title: A novel synthesis of 2-arylpyrrolo[1,2-a]pyrimid-7-ones and their structure-activity relationships as potent GnRH receptor antagonists.
abstract: In the process of developing GnRH receptor antagonists, a novel base-catalyzed cyclization of compounds 5a-b was discovered, which led to the formation of the 2-aryl pyrrolo[1,2-a]pyrimid-7-one core structures 6a-b. These intermediates were further modified at positions 1, 2, 4 and 6 to afford a series of potent GnRH antagonists with low nanomolar K(i) values.
authors.affiliation: Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, CA 92121, USA. fzhu@neurocine.com
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Zhu
authors.forename: Keith
authors.initials: K
authors.lastname: Wilcoxen
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Guo
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Gao
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Connors
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Gross
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Tucci
authors.forename: R Scott
authors.initials: RS
authors.lastname: Struthers
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Reinhart
authors.forename: Qiu
authors.initials: Q
authors.lastname: Xie
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D007202:Indicators and Reagents; D011744:Pyrimidinones; D011758:Pyrroles; D011966:Receptors, LHRH