Syntheses and structure–activity relationship studies of piperidine-substituted quinolones as nonpeptide gonadotropin releasing hormone antagonists

Abstract

Syntheses and structure–activity relationships of piperidine-substituted quinolones as nonpeptide gonadotropin releasing hormone antagonists are described. Some of substituents on the piperidine ring that were investigated included a fused phenyl group, a (6 R)-trifluoromethyl group, (6 S) and (6 R)-methyl group. This study showed that GnRH binding potency was tolerated by a small group at the 6-position of the piperidine, and blocking the 6-position by a trifluoromethyl group reduced clearance rate and increased oral bioavailability.