Tyrosine kinase 2 (Tyk2), a member of the Janus kinase (JAK) family of non-receptor tyrosine kinases, regulates the signaling of pro-inflammatory cytokines IL-12, IL-23 and type 1 IFN, and is therefore believed to be a promising small molecule target for developing orally active therapeutic agents for the treatment of autoimmune and inflammatory diseases such as psoriasis and lupus. We are particularly interested in Tyk2 JH2 (pseudokinase domain) due to its unique structural feature in the binding pocket, allowing us to target the Tyk2 dependent signaling pathway with excellent selectivity. In this presentation, discovery of 6-((2-oxo-1-substituted-1,2-dihydropyridin-3-yl)amino)imidazo[1,2-b]pyridazine derivatives as potent, selective, and orally active Tyk2 JH2 inhibitors will be described.

6-((2-Oxo-1-substituted-1,2-dihydropyridin-3-yl)amino)imidazo[1,2-b]pyridazine derivatives as potent, selective, and orally active Tyk2 JH2 inhibitors

254th National Meeting (2017)

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