title: Synthesis of 2,5-thiazole butanoic acids as potent and selective alpha(v)beta3 integrin receptor antagonists with improved oral pharmacokinetic properties.
abstract: We describe a series of 2,5 thiazole containing compounds, which are potent antagonists of the integrin alpha(v)beta3 and show selectivity relative to the other integrins, such as alpha(IIb)beta3 and alpha(v)beta6. These analogs were demonstrated to have high bioavailability relative to other relative heterocyclic analogs.
authors.affiliation: Department of Medicinal Chemistry, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. john.a.wendt@pfizer.com
authors.forename: John A
authors.initials: JA
authors.lastname: Wendt
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wu
authors.forename: Heather G
authors.initials: HG
authors.lastname: Stenmark
authors.forename: Mark L
authors.initials: ML
authors.lastname: Boys
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Downs
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Penning
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Chen
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
authors.forename: Tiffany
authors.initials: T
authors.lastname: Duffin
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Finn
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Keene
authors.forename: V Wayne
authors.initials: VW
authors.lastname: Engleman
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Freeman
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Hanneke
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Shannon
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Nickols
authors.forename: Christina N
authors.initials: CN
authors.lastname: Steininger
authors.forename: Marissa
authors.initials: M
authors.lastname: Westlin
authors.forename: Jon A
authors.initials: JA
authors.lastname: Klover
authors.forename: William
authors.initials: W
authors.lastname: Westlin
authors.forename: G Allen
authors.initials: GA
authors.lastname: Nickols
authors.forename: Mark A
authors.initials: MA
authors.lastname: Russell
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000951:Antigens, Neoplasm; D001682:Biological Availability; D002087:Butyrates / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D000882:Haplorhini; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D016023:Integrins / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*
chemical_list: D000951:Antigens, Neoplasm; D002087:Butyrates; D039302:Integrin alphaVbeta3; D016023:Integrins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013844:Thiazoles; C073878:integrin alphavbeta6