PIPERAZINYL- AND PYRROLIDINYL-CONTAINING MELANOCORTIN RECEPTOR AGONIST COMPOUNDS FOR TREATING OBESITY, DIABETES, INFLAMMATION AND ERECTILE DYSFUNCTION

摘要

Disclosed are compounds of formula 1, salts and stereoisomers thereof, and methods for their preparation. Specific examples of compounds of formula 1 include: N-{ (3S,5S)-1-{ [(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl} -5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl} -N-(4,4-dimethylcyclohexyl)acetamide, N-{ (3S,5S)-1-{ [(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl} -5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl} -N-(4,4-dimethylcyclohexyl)-3-hydroxy-2,2-dimethylpropanamide, (2S)-N-{ (3S,5S)-1-{ [(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl} -5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl} -N-(4,4-difluorocyclohexyl)tetrahydrofuran-2-carboxamide, and (2S)-N-{ (3S,5S)-1-{ [(3S,4R)-4-(2,4-difluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]carbonyl} -5-[(4-isopropylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl} -N(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide. Compounds of formula 1 have good agonistic activity to melanocortin receptors and are useful for treating or preventing obesity, diabetes, inflammation and erectile dysfunction.