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

Upender Velaparthi; Peiying Liu; Balu Balasubramanian; Joan Carboni; Ricardo Attar; Marco Gottardis; Aixin Li; Ann Greer; Mary Zoeckler; Mark D Wittman; Dolatrai Vyas

doi:10.1016/j.bmcl.2007.03.048

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

Bioorg Med Chem Lett. 2007 Jun 1;17(11):3072-6. doi: 10.1016/j.bmcl.2007.03.048. Epub 2007 Mar 19.

Authors

Upender Velaparthi¹, Peiying Liu, Balu Balasubramanian, Joan Carboni, Ricardo Attar, Marco Gottardis, Aixin Li, Ann Greer, Mary Zoeckler, Mark D Wittman, Dolatrai Vyas

Affiliation

¹ Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. upender.velaparthi@bms.com

PMID: 17398093
DOI: 10.1016/j.bmcl.2007.03.048

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.

MeSH terms

Animals
Cytochrome P-450 Enzyme Inhibitors*
Cytochrome P-450 Enzyme System / analysis
Imidazoles / chemical synthesis
Imidazoles / chemistry*
Imidazoles / pharmacology*
Inhibitory Concentration 50
Receptor, IGF Type 1 / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Cytochrome P-450 Enzyme Inhibitors
Imidazoles
Cytochrome P-450 Enzyme System
Receptor, IGF Type 1