Syntheses and structure-activity relationship studies of piperidine-substituted quinolones as nonpeptide gonadotropin releasing hormone antagonists.
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.
Jiang
Jinlong
J
Department of Medicinal Chemistry, PO Box 2000, Rahway, NJ 07065, USA. jinlong_jiang@merck.com
DeVita
Robert J
RJ
Goulet
Mark T
MT
Wyvratt
Matthew J
MJ
Lo
Jane-L
JL
Ren
Ning
N
Yudkovitz
Joel B
JB
Cui
Jisong
J
Yang
Yi T
YT
Cheng
Kang
K
Rohrer
Susan P
SP
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
D010880:Piperidines; D015363:Quinolones; D007987:Gonadotropin-Releasing Hormone