Selective inhibitors of DYRK1A are of interest for the treatment of cancer, Type 2 diabetes and neurological disorders. Optimization of imidazo [1,2-]pyridazine through structure−activity relationship exploration and drug design efforts led to the discovery of as a potent cellular inhibitor of DYRK1A with selectivity over much of the kinome. The binding mode of was elucidated with X-ray crystallography, facilitating the rational design of , an imidazo [1,2-]pyridazine with improved kinase selectivity with respect to closely related CLK kinases.

中文翻译：

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咪唑并[1,2-b]哒嗪作为 DYRK 激酶抑制剂


DYRK1A 的选择性抑制剂可用于治疗癌症、2 型糖尿病和神经系统疾病。通过构效关系探索和药物设计工作对咪唑并[1,2-]哒嗪进行优化，结果发现它是一种有效的 DYRK1A 细胞抑制剂，对大部分激酶组具有选择性。通过 X 射线晶体学阐明了 的结合模式，有助于合理设计 ，一种咪唑并[1,2-]哒嗪，其对密切相关的 CLK 激酶具有改进的激酶选择性。