Cystic fibrosis (CF) is a life-shortening autosomal genetic disease caused by loss-of-function genetic mutations in the CF transmembrane conductance regulator (CFTR) chloride channel protein. The current standard of care for CF patients is a combination treatment consisting of a CFTR potentiator with one or more CFTR correctors. However, due to the systemic and chronic nature of CF, patients are often concurrently treated with multiple medications on top of CFTR potentiator/corrector combination. Hence, the optimization of drug–drug interaction (DDI) parameters is essential during the lead optimization of CFTR modulators. We present herein the design, synthesis, and medicinal chemistry optimization of novel CFTR correctors and the unique structural changes that lead to the optimization of their DDI profiles in addition to efficacy and overall physiochemical properties.

Design, synthesis and medicinal chemistry optimization of a unique second site cystic fibrosis transmembrane conductance regulator (CFTR) corrector for delF508 CFTR mutation

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.