667402-44-0Relevant articles and documents
Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors: SAR of a series of 3-[6-(4-substituted-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one
Velaparthi, Upender,Saulnier, Mark G.,Wittman, Mark D.,Liu, Peiying,Frennesson, David B.,Zimmermann, Kurt,Carboni, Joan M.,Gottardis, Marco,Li, Aixin,Greer, Ann,Clarke, Wendy,Yang, Zheng,Menard, Krista,Lee, Francis Y.,Trainor, George,Vyas, Dolatrai
scheme or table, p. 3182 - 3185 (2010/09/18)
A series of 3-[6-(4-substitued-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one were synthesized to modulate CYP3A4 inhibition and improve aqueous solubility of our prototypical compound BMS-536924 (1), while maintaining potent IGF-1R inhibitory activity. Structure-activity and structure-solubility studies led to the identification of BMS-577098 (27), which demonstrates oral in vivo efficacy in animal models. The improvement was achieved by replacing morpholine with more polar bio-isoster piperazine and modulating the basicity of distal nitrogen with appropriate substitutions.
