Imidazole moiety replacements in the 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one inhibitors of insulin-like growth factor receptor-1 (IGF-1R) to improve cytochrome P450 profile.
A series of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one inhibitors of insulin-like growth factor receptor-1 (IGF-1R) were examined in which the pendant imidazole moiety was replaced to improve selectivity for IGF-1R inhibition over cytochrome P450 (CYP). Synthesis and SAR of these compounds is presented.
Velaparthi
Upender
U
Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. upender.velaparthi@bms.com
Liu
Peiying
P
Balasubramanian
Balu
B
Carboni
Joan
J
Attar
Ricardo
R
Gottardis
Marco
M
Li
Aixin
A
Greer
Ann
A
Zoeckler
Mary
M
Wittman
Mark D
MD
Vyas
Dolatrai
D
D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D003577:Cytochrome P-450 Enzyme System; D017526:Receptor, IGF Type 1