Design and Synthesis of Orally Bioavailable Benzimidazole Reverse Amides as Pan RAF Kinase Inhibitors

Sharadha Subramanian; Abran Costales; Teresa E Williams; Barry Levine; Christopher M McBride; Daniel Poon; Payman Amiri; Paul A Renhowe; Cynthia M Shafer; Darrin Stuart; Joelle Verhagen; Savithri Ramurthy

doi:10.1021/ml5002272

Design and Synthesis of Orally Bioavailable Benzimidazole Reverse Amides as Pan RAF Kinase Inhibitors

ACS Med Chem Lett. 2014 Jul 17;5(9):989-92. doi: 10.1021/ml5002272. eCollection 2014 Sep 11.

Affiliation

¹ Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 4560 Horton Street, Emeryville, California 94608, United States.

Abstract

Benzimidazole reverse amides were designed and synthesized as Pan RAF kinase inhibitors. Investigation of the structure-activity relationship of the compounds revealed that they were potent in vitro and exhibited desirable in vivo properties.

Keywords: CSF1R; MAP; RTKs; STKs; TKs; VEGF; colony stimulating factor-1 receptor; ras-mitogen activated protein kinase; receptor tyrosine kinases; serine threonine kinases; tyrosine kinases; vascular endothelial growth factor receptor.