新型BTK抑制剂吡唑并[3,4-c]吡唑和吡咯并[2,3-c]吡唑衍生物的设计与合成（英文）

Design and Synthesis of Novel Pyrazolo[3,4-c]pyrazol and Pyrrolo[2,3-c]pyrazol Derivatives as Potential BTK Inhibitors

本研究设计合成了一系列作为潜在布鲁顿酪氨酸激酶(BTK)抑制剂的吡唑并[3,4-c]吡唑和吡咯并[2,3-c]吡唑衍生物,并进行了体外抑制活性测试。这10个化合物在体外对BTK酶表现出不同的抑制活性,其中8a抑制活性最强(IC50=127nmol/L)。通过分子对接探索了这类吡唑并[3,4-c]吡唑衍生物与BTK可能的结合模式,为进一步的结构改造提供参考依据。

A novel series of pyrazolo[3,4-c]pyrazol and pyrrolo[2,3-c]pyrazol derivatives were designed, synthesized and biologically evaluated as potential Bruton＇s tyrosine kinase （BTK） inhibitors. Ten compounds exhibited variant inhibitory activities against BTK in vitro, and 8a showed the highest potency （IC50=127 nmol/L against BTK enzyme）. The molecular docking of compound 8a was performed to understand the probable binding mode for this novel pyrazolo[3,4-c]pyrazol derivatives with BTK, which provided a comprehensive guide for further structural modification.