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Hepatoselective Dihydroquinolizinone Bis-acids for HBsAg mRNA Degradation. | LitMetric

Hepatoselective Dihydroquinolizinone Bis-acids for HBsAg mRNA Degradation.

ACS Med Chem Lett

Medicinal Chemisty, Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, Pennsylvania 18902, United States.

Published: July 2021

AI Article Synopsis

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274061PMC
http://dx.doi.org/10.1021/acsmedchemlett.1c00228DOI Listing

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