Discovery and initial SAR of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-ones as inhibitors of insulin-like growth factor 1-receptor (IGF-1R)

Upender Velaparthi; Mark Wittman; Peiying Liu; Karen Stoffan; Kurt Zimmermann; Xiaopeng Sang; Joan Carboni; Aixin Li; Ricardo Attar; Marco Gottardis; Ann Greer; ChiehYing Y Chang; Bruce L Jacobsen; John S Sack; Yax Sun; David R Langley; Balu Balasubramanian; Dolatrai Vyas

doi:10.1016/j.bmcl.2007.01.102

Discovery and initial SAR of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-ones as inhibitors of insulin-like growth factor 1-receptor (IGF-1R)

Bioorg Med Chem Lett. 2007 Apr 15;17(8):2317-21. doi: 10.1016/j.bmcl.2007.01.102. Epub 2007 Feb 4.

Authors

Upender Velaparthi¹, Mark Wittman, Peiying Liu, Karen Stoffan, Kurt Zimmermann, Xiaopeng Sang, Joan Carboni, Aixin Li, Ricardo Attar, Marco Gottardis, Ann Greer, ChiehYing Y Chang, Bruce L Jacobsen, John S Sack, Yax Sun, David R Langley, Balu Balasubramanian, 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: 17317169
DOI: 10.1016/j.bmcl.2007.01.102

Abstract

The discovery and synthesis of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one inhibitors of insulin-like growth factor 1-receptor (IGF-1R) are presented. Installing amine containing side chains at the 4-position of pyridone ring significantly improved the enzyme potency. SAR and biological activity of these compounds is presented.

MeSH terms

Benzimidazoles
Cell Line
Humans
Inhibitory Concentration 50
Pyridines / chemical synthesis*
Pyridines / pharmacology*
Pyridones
Receptor, IGF Type 1 / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Benzimidazoles
Pyridines
Pyridones
Receptor, IGF Type 1