| Title of Invention | SUBSITUTED PHENYLSULFONAMIDE INHIBITORS OF BETA AMYLOID PRODUCTION |
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| Abstract | Compounds of Formula I, wherein R1-R8 are defined herein are provided, together with pharmaceutically acceptable salts, hydrates, metabolites, and/or prodrugs thereof. Uses of these compounds for inhibiting beta amyloid production and for the prevention and treatment of Alzheimer's Disease and Down's syndrome are described. |
| Full Text | SUBSTITUTED PHENYLSULF0NAM1DE INHIBITORS OF BETA AMYLOID PRODUCTION CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of US Patent Application No. 60/387,690, filed June 11,2002, which is incorporated by reference herein. BACKGROUND OF THE INVENTION This invention relates to small molecular compounds which inhibit beta amyloid production and have utility in the treatment of Alzheimer's disease. Alzheimer's Disease (AD) is the most common form of dementia (loss of memory) in the elderly. The main pathological lesions of AD found in the brain consist of extracellular deposits of beta amyloid protein in the form of plaques and angiopathy and intracellular neurofibrillary tangles of aggregated hyperphosphorylated tau protein. Recent evidence has revealed that elevated beta amyloid levels in the brain not only precede tau pathology but also correlate with cognitive decline. Further suggesting a causative role for beta amyloid in AD, recent studies have shown that aggregated beta amyloid is toxic to neurons in cell culture and has a detrimental effect on memory. This suggests that reducing beta amyloid levels is a viable therapeutic strategy for the treatment of AD. Beta amyloid protein is composed mainly of 39 to 42 amino acid peptides and is produced from a larger precursor protein called amyloid precursor protein (APP) by the sequential action of the proteases beta and gamma secretase. Although rare, cases of early onset AD have been attributed to genetic mutations in APP that lead to an overproduction of either total beta amyloid protein or its more aggregation-prone 42 amino acid isoform. Furthermore, people with Down's Syndrome possess an extra chromosome that contains the gene that encodes APP and thus have elevated beta amyloid levels and invariably develop AD later in life. There continues to be a need for compositions useful in inhibiting beta amyloid production and in the prevention and treatment of Alzheimer's Disease. SUMMARY OF THE INVENTION In one aspect, a method of lowering beta amyloid levels is provided which includes delivering to a patient a phenylsulfonamide compound and monitoring the beta amyloid levels in the patient. In another aspect, a method of lowering beta amyloid levels is provided which includes delivering to a patient a compound of formula I: In a further aspect, a method of preventing or treating Alzheimer's disease is provided which includes delivering to a patient, a compound of formula I: In yet another aspect, a compound of formula Ia is provided, wherein formula Ia is: In a further aspect, a compound of formula Ib is provided, wherein formula Ib is: Other aspects and advantages of the present invention are described further in the following detailed description of the preferred embodiments thereof. DETAILED DESCRIPTION OF THE INVENTION The present invention provides methods of monitoring beta amyloid production in patients at risk for, or suffering from, AD and other diseases resulting from elevated levels of beta amyloid protein in the brain. The present invention also provides methods of lowering beta amyloid levels which includes delivering to a patient a pharmaceutically acceptable amount of a compound of the invention and monitoring the levels of beta-amyloid in the patient. By the term "patient" as used herein is meant to describe a mammal which has been diagnosed as having or is at risk of having one or more of the conditions for which modulation of beta amyloid levels is desirable. Preferably, the patient is a human, domestic animal, including canines and felines, or livestock and more preferably is a human. Thus, the compounds are useful for treatment and/or prevention of a number of human and veterinary conditions. By the term "lowering beta amyloid levels" as used herein is meant to describe decreasing or inhibiting beta amyloid production in a patient. A variety of conditions can be treated by lowering beta amyloid production in a patient and include Alzheimer's Disease, dementia, Down's Syndrome, and mild cognitive impairment, among others. As used herein, the term "prevention" encompasses precluding the onset of symptoms in a patient who has been identified with or is at risk for a condition resulting from elevated levels of beta amyloid protein in the brain. The patient may not have been diagnosed with the same or have not yet presented any symptoms thereof. I. Compositions of the Invention In one embodiment, the present invention provides compounds of formula I: wherein: R1 is selected from the group consisting of H, halogen, and O; R2 is selected from the group consisting of H, halogen, and N=N; R3 is selected from the group consisting of H and halogen; R4 is selected from the group consisting of H, halogen, amino, and N=N; R5 is selected from the group consisting of H, halogen, methoxy, methyl, and O; or R1 and R2; R2 and R3; R4 and R5; or R3 and R4 are fused to form a carbon- based, naphthalene ring with the benzene ring; R6 is selected from the group consisting of H, lower alkyl, lower alkenyl, 3- phenyl-2-propyn-1-yl, benzyl, substituted benzyl, CH2 cycloalkyl, CH2-2-furan, (CH2)2SCH3, and (CH2)2NHBOC; R7 is selected from the group consisting of H, lower alkyl, and cycloalkyl; R8 is selected from the group consisting of lower alkyl, substituted alkyl, cycloalkyl, phenyl, substituted phenyl, benzyl, substituted benzyl, CH2 cycloalkyl, CH2-3-indole, CH(lower alkyl)-2-furan, CH(lower alkyl)-4-methoxyphenyl, CH(lower alkyl) phenyl, and CH(OH)-4-SCH3-phenyl; or R7 and R8 are fused to form a saturated carbon-based ring; T is R9 and R10 are H; or R9 is H and R10 is selected from the group consisting of lower alkyl, CF3, lower alkenyl, methyl-substituted alkenyl, lower alkynyl, cycloalkyl, substituted phenyl, 1-naphthyl, and CH2CH2-1,3-dioxolane; or R9 and R10 are independently selected from the group consisting of lower alkyl, lower alkenyl, phenyl, 4-substituted-phenyl, and 1-naphthyl; wherein: (i) when R5 is a methoxy; R2 is halogen and R1, R3, and R4 are H; (ii) when R5 is a methyl; R1 is halogen and R2, R3, and R4 are H; (iii) when R4 is an amino; R3 is halogen and R1, R2, and R5 are H; (iv) when R2 is N=N and R1 is O; R2 is bound to R1 to form a heterocyclic ring; (v) when R4 is N=N and R5 is O; R4 is bound to R5 to form a heterocyclic ring; and (vi) at least one of R1, R2, R3, R4, and R5 is halogen unless R1 and R2; R2 and R3; R4 and R5; or R3 and R4 are fused to form a carbon-based, naphthalene ring with the benzene ring; or a pharmaceutically acceptable salt, metabolite, hydrate, or prodrug thereof. In another embodiment, the compound is of formula 1a: wherein: R1 is selected from the group consisting of H, halogen, and O; R2 is selected from the group consisting of H, halogen, and N=N; R3 is selected from the group consisting of H and halogen; R4 is selected from the group consisting of H, halogen, amino, and N=N; R5 is selected from the group consisting of H, halogen, methoxy, methyl, and O; R6 is selected from the group consisting of H, lower alkyl, lower alkenyl, 3-phenyl-2-propyn-l-yl, benzyl, substituted benzyl, CH2 cycloalkyl, CH2-2-furan, (CH2)2SCH3, and (CH2)2NHBOC; R8 is selected from the group consisting of n-propyl, iso-propyl, iso-butyl, n-butyl, t-butyl, substituted butyl, optionally substituted hexyl, optionally substituted heptyl, cycloalkyl, CH2 cycloalkyl, CH(lower alkyl)-2-furan, CH(lower alkyl)-4- methoxyphenyl, CH(lower alkyl) phenyl, CH(OH)-4-SCH3-phenyl, and (CH2)2-S- lower alkyl; T is R9 and R10 are H; or R9 is H and R10 is selected from the group consisting of lower alkyl, lower alkenyl, methyl-substituted alkenyl, lower alkynyl, CF3, cycloalkyl, substituted phenyl, 1-naphthyl, and CH2CH2-1,3-dioxolane; or R9 and R10 are independently selected from the group consisting of lower alkyl, lower alkenyl, phenyl, 4-substituted-phenyl, and 1-naphthyl; wherein: (i) when R5 is a methoxy; R2 is halogen and R1, R3, and R4 are H; (ii) when R5 is a methyl; R1 is halogen and R2, R3, and R4 are H; (iii) when R4 is an amino; R3 is halogen and R1, R2, and R5 are H; (iv) when R2 is N=N and R1 is O; R2 is bound to R1 to form a heterocyclic ring; (v) when R4 is N=N and R5 is O; R4 is bound to R5 to form a heterocyclic ring; and (vi) one or more of R1 to R5 is a halogen; or a pharmaceutically acceptable salt, metabolite, hydrate, or prodrug thereof. In a further embodiment, the compound is of formula I: wherein: R1 is selected from the group consisting of H, halogen, and O; R2 is selected from the group consisting of H, halogen, and N=N; R3 is selected from the group consisting of H and halogen; R4 is selected from the group consisting of H, halogen, amino, and N=N; R5 is selected from the group consisting of H, halogen, methoxy, methyl, and O;or R1 and R2 or R4 and R5 are fused to form a carbon-based, unsaturated ring; R6 is selected from the group consisting of H, lower alkyl, lower alkenyl, 3- phenyl-2-propyn-1-yl, benzyl, substituted benzyl, CH2 cycloalkyl, CH2-2-furan, (CH2)2SCH3, and (CH2)2NHBOC; R7 is selected from the group consisting of H, lower alkyl, and cycloalkyl; R8 is selected from the group consisting of benzyl and substituted benzyl; T is R9 and R10 are H; or R9 is H and R10 is selected from the group consisting of lower alkyl, lower alkenyl, methyl-substituted alkenyl, CF3, lower alkynyl, cycloalkyl, substituted phenyl, 1-naphthyl, and CH2CH2-1,3-dioxolane; or T is R9 and R10 are H; or R9 is H and R10 is selected from the group consisting of lower alkyl, lower alkenyl, methyl-substituted alkenyl, CF3, lower alkynyl, cycloalkyl, substituted phenyl, 1-naphthyl, and CH2CH2-1,3-dioxolane; or R9 and R10 are independently selected from the group consisting of lower alkyl, lower alkenyl, phenyl, 4-substituted-phenyl, and 1-naphthyl; wherein: (i) when R5 is a methoxy; R2 is halogen and R1, R3, and R4 are H; (ii) when R5 is a methyl; R1 is halogen and R2, R3, and R4 are H; (iii) when R4 is an amino; R3 is halogen and R1, R2, and R5 are H; (iv) when R2 or R4 is N=N; R1 or R5 is O and R2 or R4 is bound to R1 or R5 to form a heterocyclic ring; and (v) one or more of R1 to R5 is a halogen; or a pharmaceutically acceptable salt, metabolite, hydrate, or prodrug thereof. In a further embodiment, the compound is of formula I: wherein: R1 is selected from the group consisting of H, halogen, and O; R2 is selected from the group consisting of H, halogen, and N=N; R3 is selected from the group consisting of H and halogen; R4 is selected from the group consisting of H, halogen, amino, and N=N; R5 is selected from the group consisting of H, halogen, methoxy, methyl, and O; R9 and R10 are independently selected from the group consisting of lower alkyl, lower alkenyl, phenyl, 4-substituted-phenyl, and 1-naphthyl; wherein: (i) when R5 is a methoxy; R2 is halogen and R1, R3, and R4 are H; (ii) when R5 is a methyl; R1 is halogen and R2, R3, and R4 are H; (iii) when R4 is an amino; R3 is halogen and R1, R2, and R5 are H; (iv) when R2 is N=N and R1 is O; R2 is bound to R1 to form a heterocyclic ring; (v) when R4 is N=N and R5 is O; R4 is bound to R5 to form a heterocyclic ring; and (vi) one or more of R1 to R5 is a halogen; or a pharmaceutically acceptable salt, metabolite, hydrate, or prodrug thereof. In yet another embodiment, the compound is of formula Ib: wherein: R1 is selected from the group consisting of H, halogen, and O; R2 is selected from the group consisting of H, halogen, and N=N; R3 is selected from the group consisting of H, bromine, fluorine, and iodine; R4 is selected from the group consisting of H, halogen, amino, and N=N; R5 is selected from the group consisting of H, halogen, methoxy, methyl, and O; R6 is selected from the group consisting of H, lower alkyl, lower alkenyl, 3- phenyl-2-propyn-1-yl, benzyl, substituted benzyl, CH2 cycloalkyl, CH2-2-furan, (CH2)2SCH3, and (CH2)2NHBOC; R7 is selected from the group consisting of H, lower alkyl, and cycloalkyl; R6 is selected from the group consisting of H, lower alkyl, lower alkenyl, 3- phenyl-2-propyn-1-yl, benzyl, substituted benzyl, CH2 cycloalkyl, CH2-2-furan, (CH2)2SCH3, and (CH2)2NHBOC; R7 is selected from the group consisting of lower alkyl and cycloalkyl; R8 is selected from the group consisting of cycloalkyl, phenyl, substituted phenyl, CH2 cycloalkyl, CH(lower alkyl)-2-furan, CH(lower alkyl)-4- methoxyphenyl, CH(lower alkyl) phenyl, and CH(OH)-4-SCH3-phenyl; T is R9 and R10 are H; or R9 is H and R10 is selected from the group consisting of lower alkyl, lower alkenyl, methyl-substituted alkenyl, lower alkynyl, CF3, cycloalkyl, substituted phenyl, 1-naphthyl, and CH2CH2-1,3-dioxolane; or R9 and R10 are independently selected from the group consisting of lower alkyl, lower alkenyl, phenyl, 4-substituted-phenyl, and 1-naphthyl; wherein: (i) when R5 is a methoxy; R2 is halogen and R1, R3, and R4 are H, (ii) when R5 is a methyl; R1 is halogen and R2, R3, and R4 are H; (iii) when R4 is an amino; R3 is halogen and R1, R2, and R5 are H; (iv) when R2 is N=N and R1 is O; R2 is bound to R1 is form a heterocyclic ring; and (v) when R4 is N=N and R5 is O; R4 is bound to R5 to form a heterocyclic ring; and (vi) one or more of R1 to R5 is a halogen; or a pharmaceutically acceptable salt, metabolite, hydrate, or prodrug thereof. In yet a further embodiment, the compound is of formula I: wherein: R1 is selected from the group consisting of H, halogen, and O; R2 is selected from the group consisting of H, halogen, and N=N; R3 is selected from the group consisting of H and halogen; R4 is selected from the group consisting of H, halogen, amino, and N=N; R5 is selected from the group consisting of H, halogen, methoxy, methyl, and O; or R1 and R2; R2 and R3; R4 and R5; or R3 and R4 are fused to form a carbon- based, naphthalene ring with the benzene ring; R6 is selected from the group consisting of H, lower alkyl, lower alkenyl, 3- phenyl-2-propyn-l-yl, benzyl, substituted benzyl, CH2 cycloalkyl, CH2-2-furan, (CH2)2SCH3, and (CH2)2NHBOC; R7 is selected from the group consisting of H, lower alkyl, and cycloalkyl; R8 is selected from the group consisting of cycloalkyl, phenyl, substituted phenyl, benzyl, substituted benzyl, CH2 cycloalkyl, CH(lower alkyl)-2-furan, CH(lower alkyl)-4-methoxyphenyl, CH(lower alkyl) phenyl, and CH(OH)-4-SCH3- phenyl; or R7 and R8 are fused to form a saturated carbon-based ring; T is wherein: (i) when R5 is a methoxy; R2 is halogen and R1, R3, and R4 are H; (ii) when R5 is a methyl; R1 is halogen and R2, R3, and R4 are H; (iii) when R4 is an amino; R3 is halogen and R1, R2, and R5 are H; (iv) when R2 is N=N and R1 is O; R2 is bound to R1 to form a heterocyclic ring; (v) when R4 is N=N and R5 is O; R4 is bound to R5 to form a heterocyclic ring; (vi) when each of R1, R2, R4, R5, and R6 is H, R3 is halogen, and R7 is H, then R8 is C5 to C8 alkyl or R7 and R8 are fused to form a saturated carbon-based ring; (vii) when each of R3, R4, R5, R6, and R7 is H and R1 and R2 are fused to form a carbon-based naphthalene ring, then R8 is selected from the group consisting of lower alkyl, cycloalkyl, phenyl, substituted phenyl, benzyl, substituted benzyl, CH2 cycloalkyl, CH(lower alkyl)-2-furan, CH(lower alkyl)-4-methoxyphenyl; CH(lower alkyl) phenyl, and CH(OH)-4-SCH3-phenyl; (viii) when each of R1, R2, R4, R5, and R6 is H and R3 is halogen, then R7 and R8 are not both CH3; and (ix) at least one of R1, R2, R3, R4, and R5 is halogen unless R1 and R2; R2 and R3; R4 and R5; or R3 and R4 are fused to form a carbon-based, naphthalene ring with the benzene ring; or a pharmaceutically acceptable salt, metabolite, hydrate, or prodrug thereof. In another embodiment, the compound is of formula I: wherein: R1 is selected from the group consisting of H, halogen, and O; R2 is selected from the group consisting of H, halogen, and N=N; R3 is selected from the group consisting of H and halogen; R4 is selected from the group consisting of H, halogen, amino, and N=N; R5 is selected from the group consisting of H, halogen, methoxy, methyl, and O; or R1 and R2; R2 and R3; R4 and R5; or R3 and R4 are fused to form a carbon- based, naphthalene ring with the benzene ring; R6 is selected from the group consisting of lower alkyl, lower alkenyl, 3- phenyl-2-propyn-1-yl, benzyl, substituted benzyl, CH2 cycloalkyl, CH2-2-furan, (CH2)2SCH3, and (CH2)2NHBOC; R7 and R8 are fused to form a saturated carbon-based ring; T is R9 and R10 are H; or R9 is H and R10 is selected from the group consisting of lower alkyl, lower alkenyl, methyl-substituted alkenyl, CF3, lower alkynyl, cycloalkyl, substituted phenyl, 1-naphthyl, and CH2CH2-1,3-dioxolane; or R9 and R10 are independently selected from the group consisting of lower alkyl, lower alkenyi, phenyl, 4-substiruted-phenyl, and 1-naphthyl; wherein: (i) when R5 is a methoxy; R2 is