Structure-Based Drug Design of Potent Pyrazole Derivatives against Rhinovirus Replication - Aix-Marseille Université Access content directly
Journal Articles Journal of Medicinal Chemistry Year : 2018

Structure-Based Drug Design of Potent Pyrazole Derivatives against Rhinovirus Replication

Abstract

Rhinoviruses (RVs) have been linked to exacerbations of many pulmonary diseases, thus increasing morbidity and/or mortality in subjects at risk. Unfortunately, the wide variety of RV genotypes constitutes a major hindrance for the development of Rhinovirus replication inhibitors. In the current investigation, we have developed a novel series of pyrazole derivatives that potently inhibit the Rhinovirus replication. Compounds 10e and 10h behave as early stage inhibitors of Rhinovirus infection with a broad-spectrum activity against RV-A and RV-B species (EC 50 < 0.1 μM). We also evaluate the dynamics of the emerging resistance of these promising compounds and their in vitro genotoxicity. Molecular docking experiments shed light on the pharmacophoric elements interacting with residues of the drug-binding pocket.
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Dates and versions

hal-02094656 , version 1 (09-04-2019)

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Laurène da Costa, Els Scheers, Antonio Coluccia, Alessia Rosetti, Manon Roche, et al.. Structure-Based Drug Design of Potent Pyrazole Derivatives against Rhinovirus Replication. Journal of Medicinal Chemistry, 2018, 61 (18), pp.8402-8416. ⟨10.1021/acs.jmedchem.8b00931⟩. ⟨hal-02094656⟩
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