N(R9)-S02-R[(); -R6-N(R9)-S02-N(Rs)-R8-(C1.1o)aIkyl;' -R6-N(R9)-SO2-N(R5)-R8-(C2.10)alkenyl; -Rs-N(R9)-S02-N(Rs)-R8-aryl; -R6-N(R9)-S02-N(R5)-R8-heteroaryl; -R6-N(R9)-S02-N(R5)-R8-heterocyc!yl;and -R6-N(R9)-S02-NH2; R2 is selected from the group consisting of: -hydrogen; -(C1.10)alkyl; -(C2.10)alkenyl; -aryl; -heteroaryl; -heterocyclyl; -(CM0)alkylene-Y-(CM0)alkyl; -(CMO)alkylene-y-(C2.10)alkeny]; -(C]_10)alkylene-Y-aryl; and - (C].|o)alkyl or (C2-10)alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(RS)2; -C(O)-CM0alkyl; -C(O)-O-CM0 alkyl; -N3; -aryl; -heteroaryl; -heterocyclyl; -C{0)-aryl; and -C{0)-heteroaryl; Y is -O- or -S(0)o.2-; R3 and R1 are independently selected from the group consisting of hydrogen, CJ.JO alkyl, C2-10 alkenyl, C2-J0 alkynyl, CMO alkoxy, CJ.IQ alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, CMO alkyl, or C2-10 alkenyl; R& is alkylene, alkenylene, or alkynylene, which may be interrupted by one or more-O- groups; Rg is a bond, (C1-10)alkylene, (C2-10)alkenylene, or (C2-10)alkynylene which may be interrupted by one or more -0- groups; Re is hydrogen, CMO alkyl, or aryl(C]-10)alkyl; or R9 can join together with any carbon atom of Re to form a ring of the formula or a pharmaceutical!y acceptable salt thereof. 11. The compound or salt as claimed in claim 10, wherein X is -CH(Rs)-C1.s alkylene-. 12. The compound or salt as claimed in claim 10 wherein Rg is methyl. 13. The compound or salt as claimed in claim 10 wherein Ru is -R6-N(Rg)» S02-Rs-(CMo)alkyl. 14. The compound or salt as claimed in claim 10 wherein R1.2 is -Re-NfRg)-S02-R8-aryl or -R6-N(R9)-S02-Rg-heteroaryl. 15. The compound or salt as claimed in claim 10 wherein R1.2 is-R6-N(R9)-SC2-R10. 16. The compound or salt as claimed in claim 15 wherein R9 and R10 join to form the ring. 17. A compound of the Formula (1-3): wherein: X is -CHCRs)-, -CH(RS)- (C1.l0)alkylene-, -CH(R5)- (C2-10)alkenylene-, or CH(Rs)- (C1. 10)alkylene-Y-(C i _i0)alkylene-; Ri-3 is selected from the group consisting of: -R6-N(R9C(R7)-N(Rs)-Q-Ra-(CMo)alkyl; -R6-N(R9)-C(R7)-N(Rs)-Q-R8-(C2.10)alkenyl; -Rft-NCRgJ-CCRTj-NCRsJ-Q-Rs-aryl; -R6-N(R9)-C(R7)-N(R5)-Q-Rg-heteroaryl; -IU-N(R8C(R7)-N(Rs)-Q-R8-heterocyclyl; -K6-n(K9yC(K1)-N(Rs)r, -R6-N(R9)-C(R7)-N(Rn)-Q-RS-(CM0)alkyl; -R6-N(R9)-C(R7)-N(Ri,)-Q-R8-(C2-,o)alkenyl; -R6-N(R9)-C(R7)-N(Ri])-Q-R»-aryl; -R6-N(R9)-C(R7)-N(RiL)-Q-Rg-heteroaryI; -R6-N(R9)-C(R7)-N(R| i)-Q-Rg-heterocycly!; and -R6-N(R9)-C(R7)-N(Ri])H; R2 is selected from the group consisting of: -hydrogen; -(CMo)alkyl; -(C2-10)alkenyl; -aryl; -heteroaryl; -heterocyclyl; -(CMo)alkylene-Y-(CMO)alkyl; -(C[-10)alkylene-Y-(C2-10)alkenyl; -(C1-10)alkylene-Y-aryl; and -(C1-10)alkyl or (C2_10)alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(R5)2; -C(O)-CM0 alkyl; -C(0)-0-C,.10 alkyl; -N3; -aryl; -heteroaryl; -heterocyclyl; -C(0)-aryl; and -C(0)-heteroaryl; Yis-O- or-S(0)o-2-; Q is bond, -C(O)-, or -SO2-; and A represents the atoms necessary to provide a 5- or 6- membered heterocyclic or heteroaromatic ring that contains up to three heteroatoms; R3 and R4 are independently selected from the group consisting of hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, CMO alkoxy, C1-10 alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, C1-10 alkyl, or C2-10 alkenyl; Re is (C1-10)alkylene, (C2-10)alkenylene, or (C2-10)alkynylene, which may be interrupted by one or more - O - groups; each R7 is =0 or =S; Rg is a bond, (C1-10)alkylene, (C2-10)alkenylene, or (C2-10)alkynylene, which may be interrupted by one or more - 0 - groups; R9 is hydrogen, CMO alky], or aryl(Cj-10)alkyl; or R9 can join together with any carbon atom of K$ to form a ring of the formula 20. The compound or salt as claimed in claim 17 wherein R1-3 is -R6-N(Rg)-C(R7)-N(R5)-Q-R8-(CMo)alkyl. 21. The compound or salt as claimed in claim 17 wherein R1.3 is -R6-N(R9)-C(R7)-N(Rs)-Q-R8-Q-aryI or -R6-N(R9)-C(R7)-N(R5)-Q-Rg-heteroaryl. 22. The compound or salt as claimed in claim 17 wherein Q is a bond. 23. The compound or salt as claimed in claim 17 wherein R5 is (C1-10)alkyl. 24. The compound or salt as claimed in claim 17 wherein R7 is =0. X is -CH(Rs)-, -CH(Rs)- (CM0)alkylene-,-CH(Rs)- (C2-10)alkenylene-, or CH(R5)-(CMo)alkylene-Y-(C2-10)alkylene-; Ri-4 is selected from the group consisting of: -(C2-10)alkenyl; -aryl; and -R6-aryl; R2 is selected from the group consisting of: -hydrogen; -(Cuo)alkyl; -(C2-10)alkenyl; -aryl; -heteroaryl; -heterocyclyl; -(C,.10)alkylene-Y-(CM0)alkyl; -(Q.10Jalkylene-Y-tCa-ifOalkenyl; -(C1.10)alkylene-Y-aryl; and - (C1.10)alkyl or (C2.10)alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(R5)2; -C(O)-C,.,0 alkyl; -C(O)-O-C,.,0 alkyl; -N3; -aryl; -heteroaryl; -heterocyclyl; -C(0)-aryl; and -C(0)-heteroaryl; Yis-O- or-S(O)0-2S R3 and R4 are independently selected from the group consisting of hydrogen, C[.10 alky], C2-10 alkenyl, C2-10 alkynyl, CMS alkoxy, C(.,o alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, Cwo alkyl, or C2-10 alkenyl; and Re is (C1.10)alkylene, (C2.10)alkenylene, or (C2-10)alkynylene, which may be interrupted by one or more - O - groups; or a pharmaceutical acceptable salt thereof. 26. The compound or salt as claimed in claim 25 wherein RMIS -aryl or -Rg-aryl. 27. The compound or salt as claimed in claim 26 wherein aryl is phenyl or substituted phenyl. 28. The compound or salt as claimed in claim 25 wherein Re is (C2-10)alkynylene. 29. The compound or salt as claimed in claim 25 wherein X is -CH(Rs)-C1.s alkylene-. 30. The compound or salt as claimed in claim 25 wherein R& is -(CH2)i-4-. 