Design,synthesis and biological study of BTK/JAK3 dual-target inhibitors
In the present study,the compound XL-12 from our previous work was utilized as a lead compound.Through the optimization of the terminal phenyl ring,12 target compounds were designed and synthesized.The structures of all target compounds were confirmed by 1H NMR,13C NMR,and H RMS.In vitro enzyme activity assay showed that most compounds demonstrated significant inhibitory activity toward Bruton's tyrosine kinase(BTK)and Janus kinase 3(JAK3).Among them,compound I-3 exhibited moderate cell proliferation inhibitory activity toward Daudi cells and BaF3-JAK3 cells.In the evaluation of anti-inflammatory activity in vitro,compound I-3 could effectively inhibit the production of inflammatory factors IL-6;besides,it exhibited superior anti-inflammatory activity compared to ibrutinib in xylene-induced ear swelling model in mice.
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