Design and synthesis of novel pyrazolopyrimidine-based derivatives as reversible BTK inhibitors with potent antiproliferative activity in mantle cell lymphoma

Development of Bruton’s tyrosine kinase (BTK) inhibitors is great value and significance in the treatment B-cell malignancies autoimmune diseases. Herein, a novel class pyrazolopyrimidine-based BTK were designed evaluated mantle cell lymphoma (MCL) lines. We demonstrated that target compounds had made progress improvement antiproliferative activity compared to lead compound. Compounds 13c, 13g, 13h, 13l, 13n 13o effectively MCL cells lines with single-digit micromolar potency. Furthermore, compound 13l specifically disturbed mitochondrial membrane potential increased reactive oxygen species level Z138 dose-dependent manner. induced apoptosis through caspase 3- mediated apoptotic pathway cells. Overall, this study provides valuable for developing antitumor agents.