2. Academic Validation
  3. Computer-aided identification, synthesis and evaluation of substituted thienopyrimidines as novel inhibitors of HCV replication

Computer-aided identification, synthesis and evaluation of substituted thienopyrimidines as novel inhibitors of HCV replication

  • Eur J Med Chem. 2016 Nov 10:123:31-47. doi: 10.1016/j.ejmech.2016.07.035.
Marcella Bassetto 1,  Pieter Leyssen 2,  Johan Neyts 2,  Mark M Yerukhimovich 3,  David N Frick 3,  Andrea Brancale 4
Affiliations

Affiliations

  • 1 Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff, King Edward VII Avenue, Cardiff, CF103NB, UK. Electronic address: bassettom@cardiff.ac.uk.
  • 2 Rega Institute for Medical Research, University of Leuven, Belgium.
  • 3 Department of Chemistry & Biochemistry, University of Wisconsin- Milwaukee, Milwaukee, WI 53211, USA.
  • 4 Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff, King Edward VII Avenue, Cardiff, CF103NB, UK.
PMID: 27474921 DOI: 10.1016/j.ejmech.2016.07.035
Abstract

A structure-based virtual screening technique was applied to the study of the HCV NS3 helicase, with the aim to find novel inhibitors of the HCV replication. A library of ∼450000 commercially available compounds was analysed in silico and 21 structures were selected for biological evaluation in the HCV replicon assay. One hit characterized by a substituted thieno-pyrimidine scaffold was found to inhibit the viral replication with an EC50 value in the sub-micromolar range and a good selectivity index. Different series of novel thieno-pyrimidine derivatives were designed and synthesised; several new structures showed Antiviral activity in the low or sub-micromolar range.

Keywords

Anti-HCV activity; Structure-based virtual screening; Substituted thieno-pyrimidines.

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