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

摘要: 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(IC₅₀=0.009 μmol/L)和GM-CSF诱导的TF-1细胞抑制活性(IC₅₀=0.136 μmol/L)，表明该化合物具有潜在的研发价值。

Abstract: 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( IC₅₀=0. 009 μmol/L )and GM-CSF-induced TF-1 cells(IC₅₀=0. 136 μmol/L), which proved that the compound had potential research and development value.