A new series of 1-substituted pyrazolopyrimidine derivatives were synthesized as potent BTK inhibitors and they were evaluated by enzyme-based assay and anti-proliferation against multiple B-cell lymphoma cell lines in vitro. Among these compounds, 9h exhibited the highest potency against BTK enzyme, with IC₅₀ value of 4.2 nM. In particular, 8 and 9f performed better inhibition against the proliferation of B lymphoma cell lines DOHH2 and WSU-DLCL2 than the clinical drug ibrutinb. In addition, the test toward the normal PBMC cells showed that 8 possessed low cell cytotoxicity. All these explorations indicated that 8 could serve as a valuable anti-tumor agent for B-cell lymphoblastic leukemia treatment.

合成了一系列新的1-取代的吡唑并嘧啶衍生物作为有效的BTK抑制剂，并通过基于酶的测定和针对多种B细胞淋巴瘤细胞系的体外抗增殖进行了评估。在这些化合物中，9h表现出对BTK酶的最高效力，IC ₅₀值为4.2 nM。特别是，8和9f对B淋巴瘤细胞系DOHH2和WSU-DLCL2的增殖比临床药物ibrutinb表现出更好的抑制作用。此外，对正常PBMC细胞的测试表明，其中8种具有较低的细胞毒性。所有这些探索表明，8 可以作为B细胞淋巴母细胞白血病治疗的重要抗肿瘤药。