A series of 3-substituted pyrazolopyrimidine derivatives as BTK inhibitors were designed by structure-based drug design and they were synthesized, evaluated by enzyme-based assay and anti-proliferation against Ramos and Raji cells. Most of them displayed good inhibitory activities against both BTK and B-cell lymphoblastic leukemia lines in vitro. Among them, compound 8a exhibited excellent potency (IC₅₀ = 7.95 nM against BTK enzyme, 8.91 μM against Ramos cells and 1.80 μM against Raji cells), with a better hydrophilicity (ClogP = 3.33). These explorations provided new clues to discover 3-substituted pyrazolopyrimidine derivatives as novel anti-tumor agents.

通过基于结构的药物设计，设计了一系列3-取代的吡唑并嘧啶衍生物作为BTK抑制剂，并对其进行了合成，通过基于酶的测定和对Ramos和Raji细胞的抗增殖评估。他们中的大多数在体外对BTK和B细胞淋巴母细胞白血病细胞系均表现出良好的抑制活性。其中，化合物8a表现出优异的效力（ 针对BTK酶的IC ₅₀ = 7.95 nM，针对Ramos细胞的8.91μM和针对Raji细胞的1.80μM），并具有更好的亲水性（ClogP = 3.33）。这些探索为发现3-取代的吡唑并嘧啶衍生物作为新型抗肿瘤剂提供了新的线索。