title: 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.
abstract: 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.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. upender.velaparthi@bms.com
authors.forename: Upender
authors.initials: U
authors.lastname: Velaparthi
authors.forename: Peiying
authors.initials: P
authors.lastname: Liu
authors.forename: Balu
authors.initials: B
authors.lastname: Balasubramanian
authors.forename: Joan
authors.initials: J
authors.lastname: Carboni
authors.forename: Ricardo
authors.initials: R
authors.lastname: Attar
authors.forename: Marco
authors.initials: M
authors.lastname: Gottardis
authors.forename: Aixin
authors.initials: A
authors.lastname: Li
authors.forename: Ann
authors.initials: A
authors.lastname: Greer
authors.forename: Mary
authors.initials: M
authors.lastname: Zoeckler
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wittman
authors.forename: Dolatrai
authors.initials: D
authors.lastname: Vyas
mesh_terms: 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
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D003577:Cytochrome P-450 Enzyme System; D017526:Receptor, IGF Type 1