halogen and R1, R3, and R4 are H; (ii) when R5 is a methyl; R1 is halogen and R2, R3, and R4 are H; (iii) when R4 is an amino; R3 is halogen and R1, R2, and R5 are H; (iv) when R2 is N=N and R1 is O; R2 is bound to R1 to form a heterocyclic ring; (v) when R4 is N=N and R5 is O; R4 is bound to R5 to form a heterocyclic ring; and (vi) at least one of R1, R2, R3, R4, and R5 is halogen unless R1 and R2; R2 and R3; R4 and R5; or R3 and R4 are fused to form a carbon-based, naphthalene ring with the benzene ring; or a pharmaceutically acceptable salt, metabolite, hydrate, or prodrug thereof. In yet a farther embodiment, the compound is selected from the group consisting of 2-bromo-N-[(1S, 2S)-1-(hydroxymethyl)-2- methylbutyl]benzenesulfonamide, 3-bromo-N-[(1S, 2S)-1-(hydroxymethyl)-2- methylbutyl]benzenesulfonamide, 3-chloro-N-[(1S, 2S)-1-(hydroxymethyl)-2- methylbutyl]benzenesulfonamide, 4-chloro-N-[(1S, 2S)-1-(hydroxymethyl)-2- methylbutyl]-1,2,3-benzoxadiazole-7-sulfonamide,2-chloro-4-fluoro-N-[(1S, 2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 5-chloro-N-[(1S, 2S)-1- (hydroxymethyl)-2-methylbutyl]-2-methoxybenzenesulfonamide, 2-chloro-N- [(1S, 2S)-1-(hydroxymethyl)-2-methylbutyl]-6-methylbenzenesulfonamide, 3,5-dichloro- N-[(1S, 2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 2,4-difluoro-N- [(1S, 2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide,4-fluoro-N-[(1S, 2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide,2-fluoro-N-[(1S, 2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, N-[(1S, 2S)-1- (hydroxymethyl)-2-methylbutyl]naphthalene-1-sulfonamide, N-[(1S, 2S)-1- (hydroxymethyl)-2-methylbutyl] naphthalene-2-sulfonamide, 3-amino-4-chloro-N- [(1S, 2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide, N-[(1S)-1-benzyl-2- hydroxyethyl]-4-bromobenzenesulfonanaide, 4-bromo-N-[(1S)-1-cyclohexyl-2- hydroxyethyl] benzenesulfonamide, 4-bromo-N-[(1R)-2-hydroxy-1-(4- hydroxyphenyl)ethyl] benzenesulfonamide, 4-bromo-N-[(1S)-1-(hydroxymethyl)-3- methylbutyl] benzenesulfonamide, 4-bromo-N-[(1S)-2-hydroxy-1-(1H-indol-2- ylmethyl)ethyl] benzenesulfonamide, 4-bromo-2,5-difluoro-N-[(1S,2S)-1- (hydroxymethyl-2-methylbutyl]benzenesulfonamide, 2,5-dibromo-N-[(lS,2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 3,4-dibromo-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 2,3-dichloro-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 3,4-dichloro-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 2,4,5-trichloro-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 4-bromo-2,5-difluoro-N-[(1S)- 1-(hydroxymethyl)-2-methylpropyl]benzenesulfonamide, 3,4-dichloro-N-[(1S)-1- (hydroxymethyl)-2-methylpropyl]benzenesulfonamide, 2,4,6-trichloro-N-[(1S)-1- (hydroxymethyl)-2-methylpropyl]benzenesulfonamide, 3,4-dibromo-N-[(1S)-1- (hydroxymethyl)-2,2-dimethylpropyl]benzenesulfonamide, 3,4-dichloro-N- [(1S)-1- (hydroxymethyl-2,2-dimethylpropyl]benzenesulfonamide, 2,4,5-trichloro-N-[(1S)-1- (hydroxymethyl)-2,2-dimethylpropyl]benzenesulfonamide, 2,4,6-trichloro-N-[(1S)-1- (hydroxymethyl)-2,2-dimethylpropyl]benzenesulfonamide,4-bromo-N-[(1R,2R)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 4-bromo-N-[(1S)-1- (hydroxymethyl)-1,2-dimethylpropyl]benzenesulfonamide,4-bromo-N-[1- (hydroxymethyI)-2-phenylpropyl] benzenesulfonamide, 4-bromo-N-[(1S,2R)-1- (hydroxymethyl)-2-methylbutyl] benzenesulfonamide, 4-chloro-N-[(1S)-l- (hydroxymethyl)-1,2-dimethylpropyl] benzenesulfonamide, 4-chloro-N-[1- (hydroxymethyl)-2-phenylpropyl] benzenesulfonamide, 4-chloro-N-[(1S,2R)-1- (hydroxymethyl)-2-methylbutyl] benzenesulfonamide, N-allyl-4-chloro-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl] benzenesulfonamide, N-([1, 1'-biphenyl]-4- ylmethyl)-4-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2- methylbutyl]benzenesulfonamide, tert-butyl 2-{[(4-chlorophenyl) sulfonyl][(1S,2S)- 1-(hydroxymethyl)-2-methylbutyl]amino} ethylcarbamate, 4-chloro-N-(4- chlorobenzyl)-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl] benzenesulfonamide, 4-chloro-N-(cyclobutylmethyl)-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl] benzenesulfonamide, 4-chloro-N-(3,4-dimethoxybenzyl)-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 4-chloro-N-(2-furylmethyl)-N- [(1S,2S)-1-(hydroxymethyl)-2-methylbutyl] benzenesulfonamide, 4-chloro-N- [(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]-N-[2- (methylthio)ethyl]benzenesulfonamide, 4-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2- methylbutyl]-N-(3-phenylprop-2-ynyl) benzenesulfonamide, 4-chloro-N-[(1S,2R)-1- (hydroxymethyl)-2-(4-methoxyphenyl)propyl]benzenesulfonamide, 4-chloro-N- [(1S,2R)-1-(hydroxymethyl)-2-methyloctyl] benzenesulfonamide, 4-chloro-N- [(1S,2R)-1-(hydroxymethyl)-2-phenylpropyl] benzenesulfonamide, 4-chloro-N-[(1S)- 2-ethyl-1-(hydroxymethyl)butyl] benzenesulfonamide, 4-chloro-N-[(1S,2R)-2-ethyl- 1-(hydroxymethyl)-4-methylpentyl] benzenesulfonamide, 4-chloro-N-[(1S,2S)-1- (hydroxymethyl)-2-methylpentyl] benzenesulfonamide, 4-chloro-N-[(1S,2S)-2-ethyl- 1-(hydroxymethyl)pentyl] benzenesulfonamide, 4-chloro-N-[(1S,2R)-1- (hydroxymethyl)-4-methyl-2-propylpentyl] benzenesulfonamide, 4-chloro-N- [(1S,2R)-1-(hydroxymethyl)-2-(4-methoxyphenyl) pentyl]benzenesulfonamide, 4- chloro-N-[(1S,2R)-1-(hydroxymethyl)-2-propyloctyl] benzenesulfonamide, 4-chloro- N-[(1S,2R)-1-(hydroxymethyl)-2-phenylpentyl] benzenesulfonamide, 4-chloro-N- [(1S, 2S)-1-(hydroxyraethyl)-2-methylheptyl] benzenesulfonamide, 4-chloro-N- [(1S,2S)-2-ethyI-1-(hydroxymethyl)-heptyl] benzenesulfonamide, 4-chloro-N- [(1S,2R)-1-(hydroxymethyl)-2-pentyloctyl] benzenesulfonamide, 4-chloro-N- [(1S,2S)-1-(hydroxymethyl)-2-phenylpropyl] benzenesulfonamide, 4-chloro-N- [(1S,2S)-1-(hydroxymethyl)-4-methyl-2-phenylpentyl] benzenesulfonamide, 4- chloro-N-[(1S, 2S)-1-(hydroxymethyl)-2-phenyloctyl] benzenesulfonamide, 4-chloro- N-[(1S,2R)-2-(2-furyl)-1-(hydroxymethyl)butyl] benzenesulfonamide, 4-chloro-N- [(1S,2R)-2-(2-furyl)-1-(bydroxymethyl)-4-methyl pentyl]benzenesulfonamide, 4- chloro-N-[(1S,2R)2-(2-furyl)-1-(hydroxymethyl)octyl] benzenesulfonamide, 4- chloro-N-[(1S,2S)-1-(hydroxymethyl)-2,3-dimethylbutyl] benzenesulfonamide, 4- chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-isopropyloctyl] benzenesulfonamide, 4- bromo-N-[(1S,2R)-1-(hydroxymethyl)-2-(4-methoxyphenyl) propyl]benzenesulfonamide, 4-bromo-N-[(1S,2R)-1-(hydroxymethyl)-2-methyloctyl] benzenesulfonamide, 4-bromo-N-[(1S,2R)-2-ethyl-1-(hydroxymethyl)-4- methylpentyl] benzenesulfonamide, 4-bromo-N-[(1S,2R)-1-(hydroxymethyl)-2-(4- methoxyphenyl) butyl]benzenesulfonamide, 4-bromo-N-[(1S,2R)-2-ethyl-1- (hydroxymethyl)octyl] benzenesulfonamide, 4-bromo-N-[(1S,2S)-1-(hydroxymethyl)- 2-methylpentyl] benzenesulfonamide, 4-bromo-N-[(1S,2S)-2-ethyl-1- (hydroxymethyl) pentyl] benzenesulfonamide, 4-bromo-N-[(1S,2R)-1- (hydroxymethyl)-4-methyl-2-propylpentyl] benzenesulfonamide, 4-bromo-N- [(1S,2R)-1-(hydroxymethyl)-2-propyloctyl] benzenesulfonamide, 4-bromo-N- [(1S,2S)-1-(hydroxymethyl)-2-methylheptyl] benzenesulfonamide, 4-bromo-N- [(1S,2S)-2-ethyl-1-(hydroxymethyl) heptyl] benzenesulfonamide, 4-bromo-N- [(1S,2S)-1-(hydroxymethyl)-2-phenylpropyl] benzenesulfonamide, 4-bromo-N- [(1S,2S)-1-(hydroxymethyl)-2-phenylbutyl] benzenesulfonamide, 4-bromo-N- [(1S,2R)-2-(2-furyl)-1-(hydroxymethyl)propyl] benzenesulfonamide, 4-bromo-N- [(1S,2R)-2-(2-furyl)-1-(hydroxymethyl)butyl] benzenesulfonamide, 4-bromo-N- [(1S,2R)-2-(2-furyl)-1-(hydroxymethyl)-4-methylpentyl]benzenesulfonamide, 4- bromo-N-[(1S, 2S)-1-(hydroxymethyl)-2-isopropyl-4- methylpentyl]benzenesulfonamide,4-chloro-N-[(1S, 2S)-2-ethyl-1-(hydroxymethyl) octyl] benzenesulfonamide, 4-chloro-N-[(l S,2R)-2-ethyl-1-(hydroxymethyl)octyl] benzenesulfonamide, 4-chloro- N-methyl-N-[(1S,2S)-1-(hydroxymethyl)-2- methylbutyl] benzenesulfonamide, 4-chIoro-N-[(1S,2S)-1-(hydroxymethyl)-2- methyIbutyl]-benzenesuifonamide,4-chloro-N-[(1S)-1-(hydroxymethyl)-3- methylbutyl]benzenesulfonamide-chloro-N-[(1R,2S)-hydroxy-1-methyl-2- phenylethyl] benzenesulfonamide, 4-bromo-N-[1- (hydroxymethyl)cyclopentyl]benzenesulfonamide, 4-chloro-N-[(1S)-2-cycIohexyl-1- (hydroxymethyl)ethyl]benzenesulfonamide, N-{(1S)-1-[4-(benzyloxy)benzyl]-2- hydroxyethyl}-4-chlorobenzenesulfonamide, 4-chloro-N-[(lR)-1-(hydroxymethyl)-1- methylpropyl]benzenesulfonamide, 4-bromo-N-[(1S,2S)-1-(hydroxymethyl)-2- methylbutyl]-benzenesulfonamide, 4-bromo-N-[1-(hydroxymethyl) pentyl]benzenesulfonamide, 4-bromo-N-[(1R,2S)-2-hydroxy-1-methyl-2-phenylethyl] benzenesulfonamide, 4-bromo-N-[(1S)-2-hydroxy-1- phenylethyl]benzenesulfonamide, 4-bromo-N-[(1R)-1-(hydroxymethyl)-3- methylbutyl]benzenesulfonamide, 4-chloro-N-[1- (hydroxyraethyl)cyclopentyl]benzenesulfonamide, 4-bromo-N-[1- (hydroxymethyl)butyl] benzenesulfonamide, 3-chloro-N-[1- (hydroxymethyl)butyl]benzenesulfonamide, 3-chloro-N-[(1S)-2-cyclohexyl-1- (hydroxymethyl)ethyl]benzenesulfonamide, 3-chloro-N-[(1R)-1-(hydroxymethyl)-3- (methylthio)propyl]benzenesulfonamide, 3 -chloro-N-[(1S)-1- (hydroxymethyl)propyl]benzenesulfonamide, 2-fluoro-N-[(1S)-1-(hydroxymethyl)-3- methylbutyl]benzenesulfonamide, 2-fluoro-N-[1-(hydroxymethyl)pentyl] benzenesulfonamide, 2-fluoro-N-[(1R,2S)-2-hydroxy-1-methyl-2-phenylethyl] benzenesulfonamide, 2-fluoro-N-[(1S)-2-hydroxy-1- phenylethyl]benzenesulfonamide, 2-fluoro-N-[(1R)-1-(hydroxymethyl)-3- methylbutyl]benzenesulfonamide, 2-fluoro-N-[1- (hydroxymethyl)cyclopentyl]benzenesulfonamide, N-[(1S)-2-cyclohexyl-1- (hydroxymethyl)ethyl]-2-fluorobenzenesulfonamide, 2-fluoro-N-{(1S,2S)-2-hydroxy- 1-(hydroxymethyl)-2-[4-(methylthio)phenyl]ethyl} benzenesulfonamide, 2-fluoro-N- [(1S)-1-(hydroxyl-methylethyl]benzenesulfonamide, N-[(1S)-1-benzyl-2- hydroxyethyl]-2-fluorobenzenesulfonamide, 2-fluoro-N-[(1S)-1-(hydroxymethyl)-2- methylpropyl] benzenesulfonamide, 4-bromo-N-[1- (hydroxymethyl)cyclohexyl]benzenesulfonamide,4-bromo-N-[2- (hydroxymethyl)bicyclo[2.2.1.]hept-2-yl]benzenesulfonamide, 4-bromo-N-[1- (hydroxymethyl)-2,3-dihydro-1H-inden-1-yl]benzenesulfonamide, 4-chloro-N-[1- (hydroxymethyl)cyclohexyl]benzenesulfonamide, 4-chloro-N-[1-(hydroxymethyl)-0 2,3-dihydro-1H-inden-1-yl]benzenesulfonamide, 4-chloro-N-(1-cyclobutyl-2- hydroxy-1-phenylethyl)benzenesulfonamide, 4-fluoro-N-[(1S,2S)1-(1- hydroxyethyl)-2-methylbutyl]benzenesulfonamide, N-{(1S,2S)-1- [cyclopentyl(hydroxy)methyl]-2-methylbutyl}-4-fluorobenzenesulfonamide, 4-fluoro- N-{(1S)-2-hydroxy-1-[(1S)-1-methylpropyl]octyl}benzenesulfonamide, 4-fluoro-N- {(1S)-2-hydroxy-1-[(1S)-1-methylpropyl]heptyl} benzenesulfonamide, 4-fluoro-N- {(1S)-2-hydroxy-1-[(1S)-1-methylpropyl]hexyl}benzenesulfonamide, 4-fluoro-N- {(1S,2S)-1-[hydroxy-(2-methylphenyl)methyl]-2-methylbutyl}ben2enesulfonamide, 4-fluoro-N-{(1S)-2-hydroxy-3,3-dimethyl-1-[(1S)-1- methylpropyl] butyl} benzenesulfonamide, 4-fluoro-N- {(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]-3-butenyl}benzenesulfonamide, 4-fluoro-N-{(1S)-2-hydroxy-1-[(1S)- 1-methylpropyl]-4-pentenyl}benzenesulfonamide, 4-fluoro-N-{(1S)-2-hydroxy-1- [(1S)-1-methylpropyl]butyl}benzenesulfonamide, N-{(1S,2S)-1-[(4- chlorophenyl)(hydroxy)methyl]-2-methylbutyl}-4-fluorobenzenesulfonamide, 4- fluoro-N-{(1S)-2-hydroxy-4-methyl-1-[(1S)-1-methylpropyl]-3- pentenyl}benzenesulfonamide,4-fluoro-N-{(1S)-2-hydroxy-3-methyl-1-[(1S)-1- methylpropyl]-3-butenyl} benzenesulfonamide, 4-fluoro-N-{(1S,2S)-1-[hydroxy(4- methoxyphenyl)methyl]-2-methylbutyl}benzenesulfonamide, N-{(1S)-4-(1,3-dioxan- 2-yl)-2-hydroxy-1-[(1S)-1-methylpropyl]butyl}-4-fluorobenzenesulfonamide, 4- fluoro-N-{(1S)-2-hydroxy-1-[(1S)-1-methylpropyl]-5-hexenyl}benzenesulfonamide, 4-fluoro-N-((1S,2S)-1-{hydroxy[4-(methylsulfanyl)phenyl]methyl} -2- methylbutyl)benzenesulfonamide, N-{(1S,2S)-1-[[4- (dimethylamino)phenyl](hydroxy)methyl]-2-methylbutyl}-4- fluorobenzenesulfonamide,4-fluoro-N-{(1S,2S)-1-[hydroxy(1-naphthyl)methyl]-2- methylbutyl} benzenesulfonamide, 4-bromo-N-[(1S,2S)-1-(1-hydroxyethyl)-2- methylbutyl] benzenesulfonamide, 4-bromo-N-{(1S,2S)-1- [cyclopentyl(hydroxy)methyl]-2-metfaylbutyl}benzenesulfonamide, 4-bromo-N- {(1S)-2-hydroxy-1-[(1S)-1-methylpropyl] heptyl} benzenesulfonamide, 4-bromo-N- {(1S)-2-hydroxy-1-[(1S)-1-methylpropyI]hexyl}benzenesulfonamide, 4-bromo-N- {(1S)-2-hydroxy-3,3-dimethyl-1-[(1S)-1-methylpropyl]butyl}benzenesulfonamide,4- bromo-N-{(1S)-2-hydroxy-4-methyl-1-[(1S)-1- methylpropyl]pentyl} benzenesulfonamide, 4-bromo-N-{(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]-3-butenyl}benzenesulfonamide, 4-bromo-N-{(1S)-2-hydroxy-1-[(1S)- 1 -methylpropyl]-4-pentenyl}benzenesulfonarnide, 4-bromo-N- {(1S)-2-hydroxy-1- [(1S)-1-methylpropyl]butyl}benzenesulfonamide, 4-bromo-N-{(1S,2S)-1-[(4- fluorophenyl) (hydroxy)methyl]-2-methylbutyl}benzenesulfonamide, 4-bromo-N- {(1S,2S)-1-[(4-chlorophenyl)(hydroxy)methyl]-2-methylbutyl} benzenesulfonamide, 4-bromo-N- {(1S)-2-hydroxy-4-methyl-1-[(1S)-1-methylpropyl]-3- pentenyl}benzenesulfonamide, 4-bromo-N-{(1S)-2-hydroxy-3-methyl-1-[(1S)-1- methylpropyl]-3-butenyl}benzenesulfonamide, 4-bromo-N-{(1S,2S)-1-[hydroxy(4- methoxyphenyl)methyl]-2-methylbutyl} benzenesulfonamide, 4-bromo-N-{(1S,3E)- 2-hydroxy-3-methyl-1-[(1S)-1-methylpropyl]-3 -pentenyl}benzenesulfonamide, 4- bromo-N-{(1S)-4-(1,3 -dioxan-2-yl)-2-hydroxy-1-[(1S)-1-methylpropyl]butyl} benzenesulfonamide, 4-bromo-N-{(1S)-2-hydroxy-1-[(1S)-1-methylpropyl]-5- hexenyl} benzenesulfonamide, 4-bromo-N- {(1S)-2-hydroxy-1-[(1S)-1-methylpropyl] - 3-pentynyl}benzenesulfonamide, 4-bromo-N-((1S,2S)-1-{hydroxy-[4- (methylsulfanyl)phenyl]methyl}-2-methylbutyl) benzenesulfonamide, 4-bromo-N- {(1S,2S)-1-[[4-(dimethylamino)phenyl](hydroxy) methyl]-2-methylbutyl} benzenesulfonamide, 4-chloro-N-[(1S,2S)-1-formyl-2-methylbutyl] benzenesulfonamide, 4-chloro-N-[(1S,2S)-1-(1-hydroxyethyl)-2-methylbutyl] benzenesulfonamide, 4-chloro-N-{(lS,2S)-1-[cyclopentyl(hydroxy)methyl]-2- methylbutyl}benzenesulfonamide, 4-chloro-N-{(1S)-2-hydroxy-1-[(1S)-1- methylpropyl] octyl}benzenesulfonamide, 4-chloro-N-{(1S)-2-hydroxy-1-[(1S)-1- methylpropyl] heptyl}benzenesulfonamide, 4-chloro-N-{(1S)-2-hydroxy-1-[(1S)-1- methylpropyl] hexyl} benzenesulfonamide, 4-chloro-N-{(1S)-2-hydroxy-3-methyl-1- [(1S)-1-methylpropyl]butyl}benzenesulfonamide, 4-chloro-N-{(1S,2S)-1-[hydroxy(2- methylphenyl)methyl]-2-methylbutyl}benzenesulfonamide, 4-chloro-N-{(1S)-2- hydroxy-3,3 -dimethyl-1-[(1S)-1-methylpropyl]butyl} benzenesulfonamide, 4-chloro- N-{(1S)-2-hydroxy-4-methyl-1-[(1S)-1-methylpropyl] pentyl}benzenesulfonamide, 4- chloro-N-{(1S)-2-hydroxy-1-[(1S)-1-methylpropyl]-3-butenyl}benzenesulfonamide, 4-chloro-N-{(1S)-2-hydroxy-1-[(1S)-1-methylpropyl]-4- pentenyl}benzenesulfonamide,4-chloro-N-{(1S)-2-hydroxy-1-[(1S)-1-methylpropyl] butyl}benzenesulfonamide, 4-chloro-N-{(1S,2S)-1-[(4-chlorophenyl) (hydroxy)methyl]-2-methylbutyl} benzenesulfonamide, 4-chloro-N- {(1S,2S)-1- [hydroxy(4-methoxyphenyl)methyl]-2-methylbutyl}benzenesulfonamide, 4-chloro- N-{(1S)-4-(1,3-dioxan-2-yl)-2-hydroxy-1-[(1S)-1-methylpropyl]butyl} benzenesulfonamide, 4-chloro-N- {(1S)-2-hydroxy-1-[(1S)-1-methylpropyl] -5 - hexenyl} benzenesulfonamide, 4-chloro-N- {(1S)-2-hydroxy-1-[(1S)-1-methylpropyl] - 3-pentynyl} benzenesulfonamide, 4-chloro-N-((lS,2S)-1-{hydroxy[4-(methylsulfanyl) phenyl]methyl} -2-methylbutyl) benzenesulfonamide, 4-chloro-N- { (1S,2S)-1- [[4- (dimethylamino)phenyl] (hydroxy)methyl]-2-methylbutyl} benzenesulfonamide, 4- chloro-N-{(1S,2S)-1-[hydroxy(l-naphthyl)methyl]-2- methylbutyl}benzenesulfonamide, 3-chloro-N-[(l S,2S)-1-(1 -hydroxyethyl)-2- methylbutyl]benzenesulfonamide, 3-chloro-N-{(lS,2S)-1- [cyclopentyl(hydroxy)methyl]-2-methylbutyl} benzenesulfonamide, 3-chloro-N- {(1S)- 2-hydroxy-1-[(1S)-1-methylpropyl]octyl}benzenesulfonamide, 3-chloro-N- {(1S)-2- hydroxy-1-[(1S)-1-methylpropyl]heptyl}benzenesulfonamide, 3-chloro-N- {(1S)-2- hydroxy-1-[(1S)-1-methylpropyl]hexyl}benzenesulfonamide, 3-chloro-N-{(1S)-2- hydroxy-3-methyl-1-[(1S)-1-methylpropyl]butyl}benzenesulfonamide, 3-chloro-N- {(1S)-2-hydroxy-3,3-dimethyl-1-[(1S)-1-methylpropyl]butyl}benzenesulfonamide, 3- chloro-N-{(1S)-2-hydroxy-4-methyl-1-[(1S)-1- methylpropyl]pentyl}benzenesulfonamide,3-chloro-N-{(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]-3-butenyl} benzenesulfonamide, 3-chloro-N- {(1S)-2-hydroxy-1-[(1S)- 1-methyIpropyl]-4-pentenyl}benzenesulfonamide, 3-chloro-N-{(1S)-2-hydroxy-1- [(1S)-1-methylpropyl]butyl}benzenesulfonamide, 3-chloro-N-{(lS,2S)-1-[(4- chlorophenyl)(hydroxy)methyl]-2-methylbutyl}benzenesulfonamide, 3-chloro-N- {(1S)-2-hydroxy-4-methy 1-1-[(1S)-1-methylpropyl] -3 -pentenyl} benzenesulfonamide, 3-chloro-N- {(1 S,2S)-1-[hydroxy(4-methoxyphenyl)methyl]-2- methylbutyljbenzenesulfonamide, 3-chloro-N-{(1S)-4-(1,3-dioxan-2-yl)-2-hydroxy- l-[(1S)-1-methylpropyl]butyl} benzenesulfonamide, 3-chloro-N-{(1S)-2-hydroxy-1- [(1S)-1-methylpropyl]-5-hexenyl}benzenesulfonamide, 3-chloro-N-((lS,2S)-1- {hydroxy[4-(methylsulfanyl)phenyl]methyl}-2-methylbutyl)benzenesulfonamide, N- {(1S,2S)-1-[cyclopentyl(hydroxy) methyl]-2-methylbutyl}-2- fluorobenzenesulfonamide, 2-fluoro-N-{(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]octyl}benzenesulfonamide, 2-fluoro-N- {(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]heptyl}benzenesulfonamide, 2-fluoro-N-{(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]hexyl} benzenesulfonamide, 