Bioorganic chemistry · 2023
Synthesis and evaluation of highly potent HBV capsid assembly modulators (CAMs).
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Amblard Franck, Chen Zhe, Wiseman John, Zhou Shaoman, Liu Peng, Salman Mohammad, Verma Kiran, Azadi Niloufar, Downs-Bowen Jessica, Tao Sijia, Kumari Amita, Zhang Qingling, Smith David B, Patel Dharmeshkumar, Bassit Leda, Schinazi Raymond F
Аннотация
Chronic hepatitis B virus (HBV) infection remains a major global health burden. It affects more than 290 million individuals worldwide and is responsible for approximately 900,000 deaths annually. Anti-HBV treatment with a nucleoside analog in combination with pegylated interferon are considered first-line therapy for patients with chronic HBV infection and liver inflammation. However, because cure rates are low, most patients will require lifetime treatment. HBV Capsid Assembly Modulators (CAMs) have emerged as a promising new class of compounds as they can affect levels of HBV covalently closed-circular DNA (cccDNA) associated with viral persistence. SAR studies around the core structure of lead HBV CAM GLP-26 (Fig. 1B) was performed and led to the discovery of non-toxic compound 10a displaying sub-nanomolar anti-HBV activity. Advanced toxicity and cellular pharmacology profiles of compounds 10a were also established and the results are discussed herein.