title: Identification and initial structure-activity relationships of a novel non-peptide quinolone GnRH receptor antagonist.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: DeVita
authors.forename: D D
authors.initials: DD
authors.lastname: Hollings
authors.forename: M T
authors.initials: MT
authors.lastname: Goulet
authors.forename: M J
authors.initials: MJ
authors.lastname: Wyvratt
authors.forename: M H
authors.initials: MH
authors.lastname: Fisher
authors.forename: J L
authors.initials: JL
authors.lastname: Lo
authors.forename: Y T
authors.initials: YT
authors.lastname: Yang
authors.forename: K
authors.initials: K
authors.lastname: Cheng
authors.forename: R G
authors.initials: RG
authors.lastname: Smith
mesh_terms: 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
chemical_list: D015363:Quinolones; D011966:Receptors, LHRH