2-fluoro-N-{(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]-3-butenyl}benzenesulfonamide, 2-fluoro-N-{(1S,2S)-1-[(4- fluorophenyl) (hydroxy)methyl]-2-methylbutyl} benzenesulfonamide, N- {(1S,2S)-1- [(4-chlorophenyl) (hydroxy)methyIJ-2-rnethylbutyl} -2-fluorobenzenesulfonamide, 2- fluoro-N-{(1S,2S)-1-[hydroxy(4-methoxyphenyl)methyl]-2-methylbutyl} benzenesulfonamide, N-{(1S)-4-(1,3-dioxan-2-yl)-2-hydroxy-1-[(1S)-1- methylpropyl] butyl}-2-fluorobenzenesulfonamide, 4-bromo-N-[(1S,2S)-1-(1- hydroxy-1-methylethyl)-2-methylbutyl]benzenesulfonamide, 4-bromo-N-{(1S)-2- hydroxy-1-[(1S)-1-methylpropyl]-2-pentylheptyl} benzenesulfonamide, 4-bromo-N- {(1S)-2-butyl-2-hydroxy-1-[(1S)-1-methylpropyl]hexyl}benzenesulfonamide, 4- bromo-N-{(1S)-2-hydroxy-2-isobutyl-4-methyl-1-[(1S)-1-methylpropyl]pentyl} benzenesulfonamide, 4-bromo-N-{(1S,2S)-1-[hydroxy(diphenyl)methyIJ-2- methylbutyl} benzenesulfonamide, N-{(1S)-2-allyl-2-hydroxy-1-[(1S)-1- methylpropyl]-4-pentenyl}-4-bromo benzenesulfonamide, 4-bromo-N-{(1S)-2-ethyl- 2-hydroxy-1-[(1S)-1-methylpropyl] butyl} benzenesulfonamide, N-{(1S,2S)-1-[bis(4- chlorophenyl) (hydroxy)tnethyl]-2-methylbutyl}-4-bromobenzenesulfonamide, 4- bromo-N-{(1S)-2-hydroxy-2-isopropenyl-3 -methyl-1-[(1S)-1-methylpropyl]-3 - butenyl} benzenesulfonamide, 4-bromo-N-{(1S,3E)-2-hydroxy-3-methyl-2-[(1E)-1- methyl-1-propenyl]-1-[(1S)-1-methylpropyl]-3-pentenyl} benzenesulfonamide, 4- bromo-N-{(1S)-2-(3-butenyl)-2-hydroxy-1-[(1S)-1-methylpropyl]-5- hexenyl}benzenesulfonamide, 4-bromo-N-((lS,2S)-1-{hydroxy[di(l- naphthyl)]methyl}-2-methylbutyl) benzenesulfonamide, 4-chloro-N-[(1S,2S)-1-(1 - hydroxy-1-methylethyl)-2-methyIbutyl]benzenesulfonamide, 4-chloro-N- {(1 S)-2- hexyl-2-hydroxy-1-[(IS)-1-methylpropyljoctyl} benzenesulfonamide, N- {(1 S)-2- butyl-2-hydroxy-1-[(1S)-1-methylpropyl]hexyl}-4-chlorobenzenesulfonamide, 4- chIoro-N-{(1S)-2-hydroxy-2-isobutyl-4-methyI-1-[(IS)-1- methylpropyl]pentyl} benzenesulfonamide, 4-chloro-N- {(1 S,2S)-1- [hydroxy(diphenyI)methyl]-2-methylbutyl}benzenesulfonamide,N-{(1S)-2-allyl-2- hydroxy-1-[(1S)-1-methylpropyl]-4-pentenyl}-4-chloro benzenesulfonamide, 4- chloro-N- {(1S)-2-ethyl-2-hydroxy-1-[(1S)-1-methylpropyl] butyl} benzenesulfonamide, 4-chloro-N- {(1 S)-2-hydroxy-2-isopropenyl-3 -methyl-1- [(1S)-1-methylpropyl]-3-butenyl} benzenesulfonamide, 4-chloro-N-(( 1 S,2S)-1- {hydroxy [bis(4-methoxyphenyl)]methyl} -2-methylbutyl)benzenesulfonamide, 4- chloro-N-{(lS,3E)-2-hydroxy-3-methyl-2-[(lE)-1-methyl-1-propenyl]-1-[(1S)-1- methylpropyl]-3-pentenyI}benzenesulfonamide, N-{(1S)-2-(3-butenyl)-2-hydroxy-1- [(1 S)-1-methyl propyl]-5-hexenyl}-4-chlorobenzenesulfonamide, 4-chloro-N- ((1S,2S)-1- {hydroxy [di(1-naphthyl)]methyl} -2-methylbutyl) benzenesulfonamide, 4- fluoro-N-[( 1S,2S)-1-(1-hydroxy-1-methylethyl)-2-methylbutyl]benzenesulfonamide, 4-fluoro-N- {(1S)-2-hexyl-2-hydroxy-1-[(1S)-1- methylpropyl]octyl}benzenesulfonamide, 4-fluoro-N- {(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]-2-pentylheptyl} benzenesulfonamide, N- {(1S)-2-butyl-2-hydroxy-1- [(1S)-1-methylpropyljhexyl} -4-fiuorobenzenesulfonamide, 4-fluoro-N- {(1S)-2- hydroxy-2-isopropyl-3-methyl-1-[(1S)-1-methylpropyl]butyI} benzenesulfonamide, 4-fluoro-N- {(1S)-2-hydroxy-2-isobutyl-4-methyl-1-[(1S)-1- methylpropyl]pentyl}benzenesulfonamide, N-{(1S)-2-allyl-2-hydroxy-1-[(1S)-1- methylpropyl]-4-pentenyl}-4-fluoro benzenesulfonamide, N-{(1S)-2-ethyl-2- hydroxy-1-[(1S)-1-methylpropyl] butyl} -4-fiuorobenzenesulfonamide, 4-fluoro-N- {(1S)-2-hydroxy-2-isopropenyl-3-methyl-1-[(1S)-1-methylpropyl]-3 - butenyl}benzenesulfonamide, 4-fluoro-N-((1S,2S)-1-{hydroxy[bis(4- methoxyphenyl)]methyl}-2-methylbutyl) benzenesulfonamide, 4-fluoro-N-{(1S,3E)- 2-hydroxy-3 -methyl-2- [(1E)-1-methyl-1-propenyl] -1-[(1S)-1-methylpropyl] -3- pentenyl} benzenesulfonamide, N-{(1S)-2-(3-butenyl)-2-hydroxy-1-[(1S)-1- methylpropyl]-5-hexenyl}-4-fluorobenzenesulfonamide, N-{(1S,2S)-1-[bis[4- (dimethylamino)phenyl] (hydroxy)methyl]-2-methylbutyl}-4- fluorobenzenesulfonamide, 4-fluoro-N-((1S,2S)-1-{hydroxy[di( 1-naphthyl)]methyl}- 2-methylbutyl)benzenesulfonamide, 3-chloro-N-{(1S)-2-hexyl-2-hydroxy-1-[(1S)-1- methylpropyl]octyl}benzenesulfonamide, 3-chloro-N- {(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]-2-pentylheptyl}benzenesulfonamide,N-{(1S)-2-butyl-2-hydroxy-1- [(1S)-1-methylpropyl]hexyl}-3-chlorobenzenesulfonamide, 3-chloro-N-{(1S)-2- hydroxy-2-isobutyl-4-methyl-1-[(1S)-1-methylpropyl]pentyl}benzenesulfonamide, 3- chloro-N-{(1S,2S)-1-[hydroxy(diphenyl)methyl]-2-methylbutyl}benzenesulfonamide, N- {(1S)-2-allyl-2-hydroxy-1-[(1S)-1-methylpropyl] -4-pentenyl} -3-chloro benzenesulfonamide, 3-chloro-N-{(1S)-2-ethyl-2-hydroxy-1-[(1S)-1- methylpropyl]butyl} benzenesulfonamide, N-{(1S,2S)-1-[bis(4- chlorophenyl)(hydroxy)methyl]-2-methylbutyl}-3-chlorobenzenesulfonamide,3- chloro-N-{(1S)-2-hydroxy-2-isopropenyl-3-methyl-1-[(1S)-1-methylpropyl]-3- butenyl}benzenesulfonamide, 3-chloro-N-((lS,2S)-1-{hydroxy [bis(4- methoxyphenyl)]methyl}-2-methylbutyl)benzenesulfonamide, 3-chloro-N-{(lS,3E)- 2-hydroxy-3-methyl-2-[(lE)-1-methyl-1-propenyl]-1-[(1S)-1-methylpropyl]-3- pentenyl} benzenesulfonamide, N-{(1S)-2-(3-butenyl)-2-hydroxy-1-[(1S)-1- methylpropyl]-5-hexenyl}-3-chlorobenzenesulfonamide, 2-fluoro-N-{(1S)-2-hexyl-2- hydroxy-1-[(1S)-1-methylpropyl]octyl}benzenesulfonamide, 2-fluoro-N- {(1S)-2- hydroxy-1-[(1S)-1-methylpropyl]-2-pentylheptyl}benzenesulfonamide, 2-fluoro-N- {(lS,2S)-1-[hydroxy(diphenyl)methyl]-2-methylbutyl}benzenesulfonamide, N- {(1S)-2-allyl-2-hydroxy-1-[(1S)-1-methylpropyl]-4-pentenyl} -2- fluorobenzenesulfonamide, N-{(1S)-2-ethyl-2-hydroxy-1-[(1S)-1- methylpropyl]butyl} -2-fluorobenzenesulfonamide, N- {(1S ,2S)-1-[bis(4- fluorophenyl)(hydroxy)methyl] -2-methylbutyl} -2-fluorobenzenesulfonamide, N- {(1 S,2S)-1-[bis(4-chlorophenyl)(hydroxy)methyl]-2-methylbutyl} -2-fiuoro benzenesulfonamide, 2-fluoro-N- {(1S)-2-hydroxy-2-isopropenyl-3-methyl-1-[(1S)-1- methylpropyl]-3-butenyl} benzenesulfonamide, 2-fluoro-N-((1S,2S)-1- {hydroxy[bis(4-methoxyphenyl)]methyl}-2-methylbutyl)benzenesulfonamide, 2- fluoro-N-{( 1 S,3E)-2-hydroxy-3-methyl-2-[(1E)-1-methyl-1-propenyl]-1-[(1S)-1- methylpropyl]-3-pentenyl} benzenesulfonamide, N-{(1S)-2-(3-butenyl)-2-hydroxy-1- [(1S)-1-methylpropyl] -5-hexenyl} -2-fluorobenzenesulfonamide, 4-chloro-N- [(1S)-1- cyclohexyl-2-hydroxyethyI] benzenesulfonamide, 4-chloro-N-[(1S)-2-hydroxy-1- phenylethyl] benzenesulfonamide, 4-chloro-N- [(1S)-1-(hydroxymethyl)-2- methylpropyl] benzenesulfonamide, 4-bromo-N-[(1S)-l -(hydroxymethyl)-2- methylpropyl] benzenesulfonamide, 4-iodo-N-[(1S,2S)-1-(hydroxymethyl)-2- methylbutyl] benzenesulfonamide, and 4-chloro-N-[(1S)-1-(hydroxymethyl)-2,2- dimethylpropyl] benzenesulfonamide; or a pharmaceutically acceptable salt, hydrate, metabolite, or prodrug thereof. In another embodiment, the compound is 4-chloro-N-[(1S)-2-ethyl-1- (hydroxymethyl)butyl]benzenesulfonamide or a pharmaceutically acceptable salt, metabolite, hydrate, or prodrug thereof The compounds of the invention can contain one or more asymmetric carbon atoms and some of the compounds can contain one or more asymmetric (chiral) centers and can thus give rise to optical isomers and diastereomers. While shown without respect to stereochemistry, when the compounds can contain one or more chiral centers, preferably at least one of the chiral centers is of S-stereochemistry. Most preferably, the carbon atom to which N, T, R7 and R8 are attached is of S- stereochemistry. Thus, the invention includes such optical isomers and diastereomers; as well as the racemic and resolved, enantiomerically pure stereoisomers; as well as other mixtures of the R and S stereoisomers, and pharmaceutically acceptable salts, hydrates, metabolites, and prodrugs thereof. The term "alkyl" is used herein to refer to both straight- and branched-chain saturated aliphatic hydrocarbon groups having about one to about ten carbon atoms, preferably one to eight carbon atoms and, most preferably, one to six carbon atoms. The term "lower alkyl" is used herein to refer to straight- and branched-chain saturated aliphatic hydrocarbon groups having about one to about six carbon atoms. The term "alkenyl" is used herein to refer to straight- and branched-chain alkyl groups having at least one carbon-carbon double bond and about two to about eight carbon atoms, preferably two to six carbon atoms. The term "alkynyl" is used herein to refer to straight- and branched-chain alkyl groups having at least one carbon-carbon triple bond and about two to about eight carbon atoms, preferably two to six carbon atoms. The terms "substituted alkyl", "substituted alkenyl", and "substituted alkynyl" refer to alkyl, alkenyl, and alkynyl as just described having from one to three substituents selected from the group consisting of halogen, CN, OH, NO2, amino, aryl, heterocyclic, substituted aryl, substituted heterocyclic, alkoxy, aryloxy, substituted alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio, which groups can be optionally substituted. These substituents can be attached to any carbon of an alkyl, alkenyl, or alkynyl group provided that the attachment constitutes a stable chemical moiety. The term "aryl" is used herein to refer to a carbocyclic aromatic system, which can be a single ring, or multiple aromatic rings fused or linked together as such that at least one part of the fused or linked rings forms the conjugated aromatic system. The aryl groups include, but are not limited to, phenyl, naphthyl, biphenyl, anthryl, tetrahydronaphthyl, and phenanthryl. The term "substituted aryl" refers to aryl as just defined having one or more substituents including halogen, CN, OH, NO2, amino, alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, aryloxy, substituted alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio. Preferably, a substituted aryl group is substituted with one to about four substituents. The term "heterocyclic" is used herein to describe a stable 4- to 7-membered monocyclic or a stable multicyclic heterocyclic ring which is saturated, partially unsaturated, or wholly unsaturated. The heterocyclic ring has in its backbone carbon atoms and one or more heteroatoms including N, O, and S atoms. Preferably, the heterocyclic ring has about 1 to about 4 heteroatoms in the backbone of the ring. When the heterocyclic ring contains nitrogen or sulfur atoms in the backbone of the ring, the nitrogen or sulfur atoms can be oxidized. The heterocyclic ring also includes any multicyclic ring in which any of the above defined heterocyclic rings is fused to an aryl ring. The heterocyclic ring can be attached at any heteroatom or carbon atom provided the resultant structure is chemically stable. A variety of heterocyclic groups are known in the art and include, without limitation, oxygen-containing rings, nitrogen-containing rings, sulfur-containing rings, mixed heteroatom-containing rings, fused heteroatom containing rings, and combinations thereof. Oxygen-containing rings include, but are not limited to, furyl, tetrahydrofuranyl, pyranyl, pyronyl, and dioxinyl rings. Nitrogen-containing rings include, without limitation, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, pyridyl, piperidinyl, 2-oxopiperidinyl, pyridazinyl, pyrimidinyl, pyrazinyl, piperazinyl, azepinyl, triazinyl, pyrrolidinyl, and azepinyl rings. Sulfur-containing rings include, without limitation, thienyl and dithiolyl rings. Mixed heteroatom containing rings include, but are not limited to, oxathiolyl, oxazolyl, thiazolyl, oxadiazolyl, oxatriazolyl, dioxazolyl, oxathiazolyl, oxathiolyl, oxazinyl, oxathiazinyl, morpholinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, oxepinyl, thiepinyl, and diazepinyl rings. Fused heteroatom-containing rings include, but are not limited to, benzofuranyl, benzo[b]thienyl or benzo[c]thienyl, indolyl, benazazolyl, purindinyl, pyranopyrrolyl, isoindazolyl, indoxazinyl, benzoxazolyl, anthranilyl, benzopyranyl, quinolinyl, isoquinolinyl, benzodiazonyl, naphthyridinyl, benzothienyl, pyridopyridinyl, benzoxazinyl, xanthenyl, acridinyl, and purinyl rings. As used herein, an N-substituted piperidinyl group can be defined as a substituted heterocyclic group. Among particularly desirable substituents are N-alkyl-, N-aryl-, N-acyl-, and N-sulfonyl piperidinyl groups. One particularly suitable N-acyl-piperidinyl group is N-t-butyloxycarbonyl (BOC)-piperidine. However, other suitable substituents can be readily identified by one of skill in the art. The term "substituted heterocyclic" is used herein to describe a heterocyclic group having one or more substituents including halogen, CN, OH, NO2, amino, alkyl, substituted alkyl, cycloalkyl, alkenyl, substituted alkenyl, alkynyl, alkoxy, aryloxy, substituted alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio. Preferably, a substituted heterocyclic group has 1 to about 4 substituents. The term "alkoxy" is used herein to refer to the O(alkyl) group, where the point of attachment is through the oxygen-atom and the alkyl group is optionally substituted. The term "aryloxy" is used herein to refer to the O(aryl) group, where the point of attachment is through the oxygen-atom and the aryl group is optionally substituted. The term "alkylcarbonyl" is used herein to refer to the CO(allcyl) group, where the point of attachment is through the carbon-atom of the carbonyl moiety and the alkyl group is optionally substituted. The term "alkylcarboxy" is used herein to refer to the COO(alkyl) group, where the point of attachment is through the carbon-atom of the carboxy group and the alkyl group is optionally substituted. The term "aminoalkyl" is used herein to refer to secondary and tertiary amines where the point of attachment is through the nitrogen-atom and the alkyl groups are optionally substituted. Preferably, the alkyl groups contain one to eight carbon atoms and can be either same or different. The term "halogen" refers to Cl, Br, F, or I. The term "ring" structure, e.g., when R3 and R4 can form a ring structure, includes a monocyclic structure, a bridged cyclo structure, and fused cyclo structures, unless the type of ring structure is otherwise specified. The compounds of the present invention encompass tautomeric forms of the structures provided herein characterized by the bioactivity of the exemplary compounds and drawn structures. Further, the compounds of the present invention can be used in the form of salts derived from pharmaceutically or physiologically acceptable acids, bases, alkali metals and alkaline earth metals. Physiologically acceptable acids include those derived from inorganic and organic acids. A number of inorganic acids are known in the art and include hydrochloric, hydrobromic, hydroiodic, sulfuric, nitric, and phosphoric acids, among others. Similarly, a variety of organic acids are known in the art and include, without limitation, lactic, formic, acetic, fumaric, citric, propionic, oxalic, succinic, glycolic, glucuronic, maleic, furoic, glutamic, benzoic, anthranilic, salicylic, tartaric, malonic, mallic, phenylacetic, mandelic, embonic, methanesulfonic, ethanesulfonic, panthenoic, benzenesulfonic, toluenesulfonic, stearic, sulfanilic, alginic, and galacturonic acids, among others. Physiologically acceptable bases include those derived from inorganic and organic bases. A number of inorganic bases are known in the art and include aluminum, calcium, lithium, magnesium, potassium, sodium, and zinc hydroxide compounds, among others. A number of organic bases are known in the art and include, without limitation, N,N,-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine, and procaine, among others. Physiologically acceptable alkali salts and alkaline earth metal salts can include, without limitation, sodium, potassium, calcium and magnesium salts in the form of esters, hydroxides, and carbamates. Other conventional "pro-drug" forms can also be utilized which, when delivered in such form, convert to the active moiety in vivo. These salts, as well as other compounds of the invention can be in the form of esters, carbamates and other conventional "pro-drug" forms, which, when administered in such form, convert to the active moiety in vivo. In a currently preferred embodiment, the prodrugs are esters. See, e.g., B. Testa and J. Caldwell, "Prodrugs Revisited: The "Ad Hoc" Approach as a Complement to Ligand Design", Medicinal Research Reviews, 16(3):233-241, ed., John Wiley & Sons (1996). The compounds discussed herein also encompass "metabolites" which are unique products formed by processing the compounds of formula I, Ia, or Ib by the cell or patient. Preferably, metabolites are formed in vivo. The compounds of the present invention can be prepared in a number of ways well known to one skilled in the art. The compounds of the present invention can be prepared using the methods described below, together with synthetic methods known in the synthetic organic arts or variations of these methods by one skilled in the art. See, generally, Comprehensive Organic Synthesis, "Selectivity, Strategy & Efficiency in Modern Organic Chemistry", ed., I. Fleming, Pergamon Press, New York (1991); Comprehensive Organic Chemistry, "The Synthesis and Reactions of Organic Compounds", ed. J.F. Stoddard, Pergamon Press, New York (1979). Preferred methods include, but