Abstract: Thioredoxin-interacting protein(TXNIP) inhibitors can inhibit the apoptosis of pancreatic β cells, while dual-specificity tyrosine-phosphoryation-regulated kinase 1A (DYRK1A) inhibitors can promote the proliferation of pancreatic β cells. This study used 4-benzopyrimidine as the starting material to design and synthesize benzopyrimidine-7-azaindole scaffold derivatives targeting TXNIP/DYRK1A by linking it with variously substituted 7-azaindoles via carbon chains of different lengths. A total of 12 novel quinazoline-7-azaindole derivatives were designed and synthesized, their structures confirmed by ¹H NMR and ESI-MS, and their content was determined by HPLC. Pharmacological activity assays demonstrated that all 12 compounds exhibited inhibitory effects on β-cell apoptosis, with YN-3 and YN-6 showing the strongest activity, achieving a cell survival rate exceeding 75% (compared to 43.08% in the control group). Proliferation-promoting experiments revealed that most compounds exhibited proliferative activity, with YN-1–YN-3 and YN-11 demonstrating proliferation enhancement rates greater than 125%. YN-3 exhibited the strongest combined anti-apoptotic and proliferation-promoting activities and may represent a promising new chemical entity for antidiabetic drug development.