title: Synthesis, in vitro and in silico NS5B polymerase inhibitory activity of benzimidazole derivatives.
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.
authors.affiliation: Medicinal Chemistry Research Lab, School of Pharmacy, Bharat Institute of Technology, Partapur, Meerut-250 103 (UP) India. vaishuwise@gmail.com
authors.forename: Vaishali M
authors.initials: VM
authors.lastname: Patil
authors.forename: Gurukumar K
authors.initials: GK
authors.lastname: R
authors.forename: Maksim
authors.initials: M
authors.lastname: Chudayeu
authors.forename: Satya Prakash
authors.initials: SP
authors.lastname: Gupta
authors.forename: Subeer
authors.initials: S
authors.lastname: Samanta
authors.forename: Neeraj
authors.initials: N
authors.lastname: Masand
authors.forename: Neerja
authors.initials: N
authors.lastname: Kaushik-Basu
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000187:drug effects*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D001562:Benzimidazoles; D012321:DNA-Directed RNA Polymerases; D004791:Enzyme Inhibitors; D017361:Viral Nonstructural Proteins; C031000:benzimidazole; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase