Login / Signup

Hepatoselective Dihydroquinolizinone Bis-acids for HBsAg mRNA Degradation.

Nicky HwangLiren SunDaisy NoePatrick Y S LamTianlun ZhouTimothy M BlockYanming Du
Published in: ACS medicinal chemistry letters (2021)
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.
Keyphrases
  • hepatitis b virus
  • small molecule
  • liver failure
  • physical activity
  • oxidative stress
  • binding protein
  • escherichia coli
  • ionic liquid
  • protein protein
  • multidrug resistant