Improving Metabolic Stability with Deuterium: The Discovery of BMT-052, a Pan-genotypic HCV NS5B Polymerase Inhibitor

Abstract

Iterative structure-activity analyses in a class of highly functionalized furo[2,3-<i>b</i>]pyridines led to the identification of the second generation pan-genotypic hepatitis C virus NS5B polymerase primer grip inhibitor BMT-052 (<b>14</b>), a potential clinical candidate. The key challenge of poor metabolic stability was overcome by strategic incorporation of deuterium at potential metabolic soft spots. The preclinical profile and status of BMT-052 (<b>14</b>) is described.