Imidazoquinoxaline Src-family kinase p56Lck inhibitors: SAR, QSAR, and the discovery of (S)-N-(2-chloro-6-methylphenyl)-2-(3-methyl-1-piperazinyl) imidazo-[1, 5-a] …

…, RV Moquin, J Lin, J Wityak, EJ Iwanowicz…

Index: Chen, Ping; Doweyko, Arthur M.; Norris, Derek; Gu, Henry H.; Spergel, Steven H.; Das, Jagabundhu; Moquin, Robert V.; Lin, James; Wityak, John; Iwanowicz, Edwin J.; McIntyre, Kim W.; Shuster, David J.; Behnia, Kamelia; Chong, Saeho; De Fex, Henry; Pang, Suhong; Pitt, Sydney; Shen, Ding Ren; Thrall, Sara; Stanley, Paul; Kocy, Octavian R.; Witmer, Mark R.; Kanner, Steven B.; Schieven, Gary L.; Barrish, Joel C. Journal of Medicinal Chemistry, 2004 , vol. 47, # 18 p. 4517 - 4529

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Citation Number: 56

Abstract

A series of novel anilino 5-azaimidazoquinoxaline analogues possessing potent in vitro activity against p56Lck and T cell proliferation have been discovered. Subsequent SAR studies led to the identification of compound 4 (BMS-279700) as an orally active lead candidate that blocks the production of proinflammatory cytokines (IL-2 and TNFα) in vivo. In addition, an expanded set of imidazoquinoxalines provided several descriptive QSAR ...