240815-53-6Relevant articles and documents
HETEROCYCLO-SUBSTITUTED IMIDAZOPYRAZINE PROTEIN TYROSINE KINASE INHIBITORS
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Page/Page column 24, (2009/06/27)
Novel heterocyclo-substituted imidazopyrazines and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as immunologic disorders.
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]pyrido[3,2-e]pyrazin-6-amine (BMS-279700) as a potent and orally active inhibitor with excellent in vivo antiinflammatory activity
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.
, p. 4517 - 4529 (2007/10/03)
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 models highlighting the influence of significant steric and electronic features. The H-bonding (Met319) contribution to observed binding affinities within a tightly congeneric series was found to be significant.
