title: Nonpeptide alpha V beta 3 antagonists. Part 9: Improved pharmacokinetic profile through the use of an aliphatic, des-amide backbone.
abstract: A series of alphaVbeta3 receptor antagonists lacking the amide bond of previously-reported 'chain-shortened' compounds is described. Replacement of the lone amide bond with two methylene groups in this series yields more lipophilic compounds that have longer half-lives, lower clearance, and greater oral bioavailability when administered to dogs.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. david_whitman@merck.com
authors.forename: David B
authors.initials: DB
authors.lastname: Whitman
authors.forename: Ben C
authors.initials: BC
authors.lastname: Askew
authors.forename: Le T
authors.initials: LT
authors.lastname: Duong
authors.forename: Carmen
authors.initials: C
authors.lastname: Fernandez-Metzler
authors.forename: Wasyl
authors.initials: W
authors.lastname: Halczenko
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
authors.forename: John H
authors.initials: JH
authors.lastname: Hutchinson
authors.forename: Chih-Tai
authors.initials: CT
authors.lastname: Leu
authors.forename: Thomayant
authors.initials: T
authors.lastname: Prueksaritanont
authors.forename: Gideon A
authors.initials: GA
authors.lastname: Rodan
authors.forename: Sevgi B
authors.initials: SB
authors.lastname: Rodan
authors.forename: Mark E
authors.initials: ME
authors.lastname: Duggan
mesh_terms: D000818:Animals; D001557:Benzenesulfonates / Q000737:chemistry* / Q000493:pharmacokinetics*; D004285:Dogs; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007462:Iodobenzenes / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D001557:Benzenesulfonates; D039302:Integrin alphaVbeta3; D007462:Iodobenzenes; C032365:benzenesulfonic acid