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Discovery and structure− activity relationship of 3-aminopyrid-2-ones as potent and selective interleukin-2 inducible T-cell kinase (Itk) inhibitors

JD Charrier, A Miller, DP Kay, G Brenchley…

文献索引:Charrier, Jean-Damien; Miller, Andrew; Kay, David P.; Brenchley, Guy; Twin, Heather C.; Collier, Philip N.; Ramaya, Sharn; Keily, Shazia B.; Durrant, Steven J.; Knegtel, Ronald M. A.; Tanner, Adam J.; Brown, Kieron; Curnock, Adam P.; Jimenez, Juan-Miguel Journal of Medicinal Chemistry, 2011 , vol. 54, # 7 p. 2341 - 2350

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被引用次数: 36

摘要

Interleukin-2 inducible T-cell kinase (Itk) plays a role in T-cell functions, and its inhibition potentially represents an attractive intervention point to treat autoimmune and allergic diseases. Herein we describe the discovery of a series of potent and selective novel inhibitors of Itk. These inhibitors were identified by structure-based design, starting from a fragment generated de novo, the 3-aminopyrid-2-one motif. Functionalization of the 3- ...