are not limited to, those outlined below. In certain embodiments, it may be desirable to utilize chirally pure α-amino acids, 1,2-aminoalcohols, N-sulfonyl α-amino acids, and N-sulfonyl 1,2- aminoalcohols in the reactions described herein for the production of the phenylsulfonamides of the invention. A number of methods for producing these compounds are known in the art. Among desirable methodologies are those described in US Patent Application No. 60/339,264, filed December 11, 2001, and later filed as US Patent Application No. 10/304,322 and International Patent Application PCT/US02/38119, both filed November 26, 2002, "Process for the Synthesis of Chirally Pure α-Amino-Alcohols"; US Patent Application No. 10/014,304, filed December 11, 2001, entitled "Heterocyclic Sulfonamide Inhibitors of Beta Amyloid Production", published as US-2002-0183361-A on December 5, 2002; and US Patent Application No. 10/166,896, filed June 11, 2002 and later published January 16, 2003 as US-2003-0013892-A1, entitled "Production of Chirally Pure α-Amino Acids and N-Sulfonyl α-Amino Acids". A first method of preparation for the compounds of the invention consists of reaction of a 1,2-aminoalcohol II with the appropriate sulfonyl halide in the presence of a base such as triethylamine (TEA) and in a suitable solvent to afford compounds of formula III. For compounds where R9 and R10 are hydrogen, oxidation of the N- sulfonyl primary alcohol with pyridinium chlorochromate (PCC) or under Swem conditions then affords the corresponding aldehyde IV which can be reacted with Grignard reagents to afford the secondary alcohols V as a mixture of diastereomers which can be separated by high performance liquid chromatography (HPLC) or other suitable methods (Scheme 1). A second method of preparation involves reaction of an a-amino acid or ester DC with the appropriate sulfonyl halide in the presence of a base such as triethylamine and in a suitable solvent to afford compounds of formula X (Scheme 2). The intermediate N-sulfonyl acid X (Rx=H) can be converted to the corresponding primary alcohol VIII (R9=R10=H) utilizing standard methodology such as LiAIH4 (LAH), B2H6 or cyanuric chloride/NaBH4. The intermediate N-sulfonyl ester X (Rx=alkyl, Bn) can also be reduced to the corresponding primary alcohol VIII utilizing standard methodology such as LiAIH4. Alternatively, the intermediate N- sulfonyl ester X (Rx=alkyl, Bn) can be converted to the aldehyde IV with diisobutyl aluminumhydride (DiBAL). Finally, the intermediate N-sulfonyl ester X (Rx=alkyl, Bn) can be reacted with 2 equivalents of Grignard reagent to afford the tertiary alcohols HI with R9=R10. Alternatively, for tertiary alcohols III with R9 not equal to R10, the corresponding Weinreb amide (see Scheme 7) of the N-sulfonyl acid can be prepared and subsequently reacted with R9MgX and R10MgX. In a variation of the second method to prepare the primary alcohols, an α- amino acid or ester (or N-protected derivative thereof) VI is first converted to the corresponding primary 1,2-aminoalcohol VII (using the methodology outlined in the previous paragraph), which is subsequently, after deprotection (if necessary), reacted with the appropriate sulfonyl halide (Scheme 3) to afford compounds of formula VIII. For the preparation of compounds derived from unnatural a-amino acids containing beta branching in the amino acid side chain, a method of preparation based on the work of Hruby (Tet. Lett. 38: 5135-5138 (1997)), incorporated by reference, is outlined in Scheme 4. This route entails formation of the α, β-unsaturated amide XII of the Evans chiral auxiliary from an α,β-unsaturated acid XI, followed by conjugate addition of an organocuprate, trapping of the resulting enolate anion XIII with N- bromosuccinimide (NBS), displacement of the bromide XIV with azide anion to afford XV, followed by reduction to the 1,2-aminoalcohol and subsequent sulfonylation to afford the target compound XVI. For the preparation of N-alkylated sulfonamides XVII (R6 can be alkyl, substituted alkyl, allyl, substituted allyl, benzyl, or substituted benzyl), the sulfonamide ester X can be N-alkylated by either treatment with a suitable base such as sodium hydride followed by the alkylating agent R6X or by employing Mitsunobu conditions (R6OH/DEAD, TPP). LiBH4 reduction of the N-alkylated sulfonamide ester affords the N-alkylated sulfonamide in the primary alcohol series XVII (Scheme 5). These primary alcohols XVII can be converted to N-alkylated analogs of the secondary alcohols V or aldehyde IV series by chemistry that has been outlined above. Alternatively, the N-alkylated sulfonamide esters, or their corresponding Weinreb amides, can be treated with Grignard reagents to afford the N-alkylated analogs of the tertiary alcohols III (where R9 and R10 are non-hydrogen). As previously noted (Scheme 1), the preparation of sulfonamides derived from 1,2-arrJnoalcohols in the secondary alcohol series V results in the formation of a diastereomeric mixture. An alternate method of preparation of these compounds that results in the production of a pure diastereomer is outlined in Scheme 7 for compounds derived from L-isoleucine. This method which utilizes chemistry previously employed by Ronx (Tetrahedron 50: 5354-5360 (1994)), consists of addition of Grignard reagents to the Weinreb amide XXIII (derived from the requisite a-amino acid) followed by stereospecific reduction of the ketone XXIV to afford a single diastereomeric N-protected 1,2-aminoalcohol XXV. Deprotection of this compound followed by reaction with sulfonyl chlorides affords the pure diastereomeric sulfonamide secondary alcohols of formula XXVI. Where catalysts or solvents are included in a reaction step of this invention, it is expected that other catalysts or solvents known in the art, but not mentioned herein, can be used. Those skilled in the art will readily be able to determine suitable catalysts, solvents and reaction conditions for each reaction step included in the invention. The invention includes certain types of reactions, such as enolate trapping, hydrolysis, and reduction reactions that are generally known in the art, but previously had not been applied in the novel manner of the present invention. Variations in the specific methods of accomplishing individual steps of the invention can be apparent to those in the art. Although ail of these possible variations cannot be set forth herein, such variations are contemplated to be within the scope of the present invention. II. Formulations of the Invention The compounds described herein can be formulated in any form suitable for the desired route of delivery using a pharmaceutically effective amount of one or more of the compounds of the invention. For example, the compositions of the invention can be delivered by a route such as oral, dermal, transdermal, intrabronchial, intranasal, intravenous, intramuscular, subcutaneous, parenteral, intraperitoneal, sublingual, intracrar.ial. epidural, intratracheal, intranasal, vaginal, rectal, or by sustained release. Preferably, delivery is oral. A pharmaceutically effective amount of a compound used according to the present invention can vary depending on the specific compound, mode of delivery, severity of the condition being treated, and any other active ingredients used in the formulation or the selected regimen. The dosing regimen can be adjusted to provide the optimal therapeutic response. Several divided doses can be delivered daily or a single daily dose can be delivered. The dose can however be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. As described herein, a pharmaceutically useful amount of a compound of the invention is that amount of a compound which alleviates the symptoms of the disease, e.g., AD, or which prevents the onset of symptoms, or the onset of more severe symptoms. Generally, an individual dose (i.e., per unit, e.g., tablet) of a compound of the invention can be in the range from about 1 ug/kg to about 10 g/kg, more preferably 10 mg/kg to about 5 g/kg, and most preferably about 1 mg/kg to about 200 mg/kg. Desirably, these amounts are provided on a daily basis. However, the dosage to be used in the treatment or prevention of a specific cognitive deficit or other An alternate preparation of sulfonamides derived from unnatural 1,2- aminoalcohols utilizes the Bucherer modification of the Strecker α-amino acid synthesis (Scheme 6). In this route, an aldehyde XVHI is reacted with cyanide anion and ammonium carbonate to afford the hydantoin XIX, which is hydrolyzed to the a- amino acid XX. This compound is then reduced to XXI and sulfonylated to afford the desired compounds of formula XXII. Binders can include, without limitation, cellulose, methylcellulose, hydroxymethylcellulose, polypropylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidine, gelatin, gum arabic, polyethylene glycol, starch, sugars such as sucrose, kaolin, cellulose kaolin, and lactose, among others. Lubricants can include magnesium stearate, light anhydrous silicic acid, talc and sodium lauryl sulfate, among others. Granulating agents can include, without limitation, silicon dioxide, microcrystalline cellulose, starch, calcium carbonate, pectin, crospovidone, and polyplasdone, among others. Disintegrating agents can include starch, carboxymethylcellulose, hydroxypropylstarch, substituted hydroxypropylcellulose, sodium bicarbonate, calcium phosphate, and calcium citrate, among others Emollients can include, without limitation, stearyl alcohol, mink oil, cetyl alcohol, oleyl alcohol, isopropyl laurate, polyethylene glycol, olive oil, petroleum jelly, palmitic acid, oleic acid, and myristyl myristate. Ausrnatively, the use of sustained delivery devices can be desirable, in order to avoid the necessity for the patient to take medications on a daily basis. The term "sustained delivery" is used herein to refer to delaying the release of an active agent, i.e., a compound of the invention, until after placement in a delivery environment, followed by a sustained release of the agent at a later time. A number of sustained delivery devices are known in the art and include hydrogels (US Patent Nos. 5,266,325; 4,959,217; 5,292,515), osmotic pumps (US Patent Nos. 4,295,987 and 5,273,752 and European Patent No. 314,206, among others); hydrophobic membrane materials, such as ethylenemethacrylate (EMA) and ethylenevinylacetate (EVA); bioresorbable polymer systems (International Patent Publication No. WO 98/44964 and US Patent Nos. 5,756,127 and 5,854,388); and other bioresorbable implant devices composed of, for example, polyesters, polyanhydrides, or lactic acid/glycolic acid copolymers (US Patent No. 5,817,343). For use in such sustained delivery devices, the compounds of the invention can be formulated as described herein. condition can be subjectively determined by the attending physician. The variables involved include the specific cognitive deficit and the size, age and response pattern of the patient. The compounds of the invention can be combined with one or more pharmaceutically acceptable carriers or excipients including, without limitation, solid and liquid carriers which are compatible with the compounds of the present invention. Such carriers can include adjuvants, syrups, elixirs, diluents, binders, lubricants, surfactants, granulating agents, disintegrating agents, emollients, solubilizers, suspending agents, fillers, glidants, compression aids, encapsulating materials, emulsifiers, buffers, preservatives, thickening agents, colors, viscosity regulators, stabilizers, osmo-regulators, and combinations thereof. Optionally, one or more of the compounds of the invention can be mixed with other active agents. Adjuvants can include, without limitation, flavoring agents, sweeteners, coloring agents, preservatives, and supplemental antioxidants, which can include vitamin E, ascorbic acid, butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA). Elixers and syrups can be prepared from acceptable sweeteners such as sugar, saccharine or a biological sweetener, a flavoring agent, and/or solvent. In one embodiment, a syrup can contain about 10 to about 50% of a sugar carrier. In another embodiment, the elixir can contain about 20 to about 50% of an ethanol carrier. Diluents can include materials in which the compound can be dispersed, dissolved, or incorporated. Preferably, the diluents include water, lower monovalent alcohols, monohydric alcohols, polyhydric alcohols, and low molecular weight glycols and polyols, including propylene glycol, diethylene glycol, polyethylene glycol, polypropylene glycol, glycerol, butylene glycol, 1,2,4-butanetriol, sorbitol esters, 1,2,6-hexanetriol, ethanol, isopropanol, sorbitol esters, butanediol, ethyl oleate, isopropyl myristate, ether propanol, ethoxylated ethers, propoxylated ethers, oils such as corn, peanut, fractionated coconut, arachis, sesame oils, dimethylsulfoxide (DMSO), dimethylformamide (DMF), waxes, preferably low-melting waxes, dextrin, and combinations thereof. Preferably, the diluent is water. In a further embodiment, the compositions are delivered transdermally or by sustained release through the use of a transdermal patch containing the composition and an optional carrier that is inert to the compound, is nontoxic to the skin, and allows for delivery of the compound for systemic absorption into the blood stream. Such a carrier can be a cream, ointment, paste, gel, or occlusive device. The creams and ointments can be viscous liquid or semisolid emulsions. Pastes can include absorptive powders dispersed in petroleum or hydrophilic petroleum. Further, a variety of occlusive devices can be utilized to release the active reagents into the blood stream and include semi-permeable membranes covering a reservoir contain the active reagents, or a matrix containing the reactive reagents. IV. Methods of Use The compounds of the present invention have utility for the prevention and treatment of disorders involving beta amyloid production, including cerebrovascular diseases, and the prevention and treatment of AD by virtue of their ability to reduce beta amyloid production. In preliminary studies using protease specific assays, the compounds of the invention have been shown to exhibit specific inhibition with respect to protease activity. Thus, the compounds of the present invention are useful for treatment and prevention of a variety of conditions in which modulation of beta amyloid levels provides a therapeutic benefit. Such conditions include, e.g., amyloid angiopathy, cerebral amyloid angiopathy, systemic amyloidosis, Alzheimer's Disease (AD), hereditary cerebral hemorrhage with amyloidosis of the Dutch type, inclusion body myositis, Down's syndrome and mild cognitive impairment, among others. The compounds of the present invention have also been shown to inhibit beta amyloid production. In one embodiment, a subject or patient can be monitored for circulating levels of the compounds and/or beta-amyloid levels, from time to time following administration of a compound of the invention, or during the course of treatment. A variety of assays can be utilized for this purpose, including those described below. Additionally, cellular, cell-free and in vivo screening methods, as well as radioimmunoassays and enzyme-linked immunosorbent assay (ELISA) to detect inhibitors of beta amyloid production are known in the art (See, e.g., P.D. III. Formulation Delivery The present invention provides methods of providing the compounds of the invention to a patient. The compounds can be delivered by a route such as oral, dermal, transdermal, intrabronchial, intranasal, intravenous, intramuscular, subcutaneous, parenteral, intraperitoneal, sublingual, intracranial, epidural, intratracheal, intranasal, vaginal, rectal, or by sustained release. Preferably, delivery is oral. In one embodiment, the compositions are delivered orally in solid or liquid form by powder, tablet, capsule, microcapsules, dispersible powder, granule, suspension, syrup, elixir, and aerosol. Desirably, when the compound is delivered orally, it is sub-divided in a dose containing appropriate quantities of the active ingredient. The unit dosage forms can be packaged compositions, for example packeted powders, vials, ampoules, prefilled syringes or sachets containing liquids. The unit dosage form can be, for example, a capsule or tablet itself, or it can be the appropriate number of any such compositions in package form. Preferably, the powders and tablets contain up to 99% of the active ingredient. In another embodiment, the compounds are delivered intravenously, intramuscularly, subcutaneously, parenterally and intraperitoneally in the form of sterile injectable solutions, suspensions, dispersions, and powders which are fluid to the extent that easy syringe ability exits. Such injectable compositions are sterile, stable under conditions of manufacture and storage, and free of the contaminating action of microorganisms such as bacteria and fungi. Injectable formations can be prepared by combining the compound with a liquid. The liquid can be selected from among water, glycerol, ethanol, propylene glycol and polyethylene glycol, oils, and mixtures thereof, and more preferably