Patent NZ-587997-A (NZ)
Title: Adamantyl-acetamide derivatives as inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme
Inventor: LINK JAMES T
IPC: C07D213/85
Filed: 2005-04-29
Abstract: Disclosed is a substituted adamantine compound selected from the group consisting of: N2- [2-(4-chlorophenyl)ethyl] -N1-[(E)-5-hydroxy-2-adamantyl]alaninamide; N2-[2-(3,4-dichlorophenyl)ethyl] -N1-[(E)-5-hydroxy-2-adamantyl] -N2-methylalaninamide; N2-[2-(4-chlorophenyl)-1-methylethyl] -N1-[(E)-5-hydroxy-2-adamantyl]-N2-methylalaninamide; N-[(E)-5-hydroxy-2-adamantyl]-1-{ [4-(trifluoromethyl)benzyl]amino} cyclopropanecarboxamide; 2-[(cis)-2,6-dimethylmorpholin-4-yl] -N-[(E)-5-hydroxy-2-adamantyl]propanamide; 2-azepan-1-yl-N-[(E)-5-hydroxy-2-adamantyl]propanamide; N-[(E)-5-hydroxy-2-adamantyl]-2-(6,7,9,10-tetrahydro-8H-[1,3]dioxolo[4,5-g] [3]benzazepin-8-yl)propanamide; 2-(1,3-dihydro-2H-isoindol-2-yl)-N- [(E)-5-hydroxy-2-adamantyl]propanamide; 2- [3-(4-chlorophenoxy)azetidin- 1-yl]-N-[(E)-5-hydroxy-2-adamantyl]propanamide; 2-(5-chloro-2,3-dihydro-1H-indol- 1-yl)-N-[(E)-5 -hydroxy-2-adamantyl]propanamide; N-[(E)-5-hydroxy-2-adamantyl] -2-(3-phenylazetidin-1-yl)propanamide; 2-[3-(3-fluorophenoxy)pyrrolidin-1-yl]-N-[(E)-5-hydroxy-2-adamantyl]propanamide; N-[(E)-5-hydroxy-2-adamantyl]-2-methyl-2- [2-(trifluoromethyl)pyrrolidin-1-yl]propanamide; N-[(Z)-5-hydroxy-2-adamantyl]-2-{ 4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl} acetamide; N-[(E)-5-hydroxy-2-adamantyl] -2-{ 4-[5 -(trifluoromethyl)pyridin-2-yl]piperazin-1-yl} acetamide; (2S)-N-[(E)-5-hydroxy-2-adamantyl] -2-{ 4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl} propanamide; (2R)-N- [(E)-5 -hydroxy-2-adamantyl] -2- { 4- [5 -(trifluoromethyl)pyridin-2-yl]piperazin-1-yl} propanamide; N-[(E)-5-fluoro-2-adamantyl] -2-{ 4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl} acetamide; N-[(Z)-5-fluoro-2-adamantyl] -2-{ 4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl} acetamide; N-[(E)-5-hydroxy-2-adamantyl] -2-[4-(5-methylpyridin-2-yl)piperazin-1-yl]propanamide; N-[(E)-5-hydroxy-2-adamantyl] -2-methyl-2-{ 4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl} propanamide; N-[(E)-5-hydroxy-2-adamantyl]-2-(4-pyridin-2-ylpiperazin-1-yl)propanamide; 2- [4-(4-fluorophenyl)piperazin-1-yl]-N-[(E)-5-hydroxy-2-adamantyl]propanamide; N-[(E)-5-hydroxy-2-adamantyl]-2-[4-(4-methoxyphenyl)piperazin-1-yl]propanamide; 2-[4-(5-cyanopyridin-2-yl)piperazin-1-yl]-N-[(E)-5-hydroxy-2-adamantyl]propanamide; 2-[4-(2-furoyl)piperazin-1-yl]-N-[(1R,3S)-5-hydroxy-2-adamantyl]propanamide; N-[(E)-5-hydroxy-2-adamantyl] -2-{ 4-[4-(trifluoromethyl)phenyl]piperazin-1-yl} propanamide; (2S)-N-[(E)-5-hydroxy-2-adamantyl] -2-{ 4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl} propanamide; (2R)-N-[(E)-5-hydroxy-2-adamantyl] -2-{ 4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl} propanamide; 2-[4-(6-chloropyridin-3 yl)piperazin-1-yl]-N-[(E)-5-hydroxy-2-adamantyl]propanamide; 2-(4-benzylpiperidin-1-yl)-N-[(E)-5-hydroxy-2-adamantyl]propanamide; 2-[4-(2-fluorophenoxy)piperidin-1-yl] -N-[(E)-5-hydroxy-2-adamantyl]propanamide; 2-[3-(2-fluorophenoxy)piperidin-1-yl] -N-[(E)-5-hydroxy-2- adamantyl]propanamide; N- [(E)-5 -cyano-2-adamantyl] -2-methyl-2-{ 4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl} propanamide; and N-[(E)-5-(cyanomethyl)-2-adamantyl]-2-methyl-2-{ 4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl} propanamide. Also disclosed is a pharmaceutical composistin comprisining a compound and the use of the compound for the manufacture ofa medicament for treating Cushing's syndrome, non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, hypertension, atherosclerosis, glaucoma, and osteoporosis. The compounds are useful as 11-beta-HSD inhibitors.