4-(3-磺酰基苯基)氨基-6-甲酰基吡咯并[2,3-d]嘧啶类化合物的设计、合成与生物活性

Design,synthesis and bioactivities of 4-(3-sulfonylbenzene)amino-6-formylpyrrole[2,3-d]pyrimidine derivatives

以JAK2抑制剂baricitinib和fedratinib为先导化合物,运用分子杂交药物设计原理,设计并合成了17个以4-(3-磺酰基苯基)氨基-6-甲酰基吡咯并[2,3-d]嘧啶(3)为母核、结构新颖的目标化合物,并通过JAK2激酶和粒细胞-巨噬细胞集落刺激因子(GM-CSF)诱导的TF-1细胞对所合成的化合物进行了活性测试。结果显示,多数化合物具有JAK2抑制活性,其中化合物(31)表现出较好的JAK2激酶活性(IC_(50)=0.009μmol/L)和GM-CSF诱导的TF-1细胞抑制活性(IC_(50)=0.136μmol/L),表明该化合物具有潜在的研发价值。

Taking JAK2 inhibitor baricitinib and fedratinib as the lead compounds,to design the novel 4-（3-sulfonylbenzene）amino-6-formylpyrrole[2,3-d] pyrimidine JAK2 inhibitors nucleus using the molecular hybrid drug design principle.17 target compounds were synthesized by derivatization of sulfonyl and formyl groups respectively.We used JAK2 kinase and GM-CSF-induced TF-1 cells to measure the activities of compounds.The results showed that most compounds had JAK2 inhibitory activities.Among them,compound 31 had excellent inhibitory activity on JAK2 kinase（IC_（50）=0.009 μmol/L）and GM-CSF-induced TF-1 cells（IC_（50）=0.136μmol/L）,which proved that the compound had potential research and development value.