Four new series 7a-e, 8a-e, 9a-e, and 10a-e of 7-aryl-3-substituted pyrazolo[1,5-a]pyrimidines were synthesized and tested for their RTK and STK inhibitory activity. Compound 7d demonstrated potent enzymatic inhibitory activity against TrkA and ALK2 with IC₅₀ 0.087and 0.105 μM, respectively, and potent antiproliferative activity against KM12 and EKVX cell lines with IC₅₀ 0.82 and 4.13 μM, respectively. Compound 10e showed good enzyme inhibitory activity against TrkA, ALK2, c-KIT, EGFR, PIM1, CK2α, CHK1, and CDK2 in submicromolar values. Additionally 10e revealed antiproliferative activity against MCF7, HCT116 and EKVX with IC₅₀ 3.36, 1.40 and 3.49 μM, respectively; with good safety profile. Moreover, 10e showed cell cycle arrest at the G1/S phase and G1 phase in MCF7 and HCT116 cells with good apoptotic effect. Molecular docking studies were fulfilled for compound 10e and illustrated good interaction with the hot spots of the active site of the tested enzymes.

合成了四个新系列7-芳基-3-取代的吡唑并[1,5-a]嘧啶7a -e、8a-e、9a-e和10a-e，并测试了它们的RTK和STK抑制活性。化合物7d对TrkA和ALK2表现出有效的酶抑制活性，IC ₅₀分别为0.087和0.105μM，并且对KM12和EKVX细胞系表现出有效的抗增殖活性，IC ₅₀分别为0.82和4.13μM 。化合物10e对亚微摩尔值的 TrkA、ALK2、c-KIT、EGFR、PIM1、CK2α、CHK1 和 CDK2 显示出良好的酶抑制活性。另外，10e显示了针对 MCF7、HCT116 和 EKVX 的抗增殖活性，IC ₅₀分别为 3.36、1.40 和 3.49 μM；具有良好的安全性。此外，10e在MCF7和HCT116细胞中表现出细胞周期阻滞在G1/S期和G1期，具有良好的凋亡效果。化合物10e完成了分子对接研究，表明与测试酶活性位点的热点具有良好的相互作用。