TANK-Binding Kinase (TBK1) and IkB kinase epsilon (IKKe) play a key role in the activation of the innate immune system [1,2,3]. We describe the development of a novel series of 2,4-diamino-5-cyclopropyl pyrimidines as potent inhibitors of TBK1, with good kinase selectivity and drug-like properties. These compounds have been evaluated in a range of cellular and in vivo assays, enabling us to probe the putative role of the TBK1/IKKe pathway in inflammatory diseases and cancer [4,5]. ReferencesKawai and Akira (2010) Nat. Immunol. 11, 373-384.Clark et al. (2011) Biochem. J. 434, 93-104.Clark et al. (2011) Proc. Natl. Acad. Sci. U.S.A. 108, 17093-17098.Boehm et al. (2007) Cell 129, 1065-1079.Barbie et al. (2009) Nature 462, 108-112.

Synthesis and SAR of a novel series of 2,4-diamino-5-cyclopropyl pyrimidines as selective inhibitors of TBK1/IKK&epsi;

244th National Meeting (2012)

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