Identification and initial structure-activity relationships of a novel non-peptide quinolone GnRH receptor antagonist.
Screening of the Merck sample collection for non-peptide compounds with binding affinity for the rat GnRH receptor led to the identification of the substituted quinolone (1) as a lead compound in the search for a non-peptide GnRH receptor antagonist. Substantial improvements in potency (approximately 300 fold) were achieved by addition of an alkyl amine at the 4-position, a 3,5-dimethylphenyl group at the 3-position and 6-nitro-7-chloro-substitution of the 1 H-quinolone core.
DeVita
R J
RJ
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA.
Hollings
D D
DD
Goulet
M T
MT
Wyvratt
M J
MJ
Fisher
M H
MH
Lo
J L
JL
Yang
Y T
YT
Cheng
K
K
Smith
R G
RG
D000818:Animals; D011485:Protein Binding; D015363:Quinolones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D015363:Quinolones; D011966:Receptors, LHRH