the liquid carrier is water. In one embodiment, the oil is vegetable oil. Optionally, the liquid carrier contains about a suspending agent. In a further embodiment, the compounds are delivered rectally or vaginally in the form of a conventional suppository. In yet another embodiment, the compositions are delivered intranasally or intrabronchially in the form of an aerosol. Mehta, et al., Techniques in Diagnostic Pathology, vol. 2, eds., Bullock et al, Academic Press, Boston, pages 99-112 (1991), International Patent Publication No. WO 98/22493, European Patent No. 0 652 009, and US Patent Nos. 5,703,129 and 5,593,846). The compounds can further be utilized in generating reagents useful in diagnosis of conditions associated with abnormal levels of beta amyloid. For example, the compounds of Formula I can be used to generate antibodies which would be useful in a variety of diagnostic assays. Methods for generating monoclonal, polyclonal, recombinant, and synthetic antibodies or fragments thereof, are well known to those of skill in the art. See, e.g., E. Mark and Padlin, "Humanization of Monoclonal Antibodies", Chapter 4, The Handbook of Experimental Pharmacology, Vol. 113, The Pharmacology of Monoclonal Antibodies, Springer-Verlag (June, 1994); Kohler and Milstein and the many known modifications thereof; International Patent Application No. PCT/GB85/00392; British Patent Application Publication No. GB2188638A; Amit et al., Science, 233:7'47'-753 (1986); Queen et al., Proc. Nat'l. Acad. Sci. USA, 86:10029-10033 (1989); International Patent Publication No. WO 90/07861; and Riechmann et al.. Nature, 332:323-327 (1988); Huse et al, Science, 246:1275-1281 (1988). Alternatively, the compounds of Formula I can themselves be used in such diagnostic assays. Regardless of the reagent selected (e.g., antibody or compound of Formula I), suitable diagnostic formats including, e.g., radioimmunoassays and enzyme-linked immunosorbent assays (ELISAs), are well known to those of skill in the art and are not a limitation on this embodiment of the invention. The following examples are provided to illustrate the production and activity of representative compounds of the invention and to illustrate their performance in a screening assay. One skilled in the art will appreciate that although specific reagents and conditions are outlined in the following examples, these reagents and conditions are not a limitation on the present invention. EXAMPLES Example 1 2-Bromo-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide To a solution of (S) isoleucinol (23 mg, 0.2 mmol) in THF (3 mL) was added triethylamine (46 µL, 0.24 mmol) and 2-bromobenzenesulfonyl chloride (51 mg, 0.2 mmol). The solution was stirred for 8 to 16 hours, then concentrated. The residue was dissolved in MeOH (1.5 mL) and purified by semi-preparative RP-HPLC using the following conditions: Column: Phenomenex C18 Luna 21.6 mm x 60 mm, 5 u Solvent A: Water (0.02% TFA buffer) Solvent B: Acetonitrile (0.02 % TFA buffer) Solvent Gradient: Time 0: 10 % B; 2.5 min: 10 % B; 14 min: 90 % B. Flow Rate: 22.5 mL/min The product peak was collected based on UV absorption and concentrated to give Example 1 (37.7 mg). The following compounds (Table 1; Examples 1-13) were prepared using 2- bromobenzenesulfonyl chloride, 3-bromobenzenesulfonyl chloride, 3-chloro benzenesulfonyl chloride, 4-chloro-7-chlorosulfonyl-2,1,3-benzoxadiazole, 2-chloro- 4-fluorobenzenesulfonyl chloride, 5-chloro-2-methoxy-benzenesulfonyl chloride, 2- chloro-6-methylbenzenesulfonyl chloride, 3,5-dichlorobenzenesulfonyl chloride, 2,4- difluoro benzenesulfonyl chloride, 4-fluorobenzenesulfonyl chloride, 2- fluorobenzenesulfonyl chloride, 1-naphthalenesulfonyl chloride, and 2- naphthalenesulfonyl chloride and following the procedure outlined in Example 1. This procedure is outlined in the following Scheme. Example 14 3-Amino-4-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide A. Preparation of 3-Nitro-4-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2- methylbutyl]benzenesulfonamide To a solution of S-isoleucinol (3.0 g, 25.6 mmol), triethylamine (2.85 g, 28.2 mmol) and methylene chloride (30 mL) at 0°C, was added a solution of 4- chloro-3-nitro-benzenesulfonyl chloride (6.55 g, 25.6 mmol) in CH2Cl2 (30 mL). After 15 minutes, the ice bath was removed and the reaction allowed to reach 25°C. After 16 hours, the reaction was quenched by pouring into a saturated sodium bicarbonate solution (125 mL). The organic phase was separated and washed sequentially with 1N HCl solution (100 mL), distilled water and brine, dried over MgSO4 and evaporated to give a crude solid that was recrystallized from ethyl acetate-hexane (5.52 g, 64%). MS (+ESI) 354 ([M+NH4]+). Anal. Calc'd for C12H17ClN2O5S: C, 42.80; H, 5.09; N, 8.32; Found: C, 42.82; H, 5.05; N, 8.23. B. Preparation of 3-Amino-4-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2- methylbutyl]benzenesulfonamide A standard hydrogenation bottle was charged with 3-nitro-4-chloro-N- [(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide (0.50g, 1.48 mmol), 10% palladium on carbon (0.05 g), methanol (25 mL) and hydrogen gas. It was shaken on a Parr hydrogenation apparatus for 50 minutes. The reaction mixture was filtered and the solvent evaporated to produce a crude oil that was flash chromatographed (eluant: ethyl acetate-hexane, 3-2) to afford the product as a solid, mp 89-92°C(0.12g,26%). MS (+APCI) 307.03 ([M+H]+). Anal. Calc'd for C12H19ClN2O3S: C, 46.98; H, 6.24; N, 9.13; Found: C, 47.44; H, 6.32; N, 8.88. Example 15 N-[(1S)-1-benzyl-2-hydroxyethyl]-4-bromobenzenesulfonamide To a solution of (S)-(-) 2-amino-3-phenyl-1-propanol (37 mg, 0.25 mmol) in THF (3 mL) was added triethylamine (58 uL, 0.3 mmol) and 4-bromobenzenesulfonyl chloride (63 mg, 0.25 mmol). The solution was stirred for 8 to 16 hours, then concentrated. The residue was dissolved in MeOH (1.5 mL) and purified by semi- preparative RP-HPLC using the conditions described in Example 1 to give Example 15 (9.8 mg). This procedure is outlined in the following Scheme. Example 16 4-Bromo-N-[(1S)-1-cyclohexyl-2-hydroxyethyl]benzenesulfonamide To a solution of 4-bromobenzenesulfonyl chloride (102 mg, 0.4 mmol) in THF (1 mL) was added L-cyclohexylglycine (77.4 mg, 0.4 mmol) in 1 N sodium hydroxide (1 mL). The reaction was shaken at 25°C for 16 hours, then concentrated. The residue was dissolved in THF (1 mL) and lithium aluminum hydride (1 M solution in THF, 0.8 mmol, 0.8 mL) was added and the reaction shaken for 2 hours. Water (240 µL), 15% sodium hydroxide (240 µL) and water (960 µL) were added with shaking between each addition. The reaction mixture was filtered and the filtrate concentrated and purified as described for Example 1 to give Example 16 (1.9 mg). This procedure is outlined in the following Scheme. The following compounds (Examples 16-19, Table 3) were prepared using 4- bromobenzensulfonyl chloride with L-cyclohexylglycine, D-4-hydroxyphenylglycine, D-methionine, and L-tryptophan and following the procedure outlined in Example 16. Example 20 4-Bromo-2,5-difluoro-N-[(1S,2S)-1-(hydroxymethyl)-2methylbutyl] benzenesulfonamide To a solution of (S)-isoleucinol (23 mg, 0.2 mmol) in THF (3 mL) was added triethylamine (46 pL, 0.24 mmol) and 4-bromo-2,5-difluorobenzenesulfonyl chloride (58 mg, 0.2 mmol). The solution was stirred for 8 to 16 hours. The solvent was removed and the residue purified as described for Example 1 to give Example 20 (4.7 mg). The following compounds (Table 4) were prepared using (S)-(+)-isoleucinol, (S)-(+)-2-arnino-3-methyl-1-butanol, and (S)-tert-leucinol with 4-bromo-2,5-difiuoro benzenesulfonyl chloride, 2,5-dibromobenzenesulfonyl chloride, 3,4-dibromo benzenesulfonyl chloride, 2,3-dichlorobenzenesulfonyl chloride, 3,4-dichloro benzenesulfonyl chloride, 2,4,5-trichlorobenzenesulfonyl chloride, and 2,4,6-trichloro benzenesulfonyl chloride and following the procedure outlined in Example 20. Example 33 4-Bromo-N-[(1R,2R)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide To a solution of D-isoleucine (32.8 mg, 0.25 mmol) in THF (2 mL) was added lithium aluminum hydride (1 M solution in THF) (0.8 mL, 0.8 mmol) and the solution was heated at 60°C for 4 hours. The solution was then stirred at 25°C for 8 to 16 hours. The reaction was quenched by addition of water (45 µL), 15% aqueous sodium hydroxide (45 µL) and water (105 µL) with vigorous stirring between each addition. The mixture was then filtered and concentrated. To the residue in THF (3 mL) was added triethylamine (69 µL, 0.50 mmol) and 4-bromobenzenesulfonyl chloride (63.9 mg, 0.25 mmol). The solution was stirred for 8 to 16 hours, then concentrated and the residue purified as described for Example 1 to give 50.8 mg. The following compounds (Examples 33-39, Table 5) were prepared using 4- bromobenzenesulfonyl chloride, and 4-chlorobenzenesulfonyl chloride, with D- isoleucine, L-a-methyl-valine, p-methyl-DL-phenylalanine, and L-allo-isoleucine and following the procedure outlined in Example 33. This procedure is outlined in the following Scheme. Example 40 N-Allyl-4-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl] benzenesulfonamide To a solution of L-isoleucine methyl ester hydrochloride (1.82 g, 10 mmol) and 4-chlorobenzenesulfonyl chloride (2.11 g, 10 mmol) in CH2Cl2 was added triethylamine (4.18 mL, 30 mmol). The mixture was stirred at 25°C for 16 hours, then filtered and concentrated. The crude product was purified by flash chromatography over silica gel using 10% ethyl acetate in hexane to give N-4-chlorobenzenesulfonyl L-isoleucine methyl ester 3.53 g. To a solution of N-4-chlorobenzenesulfonyl L-isoleucine methyl ester (80 mg, 0.25 mmol) in a mixture of DCM (1.5 mL) and THF (1.5 mL) was added allyl alcohol (17 µL, 0.25 mmol), triphenylphosphine (66 mg, 0.25 mmol) and diethylazodicarboxylate (39 µL, 0.25 mmol). The reaction was shaken at 25°C for 24 hours. Lithium borohydride (11 mg, 0.5 mmol) was added to this reaction solution and the reaction was shaken at 45°C for 24 hours then quenched by addition of water (2 mL) and extracted into ethyl acetate (3.5 mL). The organic phase was evaporated and the residue purified as described for Example 1 to give 11.6 mg. The following compounds (Examples 40-48, Table 6) were prepared using allyl alcohol, 4-biphenylmethanol, t-butyl N-(2-hydroxyethyl)-carbamate, p- chlorobenzyl alcohol, cyclobutanemethanol, 3,4-diraethoxybenzyl alcohol, furfuryl alcohol, 2-(methylthio)ethanol, and 3-phenyl-2-propyn-1-ol and following the procedure outlined in Example 40. This procedure is outlined in the following Scheme. Example 49 4-Chloro-N-[(1S,2R)-1-(hydroxymethyl)-2-(4-methoxyphenyl)propyl] benzenesulfonamide Part 1: A solution of 2-pentenoic acid (4.05 mL, 40 mmol) in THF (100 mL) was cooled to -78°C. Triethylamine (5.85 mL, 42 mmol) and trimethylacetyl chloride (pivaloyl chloride) (5.17 mL, 42 mmol) were added via syringe in that order. The dry ice bath was replaced with an ice bath and the reaction stirred at 0°C for 1 hour, then the reaction was recooled to -78°C. In a separate flask 4-(R)-4-benzyl-2- oxazolidinone (7.0 g, 40 mmol) was dissolved in THF (100 mL) and cooled to -78°C, then n-butyl lithium (1.6 M, 25 mL) was added via syringe. The mixture was stirred for 20 minutes then the above reaction mixture was added by removing the septum and pouring quickly from one flask to the other (Note* attempts to transfer reaction mixture via cannula failed due to the suspended triethylammonium chloride in the mixture). The resulting mixture was stirred at -78°C for 30 minutes then allowed to warm to 25°C for 1 to 2 hours before quenching with saturated aqueous NH4Cl solution (100 mL). Volatiles were removed on the rotary evaporator and the aqueous slurry was diluted with water (200 mL) and extracted with ethyl acetate (2 x 200 mL). The combined organic phase was dried over MgSO4, filtered and concentrated. The product may crystallize out of solution and be of high purity. If purification is required, the crude product can be purified by flash chromatography using 20-30% ethyl acetate in hexane. Part 2: To a copper (I) bromide-dimethyl sulfide complex (246 mg, 1.2 mmol) in THF/DMS (2:1,15 mL), cooled to -40° C, was added 4-methoxyphenyl magnesium bromide (4.8 mL 0.5 M solution in THF, 2.4 mmol). The solution was allowed to stir for 10 minutes while warming to -15° C. The mixture was recooled to -40° C and the product from Part 1 (245 mg, 1 mmol) in THF (6 mL) was added. The solution was stirred at 25°C for 8 to 16 hours. The solution was cooled to -78° C and N- bromosuccinimide (356 mg, 2 mmol) in THF (2 mL) was added. The solution was allowed to warm to 0° C and shaken at 0° C for 3 hours. The reaction was quenched with a 1:1 solution of saturated ammonium carbonate and 0.5 N potassium bisulfate (5 mL). The organic phase was decanted off and concentrated. Part 3: To the product from Part 2 dissolved in acetonitrile (5 mL) was added tetramethylguanidine azide (0.6 mL, 4 mmol). The solution was stirred for 72 to 120 hours. The solution was concentrated to dryness, redissolved in CH2Cl2 and 1 N HCl (2 mL) was added. The layers were separated and the organic layer was filtered through a pad of silica gel, washed with CH2Cl2 (5 mL) and concentrated. Part 4: To the product from Part 3 (131 mg, 1 mmol) in THF (5 mL) at 0° C was added lithium aluminum hydride (1M solution in THF) (2 mL, 2 mmol) and the solution stirred at 25°C for 4 hours. The reaction was quenched by addition of water (114 µL), 15% aqueous sodium hydroxide (114 µL), and water (266 µL) with vigorous stirring between each addition. The mixture was then filtered and concentrated. Part 5: To the solution from Part 4 (0.5 mmol) in THF (2 mL) was added triethylamine (83.7 uL, 0.6 mmol) and 4-chlorobenzenesulfonyl chloride (130.8 mg, 0.5 mmol). The solution was stirred for 8 to 16 hours, then concentrated. The solvent was removed and the residue purified as described for Example 1 to give 50.8 mg. The following compounds (Examples 49-70, Table 7) were prepared using 4- chlorobenzenesulfonyl chloride with crotonic acid, 2-pentenoic acid, 2-hexenoic acid, 2-octenoic acid, cinnamic acid, furylacrylic acid, and 4-methyl-2-pentenoic acid and methyl, ethyl, isobutyl, 4-methoxyphenyl, hexyl and phenyl magnesium bromide and following the procedure outlined in Example 49. This procedure is outlined in the following Scheme. The following compounds (Examples 71-87, Table 8) were prepared using 4- bromobenzenesulfonyl chloride with crotonic acid, 2-pentenoic acid, 2-hexenoic acid, 2-octenoic acid, cinnamic acid, b-(3-pyridyl)-acrylic acid, furylacrylic acid, and 4- methyl-2-pentenoic acid and methyl, ethyl, isobutyl, 4-methoxyphenyl, and hexyl magnesium bromide and following the procedure outlined in Example 49. Example 88 4-Chloro-N-[(1S,2S)-2-ethyl-1-(hydroxymethyl)octyl]benzenesulfonamide Following the procedure outlined in Example 49 (Part 1 and 2), 2-pentenoic acid was coupled with 4-(R)-4-benzyl-2-oxazolidinone to give (R)-3-(2'-pentenyl)-4- benzyl-2-oxazolidinone. Addition of hexyl magnesium bromide was followed by trapping by N-bromosuccinimide. After workup, flash chromatography over silica gel using 5% ether in hexane, gave approximately a 2:1 mixture of (lR-2R):(lR-2S)-3- (2'-bromo-3'ethylnonanyl)-4-benzyl-2-oxazolidinone. Each isomer was converted to the corresponding sulfonylated amino alcohol following the procedure in Example 49, (Steps 3-5). Example 90 4-Chloro-N-methyl-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl] benzenesulfonamide To a solution of 4-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl] benzenesulfonamide (0.10 g, 0.343 mmol) dissolved in DMF (2.0 mL) was added potassium carbonate (47 mg, 0.343 mmol). After 30 minutes, the reaction mixture was cooled to 0°C and iodomethane (50 µL, 0.686 mmol) was added. After 2 hours, the ice bath was removed and the reaction mixture was stirred at 25°C for 24 hours. The insolubles were then filtered off and the DMF solution was diluted with EtOAc (50 mL) and washed sequentially with 10% citric acid (50 mL) and saturated brine (50 mL), dried over MgSO4 and evaporated to a clear oil which was washed with Et2O and then purified by flash chromatography (eluant: 95-5 CHCl3/iPrOH) to afford the desired product as a clear oil (71 mg, 68%). Mass Spectrum (+APCI): 306 ([M+H]+). Anal: Calc'd for C13H20CINO3S: C, 51.06; H, 6.59; N, 4.58. Found: C, 51.15; H, 6.73; N, 4.36. Example 91 4-Chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide To a solution of (S)-isoleucinol (17.6 mg, 0.15 mmol) in CH3CN (600 µL) was added Et3N (300 L, 1M in CH3CN) and 4-chlorobenzenesulfonyl chloride (21.07 mg, 0.1 mmol) as a solution in CH3CN (400 L). The vial was capped and shaken for 8 to 12 hours at 40°C. The solvent was removed, and the oil was dissolved in EtOAc (1 mL). The resulting solution was washed with 1M HCl (2 x 1mL). The solvent was removed in vacuo, and the residue dissolved in 1.6 mL DMSO (0.03 M). The following compounds (Examples 91-119, Table 10) were prepared using 4-chloro, 4-bromo, 3-chloro, and 3-fluorobenzenesulfonyl chloride with (S)- isoleucinol, L-leucinol, DL-2-amino-1-hexanol, (1S, 2R)-(+)-phenyl-propanolamine, (S)-(+)-2-phenylglycinol, (R)-(-)-leucinol, 1-amino-1-cyclopentanemethanol, DL-2- amino-1-pentanol, (S)-2-amino-3-cyclohexyl-1-propanol, H-tyrosinol(bzl), (R)-(+)- methioninol, (S)-(+)-2-amino-1-butanol, (lS,2S)-(+)-thiomicamine, L-alaninol, L- phenylalaninol, L-valinol, and (R)-(+)-2-amino-2-methyl-1-butanol following the procedure outlined in Example 91. This procedure is outlined in the following Scheme. Part 1: To a suspension of 1-amino-1-cyclohexane carboxylic acid (5 g, 35 mmol) and THF (100 mL) was added borane dimethyl sulfide (50 mL, 2M in THF) at 0 °C. The cold bath was allowed to expire and the reaction was stirred at 25 °C for 24 hours. NaOH (3M, 100 mL) was added and the mixture was stirred for 4 hours. The reaction mixture was saturated with K2CO3 and extracted with Et2O (2 x 100 mL). The combined organic extracts were washed with brine (100 mL) and dried over MgSO4 and evaporated to give 4.35 g (96%) of the desired amino alcohol. Part 2: The amino alcohol was sulfonylated as in example 91. The following compounds (Examples 120-125, Table 11) were prepared using the following amino acids: 1-amino-1-cyclohexane carboxylic acid, 2-amino-2- norbomane carboxylic acid, d, 1-1-aminoindane-1-carboxylic acid, and d-1-2- cyclobutyl-2-phenylglycine with 4-bromo and 4-chlorobenzenesuIfonyI chloride following the procedure outlined for example 120. This procedure is outlined in the following Scheme. To a solution of 4-chlorobenzenesulfonyl chloride (1.93 g, 9.1 mmol) in CH3CN (25 mL) and (S)-isoleucinol (1.07 g, 9.1 mmol) was added Et3N (1.91 mL, 13.7 mmol). The reaction mixture was stirred at 25 °C for 30 minutes. The solvent was removed and the oil was dissolved in CH2Cl2 (20 mL). The solution was washed with water (2 x 20 mL) and dried over Na2SO4. The solvent was removed to give N-4- chloro benzenesulfonyl isoleucinol, which was carried on without further purification. To a stirred solution of N-4-chlorobenzenesulfonyl isoleucinol (~9.1 mmol) in CH2Cl2 (100 mL) was added a mixture of pyridinium chlorochromate (5.88 g, 27.3 mmol) and silica gel (~6 g). The resulting slurry was stirred at 25 °C until the alcohol was consumed by TLC analysis. The reaction mixture was diluted with Et2O (250 mL) and filtered through wet silica gel (eluant: 20% EtOAc/ hex). Following removal of solvent, the residue was subjected to a Biotage™ eluting with 10→20% EtOAc/hex to give 1.94 g (74%, two steps) of the aldehyde (LCMS = 288.14 (M-H), rt = 1.07 min). Example 165 4-Chloro-N-[(1S,2S)-1-(hydroxyethyl)-2-methylbutyl]benzenesulfonamide To a solution of the aldehyde from Example 165A (23.1 mg, 80 mmol) in THF (400 µL) was added methyl magnesium bromide (400 µL, 1.0 M in THF, 5 eq). The vial was capped and agitated at 50 °C for 12 hours. The reaction was quenched with saturated aqueous NH4Cl (1.5 mL) and EtOAc (1 mL). The organic layer was transferred into a tared vial and the aqueous layer was extracted with EtOAc (1 mL). The combined organics were concentrated (Savant, medium heat) and the resulting mixture of diastereomers was dissolved in DMSO such that the final concentration was 30 mM. The following compounds (Examples 126-210, Table 12) were prepared using N-4-fluoro, 4-bromo, 4-chloro, 3-chloro and 2-fluorophenylsulfonyl isoleucinal with methylmagnesium bromide, cyclopentylmagnesium bromide, hexylmagnesium bromide, pentylmagnesium bromide, butylmagnesium bromide, isopropylmagnesium bromide, o-tolylmagnesium bromide, tert-butylmagnesium bromide, isobutylmagnesium bromide, vinylmagnesium bromide, allylmagnesium bromide, ethylmagnesium bromide, 4-fluorophenylmagnesium bromide, 4- chlorophenylmagnesium bromide, 2-methyl-1-propenylmagnesium bromide, isopropenyimagnesium bromide, 4-anisylmagnesium bromide, 1-methyl-1- propenylmagnesium bromide, 2-[2-(1,3-dioxanyl)]ethylmagnesium bromide, 3- butenylmagnesium bromide, 1-propynylmagnesium bromide, 4- thioanisolemagnesium bromide, 4-N,N-dimethylanilinemagnesium bromide, and 1- naphthylmagnesium bromide following the procedures outlined in examples 165A and 165. This procedure is outlined in the following Scheme. Example 211 4-Bromo-N-[(1S,2S)-1-(1-hydroxy-1-methylethyl)-2-ethylbutyl]benzenesulfonamide Part 1: To a solution of 4-bromobenzenesulfonyl chloride (1.278 g, 5 mmol) in CH3CN (20 mL) was added (L)-isoleucine methyl ester hydrochloride (908.5 mg, 5 mmol) as a solution in CH3CN (10 mL) and Et3N (1 mL, 7.2 mmol). The reaction mixture was heated at 50 °C with shaking for 3 days. The solvent was removed and the oil was dissolved in EtOAc (10 mL). The solution was washed with water (5 mL). sat. NH4OH (5 mL), brine (5 mL), and dried over MgSO4. The solvent was removed to give 1.62 g (89%) of the desired sulfonamide ester. To a solution of the sulfonamide ester (45.5 mg, 0.125 mmol) in THF (500 µL) was added methyl magnesium bromide (333 µL, 3.0 M in THF, 8 eq). The vial was capped and agitated at 50 °C for 12 hours. The reaction was quenched with saturated NH4Cl (1.5 mL) and EtOAc (1 mL). The organic layer was transferred into a tared vial and the aqueous layer was extracted with EtOAc (1 mL). The combined organic extract was concentrated (Savant, medium heat) and the product was dissolved in DMSO such that the final concentration was 30 mM. The following compounds (Examples 211-271, Table 13) were prepared using (from part 2) N-4-bromo, 4-chloro, 4-fluoro, 3-chloro and 2-fluorobenzenesulfonyl isoleucine methyl ester with methylmagnesium bromide, hexylmagnesium bromide, pentylmagnesium bromide, butylmagnesium bromide, isopropyhnagnesium bromide, isobutylmagnesium bromide, allylmagnesium bromide, ethylmagnesium bromide, 4- fluorophenylmagnesium bromide, 4-chlorophenylmagnesium bromide, 2-methyl-1- propenylmagnesium bromide, isopropenylmagnesium bromide, 4-anisylmagnesium bromide, 1 -methyl- 1-propenylmagnesium bromide, 3 -butenylmagnesium bromide, 1- propynylmagnesium bromide, 4-N,N-dimethylanilinemagnesium bromide, and 1- naphthylmagnesium bromide following the procedure outlined in example 211. This procedure is outlined in the following Scheme. Example 272 4-Chloro-N-[(1S)-1-cyclohexyl-2-hydroxyethyl]benzenesulfonamide A. Preparation of (aS)-α-[[(4-chlorophenyl)sulfonyl]amino]cyclohexaneacetic acid To a solution of S-cyclohexylglycine (1.00 g, 5.16 mmol) in H2O (10 mL) and THF (11 mL) was added 4-chlorobenzenesulfonyl chloride (1.53 g, 7.23 mmol) followed by 2.5N NaOH (8.26 mL) at 25°C with stirring. After 24 hours, the reaction was quenched by addition of 6 N HC1 until pH=2. The reaction mixture was then extracted with EtOAc (2x50 mL). The combined organic extracts were washed with saturated brine (2x50 mL), dried over MgSO4, and evaporated to afford a white solid. This white solid was taken up in Et2O, filtered and evaporated to afford an amorphous white solid which after washing with hexane afforded 0.90 g (52%) of product, mp 120-128°C. Mass Spectrum (+ESI): 354 ([M+Na]+). Anal: Calc'd for C14H18ClNO4S: C, 50.68; H, 5.47; N, 4.22. Found: C, 50.59; H, 5.46; N, 4.19. B. Preparation of 4-Chloro-N-[(1S)-1-cyclohexyl-2-hydroxyethyl] benzenesulfonamide To a solution of LAH (1.0 M in THF, 1.5 mL, 1.5 mmol) was added dropwise at 0°C a solution of (αS)-α-[[(4- chlorophenyl)sulfonyl]amino]cyclohexaneacetic acid (0.50 g, 1.507 mmol) in THF (8.0 mL). After the addition was complete, the reaction mixture was allowed to warm to 25°C. After 24 hours, the reaction was quenched by sequential addition of H2O (60 µL), 15% NaOH (60 µL) and H2O (180 µL). The precipitate was filtered and washed with THF. The combined THF solution was evaporated to a clear oil which afforded a white solid after washing with hexane. This white solid was purified by flash chromatography (eluant: 1-1 hexane/ethyl acetate), washed with hexane and pumped on to afford 0.179 g (37%) of the desired product as a white solid, mp 115-118°C. Mass Spectrum (+APCI): 318 ([M+H]+). Anal: Calc'd for C14H20ClNO3S: C, 52.91; H, 6.34; N, 4.41. Found: C, 52.16; H, 6.25; N, 4.40. Example 273 4-Chloro-N-[(1S)-2-hydroxy-1-phenylethyl]benzenesulfonamide To a solution of S-2-phenyl-glycinol (0.50 g, 3.645 mmol) and Et3N (0.561 mL, 4.01 mmol) in CH2Cl2 (7.5 mL) was added dropwise at 0°C a solution of 4-chloro benzenesulfonyl chloride (0.769 g, 3.645 mmol) in CH2Cl2 (7.5 mL). After the addition was complete, the reaction mixture was allowed to warm to 25°C. After 24 hours, the reaction was diluted with CH2Cl2 (20 mL) and washed sequentially with saturated sodium bicarbonate (30 mL), 1N HCl (30 mL), H2O (30 mL) and saturated brine (30 mL), dried over MgSO4 and evaporated to a white solid which was washed with hexane twice. This white solid was purified by flash chromatography (eluant: 1-1 hexane/ethyl acetate), washed with hexane and pumped on to afford 0.347 g (29%) of the desired product as a white solid, mp 127-128°C. Mass Spectrum (+APCI): 329 ([M+NH4]+). Anal: Calc'd for C14H14ClNO3S:C, 53.93; H, 4.53; N, 4.49. Found: C, 53.96; H, 4.49; N, 4.39. Example 274 4-ChIoro-N-[(1S)-1-(hydroxymethyl)-2-methylpropyl]benzenesulfonamide To a solution of S-valinol (0.52 g, 5.0 mmol), triethylamine (0.55 g, 5.5 mmol) and methylene chloride (10 mL) at 0°C, was added a solution of 4- chlorobenzenesulfonyl chloride (1.06 g, 5.0 mmol) in CH2Cl2 (5 mL). After 15 minutes the ice bath was removed and the reaction allowed to reach 25°C. After 16 hours, the reaction was quenched by pouring into saturated sodium bicarbonate solution (20 mL) and additional methylene chloride (15 mL). The organic phase was separated and washed sequentially with 1N HCl solution (20 mL), distilled water and brine, dried over MgSO4 and evaporated to give a colorless oil that crystallized upon standing, mp 83-85°C (1.30 g, 94%). MS (+ESI) 278.1 ([M+H]+); 257.2; 237.1. Anal. Calc'd for C11H16ClNO3S: C, 47.56; H, 5.81; N, 5.04. Found: C, 47.78; H, 5.81; N, 4.99. Example 275 4-Bromo-N-[(1S)-1-(hydroxymethyl)-2-methylpropyl]benzenesulfonamide To a solution of S-valinol (0.52 g, 5.0 mmol), triethylamine (0.55 g, 5.5 mmol) and methylene chloride (10 mL) at 0°C, was added a solution of 4- bromobenzenesulfonyl chloride (1.28 g, 5.0 mmol) in CH2Cl2 (5 mL). After 15 minutes the ice bath was removed and the reaction allowed to reach 25 °C. After 16 hours, the reaction was quenched by pouring into saturated sodium bicarbonate solution (20 mL) and additional methylene chloride (15 mL). The organic phase was separated and washed sequentially with 1N HCl solution (20 mL), distilled water and brine, dried over MgSO4 and evaporated to give a colorless oil that crystallized upon standing under vacuum, mp 89-94°C (1.49 g, 93%). MS (+APCI) 324.03 ([M+H]+). Anal. Calc'd for C11H16BrNO3S: C, 41.00; H, 5.00; N, 4.35; Found: C, 41.09; H, 4.85; N, 4.28. Example 276 4-Iodo-N-[(lS,2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide To a solution of S-isoleucinol (0.50 g, 4.26 mmol), triethylamine (0.47 g, 4.68 mmol) and methylene chloride (10 mL) at 0°C, was added a solution of 4-iodo benzenesulfonyl chloride (1.29 g, 4.26 mmol) in CH2C12 (5 mL). After 15 minutes the ice bath was removed and the reaction allowed to reach 25°C. After 16 hours, the reaction was quenched by pouring into saturated sodium bicarbonate solution (22 mL) and additional methylene chloride (15 mL). The organic phase was separated and washed sequentially with 1N HCl solution (25 mL), distilled water and brine, dried over MgSO4 and evaporated to give a crude solid that was recrystallized from ethyl acetate-hexane, mp 118-120°C (1.07 g, 66%). MS (+APCI) 383.96 ([M+H]+); 283.81; 191.95. Anal. Calc'd for C12HI8INO3S: C, 37.61; H, 4.73; N, 3.65; Found: C, 37.55; H, 4.61; N, 3.61. Example 277 4-Chloro-N-[(1S)-1-(hydroxymethyl)-2,2-dimethylpropyl]benzenesulfonamide To a solution of S-tert-leucinol (0.20 g, 1.70 mmol), triethylamine (0.19 g, 1.87 mmol) and methylene chloride (10 mL) at 0°C, was added a solution of 4-chloro benzenesulfonyl chloride (0.36 g, 1.70 mmol) in CH2Cl2 (5 mL). After 15 minutes the ice bath was removed and the reaction allowed to reach 25°C. After 16 hours, the reaction was quenched by pouring into saturated sodium bicarbonate solution (20 mL) and additional methylene chloride (15 mL). The organic phase was separated and washed sequentially with 1N HCl solution (20 mL), distilled water and brine, dried over MgSO4 and evaporated to give the desired product as a white solid, mp 128- 130°C (0.46 g, 94%). MS (+APCI) 292.06 ([M+H]+). Anal. Calc'd for C12H18ClNO3S: C, 49.39; H, 6.22; N, 4.80; Found: C, 49.40; H, 6.17; N, 4.79. Example 278 - Repressor Release Assay (RRA) The beta amyloid inhibitory activity of the compounds of the present invention was determined using the Repressor Release Assay (RRA). See, Table 17. A compound was considered active in RRA if it leads to at least a 1.5 fold increase in luciferase activity at 10 ug/mL and was non-toxic. A. Cell Culture CH0-K1 cells were cultured in whole DMEM media (DMEM - High Glucose with 10% fetal bovine serum, 1% Non-essential Amino Acids, and 1% Penicillin-Streptomycin) at 37°C with 5% CO2. Two million cells were plated into 10-cm dishes 24 hrs prior to transfection. Transient transfections were completed as recommended by Gibco BRL using their Lipofectamine Plus system. First, 6 µg of pRSVO-luc and 6 µg of APP-1acI construct DNA were added to 460 µL Opti-Mem transfection media and incubated with 30 µL Plus reagent for 15 minutes. Then, a lipid mixture of 40 µL Lipofectamine reagent and 460 µL Opti-Mem transfection media was incubated with the DNA-Plus reagent mixture for 15 minutes. During the DNA-lipid incubation, the CHO-K1 cells were washed once and covered in 5.0 mL DMEM media without Penicillin-Streptomycin. The DNA-lipid preparation was then layered onto these cells and incubated at 37°C overnight. One and one half million transfected cells per well (100 µL total volume) were plated into sterile, opaque Packard 96-well Culture-Plates in clear DMEM whole media (DMEM - without phenol red) and incubated at 37°C with 5% CO2 for 3-5 hours. B. Compound Dilution Compounds were diluted using two different protocols; one protocol was used for compounds supplied neat (weighed powder in vial) and the other protocol was used for compounds supplied in solution (20 mM in DMSO in 96-well plates). For both protocols. 25 mM Hepes and 25 mM Hepes/1% DMSO were prepared fresh to be used as diluent. The Hepes/DMSO was used as the diluent control on all experimental plates. The following table depicts the steps for compound dilution (please note that the last step was the addition of compound to cells/media in tissue culture plate). Because some compounds were present in 96-well format, at 20 mM, the following represents the protocol for their dilution (note that an average molecular weight of these compounds was used to calculate these cilutions and as above, the last step was the addition of compound to cells/media in tissue culture plate). Once the compounds were diluted, they were applied ir duplicate on cells in tissue culture plates (prepared above). Cells were incubated with compound at 37°C with 5% CO2 for an additional 36-48 hours. C. Assay Measurement Luciferase assays (LucLite reagent, Packard) were performed and were read on a Packard TopCount instrument. Media was removed from each 96-well plate and replaced with 100 µL PBS per well (with Mg2+ and Ca2+). An equal volume (100 µL) of the LucLite lysis/substrate buffer was added to each well and the plates were sealed and mixed in the dark on a rotary shaker for 15-30 minutes at room temperature. Luciferase readings were then taken on the TopCount instrument. Measurements were expressed as relative light units (RLU) and are calculated and analyzed in MS Excel as follows: D. Analysis of data "Fold Increase" refers to the amount of luciferase activity (measured in relative light units) over diluent control. "SEM" refers to the standard error of the mean for fold increase. "Activity": A compound is considered active if it results in at least a 1.5 fold increase in luciferase activity at 10 µg/µL. 1=non-toxic, 0=toxic in Table 17. "Toxicity" is determined by loss of signal (≤ 0.75 fold increase). E. Standard beta amyloid inhibitor The reference gamma secretase inhibitor DAPT (LY374973, AN37124: Dovey, H.F. et al, J. Neurochem. 