Abstract
Hepatitis C virus (HCV) NS5B polymerase is the key replicating protein of the virus and thus an attractive target for drug development. Here we report on the synthesis and biological evaluation of a new series of benzimidazole derivatives as HCV NS5B inhibitors. This yielded compound 6b and 6d bearing 2-(2-benzyloxy)phenyl and 2-(4- methylbenzyloxy)phenyl moieties, respectively, as promising leads. Binding mode of compound 6d in allosteric pocket (AP)-1 of NS5B will form the basis for future structure-activity relationship optimization.
Keywords: HCV, NS5B polymerase, Benzimidazole derivatives, RNA-dependent RNA polymerase, methylbenzyloxy, hepatocellular carcinoma, orthotopic liver transplants, CMV, RdRp, QSAR
Medicinal Chemistry
Title:Synthesis, In Vitro and In Silico NS5B Polymerase Inhibitory Activity of Benzimidazole Derivatives
Volume: 8 Issue: 4
Author(s): Vaishali M. Patil, Gurukumar K. R., Maksim Chudayeu, Satya Prakash Gupta, Subeer Samanta, Neeraj Masand and Neerja Kaushik-Basu
Affiliation:
Keywords: HCV, NS5B polymerase, Benzimidazole derivatives, RNA-dependent RNA polymerase, methylbenzyloxy, hepatocellular carcinoma, orthotopic liver transplants, CMV, RdRp, QSAR
Abstract: Hepatitis C virus (HCV) NS5B polymerase is the key replicating protein of the virus and thus an attractive target for drug development. Here we report on the synthesis and biological evaluation of a new series of benzimidazole derivatives as HCV NS5B inhibitors. This yielded compound 6b and 6d bearing 2-(2-benzyloxy)phenyl and 2-(4- methylbenzyloxy)phenyl moieties, respectively, as promising leads. Binding mode of compound 6d in allosteric pocket (AP)-1 of NS5B will form the basis for future structure-activity relationship optimization.
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Cite this article as:
M. Patil Vaishali, K. R. Gurukumar, Chudayeu Maksim, Prakash Gupta Satya, Samanta Subeer, Masand Neeraj and Kaushik-Basu Neerja, Synthesis, In Vitro and In Silico NS5B Polymerase Inhibitory Activity of Benzimidazole Derivatives, Medicinal Chemistry 2012; 8 (4) . https://dx.doi.org/10.2174/157340612801216120
DOI https://dx.doi.org/10.2174/157340612801216120 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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