title: Design and structure-activity relationships of 2-alkyl-3-aminomethyl-6-(3-methoxyphenyl)-7-methyl-8-(2-fluorobenzyl)imidazolo[1,2-a]pyrimid-5-ones as potent GnRH receptor antagonists.
abstract: SAR studies of 7-phenylpyrrolo[1,2-a]pyrimid-4-ones 1 and 2, and 2-phenylimidazolo[1,2-a]pyrimidines 3 and 4, as nonpeptide human GnRH receptor antagonists, lead us to believe that the aromatic ring at position-2 of 4 is no longer crucial for the binding once an aryl group is incorporated at postion-6. We report here the use of a 2-alkyl group on the imidazolo[1,2-a]pyrimidone core to generate potent GnRH receptor antagonists. This discovery enabled us to obtain smaller but equally potent GnRH receptor antagonists.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, California 92121, USA.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Zhu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Guo
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Gross
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Gao
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Connors
authors.forename: R Scott
authors.initials: RS
authors.lastname: Struthers
authors.forename: Qiu
authors.initials: Q
authors.lastname: Xie
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Tucci
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Reinhart
authors.forename: Dongpei
authors.initials: D
authors.lastname: Wu
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D015195:Drug Design; D006801:Humans; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D011744:Pyrimidinones; D011966:Receptors, LHRH