31. A compound of the Formula (1-5); wherein: X is -CH(R5)-, -CH(Rs)- (CM0)alkylene-, -CH(R1)- (C10Jalkenylene-, or CH(R5)-(C 1.1 o)alky lene-Y-(C 1.10)alky lene-; R1-5 is selected from the group consisting of: -heteroaryl; -heterocyclyl; -Re- heteroaryl; and -Rs-heterocyclyl; R2 is selected from the group consisting of: -hydrogen; -(CMo)aIkyI; - -heteroary]; -heterocyclyl; -(CM0)alkylene-Y-(C1-lo)alkyl; -(C1-10)alkylene-Y-(C2-10)alkenyl; -(C1-10)alkylene-Y-aryl; and -(C1-10)alkyl or (C2-10)alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(R1)2; -C(0)-C1.10alkyl; -C(O)-O-CM0alkyl; -N3; -aryl; -heteroaryl; -heterocyclyl; -C(0)-aryl; and -C(0)-heteroaryl; Yis-O- or-S(O)0-2-; R3 and R4 are independently selected from the group consisting of hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C[-10 alkoxy, CM0 alkylth10, amino, atkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, C1-10 alkyl, or C2-10 alkenyl; and R& is (C1-10)alkylene, (C2-10)alkenylene, or (C2-10)alkynylene, which may be interrupted by one or more -O- groups; or a pharmaceutical acceptable salt thereof. 32. The compound or salt as claimed in claim 31 wherein R1.5 -heteroaryl or - Re-heteroaryl. 33. The compound or salt as claimed in claim 31 wherein R1-5 -heterocyclyl or - R$ -heterocyclyl. 34. The compound or salt as claimed in claim 31 wherein X is -CH(Rs)-C1-5 akylene-. 35. The compound or salt as claimed in claim 31 wherein Re is -(CH2)M-. (1-6) wherein: X is -CH(Rs)-, -CH(Rs)- (CM0)alkylene-, -CH(R5)- (C2.10)alkenylene-, or CH(Rs)-(C1-,o)alkylene-Y-(C,.10)alkylene-; Ri -6 is selected from the group consisting of: -(CM0)alkyl; -aryl; -heteroaryl; -heterocyclyl; -(C2.10)alkenyl; -R6-aryl; -Re- heteroaryl; -Ra-heterocyclyl; R2 is selected from the group consisting of: -hydrogen; -(CM0)alkyl; -(C2.10)aIkenyI; -aryl; -heteroaryl; -heterocyclyl; -(C1.i0)alkylene-Y-{C!.10)aiky]; - (C1-10)aIkyIene-Y-(C2.10)aIkenyi; -(C[-10)alkylene-Y-aryl; and - (Cu10)alkyl or (C2-10)alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(R5)2; -C(O)-CM0alkyl; -C(O)-O-CM0alkyl; -N3; -aryl; -heteroaryl; -heterocyclyl; -C(0)-aryI; and -C(0)-heteroaryJ; Y is - O - or -S(0)D-2-; R3 and R4 are independently selected from the group consisting of hydrogen, Cj.10 alkyl, C2.10 alkenyl, C2.10 alkynyl, Cuoalkoxy, C1-10 alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, CMO alkyl, or C2-10 alkenyl; and R6 is (C1.10)alkylene, (C2-10)aikenylene, or (C2-10)alkynylene, which may be interrupted by one or more - O - atoms; or a pharmaceutical acceptable salt thereof. 37. The compound or salt as claimed in claim 36 wherein -S(0)o.2- is -S-. 38. The compound or salt as claimed in claim 36 wherein -S(0)o-2- is -SO-. 39. The compound or salt as claimed in claim 36 wherein -S(0)o-2- is -S(0)2-. 40. The compound or salt as claimed in claim 36 wherein R1-6 is (C].|o)alkyl. 41. The compound or salt as claimed in claim 36 wherein Ri-eis aryl. 42. The compound or salt as claimed in claim 36 wherein R1-6 is substituted aryl. 43. The compound or salt as claimed in claim 36 wherein Ri.g is heteroaryl. 