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Fused pyridine derivatives R 0450 Facile Synthesis of 1,2,3,4-Tetrahydrobenzo[b][1,8]-naphthyridin-2-one via Baylis-Hillman Adducts. -The title compounds, e.g. (IV), are obtained from Baylis-Hillman adducts (I) via Johnson-Claisen rearrangement and tandem reduction-double cyclization. Benzo[b][1,8]naphthyridine derivatives are used as potent DNA-intercalating agents, mGlu1 antagonists, and Src kinase inhibitors. -(CHEN, D.; XU, J.; YANG*, C.; XIE, Y.; Chin.

Chronic hepatitis B virus (HBV) infection is a worldwide disease that causes thousands of deaths per year. Currently, there is no therapeutic that can completely cure already infected HBV patients due to the inability of humans to eliminate covalently closed circular DNA (cccDNA), which serves as the template to (re)initiate an infection even after prolonged viral suppression. Through phenotypic screening, we discovered xanthone series hits as novel HBV cccDNA reducers, and subsequent structure optimization led to the identification of a lead compound with improved antiviral activity and pharmacokinetic profiles. A representative compound 59 demonstrated good potency and oral bioavailability with no cellular toxicity. In an HBVcircle mouse model, compound 59 showed excellent efficacy in significantly reducing HBV antigens, DNA, and intrahepatic cccDNA levels.