6-SUBSTITUTED SULFONYL AZABICYCLO[3.2.1]OCTANES USEFUL TO INHIBIT 11Beta-HYDROXYSTEROID DEHYDROGENASE TYPE-1
AssigneeSchering Corporation
InventorsCraig D. Boyle, Samuel Chackalamannil, Unmesh Shah, Claire M. Lankin
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Abstract
In its many embodiments, the present invention relates to a novel class of 6-substituted sulfonyl-1,3,3-trialkyl-6-azabicyclo[3.2.1]octane compounds useful to inhibit 11β-hydroxysteroid dehydrogenase type-I, pharmaceutical compositions containing the compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more conditions associated with the expression of 11β-hydroxysteroid dehydrogenase type-I using such compounds or pharmaceutical compositions.
Claims19
A compound represented by the structural Formula I:
- or a pharmaceutically acceptable salt, solvate, ester or prodrug of said compound, wherein:
- R1 represents alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, arylalkenyl, heteroaryl or heteroarylalkyl;
- and
- R2-R4 independently represent alkyl;
- with the exception of those compounds wherein:
- R2-R4 each represent methyl;
- and
- R1 represents phenyl substituted by substituted alkoxycarbonyl, substituted alkylcarbonyloxy, substituted sulfonylamino, substituted carbonylamino, or unsubstituted or substituted aminocarbonyl;
- and excluding the following compounds:
- 1,3,3-trimethyl-6-[(phenylmethyl)sulphonyl]-6-azabicyclo[3.2.1]octane;
- 6-[(3,4-difluorophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 6-[(4-aminophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 1,3,3-trimethyl-6-[[4-(5-phenyl-2-oxazolyl)phenyl]sulfonyl]-6-azabicyclo[3.2.1]octane;
- 6-[(2-methyl-5-tert-butylphenyl)sulfonyl]-6-azabicyclo[3.2.1]octane;
- 6-[[3-(4,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 6-[[5-2,6-dichloro-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)phenoxy]-2-hydroxyphenyl]sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 1,3,3-trimethyl-6-[[5-[2-[[2-(2-oxo-1-imidazolidinyl)ethyl]amino]-4-pyrimidinyl]-2-thienyl]sulfonyl]-6-azabicyclo[3.2.1]octane;
- 6-[(4-ethoxyphenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 1,3,3-trimethyl-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-6-azabicyclo[3.2.1]octane;
- 6-[(2,3-dichlorophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 3-[(1,3,3-trimethyl-6-azabicyclo[3.2.1]oct-6-yl)sulfonyl]benzoic acid;
- 3-[(1,3,3-trimethyl-6-azabicyclo[3.2.1]oct-6-yl)sulfonyl]benzoic acid methyl ester;
- 1,3,3-trimethyl-6-[(3-nitrophenyl)sulfonyl]-6-azabicyclo[3.2.1]octane;
- 4-[(1,3,3-trimethyl-6-azabicyclo[3.2.1]oct-6-yl)sulfonyl]benzoic acid;
- 1,3,3-trimethyl-6-[(2,3,5,6-tetramethylphenyl)sulfonyl]-6-azabicyclo[3.2.1]octane;
- 1,3,3-trimethyl-6-[(2-nitrophenyl)sulfonyl]-6-azabicyclo[3.2.1]octane;
- 6-[(4-acetylphenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 6-[(2,5-dimethylphenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 6-[(4-methoxyphenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 6-[(5-bromo-2-ethoxyphenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 6-[(2,5-dibromophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 6-[(2,4-difluorophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 6-[(5-bromo-6-chloro-3-pyridinyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 6-[(2,5-dichlorophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- 1,3,3-trimethyl-6-phenylsulfonyl-6-azabicyclo[3.2.1]octane;
- 6-(1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-ylsulfonyl)benzo[d]oxazol-2(3H)-one;
- 6-(1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-ylsulfonyl)benzo[cd]indol-2(1H)-one;
- 3-((1R,5S)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-ylsulfonyl)-1H-pyrazolo[3,4-b]pyridine;
- 2,2,2-trifluoro-1-(8-(1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-ylsulfonyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone;
- 6-[(4-tert-butylphenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane;
- and
- 6-[(3-aminophenyl)sulfonyl]-1,3,3-trimethyl-6-azabicyclo[3.2.1]octane.
A compound selected from the group consisting of:
- or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof.
A method of inhibiting 11β-hydroxysteroid dehydrogenase type-I in a cell, comprising contacting said cell with an effective amount of at least one compound of the Formula I:
- or a pharmaceutically acceptable salt, solvate, ester or prodrug of said compound, wherein:
- R1 represents alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, arylalkenyl, heteroaryl or heteroarylalkyl;
- and
- R2-R4 independently represent alkyl.
A method for treating one or more conditions associated with expression of 11β-hydroxysteroid dehydrogenase type-I comprising administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula I:
- or a pharmaceutically acceptable salt, solvate, ester or prodrug of said compound, wherein:
- R1 represents alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, arylalkenyl, heteroaryl or heteroarylalkyl;
- and
- R2-R4 independently represent alkyl.
A method for treating one or more conditions associated with expression of 11β-hydroxysteroid dehydrogenase type-I comprising administering to a patient in need thereof a therapeutically effective amount of at least one compound selected from the group consisting of:
- or a pharmaceutically acceptable salt, solvate, ester or prodrug thereof.
Dependencies are inferred from the claim text.