44. The compound or salt as claimed in any one of claims 3,10,17,25,31 aid 36 wherein R3 and R4 are independently hydrogen, alkyl, halogen, or nitro. 45. The compound or salt as claimed in any one of claims 3,10,17,25,31 and 36 wherein R3 and R4 are both methyl. 46. The compound or salt as claimed in any one of claims 3,10,17,25,31 and 36 wherein R2 is hydrogen. 47. The compound or salt as claimed in any one of claims 3,10,17,25,31 and 36 wherein R2 is (CMO) alkyl. 48. The compound or salt as claimed in any one of claims 3,10,17,25,31 and 36 wherein R2 is-(C1-10)alkylene-0-( C1-10) alkyl. 49. A pharmaceutical composit10n comprising a pharmaceutically effective amount of a compound as claimed in any one of claims 1,2,3,10,17,25,31 and 36 in combinat10n with a pharmaceutically acceptable carrier. R.2 is selected from the group consisting of: -hydrogen; - -heteroaryl; -heterocyclyl; -(C1-i0)alkylene-Y-CCL.,o)alkyl; -(C1-10)alkylene-Y-(C2-10)alkenyl; -(C1-10)alkylene-Y-aryl; and -(C1.10)alkyl or (C2-10)alkenyI substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(R5}2; -C(O)-C,.10alkyl;-C(O)-O-C|-10 alkyl; -N3; -aryl; -heteroaryl; -heterocyclyl; -C(0)-aryl; and -C(0)-heteroaryI; Y is - O - or -S(O)0-2-; R3 and R4 are independently selected from the group consisting of hydrogen, C1.10 alkyl, C2-10 alkenyl, C2-10 alkenyl, Cj.10 alkoxy, C1.10 alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, CMO alkyl, or C2-10 alkenyl; Rs is (C1-10)alkylene, (C2.10)alkenylene, or (C2.10)alkynylene, which may be interrupted by one or more - O - atoms; and R9 is hydrogen, C1-10 alkyl, or aryl(C|,i0)alkyl; or R9 can join together with any carbon atom of Re to form a ring of the formula wherein: X is -CH(Rs)-, -CH(R5)- (CM0)alkylene-, -CH(R5)- (C2-10)alkenylene-, or CH(R5)-(CMo)alkylene-Y-(CHo)alkylenes Ri-6 is selected from the group consisting of. -(C1.w)a]kyi; -aryl; -heteroaryl; -heterocyclyl; -(C2-10)alkenyl; -Rfi-aryl; -R6- heteroaryl; -Re-heterocyclyl; R2 is selected from the group consisting of: -hydrogen; -(C,.,0)alky]; -(C2-10)alkenyl; -aryl; -heteroaryl; -heterocyclyl; -(C1.10)alkylene-Y-(CMo)alkyl; -(CMO)alkylene-Y-(C2.10)alkeny]; -(Cs-10)alkylene-Y-aryl; and - (C1-10)alkyl or (C2-10)alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(RS)2; -C(O)-C,.,0 alkyl; -C(0)-0-C,.,oalkyl; -N3; -aryl; -heteroaryl; -heterocyclyl; -C(0)-aryl; and -C(0)-heteroaryl; Yis-0- or-S(0)o-2-; R3 and R4 are independently selected from the group consisting of hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, C].10 alkyl, or C2-10 alkenyl; and R6 is (C1-10)alkylene, (C2-10)alkenylene, or (Cj-10Jalkynylene, which may be interrupted by one or more - 0 - atoms; or a pharmaceutical acceptable salt thereof. 