Design And Synthesis Of BAP-1 Inhibitors

BACKGROUND: Tumors pose a severe threat to human health, with malignant tumors requiring complex targeted therapies. BRCA1-binding protein 1 (BAP1), a key deubiquitinase, plays dual roles in tumorigenesis and progression, making it a promising therapeutic target. The second-generation BAP1 inhibitor IBAP-II exhibits good activity but suffers from poor solubility, limiting its clinical application. OBJECTIVES: To design and synthesize novel BAP1 inhibitors with improved properties based on IBAP-II, addressing its solubility issue and enhancing inhibitory potential. METHODS: H NMR spectroscopy. RESULTS: All five compounds were successfully synthesized with yields ranging from 27.86% to 51.07%. NMR data validated their target structures and structural modifications (e.g., hydroxyl/nitro relocation, ring structure adjustment) were confirmed to potentially improve solubility and binding affinity. CONCLUSION: This study provides feasible synthetic routes for novel BAP1 inhibitors with optimized structures, laying a foundation for subsequent biological activity evaluations and offering new prospects for targeted tumor therapy, especially for small cell lung cancer.