Triazole derivatives as inhibitors of 11-β-hydroxysteroid dehydrogenase-1
View Patent ↗Triazole derivatives 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 represented by formula I:
or a pharmaceutically acceptable salt thereof wherein:
2 of X, Y and Z represent nitrogen atoms, and the other represents an oxygen atom;
R 1 and R 2 are taken together with the atom to which they are attached and represent a cyclobutyl group, optionally substituted with 1-2 fluorine atoms, and R 3 represents hydrogen or a fluorine atom;
or R 1 represents methyl,
R 2 represents methyl or a fluorine atom and
R 3 represents a fluorine atom.
2. A compound in accordance with claim 1 selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
3. A pharmaceutical composition comprised of a compound in accordance with claim 1 in combination with a pharmaceutically acceptable carrier.
4. A method of treating hypertension in a mammalian patient in need of such treatment comprising administered to the patient an anti-hypertensive effective amount of a compound in accordance with claim 1 .
5. A method of treating diabetes in a mammalian patient in need of such treatment comprising administering to the patient a compound in accordance with claim 1 in an amount that is effective to treat diabetes.
6. A method of treating obesity in a mammalian patient in need of such treatment comprising administering to the patient a compound in accordance with claim 1 in an amount that is effective to treat obesity.
7. A compound which is: 5-(1,1-Difluoroethyl)-3-(4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-1,2,4-oxadiazole; or a pharmaceutically acceptable salt thereof.
8. A compound which is: 5-(3,3-Difluorocyclobutyl)-3-(4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-1,2,4-oxadiazole; or a pharmaceutically acceptable salt thereof.
9. A compound which is: 5-(1-Fluoro-1-methylethyl)-3-(4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-1,2,4-oxadiazole; or a pharmaceutically acceptable salt thereof.
10. A compound which is: 2-(1,1-Difluoroethyl)-5-(4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-1,3,4-oxadiazole; or a pharmaceutically acceptable salt thereof.