76: 173-181 (2001)) was prepared as outlined in WO 98/22494 and tested in RRA and exhibited a 6.0-28.1 fold increase in luciferase activity at 20 µg/mL. All publications cited in this specification are incorporated herein by reference. While the invention has been described with reference to a particularly preferred embodiment, it will be appreciated that modifications can be made without departing from the spirit of the invention. Such modifications are intended to fall within the scope of the appended claims. WE CLAIM : 1. A compound of Formula 1a: wherein: R1 is selected from the group consisting of H, halogen, and O; R2 is selected from the group consisting of H, halogen, and N-N; R3 is selected from the group consisting of H, and halogen: R4 is selected from the group consisting of H, halogen, amino, and N=N; R5 is selected from the group consisting of H, halogen, methoxy, methyl and O; R6 is sekcted from the group consisting of H, lower alkyl, lower alkenyl, 3-phenyl-2- propyn-1-yl, benzyl, substituted benzyl. CH3 cycloalkyl. CH2-2-furan. (CH2)2SCH3, and (CH2)2NHBOC: R8 is selected from the group consisting of a lower alkyl or S-stereochemistry at the carbon atom to which N and T are attached, cycloalkyl, CH2 cycloalkyl, CH(lower alkyl)-2-furan, CH(lower alkyl)-4-methoxyphenyl, CH(lower alkyl) phenyl, CH(OH)-4- SCH3-phenyl, and (CH2)2-S-lower alkyl; T is R9 and F are H: or R9 is H and R1 is selected form the group consisting of lower alkyl, lower alkenyl, CF. methyl-substituted alkenyl. lower alkynyl, cycloalkyl, substituted phenyl, 1-naphthyl, and CH2CH2-1.3-dioxolane; or R9 and R10 are independently selected from the group consisting of lower alkyl, lower alkenyl, phenyl, 4-substituted-phenyl, and 1-naphthyl; wherein: (i) when R5 is a methoxy; R2 is halogen and R1, R3, and R4 are H; (ii) when R5 is a methyl; R1 is halogen and R2, R3, and R4 are H; (iii) when R4 is an amino; R3 is halogen and R1, R2 and R5 are H; (iv) when R2 is N=N; R1 is O and R2 is bound to R1 to form a heterocyclic ring; (v) when R4 is N=N and R3, is O; R4 is bound to R5 to form a heterocyclic ring; (vi) one or more of R1 to R5 is a halogen; (vii) when R3 is halogen, R8 is butyl and R9 and R10 are H, at least one of R1, R2, R4 and R5 is not H; and (viii) when R3 is halogen, R8 is butyl and t is ---C=O, at least one of R1, R2, R4 and R5 is not H; or a pharmaceutically acceptable salt, hydrate, or prodrug thereof. 2. The compound as claimed in claim 1 wherein: T is: R1, R2, R4, R5, R6, R7, R9, and R10are H; R3 is halogen: and R8 is lower alkyl of S-stereochemistry at the carbon atom to which N, and T are attached. 3. The compound as claimed in claim 1. wherein said pharmaceutically acceptable salt of said compound is selected from the group consisting of salts of sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, diethanolamine. ethylene amine, salts of bases, and mixtures thereof. 4. A compound selected from the group consisting of 2-bromo-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulibnamide, 3-bromo-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide. 3-chloro-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 4-chloro-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl]-1,2,3-benzoxadiazole-7-sulfonamide, 2-chloro-4-fluoro- N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulibnamide, 5-chloro-N-[(1S,2S)- 1 -(hydroxymethyl)-2-methylbutyl]-2-methoxybenzenesulfonamide, 2-chloro-N-[( 1 S,2S)- 1-(hydroxymethyl)-2-mcthylbutyl]-6-mcthylbcnzenesulfonamidc. 3.5-dichloro-N- [(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 2,4-difluoro-N- [(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 4-fluoro-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 2-fluoro-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, N-[(1S,2S)-1-(hydroxymethyl)-2- methylbutyl]naphthalene-l-sulfonamide, N-[(1S,2S)-1-(hydroxymethyl)-2- methylbutyl] naphthalene-2 -sulfonamide 3-amino-4-chloro-N-[(1S,2S)-1- (hydroxymethyl)-2- methylbutyl]benzenesulfonamide, N-[(1S)-1-benzyl-2-hydroxyethyl]- 4- bromobenzenesulfonamide, 4-bromo-N-[(1S)-1-cyclohexyl-2- hydroxyethyl] benzenesulfonamide, 4-bromo-N-[(1R)-2-hydroxy-1-(4- hydroxyphenyl)ethyl] benzenesulfonamide, 4-bromo-N-[(1S)-l-(hydroxymethyl)-3- methylbutyl] benzenesulfonamide, 4-bromo-N-[(1S)-2-hydroxy-1-(1 H-indol-2- ylmethyl)ethyl] benzenesulfonamide, 4-bromo-2,5-difluoro-N-[(l S,2S)-1- (hydroxymethyl-2- methylbutyl]benzenesulfonamide, 2,5-dibromo-N-[(1S,2S)-1- (hydroxymethyl)-2- me hylbutyl] benzenesulfonamide, 3,4-dibromo-N-[(1S,2S)-1- (hydroxymethyl)-2- methylbutyl]benzenesulfonamide, 2,3-dichloro-N-[(1S,2S)-1- (hydroxymethyl)-2- me hylbutyl] benzenesulfonamide, 3,4-dichloro-N-[(1S,2S)-l- (hydroxymethyl)-2- me hylbutyl] benzenesulfonamide, 2,4,5-trichloro-N-[(1S,2S)-1- (hydroxymethyl)-2- me hylbutyl] benzenesulfonamide, 4-bromo-2,5-difluoro-N-[( 1S)-1-(hydroxymethyl)-2- me hylpropyl] benzenesulfonamide, 3,4-dichloro-N-[( 1S)-1- (hydroxymethyl)-2- me hylpropyl] benzenesulfonamide, 2,4.6-trichloro-N-[f 1S)-1- (hydroxymethyl)-2- me hylpropyl] benzenesulfonamide, 3,4-dibromo-N-[(1S)-1- (hydroxymethyl)-2,2- dimethylpropyl]benzenesulfonamide, 3,4-dichloro-N-[(1S)-1- (hydroxymethyl)-2,2- dimethylpropyl]benzenesulfonamide, 2,4,5-trichloro-N-[(1S)-1- (hydroxymethyl)-2,2- dimethylpropyl]benzenesulfonamide 2,4,6-trichloro-N-[(1S)-1-(hydroxymethyl)-2,2- dimethylpropyl] benzenesulfonamide. 4-bromo-N-[( 1 R,2R)-1- (hydroxymethyl)-2- methylbutyl] benzenesulfonamide, 4-bromo-N-[(1S)-1- (hydroxymethyl)-1,2- dmethylpropyl]benzenesulfonamide, 4-bromo-N-[1- (hydroxymethyl)-2-phenylpropyl] benzenesulfonamide, 4-bromo-N-[(1S,2R)-1-(hydroxymethyl)-2-methylbutyl] benzenesulfonamide, 4-chloro-N-[( 1S)-1-(hydroxymethyl)-1,2-dimethylpropyl] benzenesulfonamide, 4-chloro-N-[1- (hydroxymethyl)-2-phenylpropyl] benzenesulfonamide, 4-chloro-N-[(1S,2R)-1- (hydroxymethyl)-2-methylbutyl] benzenesulfonamide, N-allyl-4-chloro-N-[(1S,2S)-l- (hydroxymethyl)-2-methylbutyl] benzenesulfonamide, N-(1, 1'-biphenyl]-4-ylmethyl)-4- chloro-N-[(1S, 2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, tert-butyl 2- {[(4-chlorophenyl) sulfonyl][(1S ,2S)-1-(hydroxymethyl)-2- methylbutyl]amino}ethylcarbamate, 4-chloro-N- (4-chlorobenzyl)-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 4- chloro-N-(cyclobutylmethyl)-N- [(1S,2S)-1-(hydroxymethyl)-2-methylbutyl] buzenesulfonamide, 4-chloro-N-(3,4- dimethoxybenzyl)-N-[(1S,2S)-1-(hydroxymethyl)- 2-methylbutyl]benzenesulfon- amide, 4- chloro-N-(2-furylmethyl)-N-[(1S,2S)-l- (hydroxymethyl)-2-methylbutyl]benzenesulfonamide, 4-chloro-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl]-N-[2- (methylthio)ethyl]benzenesulfonamide, 4-chloro- N-[(1S,2S)-1-(hydroxymethyl)-2- methylbutyl]-N-(3-phenylprop-2-ynyl) benzenesulfonamide, 4-chloro-N-[(1S,2R)-1- (hydroxymethyl)-2-(4-methoxyphenyl) propyl]benzenesulfonamide, 4-chloro-N-[(1S,2R)- 1 -(hydroxymethyl)-2-methyloctyl] benzenesulfonamide, 4-chloro-N-[(1S,2R)-1- (hy droxymethyl)-2-phenylpropyl] benzenesulfonamide, 4-chloro-N-[( 1 S)-2-ethyl-1- (hydroxymethyl)butyl] benzenesulfonamide, 4-chloro-N-[(1S,2R)-2-ethyl-1- (hydroxymethyl)-4-methylpentyl] benzenesulfonamide, 4-chloro-N-[(1S,2S)-1- (hydroxymethyl)-2-methylpentyl ] benzenesulfonamide, 4-chloro-N-[(1S,2S)-2-ethyl-1- (hydroxymethyl)pentyl] benzenesulfonamide, 4-chloro-N-[(1S,2R)-1-(hydroxymethyl)-4- methyl-2-propylpentyl] benzenesulfonamide, 4-chloro-N-[(1S,2R)-1-(hydroxymethyl)-2- (4-methoxyphenyl) penyl]benzenesulfonamide, 4-chloro-N-[(1S,2R)-1-(hydroxymethyl)- 2-propyloctyl] benzenesulfonamide, 4-chloro-N-methyl-N-[(1S,2S)-1- (hydroxymethyl)-2-methylbutyl] benzenesulfonamide, 4-chloro-N-[(1S)-1- (hydroxymethyl)-3-methylbutyl] benzenesulfonamide, 4-chloro-N-[( 1 R,2S)-2-hydroxy-1- methyl-2-phenylethyl] benzenesulfonamide, 4-bromo-N-[1- (hydroxymethyl)cyclopentyl]bcnzenesulfonamide. 4-chloro-N-[(1S)-2-cyclohexyl-1-(hydroxymethyl)ethyl]benzenesulfonamide, N-{(1S)-1- [4-(benzyloxy)benzyl]-2- hydroxyethyl} -4-chlorobenzenesulfonamide. 4-chloro-N-[( 1R)- 1 -(hydraxymethyl)-1- methylpropyl]benzenesultbnamide, 4-bromo-N-[( 1 S,2S)-1- (hydroxymethyl )-2- methylbutyl]-benzenesu,fonamide, 4-bromo-N-[1 -(hydroxymethyl) pentyl] benzencsulfonamide. 4-bromo-N-[(1R.2S)-2-hydroxy-1-methyl-2-phenylethyl] benzen.sulfonamidc. 4-bromo-N-[(1S)-2-hydroxy-1-phenylethl]benzenesulfonamide, 4- bromo- N-[(1R)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide, 4-chloro-N-[1 - (hydroxymethyl)cyclopentyl]benzenesulfonamide, 4-bromo-N-[1-(hydroxymethyl)butyl] benzenesulfonamide, 3-chloro-N-[1-(hydroxymethyl)butyl]benzenesulfonamide, 3- chloro-N-[(1S)-2-cyclohexyl-1-(hydroxymethyl)ethyl]bcnzenesulfonamide, 3-chloro-N- [(1R)-1-(hydroxymethyl)-3-(methylthio)propyl]benzenesulfonamide. 3-chloro-N-[(1S)-1- (hydroxymethyl)propyl]benzenesulfbnamide, 2-fluoro-N-[(1S)-1-(hydroxymethyl)-3- methyl]butyl] benzenesulfonamide, 2-fluoro-N-[1 -(hydroxymethyl)pentyl] benzenesulfonamide, 2-f uoro-N-[(1R,2S )-2-hydroxy-1-methyl-2-phenylethyl] benzenesulfonamide, 2-fluoro-N-[(1S)-2-hydroxy-1-phenylethyl]benzenesulfonamide, 2- tluoro -N-[( 1R)-1-(hydroxymethyl)-3-methylbutyl]benzenesulfonamide, 2-fluoro-N-[1- (hydroxymethyl)cyclopentyl]benzenesulfonamide, N-[(1S)-2-cyclohexyl-1- (hydroxymethyl)ethyl]-2-fluorobenzenesulfonamide, 2-fluoro-N-{(1S,2S)-2-hydroxy-1- (hydroxymethyl)-2-[4-(methylthio)phenyl]ethyl] benzenesulfonamide, 2-fluoro-N-[(1S)- 1 -(hydroxyl-methylethyl]benzenesulfonamide, N-[( 1S)-1-benzyl-2-hydroxyethyl]-2- fluorobenzenesulfonamide, 2-fluoro-N-[(1S)-1-(hydroxymethyl)-2-methylpropyl] benzenesulfonamide, 4-bromo-N-[ 1 -(hydroxymethyl)cyclohexyl|benzenesulfonamide, 4- bromo-N-[2-(hydroxymethyl)bicyclc [2.2.1 .]hept-2-yl]benzenesulfonamide, 4-bromo-N- [1 -(hydroxymethyl)-2,3-dihydro-1H-inden-1-yl] benzenesulfonamide. 4-chloro-N-[1 - (hydroxymethyl)cyclohexyl]benzenesulfonamide. 4-chloro-N-[1-(hydroxymethyl)-2,3- dihydro-1H-inden-1-yl]benzenesulfonamide, 4-chloro-N-( 1 -cyclobutyl-2-hydroxy-1- phenylethyl)benzenesulfonamide. 4-fluoro-N-[(1S,2S)-1-(1-hydroxyethyl)-2- methylbutyl] benzenesulfonamide, N-((1S,2S)-1-[cyclopentyl(hydroxy)mefhyl]-2- methylbutyl}-4-fluorobenzenesulfonamide, 4-fluoro-N- {(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]octyl} benzenesulfonamide. 4-fluoro-N- ((1S)-2-hydroxy-1-[(1S)-1- methylpropyl]heptyl} benzenesulfonamide, 4-fluoro-N- ((1S)-2-hydroxy-1-[(1S)-1- melhylpropyl]hexyl}benzenesulfonamide, 4-fluoro-N-{(1S,2S)-1-[hydroxy(2- methylphenyl)methyl]-2-methylbutyl}benzenesulfonamide. 4-fluoro-N-{(1S)-2-hydroxy- 3 ,3-dimefhyl-1-[(1S)-1-methylpropyl]butyl}benzenesulfonamide, 4-fluoro-N-((1S)-2- hydroxy-1-[(1S)-1-methylpropyl]-3-butenyl} benzenesulfonamide, 4-fluoro-N- {(1S)-2- hydroxy-1-1 (1S)-1-methylpropyl ]-4-pentenyl} benzenesulfonamide, 4-fluoro-N- {(1S)-2- hydroxy-1-[(1S)-1-methylpropyljbutyl}benzenesulfonamide, N-[(1S,2S)-1-[(4- chlorophenyl)(hydroxy)methyl]-2-methylbutyl}-4-fluorobenzenesulfonamide, 4- fluoro- N-{(1S)-2-hydroxy-4-methyl-1-[(1S)-1-methylpropyl]-3-pentenyl}b- enzenesulfonamide, 4- fluoro- N-{(1S)-2-hydroxy-3-methyl-1-[(1S)-1-methylpropyl]-3-butenyl}benzenesulfo- namide, 4-fluoro-N-{(1S,2S)-1-[hydroxy(4-methoxyphenyl)methyl]-2- methyl butyl} benzenesulfonamide, N- {(1S)-4-(1,3-dioxan-2-yl)-2-hydroxy-1-[(1S)-b methylpropyl] butyl)-4-fluorobenzenesulfonamide, 4-fluoro-N-{(1S)-2-hydroxy-1-[(1S)-1- methylpropyl ]-5-hexenyl} benzenesulfonamide, 4-fluoro-N-((1S,2S)-1-{hydroxy[4- (methylsulfanyl)phenyl]methyl}-2-methylbutyl)benzenesulfonamide, N-{(1S,2S)-1-[[4- (dimethylamino)phenyl](hydroxy)methyl]-2-methylbutyl}-4-fluorobenzenesulfonamide, 4-fluoro-N- {(1S,2S)-1-[hydroxy( 1-naphthyl)methyl]-2-methylbutyl}b- benzenesulfonamide, 4-bromo-N-[(1S,2S)-1-(1-hydroxyethyl)-2-methylbutyl] benzenesulfonamide, 4-bromo-N- {(1S,2S)-1-[cyclopentyl(hydroxy)methyly]-2- methylbutyl]benzenesulfonamide, 4-bromo-N-{(1S)-2-hydroxy-1-[(1S)-1- methylpropyl] heptyl}benzenesulfonamide, 4-bromo-N-1 (1S)-2-hydroxy-1-[(1S)-1- methylpropyl] hexyl)benzenesulfonamide, 4-bromo-N- ((1S)-2-hydroxy-3,3-dimethyl-1- [(1S)-1- mehylpropyl [butyl] benzenesulfonamide, 4-bromo-N- [(1S)-2-hydroxy-4- methyl-1- [(1S)-1-mothylpropyl]pentyl} benzenesulfonamide, 4-bromo-N- {(1S )-2- hydroxy-1-[(1S)- 1-methylpropyl]-3-butenyl} benzenesulfonamide, 4-bromo-N-{(1S)-2- hydroxy-1-[(1S)-1- methylpropyl]-4-pentenyl}benzenesulfonamide, 4-bromo-N-1(1 S)-2- hydroxy-1-[(1 S)-1- methylpropyl] butyl}benzenesulfonamide, 4-bromo-N- {(1S,2S)-1-[(4- fluorophenyl) (hydroxy)methyl]-2-methylbutyl} benzenesulfonamide, 4-bromo-N- {(1S,2S)-1-[(4- chlorophenyl)(hydroxy)methyl]-2-methylbutyl}benzenesulfona- mide, 4- bromo-N-{(1S)- 2-hydroxy-4-methyl-1-[(1S)-1-methylpropyl]-3-penten- yl} benzenesulfonamide, 4- bromo-N-((1S)-2-hydroxy-3-methyl-1-[(1S)-1-methylpropyl]-3- butenyl} benzenesulfonamide. 4-bromo-N- {(1S,2S)-1-[hydroxy(4-methoxyphenyl) methyl]-2- methylbutyl} benzenesulfonamide, 4-bromo-N-{(1S,3E)-2-hydroxy-3-methyl- 1-[(1S)-1- methylpropyl]-3-pentenyl}benzenesulfonamide, 4-bromo-N- {(1 S)-4-(1,3- dioxan-2-yl)-2- hydroxy-1-[(1S)-1-methylpropyl]butyl}benzenesulfonamide, 4-bromo-N- {(1S)-2- hydroxy-1-[(1S)-1-methylpropyl]-5-hexenyl]benzenesulfonamide, 4-bromo-N- {(1S)-2- hydroxy-1-[(1S)-1-methylpropyl]-3-pentynyl}benzenesulfonamide, 4-bromo-N- ((1S,2S)- 1 -{hydroxy[4-(methylsulfanyl)phenyl]methyl} -2-methylbutyl) benzencsulfonamide, 4- bromo-N- {(1S,2S)-1-[[4-(dimethylamino)phenyl](hydroxy) methyl]-2-methylbutyl} benzencsulfonamide, 4-chloro-N-[(1 S,2S)-1-(1 -hydroxyethyl)-2- methylbutyl] benzencsulfonamide, 4-chloro-N-{(1S,2S)-1- [cyclopentyl(hydroxy)methyl]-2- methylhutyl}benzenesulfonamide, 4-chloro-N-{(1S)-2- hydroxy-1-[(1S)-1-methylpropyl] octyl}benzenesulfonamide, 4-chloro-N-{(1S)-2- hydroxy-1-[(1S)-1-methylpropyl]heptyl} benzencsulfonamide, 4-chloro-N - ((1S)-2- hydroxy-1-[(1S)-1-methylpropyl]hexyl} benzencsulfonamide, 4-chloro-N-} (1S)-2- hydroxy-3 -methyl-1-[(1S)- 1,-methylpropyl] butyl}benzenesulfonamide, 4-chloro-N- {(1S,2S)-1-[hydroxy(2-methylphenyl)methyl]-2- methylbutyl]benzenesulfonami- de, 4- chloro-N-{(1S)-2-hydroxy-3,3-dimethyl-1-[(1S)- 1-methylpropyl] butyl} benzenesulfonamide, 4-chloro-N- {(1S)-2-hydroxy-4-methyl-1- [(1S)-1- methylpropyl]pentyl} benzenesulfonamide, 4-chloro-N-{(1S)-2-hydroxy-1-[(1S)- 1 - methylpropyl]-3-butenyl] benzenesulfonamide, 4-chloro-N- {(1S)-2-hydroxy-1-[(1S)-1- methylpropyl] -4-pentenyl} benzenesulfonamide, 4-chloro-N - ((1S)-2-hydroxy-1-[(1S)-1- methylpropyl] butyl] benzenesulfonamide, 4-chloro-N-{(lS,2S)-1-[(4- chlorophenyl) (hydroxy)methyl]-2-methylbutyl} benzenesulfonamide, 4-chloro-N- {(1S,2S)-1-[hydroxy (4-methoxyphenyl)methyl]-2-methylbutyl}benzenesulfonam- ide. 4- chloro-N- [(1S)-4- (1,3-dioxan-2-yl)-2-hydroxy-1-[(1S)-1- methylpropyl]butyl}benzenesulfonamide, 4- chloro-N- {(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]-5-hexenyl} benzenesulfonamide, 4- chloro-N- {(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]-3-pentynyl}benzenesulfonamide, 4- chloro-N-(( 1 S,2S)-1- {hydroxy[4- (methylsulfanyl)phenyl]methyl}-2-methylbutyl) benzencsulfonamide, 4-chloro-N- {(1 S,2S)-1-f [4-(dimethylamino)phenyl](hydroxy) methyl]-2-methylbutyl} benze- nesulfonamide, 4-chloro-N- {(1S,2S)-1-[hydroxy( 1- naphthyl)methyl]-2- methylbutyl}benzenesulfonamide, 3-chloro-N-[(1S,2S)-1-(1 - hydroxyethyl)-2- methylbutyl]benzenesulfonamide, 3-chloro-N-((1S,2S)-1-[cyclopentyl (hydroxy)methyl]-2-methylbutyl}benzenesulfonamide, 3-chloro-N-{(1S)-2-hydroxy-1- [(1S)-1-methylpropyl]octyl} benzenesulfonamide, 3-chloro-N- {(1S)-2-hydroxy-1-[(1S)- methylpropyl]heptyl} benzenesulfonamide, 3-chloro-N-((1S)-2-hydroxy-1-[(1S)-1- methylpropyl]hexyl} benzenesulfonamide, 3-chloro-N- {(1S)-2-hydroxy-3-methyl-1- [(1S)-1-methylpropyl]butyl} benzenesulfonamide, 3-chloro-N-((1S)-2-hydroxy-3,3- dimethyl-1-(1S)-1-methylpropyl]butyl}benzenesulfonamide, 3-chloro-N-{(1S)-2- hydroxy-4-methyl-1-[(1S)-1-methylpropyl]pentyl} benzenesulfonamide. 3-chloro-N- (1S)-2-hydroxy-1-[(1S)-1-methylpropyl]-3-butenyl}benzenesulfonamide, 3-chloro-N- (1S)-2-hydroxy-1-[(1S)-1-methylpropyl]-4-pentyl}benzenesulfonamide, 3-chloro-N- {(1S)-2-hydroxy-1-[(1S)-1-methylpropyl]butyl}benzenesulfonamide, 3-chloro-N- {(1S,2S)-1-[(4-chlorophenyl)(hydroxy)methyl]-2-methylbutyl}benzenesulfona- mide, 3- chloro-N-{(1S)-2-hydroxy-4-methyl-1-[(1S)-1-methylpropyl]-3-pente- nyl} bezenesulfonamide, 3-chloro-N-{(1S,2S)-1-[hydroxy(4-methoxyphenyl)methyl]-2- methylbutyl]benzenesulfonamide, 3-chloro-N-{(1S)-4-(1,3-dioxan-2-yl)-2-hydroxy-1- [(1S)- 1-methylpropyl] butyl] benzenesulfonamide, 3-chloro-N-{(1S)-2-hydroxy-1-[(1S)- 1-methylpropyl]-5-hexenyl] benzenesulfonamide, 3-chloro-N-(( 1 S,2S)-1-{hydroxy[4- (methylsulfanyl)phenyl]methyl} -2-methylbutyl)benzenesulfonamide, N-{( 1S,2S)-1- [cyclopentylthydroxy)methyl]-2-methylbutyl} -2-fluorobenzenesulfonamide. 2-fluoro-N- {(1S)-2-hydroxy-1-[(1S)-1-methylpropyljoctyl}benzenesulfonamide, 2-fluoro-N-{(1S)- 2-hydroxy-1- [(1S)-1-methylpropyljheptyl} benzenesulfonamide, 2-fluoro-N- {(1S)- 2- hydroxy-1-[(1S)-1-methylpropyl]hexyl} benzenesulfonamide, 2-fluoro-N-[(1S)-2- hydroxy-1-[(1S)-1-methylpropyl]-3-butenyl} benzenesulfonamide, 2-fluoro-N-{(1 S,2S)- 1-[4-fluorophenyl)(hydroxy)methyl]-2-methylbutyl}benzenesulfonamide, N- {(1S,2S)- 1- [(4 chlorophenyl)(hydroxy)methylJ-2-methylbutyl}-2-fluorobenzenesulfona- mide. 2- fluro-N-{(1S,2S)-1-[hydroxy(4-methoxyphenyl)methyl]-2-methylbuty- 1} benzenesulfonamide, N-[(1S)-4-(1,3-dioxan-2-yl)-2-hydroxy-1-[(1S)-1-methylpropyl] butyl}-2-flu- orobenzenesulfonamide, 4-bromo-N-[(1S,2S)-1-(1-hydroxy-1-methylethyl)- 2-n ,ethylbuty 1 ] benzenesulfonamide, 4-bromo-N- {(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]-2-pentylheptyl) benzenesulfonamide, 4-bromo-N- {(1S)-2-butyl-2- hydroxy-1-[(1S)-1-methylpropyl]hexyl} benzenesulfonamide, 4-bromo-N- {(1S)-2- hydroxy-2-isobutyl-4-methyl-1-[(1S}-1-methylpropyl]pentyl} benzenesulfonamide, 4- bromo-N-{(1S,2S)-1-[hydroxy(diphenyl)methyl]-2-methylbutyl) benzenesulfonamide. N-{(1S)-2-allyl-2-hydroxy-1-[(1S)-1-methylpropyl]-4-pentenyl}-4- bromobenzenesulfonamide, 4-bromo-N-{( 1 S)-2-ethyl-2-hydroxy-1-[(1S)- 1-methylpropyl] butyl} benzenesul- fonamide, N-{(lS,2S)-1-[bis(4-chlorophenyl)(hydroxy)methyl]-2- methylbutyl}-4-bromobenzenesulfonamide, 4-bromo-N-{(1S)-2-hydroxy-2-isopropenyl- 3-methyl-1-[(1S)-1-methylpropyl]-3-butenyl}benzenesulfonamide, 4-bromo-N-{(1S,3 E)- 2-hydroxy-3-methyl-2-[( 1E)-1-methyl-1-propenyl]-1-[(1S)-1-methylpropyl]- 3-penteny 1} benzenesulfonamide, 4-bromo-N- {(1S)-2-(3-butenyl)-2-hydroxy-1-[(1S)-1- methylpropyl]-5-hexenyl] benzenesulfonamide, 4-bromo-N-(( 1 S,2S)-1-{hydroxy[di( 1 - naphthl)]methyl} -2-methylbutyl)benzenesulfonamide, 4-chloro-N-[( 1S,2S)-1-(1 - hydrox) -1-methylethyl)-2-methylbutyl]benzenesulfonamide, 4-chloro-N- ((1 S)-2-hexyl- 2-hydro xy-1-[(1S)-1-methylpropyl]octyl} benzenesulfonamide, N- {(1S)-2-butyl-2- hydroxy-1-[(1S)-l -methylpropyljhexyl}-4-chlorobenzenesulfonamide. 