Design and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase

• Published in: Bioorganic & medicinal chemistry letters Vol. 29; no. 24; pp. 126104 - 126110
• Main Authors: Liu, Hong, Dai, Xing, He, Shuwen, Brockunier, Linda, Marcantonio, Karen, Ludmerer, Steven W., Li, Fangbiao, Feng, Kung-I, Nargund, Ravi P., Palani, Anandan
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.12.2019; Elsevier
• Subjects: Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Benzofurans - chemical synthesis; Benzofurans - chemistry; Benzofurans - pharmacology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Dose-Response Relationship, Drug; Drug Design; Hepatitis C virus; Life Sciences & Biomedicine; Microbial Sensitivity Tests; MK-8876; Molecular Structure; Non-nucleoside inhibitors (NNI); NS5B polymerase; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Structure-Activity Relationship; Tetracyclic structure; Viral Nonstructural Proteins - antagonists & inhibitors; Viral Nonstructural Proteins - metabolism; MK-8876; NS5B polymerase; Tetracyclic structure; Non-nucleoside inhibitors (NNI); Hepatitis C virus; IN-VITRO; DEPENDENT RNA-POLYMERASE; HEPATITIS-C VIRUS; CRYSTAL-STRUCTURE; RIBAVIRIN

[Display omitted] •N-linked and C-linked tetracyclic benzofuran-based compounds were made and evaluated as HCV 5B non-nucleoside inhibitors.•Tetracyclic benzofuran-based structures maintained broad spectrum anti-replicon potency profiles.•Compounds demonstrated moderate to excellent oral bioavailabi...