Evaluation of the anti-hepatitis C virus effect of novel potent, selective, and orally bioavailable JNK and VEGFR kinase inhibitors

…, TI Lin, D Surleraux, S Chakravarty, A Scholliers…

Index: Raboisson, Pierre; Lenz, Oliver; Lin, Tse-I; Surleraux, Dominique; Chakravarty, Sarvajit; Scholliers, Annick; Vermeiren, Katrien; Delouvroy, Frederic; Verbinnen, Thierry; Simmen, Kenneth Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 7 p. 1843 - 1849

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Citation Number: 14

Abstract

Screening of a focused library of TGF beta kinase inhibitors in the cellular HCV replicon model with luciferase read out yielded a number of low micromolar HCV inhibitors. Medicinal chemistry driven optimization resulted in the discovery of 4-[2-(5-bromo-2-fluoro- phenyl) pteridin-4-ylamino]-N-[3-(2-oxopyrrolidin-1-yl) propyl] nicotinamide 36 with a replicon EC50 of 64nM, associated with a selective kinase inhibitory profile for human ...