Aryl-substituted aminobenzimidazoles targeting the hepatitis C virus internal ribosome entry site

• Published in: Bioorganic & medicinal chemistry letters Vol. 24; no. 14; pp. 3113 - 3117
• Main Authors: Ding, Kejia, Wang, Annie, Boerneke, Mark A., Dibrov, Sergey M., Hermann, Thomas
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.07.2014; Elsevier
• Subjects: Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Antivirals; Benzimidazoles - chemical synthesis; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Dose-Response Relationship, Drug; HCV; Hepacivirus - drug effects; Hepacivirus - genetics; Hepatitis C virus; Life Sciences & Biomedicine; Ligands; Models, Molecular; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; Ribosomes - metabolism; RNA targeting; RNA, Viral - genetics; RNA, Viral - metabolism; Science & Technology; Structure-Activity Relationship; Translation inhibitor; HCV; Translation inhibitor; RNA targeting; Antivirals; MYOTONIC-DYSTROPHY TYPE-1; DESIGN; SMALL MOLECULES; RNA; THERAPIES; LOOPS; BINDING
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2014.05.009

We describe the exploration of N1-aryl-substituted benzimidazoles as ligands for the hepatitis C virus (HCV) internal ribosome entry site (IRES) RNA. The design of the compounds was guided by the co-crystal structure of a benzimidazole viral translation inhibitor in complex with the RNA target. Structure-binding activity relationships of aryl-substituted benzimidazole ligands were established that were consistent with the crystal structure of the translation inhibitor complex.