title: Synthesis and biological evaluation of nonpeptide integrin antagonists containing spirocyclic scaffolds.
abstract: Analogues of isoxazoline alpha(v)beta(3) antagonist 1 designed to further restrict the four carbon alkyl tether were prepared by incorporating two spirocyclic scaffolds, 1-oxa-2-azaspiro[4,5]dec-2-ene and 1-oxa-2,7-diazaspiro[4,4]non-2-ene. Additional optimization provided potent antagonists of both alpha(v)beta(3) and alpha(5)beta(1) which are selective over GPIIb/IIIa.
authors.affiliation: Bristol-Myers Squibb Company, Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Smallheer
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Weigelt
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Woerner
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Wells
authors.forename: Wayne F
authors.initials: WF
authors.lastname: Daneker
authors.forename: Shaker A
authors.initials: SA
authors.lastname: Mousa
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Wexler
authors.forename: Prabhakar K
authors.initials: PK
authors.lastname: Jadhav
mesh_terms: D001665:Binding Sites / Q000502:physiology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000378:metabolism; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D007093:Imidazoles; D016023:Integrins