Structure-based design of novel class II c-Met inhibitors: 2. SAR and kinase selectivity profiles of the pyrazolone series

…, D Choquette, ND D'Angelo, J Germain…

Index: Liu, Longbin; Norman, Mark H.; Lee, Matthew; Xi, Ning; Siegmund, Aaron; Boezio, Alessandro A.; Booker, Shon; Choquette, Debbie; D'Angelo, Noel D.; Germain, Julie; Yang, Kevin; Yang, Yajing; Zhang, Yihong; Bellon, Steven F.; Whittington, Douglas A.; Harmange, Jean-Christophe; Dominguez, Celia; Kim, Tae-Seong; Dussault, Isabelle Journal of Medicinal Chemistry, 2012 , vol. 55, # 5 p. 1868 - 1897

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Citation Number: 37

Abstract

As part of our effort toward developing an effective therapeutic agent for c-Met-dependent tumors, a pyrazolone-based class II c-Met inhibitor, N-(4-((6, 7-dimethoxyquinolin-4-yl) oxy)- 3-fluorophenyl)-1, 5-dimethyl-3-oxo-2-phenyl-2, 3-dihydro-1 H-pyrazole-4-carboxamide (1), was identified. Knowledge of the binding mode of this molecule in both c-Met and VEGFR-2 proteins led to a novel strategy for designing more selective analogues of 1. Along with ...