52. A novel intermediate compound of the Formula V: wherein: X is -CH(Rs)-, -CH(R5)- (CM0)a!ky[ene-, -CH(R5)- (C2-10)alkenylene-, or CH(R5)-(C1.10)alkylene-Y-(CMO)alkylene-; Ri-6 is selected from the group consisting of. -(C,.10)alkyl; -aryl; -heteroaryl; -heterocycly]; -(C2.10)alkenyl; -Re-aryl; -Re- heteroaryl; -Re-heterocyclyl; R2 is selected from the group consisting of: -hydrogen; -(CM0)alkyl; -(C2-10)alkenyl; -aryl; -heteroaryl; -heterocyclyl; -(C1.10)alkylene-Y-(CMO)alkyl; - (C1-10)alkylene-Y-(C2-10)alkenyl; -(C|.10)alkylene-Y-aryl; and -(C1.10)alkyl or (C2-10)alkenyl substituted by one or more substituents selected from the group consisting of -OH; -halogen; -N(RS)2; -C(O)-CM0 alkyl; -C(0)-0-C,.10alkyl; -N3; -aryl; -heteroaryl; -heterocyclyl; -C(0)-aryl; and -C(0)-heteroaryl; Y is - O - or -S(O)0-2S R3 and R4 are independently selected from the group consisting of hydrogen, CJ.10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1.10 alkoxy, C1-10 alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, CMO alkyl, or C2-10 alkenyl; and Re is (C1-10)alkylene, (C2-10)alkenylene, or (C2-10)alkynylene, which may be interrupted by one or more - O - atoms; or a pharmaceutical acceptable salt thereof. wherein: Ri.,,2,3 is Ri-i in LIX-1, Ri.2 in LiX-2, and R1.3 in LlX-3; X is -CH(RS)-, -CH(R5)- (CM0)alkylene-, -CH(R5)- (C2-10)alkenylene-, or CH(R;)-(CMo)alkylene-Y-(C,-10)alkylene-; Ri-i is selected from the group consisting of: -R6-C(R7)-Z-Rg-(CM0)alky]; -R6-C(R7)-Z-R8-(C2-10)alkenyl; -R6-C(R7)-Z-R8-aryl; -R6-C(R7}-Z-R8-heteroaryl; -R6-C(R7)-2-Rg-heterocyc!yl; -R6-C(R7)-Z-H; -R6-N(R9)-C(R7)-R8-(Cu,o)alkyl; -R6-N(R9)-C(R7)-Rg-(CMo)atkenyl; -R6-N(R9)-C(R7)-R8-aryl; -R6-N(R9)-C(R7)-R8-heteroaryl; -R6-N(R9)-C(R7)-R8-heterocyclyl;and -R6-N(R9) -C(R7)-R10; Ri-2 is selected from the group consisting of. -R6-N(R9)-S02-R8-(CMo)alkyl; -R6-N(R9)-S02-R8-(C2-,o)alkenyl; -R6-N(R9)-S02-R8-aryI; -R6-N(R9)-S02-Rg-heteroaryl; -R6-N(R9)-S02-R8-heterocyclyl; -R6-N(R9)-SO2-Rl0; -R6-N(R9)-S02-N(R5)-R8-(CMo)alkyI; -R6-N(R9)-S02-N(Rs)-R8-(CMo)alkenyl; -R6-N(R9)-S02-N(R5)-R8-aryl; -R6-N(R9)-S02-N(Rs)-R8-heteroaryl; -R6-N -R6-N(R9)-S02-NH2; R1.3 is selected from the group consisting of: -R6-N(R9)-C(R7)-N(R5)-Q-Rs-(CMo)alkyl; -R6-N(R9)-C(R7)-N(R5)-Q-R8-(CMo)alkenyI; -R6-N(R9)-C(R7)-N(R5)-Q-R8-aryl; -R6-N(R9)-C(R7)-N(R5)-Q-R8-heteroaryl; -R6N(R9)- C(R7)-N(R5)-Q-R8-heterocyclyl; -R6-N(R9)-C(R7)-N(R5)2; -R6-N(R9)-C(R7)-N(Rii)-Q-R8-(C2.10)alkyl; -R6N(R9)-C(R7)-N(R,i)-Q-R8-(C2.10)alkenyl; -Rs-NtR^-CfR.J-NtRnJ-Q-Rg-aryl; -Re-NtR^-CtR-O-NtRiO-Q-Rs-heteroaryl; -R6-N(R9)-C(R7)-N(Ri ,)-Q-Rs-heterocyclyl; and -R6-N(R9)-C{R7)-N(Rn)H; R2 is selected from the group consisting of: -hydrogen; -(Ci.10)alkyl; -(C2.io)alkenyl; -aryl; -heteroaryl; -heterocyclyl; -(CMO)alkylene-Y-(CM0)alkyl; -(C,.io)aIkyIene-Y-(C2-io)aIkenyi; -(Ci.io)alkylene-Y-aryl; and -(C].io)a!kyl or (C2-io)alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(Rs)2; -C(O)-CM0alkyl; -C(O)-O-CM0alkyl; -N3; -aryl; -heteroaryl; -heterocyclyl; -C(0)-aryl; and -C(0)-heteroaryl; Yis-0- or-S(O)0-2; Z is-N(R5)-, -0-, or S-; Q is a bond, -CO-, or-S02-; A represents the atoms necessary to provide a 5- or 6-membered heterocyclic or heteroaromatic ring that contains up to three heteroatoms; R3 and R4 are independently selected from the group consisting of hydrogen, C1-10 alkyl, C2-10 alkenyi, C2.10 aikynyl, C]-10 aikoxy, C1-10 alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, CMO alkyl, or C2-10 alkenyi; R.,5 is (C1-10)alkylene, (C2-10)alkenylene( or (C2.(o)alkynylene, which may be interrupted by one or more - O - groups; R7 is -O- or =S; Rs is a bond, (C].10)alkylene, (C2.10)alkenylene, or (C2-jo)alkynylene, which may be interrupted by one or more - 0 - groups; R9 is hydrogen, C1-10 alkyl, or arylalkyl; or Rg can join together with any carbon wherein: RM.s is RM in LIX-4, and R1.5 in LIX-5; X is -CH(RsK -CH(R5 (CM0)alkylene-, -CH(R5)- (C2-10)aIkenylene-, or CH(R5)-(CM0)alkylene-Y-(C1.]o)alkylene-; RM is selected from the group consisting of. -(C2.]o)alkenyI; -aryl; and -Re-aryl; R1.5 is selected from the group consisting of: -heteroaryl; -heterocyclyl; -Re- heteroaryl; and -Re-heterocyclyl; R2 is selected from the group consisting of: hydrogen; -alkyl; -(C2-10)alkenyl; -aryl; -heteroaryl; -heterocyclyl; -(CM0)alkylene-Y-(C,.10)alkyl; -(C[.10)alkylene-Y-(C2-10)alkenyl; -(Cj.)o)alkyIene-Y-aryl; and -(C[-10)alkyl or (C2-10)alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(RS)2; -C(O)-CM0alkyl; -C(O)-O-CM0 alkyl; -N3; -aryl; -heteroaryl; -heterocyclyl; -C(0)-aryl; and -C(0)-heteroaryI; Y is-O- or -S(0)o-2-; R3 and R4 are independently selected from the group consisting of hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkenyl, CMO alkoxy, CMO alkylthto, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, Co alkyl, or C2-10 alkenyl; and R6 is (C1-10)alkylene, (C2-10)alkenylene, or (C2.u)alkynylene, which may be interrupted by one or more - 0 - groups; or a pharmaceutical acceptable salt thereof. wherein X is -CH(Rs)-, -CH(Rs)- (CM0)alkylene-, -CH(Rs)- (C2-10)alkenylene-, or CH(R5)-(C1.10)alkylene-Y-(CMQ)alkylene-; R2 is selected from the group consisting of. -hydrogen; -(CH0)alkyl; -(C2-10)alkenyl; -aryl; -heteroaryl; -heterocyclyl; -(CMO)alkylene-Y-(C1.10)alkyl; -(C|_,0)a]ky]ene-Y-(C2-10)alkeny]; -(C].1())alkylene-Y-aryl; and -(C1.10)alkyl or (C2-10)alkenyl substituted by one or more substituents selected from the group consisting of: -OH; -halogen; -N(R5)2; -C(0)-CMO alkyl; -C(O)-O-CM0alkyl; -N3; -aryJ; -heteroaryl; -heterocyclyl; -C(0)-aryl; and -C(0)-heteroaryl; Yis-O- or-S(O)0-2-; R3 and R4 are independently selected from the group consisting of hydrogen, C1-10 alkyl, C2.10 