title: Uracils as potent antagonists of the human gonadotropin-releasing hormone receptor without atropisomers.
abstract: Uracil derivatives were designed and synthesized to avoid atropisomers observed in the 6-methyluracils as antagonists of the human GnRH receptor. Optimization at the 1- and 5-positions of the uracil resulted in potent compounds such as 24 (Ki=0.45 nM).
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences, Inc. 12790 El Camino Real, San Diego, CA 92130, USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Guo
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chen
authors.forename: Charles Q
authors.initials: CQ
authors.lastname: Huang
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Gross
authors.forename: Joseph
authors.initials: J
authors.lastname: Pontillo
authors.forename: Martin W
authors.initials: MW
authors.lastname: Rowbottom
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Scott
authors.initials: S
authors.lastname: Struthers
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Tucci
authors.forename: Qiu
authors.initials: Q
authors.lastname: Xie
authors.forename: Warren
authors.initials: W
authors.lastname: Wade
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Zhu
authors.forename: Dongpei
authors.initials: D
authors.lastname: Wu
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D006801:Humans; D007536:Isomerism; D015394:Molecular Structure; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D014498:Uracil / Q000737:chemistry / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: D011966:Receptors, LHRH; D014498:Uracil