Resurrecting the Condemned: Identification of N-Benzoxaborole Benzofuran GSK8175 as a Clinical Candidate with Reduced Metabolic Liability

摘要

Recently, in a program designed to improve the metabolic stability of the HCV inhibitor GSK5852, N-benzoxaborole benzofuran (GSK8175) emerged as a clinical candidate that not only retains the broad-spectrum activity against HCV subgenomic replicons but is free of the N-benzylboronic acid structure, which is a metabolic liability, and probably the cause of low in vivo clearance in preclinical species. This Viewpoint discusses some medicinal chemistry issues involved in the identification of GSK8175.