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

Bassetto, Marcella, Leyssen, Pieter, Neyts, Johan, Yerukhimovich, Mark M., Frick, David N. and Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419 2016. Computer-aided identification, synthesis and evaluation of substituted thienopyrimidines as novel inhibitors of HCV replication. European Journal of Medicinal Chemistry 10.1016/j.ejmech.2016.07.035

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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 characterised 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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Structure-based virtual screening; Substituted thieno-pyrimidines; Anti-HCV activity
Publisher:	Elsevier
ISSN:	0223-5234
Date of First Compliant Deposit:	26 July 2016
Date of Acceptance:	18 July 2016
Last Modified:	06 Jan 2024 08:12
URI:	https://orca.cardiff.ac.uk/id/eprint/93327

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