Structure based optimization of chromen-based TNF-α converting enzyme (TACE) inhibitors on S1′ pocket and their quantitative structure–activity relationship (QSAR) study

A series of chromen-based TACE inhibitors were designed to bind in S1′ pocket of TACE enzyme based on their docking study. The newly prepared analogues were evaluated in vitro assays and the most potent inhibitor (15l) was evaluated in pharmacokinetic model and in vivo pharmacological model. QSAR equation of the chromen-based TACE inhibitors is reliable in internal and external test set and its docking study confirms the equation.