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Inhibition of the Replication of Different Strains of Chikungunya Virus by 3-Aryl-[1,2,3]triazolo[4,5- d] pyrimidin-7(6 H)-ones

AuthorsGómez-SanJuan, Asier; Gamo, Ana María ; Delang, Leen; Pérez-Sánchez, Alfonso; Amrun, S. N.; Abdelnabi, R.; Jacobs, S.; Priego, Eva María ; Camarasa Rius, María José ; Jochmans, D.; Leyssen, Pieter; Ng, L. F. P.; Querat, Guilles; Neyts, J.; Peréz-Pérez, María-Jesús
KeywordsChikungunya virus
Physicochemical properties
Issue Date2018
PublisherAmerican Chemical Society
CitationACS Infectious Diseases 4: 605-619 (2018)
AbstractThe re-emergence of chikungunya virus (CHIKV) is a serious global health threat. CHIKV is an alphavirus that is transmitted to humans by Aedes mosquitoes; therefore, their wide distribution significantly contributes to the globalization of the disease. Unfortunately, no effective antiviral drugs are available. We have identified a series of 3-aryl-[1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones as selective inhibitors of CHIKV replication. New series of compounds have now been synthesized with the aim to improve their physicochemical properties and to potentiate the inhibitory activity against different CHIKV strains. Among these newly synthesized compounds modified at position 3 of the aryl ring, tetrahydropyranyl and N-t-butylpiperidine carboxamide derivatives have shown to elicit potent antiviral activity against different clinically relevant CHIKV isolates with 50% effective concentration (EC) values ranging from 0.30 to 4.5 μM in Vero cells, as well as anti-CHIKV activity in human skin fibroblasts (EC = 0.1 μM), a clinically relevant cell system for CHIKV infection.
Publisher version (URL)http://dx.doi.org/10.1021/acsinfecdis.7b00219
Identifiersdoi: 10.1021/acsinfecdis.7b00219
issn: 2373-8227
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