title: Antagonists of inhibitor of apoptosis proteins based on thiazole amide isosteres.
abstract: A series of IAP antagonists based on thiazole or benzothiazole amide isosteres was designed and synthesized. These compounds were tested for binding to the XIAP-BIR3 and ML-IAP BIR using a fluorescence polarization assay. The most potent of these compounds, 19a and 33b, were found to have K(i)'s of 20-30 nM against ML-IAP and 50-60 nM against XIAP-BIR3.
authors.affiliation: Department of Discovery Chemistry, Genentech, Inc. 1 DNA Way, South San Francisco, CA 94080, USA. fcohen@gene.com
authors.forename: Frederick
authors.initials: F
authors.lastname: Cohen
authors.forename: Michael F T
authors.initials: MF
authors.lastname: Koehler
authors.forename: Philippe
authors.initials: P
authors.lastname: Bergeron
authors.forename: Linda O
authors.initials: LO
authors.lastname: Elliott
authors.forename: John A
authors.initials: JA
authors.lastname: Flygare
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Franklin
authors.forename: Lewis
authors.initials: L
authors.lastname: Gazzard
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Keteltas
authors.forename: Kevin
authors.initials: K
authors.lastname: Lau
authors.forename: Cuong Q
authors.initials: CQ
authors.lastname: Ly
authors.forename: Vickie
authors.initials: V
authors.lastname: Tsui
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Fairbrother
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D032701:Biomimetics; D018360:Crystallography, X-Ray; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000577:Amides; D051034:Inhibitor of Apoptosis Proteins; D010455:Peptides; D013844:Thiazoles