alkenyl, C2-10 alkynyl, C]-10 alkoxy, C1-10alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, CMO alkyl, or C2-10 alkenyl; R& is (C1-10)alkylene, (C2-10)aIkenylene, or (C2-10)aIkynyIene, which may be interrupted by one or more - 0 - atoms; and R9 is hydrogen, CMO alkyl, or aryl(C1-10)alkyl; or R9 can join together with X is -CH(R5)-, -CH(R5)- (CM0)alkylene-, -CH(Rs)- (C2-10)alkeny!ene-, or CH(R5)-(C1.1o)alkylene-Y-(C1.,o)alkylene-; Yis-O- or-S(O)0.2-; BOC is /err-butoxycarbonyl; R3 and R4 are independently selected from the group consisting of hydrogen, C1-loalkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, d-10 alkyl, or C2.10 alkenyl; Re is (C1-10)alkylene, (C2-10)aIkenyIene, or (C2.10)aIkynyiene, which may be interrupted by one or more - O - atoms; R9 is hydrogen, C1-10 alkyl, or aryl(Cj.10)alkyl; or R9 can join together with any R3 and R4 are independently selected from the group consisting of hydrogen, CL10 alkyl, C2-10 alkenyl, C2-10 alkynyl, Cl-lo alkoxy, C1-10 alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each R5 is independently hydrogen, C1-10 alkyl, or C2-10 alkenyl.; and T is selected from nitro and amino; or a pharmaceutically acceptable salt thereof. X is -CH(R5)-, -CH(R3)- (C1-10)alkylene-, -CH(R5)- (C2-10)alkenylene-, or CH(R5)-(C1.10)alkylene-Y-(CMo)alkylene-; Y is -O- or -S(O)0-2-; R1.5 is selected from the group consisting of: -heteroaryl; -heterocyclyl; -Re- heteroaryl; and -Rfi-heterocyclyl; RM is selected from the group consisting of: -(C2.,o)alkenyl; -aryl; and -R6-aryl; R3 and R4 are independently selected from the group consisting of hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, d-10 alkoxy, C1-i0 alkylth10, amino, alkylamino, dialkylamino, halogen, and nitro; each Rs is independently hydrogen, CMO alkyl, or C2-10 alkenyl; Re is (C1-10)alkylene, (C2-10)alkenylene, or (C2-10)alkynylene, which may be interrupted by one or more - O - groups; and T is selected from nitro and amino; or a pharmaceutical ly acceptable salt thereof.

Documents:

2763-chenp-2004 abstract.pdf

2763-chenp-2004 abstrcat duplicate.pdf

2763-chenp-2004 assignment.pdf

2763-chenp-2004 claims duplicate.pdf

2763-chenp-2004 claims.pdf

2763-chenp-2004 correspondence-others.pdf

2763-chenp-2004 correspondence-po.pdf

2763-chenp-2004 decsription (complete) 2.pdf

2763-chenp-2004 decsription (complete) 3.pdf

2763-chenp-2004 decsription (complete) 4.pdf

2763-chenp-2004 decsription (complete) duplicate 2.pdf

2763-chenp-2004 decsription (complete) duplicate 3.pdf

2763-chenp-2004 decsription (complete) duplicate 4.pdf

2763-chenp-2004 decsription (complete) duplicate.pdf

2763-chenp-2004 decsription (complete).pdf

2763-chenp-2004 form-1.pdf

2763-chenp-2004 form-18.pdf

2763-chenp-2004 form-3.pdf

2763-chenp-2004 form-5.pdf

2763-chenp-2004 pct.pdf

2763-chenp-2004 petition.pdf