Pyrazole carboxamides as inhibitors of 11-β-hydroxysteroid dehydrogenase-1
View Patent ↗Pyrazole carboxamides of structural formula I are selective inhibitors of the 11β-hydroxysteroid dehydrogenase-1. The compounds are useful for the treatment of diabetes, such as noninsulin-dependent diabetes (NIDDM), hyperglycemia, obesity, insulin resistance, dyslipidemia, hyperlipidemia, hypertension, Metabolic Syndrome, and other symptoms associated with NIDDM.
1. A compound of structural formula I:
or a pharmaceutically acceptable salt thereof, wherein
each n is independently 0, 1, or 2;
R 1 is methyl;
R 2 is aryl or heteroaryl, or heteroarylmethyl, wherein aryl and heteroaryl are unsubstituted or substituted with one to four R 6 substituents;
R 3 is hydrogen, chlorine, or methyl;
R 4 and R 5 together with the nitrogen atom to which they are attached form a 5- to 7-membered ring saturated heterocycle optionally containing an additional heteroatom selected from O, S, and NC 0-4 alkyl wherein said heterocycle optionally fused with a benzene ring and wherein said heterocycle or optionally benzo-fused heterocycle is unsubstituted or substituted with one to three substituents independently selected from halogen, C 1-4 alkyl, trifluoromethyl, and (CH 2 ) n aryl wherein aryl is unsubstituted or substituted with one to three substituents independently selected from halogen and C 1-4 alkyl; and
each R 6 is independently selected from the group consisting of: amino, C 1-4 alkylamino, di(C 1-4 alkyl)amino, halogen, cyano, C 1-4 alkyl, hydroxy, C 1-4 alkoxy, C 1-4 alkylthio, C 1-4 alkylsulfonyl, trifluoromethyl, trifluoromethoxy, aryl, and heteroaryl;
wherein aryl and heteroaryl are unsubstituted or substituted with one to three substituents independently selected from cyano, halogen, hydroxy, C 1-4 alkoxy, C 1-4 alkyl, trifluoromethyl, and trifluoromethoxy.