4-chloro-N-{(1S)- 2-hydroxy-2-isobutyl-4-methyl-1-[(1S)-1-methylpropyl]pentyl}benzenesulfon- amide, 4- chloro-N- ((1S,2S)-1-[hydroxy(diphenyl)methyl]-2-methylbutyl}benz- enesulfonamide. N- {(1S)-2-allyl-2-hydroxy-1-[(1S)-1-methylpropyl]-4-pentenyl}-4- chlorobenzenesulfonamide, 4-chloro-N- ((1S)-2-ethy 1-2-hydroxy-1-[(1S)-1-methylpropyl] butyl} beazenesulfonamide, 4-ehloro-N-{(1S)-2-hydroxy-2-isopropenyl-3-methyl-1- [(1S)-1-methylpropyl]-3-butenyl}benzenesulfonamide, 4-chloro-N-((1S,2S)-1- {hydroxy [bis(4-methoxyphenyl)]methyl}-2-methylbutyl)benzenesulfonamide, 4-chloro-N- {(1S,3E)-2-hydroxy-3-methyl-2-[(1E)-1-methyl-1-propenyl]-1-[(1S)-1- methylpropyl] 3- pentenyl j benzenesulfonamide, N- ((1 S)-2-(3-butenyl)-2-hydroxy-1-[(1S)-1- methylpropyl]-5-hexenyl} -4-chlorobenzenesulfonamide, 4-chloro-N-(( 1 S,2S)-1- [hydroxy|di(l-naphthyi)]methyl}-2-:;nethylbutyl)benzenesulfonamide, 4-fluoro-N- [(1S,2S)-1-(1-hydroxy-1-methylethyl)-2-methylbutyl]benzenesulfonamide, 4-fluoro-N- !(1 S)-2-hjx\l-2-hydroxy-1-[(1S)-1-rnethylpropyl]oety 11benzenesulfonamide, 4-fluoro-N- [ (1 S)-2-hydroxy-1-[(IS.)-1-methylpr3pyl]-2-pentylheptyl} benzenesulfonamide- , N- [ (1 S)-2-bi it>l-2-hydroxy-1-[(1S)-1-methylpropyl]hexyl}-4-iluorobenzene- sulfonamide. 4- fluro-N-{(1S)-2-hydroxy-2-isopropyl-3-methyl-1-[(1S)-1-methylpropyl]buty- 1 } benzenesulfonamide. 4-fluoro-N- ((1S)-2-hydroxy-2-isobutyl-4-methyl-1-[(1S)-1- methylpropyl]pentyl] benzenesulfonamide. N- {(1S)-2-allyl-2-hydroxy-1-[(1S)-1- methylpropyl]-4-pentenyl}-4-fluorobenzenesulfonamide, N-((1S)-2-ethyl-2-hydroxy-1- [(1S)-1-methylpropyl] butyl] -4-fluorobenzenesulfonamide, 4-fluoro-N- {(1S)-2-hydroxy- 2-isopropenyl-3-methyl-1-[(1S)-1-methylpropyl]-3-butenyl} benzenesulfonamide, 4- fluoro-N-((1S,2S)-1- {hydroxy[bis(4-methoxyphenyl)}methyl} -2-methylb- utyl) benzenesulfonamide. 4-fluoro-N- {(1S,3E)-2-hydroxy-3-methyl-2-[( 1E)-1-methyl-1- propenylj - 1-[( 1S)-1-methylpropyl]-3-pentenyl) benzenesulfonamide, N-{( 1 S)-2-(3- butenyl)-2-hydroxy-1-[(1S)-1-methylpropyl]-5-hexenyl} -4-fluorobenzenesulfonamide. N- ((1S,2S)-1-[bisf4-(dimethylamino)phenyl](hydroxy)methyl-2-methylbutyl}-4- fluorobenzenesulfonamide, 4-fluoro-N-(( 1S,2S)-1- {hydroxy[di( 1 -naphthyl)]methyl} -2- methylbutyl)benzenesulfonamide, 3-chloro-N- {(1S)-2-hexyl-2-hydroxy-1-[(1S)-1- methylpropyl]octyl} benzenesulfonamide, 3-chloro-N- {(1S)-2-hydroxy-1-[(1S)-1- n iethylpropyl]-2-pentylheptyl) benzenesulfonamide, N- {(1 S)-2-butyl-2-hydroxy-1-[(1S)- 1 methylpropyl]hexyl}-3-chlorobenzenesuJfonamide, 3-chloro-N- [ (1 S)-2-hydroxy-2- isobutyl-4-methyl-1-[(1S)-1-methylpropyl Jpenty 1} benzenesulfonamide, 3-chloro-N- (1S,2S)-1-[hydroxy(diphenyl)methyl]-2-methlbutyl} benzenesulfonamide, N- {(1S)-2- allyl-2-hydroxy-1-[(1S)-1-methylpropyl]-4-pentenyl]-3-chlorobenzenesulfon- amide, 3- choro-N-[(1S)-2-ethyl-2-hydroxy-]-[(1S)-1-methylpropyl]butyl]be- nzenesuJfonamide, N- {(1S,2S)-1-[bis(4-chlorophenyl)(hydroxy)methyl]-2-methylbutyl)-3-chlorobe- benzenesulfonamide, 3-chloro-N- ((1S)-2-hydroxy-2-isopropenyl-3-methyl-1-[(1S)- 1- methylpropyl]-3-butenyl} benzenesulfonamide, 3-chloro-N-(( 1S,2S)-1- {hydroxy[bis(4- methoxyphenyl)]methyl}-2-methylbutyl)benzenesulfonamide, 3-chloro-N-{(1S,3E)-2- hydroxy-3-methyl-2-[(1E)-1-methyl-1-propenyl]-1-[(1S)-1-methylpropyl]-3- pentenyl} benzenesulfonamide, N-[(1S)-2-(3-butenyl)-2-hydroxy-1-[(1S)-1-methylpropyl]- 5- hexenyl)-3-chlorobenzenesulfonamide, 2-fluoro-N- {(1S)-2-hexyl-2-hydroxy-1-[(1S)- 1 - methylpropyl]octyl}benzenesulfonamide. 2-fluoro-N- {(1S)-2-hydroxy-1-[(1S)-1- methylpropyl]-2-pentylheptyl}benzenesulfonamide, 2-fluoro-N-{(1S,2S)-1-[hydroxy (diphenyl)methyl]- 2-methylbutyl]benzenesulfonamide, N-{(1S)-2-allyl-2-hydroxy-1- [(1S)-1-methylpropyl]-4-pentenyl}-2-fluorobenzenesulfonamide, N-((1S)-2-ethyl-2- hydroxy-1-[(1S)-1-methylpropyl]butyl}-2-fluorobenzenesulfonamide, N-{(1S,2S)-1- [bis (4-fluorophenyl)(hydroxy)methyl]-2-methylbutyl}-2-fluorobenzenesulfon- amide, N- ( 1S, 2S)-1-[bis(4-chlorophenyl)(hydroxy)methyl]-2-methylbutyl}-2- - fluorobenzenesulfonamide, 2-fluoro-N-{(1S)-2-hydroxy-2-isopropenyl-3-methyl-1- [(1S)-1- methylpropyl]-3-butenyl} benzenesulfonamide, 2-fluoro-N-((1S,2S)-1-[hydroxy bis(4- methoxyphenyl)] methyl) -2-methylbutyl)benzenesulfonamide, 2-fluoro-N- (1S,3E)-2- hydroxy-3-methyl-2-[(1E)-1-methyl-1-propenyl]-1-[(1S)-1-methylpropyl]-3- pentenyl} benzenesulfonamide. N- {(1S )-2-( 3 -butenyl)-2-hydroxy-1-[(1S)-1- methylpropyl]- 5-hexenyl}-2-fluorobenzenesulfonamide, 4-chloro-N-[(1S)-1-cyclohexyl- 2-hydroxyethylbenzenesulfonamide, 4-chloro-N - [(1S )-2 -hydroxy-1-phenylethyl] benzenesulfonamide, 4- chloro-N-[(1S)-1-(hydroxymethyl)-2-methylpropyl] benzenesulfonamide, 4-bromo-N-[( 1S)-1-(hydro xymethyl)-2-methylpropyl] benzenesulfonamide, 4-iodo-N-[( 1 S,2S)-1- (hydroxymethyl)-2-methylbutyl] benzenesulfonamide, and 4-chloro-N-[(1S)-1- (hydroxymethyl)-2,2-dimethylpropyl] benzenesulfonamide; or a pharmaceutically acceptable salt, hydrate, or prodrug thereof. 5. The compound as claimed in claim 1. which is 4-chloro-N-[(1S, 2S)-2-ethyl-1- hydroxymethyl)butyl]benzenesulfor amide or a pharmaceutically acceptable sait, hydrate. or prodrug thereof. 6. The compound as claimed in claim 1, wherein R3 is halogen and R8 is a lower alkyl of S-stereochemistry at the carbon atom to which N and T are attached; or a pharmaceutically acceptable salt. 7. A pharmaceutical composition comprising a physiologically compatible carrier and a compound as claimed in claim 1. 8. A compound of Formula I: wherein : R is selected from the group consisting of H. halogen, and O; R is selected from the group consisting of 11, halogen, and N=N; R is selected from the group consisting of H and halogen; R is selected from the group consisting of H, halogen, amino, and N=N; R is selected from the group consisting of H, halogen, methoxy. methyl, and O; or R and R2 or R4 and R5 are fused to form a carbon-based, unsaturated ring; R is selected from the group consisting of H, lower alkyl. lower alkenyl, 3-phenyl-2- propyn-1-yl, benzyl, substituted benzyl. CH2 cycloalkyl, CH2-2-furan. (CH2 )2SCH3, and (CH2)2NHBOC: R is selected from the group consisting of H, lower alkyl, and cycloalkyl; R is selected from the group consisting of benzyl and substituted benzyl; T is R9 and R10 are H; or R9 is H and Rl0 is selected from the group consisting of lower alkyl, lower alkenyl, CF3, methyl-substituted alkenyl, lower alkynyl, cycloalkyl. substituted phenyl, 1-naphthyl, and CH2CH2-1.3-dioxolane; or R9 and R10 are independently selected from the group consisting of lower alkyl, lower alkenyl, phenyl, 4-substituted-phenyl, and 1-naphthyl: wherein: (i) when R5 is a methoxy; R; is halogen and R1, R3, and R4 are H; (ii) when R5 is a methyl; R1 is halogen and R2, R3 and R4 are H; (iii) when R4 is an amino: R3 is halogen and R1, R2, and R5 are H; (iv) when R2 is N=N and R1 is O and R2 is bound to R1 to form a heterocyclic ring (v) when R4 is N=N and R5 is O and R1 is bound to R5 to form a heterocyclic ring: and (vi) one or more of R1 to R5 is a halogen: or a pharmaceutically acceptable salt, hydrate, or prodrug thereof. 9. A pharmaceutical composition comprising a physiologically compatible carrier and a compound as claimed in claim 8. 10. A compound of Formula Ib: therein: R1 is selected from the group consisting of H, halogen, and O; R2 is selected from the group consisting of H. halogen, and N=N; R3 is selected from the group consisting of H, bromine, fluorine, and iodine: R4 is selected from the group consisting of H, halogen, amino, and N=N; R5 is selected from the group consisting of H, halogen, methoxy, methyl, and O: R6, is selected from the group consisting of H, lower alkyl, lower alkenyl, 3-phenyl-2- propyn-1-yl, benzyl, substituted benzyl, CH2 cycloalkyl, CH2-2-furan, (CH2)2SCH; and ( CH2)2NHBOC: R7 is selected from the group consisting of H, lower alkyl, and cycloalkyl; T is R9 and R10 are H; or R9 is H and R10 is selected form the group consisting of lower alkyl, lower alkenyl, CF3. methyl-subitituted alkenyl, lower alkynyl, cycloalkyl, substituted phenyl, 1-naphlhyl, and (OH2)CH2- 1. 3-dioxolane; or R9 and R10 are independently selected from the group consisting of lower alkyl, lower alkenyl, phenyl, 4-substituted-pheny], and 1-naphthyl; wherein: (i) when R5 is a methoxy; R2 is halogen and R1, R3, and R4 are H; (ii) when R5 is a methyl; R1 is halogen and R2, R3 and R4 are H; (iii) when R4 is an amino; R3 is halogen and R1, R2 and R5 are H; (iv) when R2 or R4 is N=N; R or R5 is O and R2 or R4 is bound to R1 or R5 to form heterocyclic ring; and (v) one or more of R1 to R5 is a halogen; or a pharmaceutically acceptable salt, hydrate, or prodrug thereof. 11. A pharmaceutical composition comprising a physiologically compatible carrier and a compound is claimed in claim 10. 1 2. A con pound of Formula I: wherein: R1 is selected from the group consisting of H, halogen, and O; R2 is selected from the group consisting of H, halogen, and N=N; R3 is selected from the group consisting of H and halogen; R4 is selected from the group consisting of H, halogen, amino, and N=N; R5 is selected from the group consisting of H, halogen, methoxy, methyl and O; R6 is selected from the group consisting of H, lower alkyl, lower alkenyl. 3-phenyl-2- propyn-1-yl, benzyl, substituted benzyl. CH2 cycloalkyl, CH2-2-furan, (CH2)2SCH3, and (CH2)2NHBOC: R7 is selected from the group consisting of lower alkyl and cycloalkyl; R8 is selected from the group consisting of cycloalkyl, phenyl, substituted phenyl, CH2 cycloalkyl, CH(lower alkyl)-2-furan, CH(lower alkyl)-4-methoxyphenyl, CH(lower alkyl) phenyl. and CH(OH)-4-SCH3-phenyl; T is R9 and R10 are H; or R9 is H and R10 is selected form the group consisting of lower alkyl, lower alkenyl, CF3. methyl-substituted alkenyl, lower alkynyl, cycloalkyl, substituted phenyl, 1-naphthyl, and CH2CH:-1 ,3-dioxolane; or R9 and R10 are independently selected from the group consisting of lower alkyl, lower alkenyl, phenyl, 4-substituted-phenyl, and 1-naphthyl; wherein (i) when R5 is a methoxy; R2 is halogen and R1, R3, and R1 are H; (ii) when R5 is a methyl; R1 is halogen and R2, R3 and R1 are H; (iii) when R4 is an amino: R3 is halogen and R1, R2 and R5 are H; (iv) when R2 is N=N; R1 is O and R2 is bound to R1 to form a heterocyclic ring: (v) when R2 is N =N and R5 is O; R4 is bound to R5 to form a heterocyclic ring; and (vi) one or more of R1 to R5 is a halogen; or a pharmaceutically acceptable salt, hydrate, or prodrug thereof. 13. A pharmaceutical composition comprising a physiologically compatible carrier and a compound as claimed in claim 12. 14. A compound of Formula I: wherein: R1 is selected from the group consisting of H, halogen and O; R2 is selected from the group consisting of H, halogen, and N:=N; R3 is selected from the group consisting of H and halogen; R4 is selected from the group consisting of H, halogen, amino, and N=N; R5 is selected from the group consisting of H, halogen, methoxy, methyl and O; or R1 and R; R2 and R3 ; R4 and R5; or R3 and R4 are fused to form a carbon-based, naphthalene ring with the benzene ring; R6 is selected from the group consisting of H, lower alkyl, lower alkenyl, 3-phenyl-2- propyn-1-yl, benzyl, substituted benzyl, CH; cycloalkyl, CH2-2-furan, (CH2)2SCH3 and (CH2)2NHBOC: R7 is selected from the group consisting of H, lower alkyl and cycloalkyl; R8 is selected from the group consisting of cycloalkyl. phenyl. substituted phenylbenzyl. substituted benzyl, CH2cycloalkyl, CH(lower alkyl )-2-furan. CH( lower alkyl)-4- nethoxyphenyl. CH(lower alkyl) phenyl. and CH(OH)-4-SCH3-phenyl;or R7, and R8 are fused to form a saturated carbon-based ring; T is (i) when R5 is a methoxy; R2 is halogen and R1, R3, and R4 are H; (ii) when R5 is a methyl; R1 is halogen and R2, R3, and R4 are H; (iii) when R4 is an amino; R3 is halogen and R1, R2, and R5 are H; (iv) when R2 is N=N and R1 is O; R2 is bound to R1 to form a heterocyclic ring; (v) when R4 is N==N and R5 is O; R4 is bound to R5 to form a heterocyclic ring; (vi) when each of R1, R2, R4, R5, and R6 is H, R3 is halogen, and R7 is H, then R8 is C5 to C8 alkyl or R7 and R8 are fused to form a saturated carbon-based ring; (vii) when each of R3, R4, R5, R6, and R7 is H and R1, and R2, are fused to format carbon-based naphthalene ring, then R8 is selected from the group consisting of-lower alkyl, cycloalkyl, phenyl, substitutec phenyl, benzyl, substituted benzyl, CH2 cycloalkyl, C H(lower alkyl)-2-furan, CH(lower alkyl)-4-methoxyphenyl; CH(lower alkyl) phenyl, and CH(OH)-4-SCH3 phenyl; (viii) when each of R1, R2, R4 and R5 and R6 is H and R3 is halogen, then R7 and R8 are not both CH; and (ix) at least one of R1, R2, R3, R4, and R5 is halogen unless R1, and R2; R2 and R3, R4 and R5 or R3, and R4 are fused to form a carbon-based, naphthalene ring with the benzene ring; or a pharmaceutically acceptable salt, hydrate, or prodrug thereof. 15. A pharmaceutical composition comprising a physiologically compatible carrier and a compound as claimed in claim 14. 16. A compound of Formula 1: wherein: R is selected from the group consisting of H. halogen, and O; R is selected from the group consisting of H. halogen, and N~N; R is selected from the group consisting of H and halogen; R is selected from the group consisting of H, halogen, amino, and N=N; R is selected from the group consisting of H, halogen, methoxy, methyl and O: or R1 and R2; R2 and R3 ; R4 and R5; or R3 and R4 are fused to form a carbon-based, naphthalene ring with the benzene ring; R6 is selected from the group consisting of lower alkyl, lower alkenyl, 3-phenyl-2propyn- 1-yl, benzyl, substituted benzyl, CH2 cycloalkyl CH2-2-furan, (CH2)2 SCH3, and (CH2) 2N IBOC; R7 and R8 are ilised to form a saturated carbon-based ring. T is R nd R10 are H; or R is H and R , is selected form the group consisting of lower alkyl, lower alkenyl. CF,. methyl-substiluted alkenyl. lower alkynyl, cycloalkyl. substituted phenyl, l-naphthyl, and CH CH2-1,3-dioxolane;or R9 nd R10 are independently selected from the group consisting of lower alkyl, lower alkenyl. phenyl. 4-substituted-pheny], and l-naphthyl; wherein: (i) when R5 is a methoxy: R2 is halogen and R1, R3 and R4 are H; (ii) when R5 is a methyl; R1 is halogen and R2, R3 and R4 are H; (iii) when R4 is an amino: R3 is halogen and R1, R2 and R5 are H; (iv) when R2 is N=N; R1 is O and R2 bound to R1 to form a heterocyclic ring; (v) when R4 is N=N and R:, is O and R4 is bound to R5 to form a heterocyclic ring; and (vi) at least one R1, R2, R3, R4 and R5 is halogen unless R1, and R2; R2 and R3, R4 and R5, or R3 and R4 are fused to form a carbon-based, naphthalene ring with the benzene ring; or a pharmaceutically acceptable salt, metabolite, hydrate, or prodrug thereof. 17. A pharmaceutical composition comprising a physiologically compatible carrier and a compound as claimed in claim 16. 18. A composition for lowering beta amyloid levels in a patient, said composition comprising a pharmaceutically acceptable amount of a compound as claimed in any of claims 1 to 6, 8, 10, 12, 14 or 16. 19. A composition for preventing or treating Alzheimer's disease, Down's Syndrome, mild cognitive impairment and other beta amyloid-involved diseases, said composition comprising a pharmaceutically acceptable amount of a compound as claimed in any of claims 1 to 6, 8, 10, 12, 14 or 16. Compounds of Formula I, wherein R1-R8 are defined herein are provided, together with pharmaceutically acceptable salts, hydrates, metabolites, and/or prodrugs thereof. Uses of these compounds for inhibiting beta amyloid production and for the prevention and treatment of Alzheimer's Disease and Down's syndrome are described. |
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| Patent Number | 226745 | ||||||||||||||||||||||||||||||
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| Indian Patent Application Number | 1796/KOLNP/2004 | ||||||||||||||||||||||||||||||
| PG Journal Number | 52/2008 | ||||||||||||||||||||||||||||||
| Publication Date | 26-Dec-2008 | ||||||||||||||||||||||||||||||
| Grant Date | 24-Dec-2008 | ||||||||||||||||||||||||||||||
| Date of Filing | 25-Nov-2004 | ||||||||||||||||||||||||||||||
| Name of Patentee | WYETH | ||||||||||||||||||||||||||||||
| Applicant Address | FIVE GIRALDA FARMS, MADISON, NJ | ||||||||||||||||||||||||||||||
Inventors:
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| PCT International Classification Number | A61K 31/18 | ||||||||||||||||||||||||||||||
| PCT International Application Number | PCT/US03/18198 | ||||||||||||||||||||||||||||||
| PCT International Filing date | 2003-06-09 | ||||||||||||||||||||||||||||||
PCT Conventions:
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