目标：在我们的研究中，设计、合成并评估了具有吡咯[3,2-d]嘧啶和吡咯[3,4-d]嘧啶结构的化合物对血液肿瘤的生物活性。方法：采用ADP-Glo发光法、MTT [3-(4,5)-二甲基噻唑市(锌)1]-3,5-二苄基四唑市(锌)化合物评估生物活性，进行西方印迹和流式细胞术评价。结果：含吡咯[3,2-d]嘧啶的A1，A5和A7化合物能够以亚纳摩尔水平抑制磷脂酰肌醇3-激酶δ（PI3Kδ），并显示出良好的δ异构体选择性。A1，A5和A7对SU-DHL-6细胞具有显著的抑制作用，并对Akt的磷酸化有有效的浓度依赖性抑制作用。A7能够诱导SU-DHL-6细胞凋亡，并导致细胞周期停滞。对接研究表明，A1，A5和A7通过关键的氢键相互作用与PI3Kδ结合紧密。结论：本研究表明，使用吡咯[3,2-d]嘧啶可以促进新型高效且选择性的PI3Kδ抑制剂的设计。

Aim: In our study compounds with pyrido[3,2-d]pyrimidine and pyrido[3,4-d]pyrimidine were designed, synthesized and evaluated for their biological activity against hematologic tumors. Methods: The biological activity of compounds was evaluated by ADP-Glo Luminescence assay, MTT [3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide] assay, western blotting and flow cytometry, respectively. Results: Compounds A1, A5 and A7 containing pyrido[3,2-d]pyrimidine inhibited phosphoinositide 3-kinase-δ (PI3Kδ) at subnanomolar levels and had good δ-isoform selectivity. A1, A5 and A7 showed significant inhibitory effects against SU-DHL-6 cells and effectively inhibited Akt phosphorylation in a good concentration-dependent manner. A7 induced apoptosis and caused cell cycle arrest in SU-DHL-6 cells. Docking studies showed that A1, A5 and A7 bound tightly to PI3Kδ through key hydrogen bonding interactions. Conclusion: This study suggests that employing pyrido[3,2-d]pyrimidine can facilitate the design of novel potent and selective PI3Kδ inhibitors.