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Hepatoselective Dihydroquinolizinone Bis-acids for HBsAg mRNA Degradation.

Basic Information

ID: ALA4808208

Journal: ACS Med Chem Lett

Title: Hepatoselective Dihydroquinolizinone Bis-acids for HBsAg mRNA Degradation.

Authors: Hwang N, Sun L, Noe D, Lam PYS, Zhou T, Block TM, Du Y.

Abstract: Chronic hepatitis B (CHB) is characterized by high levels of hepatitis B virus (HBV) surface antigen (HBsAg) in blood circulation. A major goal of CHB interventions is reducing or eliminating this antigenemia; however, there are currently no approved methods that can do this. A novel family of compounds with a dihydroquinolizinone (DHQ) scaffold has been shown to reduce circulating levels of HBsAg in animals, representing a first for a small molecule. Reductions of HBsAg were a result of the compound's effect on HBsAg mRNA levels. However, commercial development by Roche of a DHQ lead compound, RG-7834, was stopped due to undisclosed toxicity issues. Herein we report our effort to convert the systemic RG7834 compound to a hepatoselective DHQ analog to limit its distribution to the bloodstream and thus to other body tissues.

CiteXplore: 34267883

DOI: 10.1021/acsmedchemlett.1c00228

Patent ID: