title: 3-(2-aminoalkyl)-1-(2,6-difluorobenzyl)-5- (2-fluoro-3-methoxyphenyl)-6-methyl-uracils as orally bioavailable antagonists of the human gonadotropin releasing hormone receptor.
abstract: Uracils possessing N-3 side chains derived from various amino alcohols were designed and synthesized as potent human gonadotropin releasing hormone receptor antagonists. The compounds herein presented displayed superior metabolic stability than their predecessor molecules. Selected compounds from this series featured good oral bioavailability in mice and cynomolgus monkeys.
authors.affiliation: Departments of Medicinal Chemistry, Endocrinology, and Preclinical Development, Neurocrine Biosciences Inc., 10555 Science Center Drive, San Diego, CA 92121, USA. ftucci@neurocrine.com
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Tucci
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: Patrick J
authors.initials: PJ
authors.lastname: Connors
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Gao
authors.forename: Martin W
authors.initials: MW
authors.lastname: Rowbottom
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: Ta Kung
authors.initials: TK
authors.lastname: Chen
authors.forename: Haig
authors.initials: H
authors.lastname: Bozigian
authors.forename: Anne L
authors.initials: AL
authors.lastname: Killam Bonneville
authors.forename: Andrew
authors.initials: A
authors.lastname: Fisher
authors.forename: Liping
authors.initials: L
authors.lastname: Jin
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D011974:Receptors, LH / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D011974:Receptors, LH; D014498:Uracil