Optimization of 3-aminotetrahydrothiophene 1,1-dioxides with improved potency and efficacy as non-electrophilic antioxidant response element (ARE) act...
Basic Information
ID: ALA5257107
Journal: Bioorg Med Chem Lett
Title: Optimization of 3-aminotetrahydrothiophene 1,1-dioxides with improved potency and efficacy as non-electrophilic antioxidant response element (ARE) activators.
Authors: Jo J, Kim J, Ibrahim L, Kumar M, Iaconelli J, Tran CS, Moon HR, Jung Y, Wiseman RL, Lairson LL, Chatterjee AK, Bollong MJ, Yun H.
Abstract: Activating NRF2-driven transcription with non-electrophilic small molecules represents an attractive strategy to therapeutically target disease states associated with oxidative stress and inflammation. In this study, we describe a campaign to optimize the potency and efficacy of a previously identified bis-sulfone based non-electrophilic ARE activator 2. This work identifies the efficacious analog 17, a compound with a non-cytotoxic profile in IMR32 cells, as well as ARE activators 18 and 22, analogs with improved cellular potency. In silico drug-likeness prediction suggested the optimized bis-sulfones 17, 18, and 22 will likely be of pharmacological utility.
CiteXplore: 37116763
DOI: 10.1016/j.bmcl.2023.129306
Patent ID: ┄