Adamantyl, phenyl, and benzyl ketone derivatives as inhibitors of 11β-hydroxysteroid dehydrogenase type I useful in the treatment of diseases and preparation and pharmaceutical compositions thereof
Vicker N., Su X., Pradaux-Caggiano F., Potter BVL.
Title compds. I and their pharmaceutical compns. are prepd. and disclosed as inhibitors of 11β-hydroxysteroid dehydrogenase type I (11β-HSD1) useful in the treatment of diseases. Compds. I [X and Z independently = (un)satd. C1-3 carbon chain; Y = S, SO, SO2, CH=CH, CH2CH2, or O; R1 = 1-adamantyl, 2,4,6-trimethylphenyl, 1-(4-chlorophenyl)C3-6 cycloalkyl, or 2-(4-chlorophenyl)propan-2-yl; R2 = (un)substituted 5- to 6- membered N-contg. heteroaryl; with the provision that when R1 = 1-adamantyl and X-Y-Z = CH2S, CH2SO, or CH2SO2, then R2 ≠ 1-methylimidazol-2-yl; or when R1 = 1-adamantyl and X-Y-Z = CH2O, then R2 ≠ 2-methylpyridinyl] are claimed. For example, compd. II was prepd. via substitution of 2-bromo-1-[1-(4-chlorophenyl)cyclopropyl]ethanone with 2-mercapto-1-methylimidazole. Select I were assayed for 11β-HSD1 inhibition and compd. II was found to possess >60% inhibition at 1 μM concn. [on SciFinder(R)]