title: 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 (6R)-trifluoromethyl group, (6S) and (6R)-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.
authors.affiliation: Department of Medicinal Chemistry, PO Box 2000, Rahway, NJ 07065, USA. jinlong_jiang@merck.com
authors.forename: Jinlong
authors.initials: J
authors.lastname: Jiang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: DeVita
authors.forename: Mark T
authors.initials: MT
authors.lastname: Goulet
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Wyvratt
authors.forename: Jane-L
authors.initials: JL
authors.lastname: Lo
authors.forename: Ning
authors.initials: N
authors.lastname: Ren
authors.forename: Joel B
authors.initials: JB
authors.lastname: Yudkovitz
authors.forename: Jisong
authors.initials: J
authors.lastname: Cui
authors.forename: Yi T
authors.initials: YT
authors.lastname: Yang
authors.forename: Kang
authors.initials: K
authors.lastname: Cheng
authors.forename: Susan P
authors.initials: SP
authors.lastname: Rohrer
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004285:Dogs; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D010880:Piperidines / Q000138:chemical synthesis* / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D015363:Quinolones / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D010880:Piperidines; D015363:Quinolones; D007987:Gonadotropin-Releasing Hormone