Antagonists of inhibitor of apoptosis proteins based on thiazole amide isosteres.
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.
Cohen
Frederick
F
Department of Discovery Chemistry, Genentech, Inc. 1 DNA Way, South San Francisco, CA 94080, USA. fcohen@gene.com
Koehler
Michael F T
MF
Bergeron
Philippe
P
Elliott
Linda O
LO
Flygare
John A
JA
Franklin
Matthew C
MC
Gazzard
Lewis
L
Keteltas
Stephen F
SF
Lau
Kevin
K
Ly
Cuong Q
CQ
Tsui
Vickie
V
Fairbrother
Wayne J
WJ
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*
D000577:Amides; D051034:Inhibitor of Apoptosis Proteins; D010455:Peptides; D013844:Thiazoles