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• W4323852971 startingPage "129235" @default.
• W4323852971 abstract "As a mediator of pro-inflammatory cytokines, TYK2 is an attractive target to treat autoimmunity diseases. Herein, we reported the design, synthesis, and structure-activity relationships (SARs) of N-(methyl-d3) pyridazine-3-carboxamide derivatives as TYK2 inhibitors. Among them, compound 24 exhibited acceptable inhibition activity against STAT3 phosphorylation. Furthermore, 24 showed satisfactory selectivities toward other members of JAK family and performed a good stability profile in liver microsomal assay. Pharmacokinetics (PK) study indicated that compound 24 has reasonable PK exposures. In anti-CD40-induced colitis models, compound 24 was orally highly effective with no significant hERG and CYP isozymes inhibition. These results indicated that compound 24 was worthy of further investigation for the development of anti-autoimmunity diseases agents." @default.
• W4323852971 created "2023-03-11" @default.
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• W4323852971 date "2023-04-01" @default.
• W4323852971 modified "2023-10-17" @default.
• W4323852971 title "Design, synthesis and biological evaluation of novel N-(methyl-d) pyridazine-3-carboxamide derivatives as TYK2 inhibitors" @default.
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• W4323852971 doi "https://doi.org/10.1016/j.bmcl.2023.129235" @default.
• W4323852971 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36907336" @default.
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