title: Zwitterionic uracil derivatives as potent GnRH receptor antagonists with improved pharmaceutical properties.
abstract: A novel series of potent zwitterionic uracil GnRH antagonists were discovered that showed reduced liability for CYP3A4 enzyme inhibition.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12780 El Camino Real, San Diego, CA 92130, USA.
authors.forename: Colin F
authors.initials: CF
authors.lastname: Regan
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: Mi
authors.initials: M
authors.lastname: Chen
authors.forename: Wanlong
authors.initials: W
authors.lastname: Jiang
authors.forename: Jaimie K
authors.initials: JK
authors.lastname: Rueter
authors.forename: Timothy
authors.initials: T
authors.lastname: Coon
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Michael S
authors.initials: MS
authors.lastname: Brown
authors.forename: Steve F
authors.initials: SF
authors.lastname: Betz
authors.forename: R Scott
authors.initials: RS
authors.lastname: Struthers
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.forename: Jenny
authors.initials: J
authors.lastname: Wen
authors.forename: Ajay
authors.initials: A
authors.lastname: Madan
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Zhu
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry*; D015195:Drug Design; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry; D006801:Humans; D007477:Ions; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D007477:Ions; D010455:Peptides; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D014498:Uracil; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human