title: N-Aryl-gamma-lactams as integrin alphavbeta3 antagonists.
abstract: Novel alphavbeta3 antagonists based on the N-aryl-gamma-lactam scaffold were prepared. SAR studies led to the identification of potent antagonists for alphavbeta3 receptor with excellent selectivity against the structurally related alpha(IIb)beta3 receptor. Additional interactions of N-aryl-gamma-lactam derivatives with alphavbeta3 were found when compared to c(-RGDf[NMe]V-) peptide antagonist. The effects of the conformation and configuration of the gamma-lactam core on the binding were also assessed.
authors.affiliation: Chemistry Research and Discovery, Amgen Inc., One Amgen Center Dr., Thousand Oaks, CA 91320, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Xi
authors.forename: Stephen
authors.initials: S
authors.lastname: Arvedson
authors.forename: Shawn
authors.initials: S
authors.lastname: Eisenberg
authors.forename: Nianhe
authors.initials: N
authors.lastname: Han
authors.forename: Michael
authors.initials: M
authors.lastname: Handley
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.forename: Qi
authors.initials: Q
authors.lastname: Huang
authors.forename: Alexander
authors.initials: A
authors.lastname: Kiselyov
authors.forename: Qingyian
authors.initials: Q
authors.lastname: Liu
authors.forename: Yuelie
authors.initials: Y
authors.lastname: Lu
authors.forename: Gladys
authors.initials: G
authors.lastname: Nunez
authors.forename: Timothy
authors.initials: T
authors.lastname: Osslund
authors.forename: David
authors.initials: D
authors.lastname: Powers
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Tasker
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Tingjian
authors.initials: T
authors.lastname: Xiang
authors.forename: Shimin
authors.initials: S
authors.lastname: Xu
authors.forename: Jiandong
authors.initials: J
authors.lastname: Zhang
authors.forename: Jiawang
authors.initials: J
authors.lastname: Zhu
authors.forename: Richard
authors.initials: R
authors.lastname: Kendall
authors.forename: Celia
authors.initials: C
authors.lastname: Dominguez
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D007769:Lactams / Q000138:chemical synthesis / Q000494:pharmacology*; D008024:Ligands; D008968:Molecular Conformation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D039302:Integrin alphaVbeta3; D007769:Lactams; D008024:Ligands; D019039:Platelet Glycoprotein GPIIb-IIIa Complex