The discovery and optimization of a novel class of potent, selective, and orally bioavailable anaplastic lymphoma kinase (ALK) inhibitors with potential utility for the …

…, M Potashman, K Romero, JC Stellwagen…

Index: Lewis, Richard T.; Bode, Christiane M.; Choquette, Deborah M.; Potashman, Michele; Romero, Karina; Stellwagen, John C.; Teffera, Yohannes; Moore, Earl; Whittington, Douglas A.; Chen, Hao; Epstein, Linda F.; Emkey, Renee; Andrews, Paul S.; Yu, Violeta L.; Saffran, Douglas C.; Xu, Man; Drew, Allison; Merkel, Patricia; Szilvassy, Steven; Brake, Rachael L. Journal of Medicinal Chemistry, 2012 , vol. 55, # 14 p. 6523 - 6540

Full Text: HTML

Citation Number: 23

Abstract

A class of 2-acyliminobenzimidazoles has been developed as potent and selective inhibitors of anaplastic lymphoma kinase (ALK). Structure based design facilitated the rapid development of structure–activity relationships (SAR) and the optimization of kinase selectivity. Introduction of an optimally placed polar substituent was key to solving issues of metabolic stability and led to the development of potent, selective, orally bioavailable ALK ...