From Oxetane to Thietane: Extending the Antiviral Spectrum of 2'-Spirocyclic Uridines by Substituting Oxygen with Sulfur.

Autor:	Grosse S; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Tahri A; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Raboisson P; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Houpis Y; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Stoops B; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Jacoby E; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Neefs JM; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Van Loock M; Janssen Global Public Health, R&D, Turnhoutseweg 30, 2340 Beerse, Belgium., Goethals O; Janssen Global Public Health, R&D, Turnhoutseweg 30, 2340 Beerse, Belgium., Geluykens P; Charles River, Discovery, Turnhoutseweg 30, 2340 Beerse, Belgium., Bonfanti JF; Janssen Research and Development, Chaussée du Vexin, 27100 Val de Reuil, France., Jonckers THM; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2022 Nov 28; Vol. 13 (12), pp. 1879-1884. Date of Electronic Publication: 2022 Nov 28 (Print Publication: 2022).
DOI:	10.1021/acsmedchemlett.2c00372
Abstrakt:	In continuation of our efforts of finding novel nucleoside inhibitors for the treatment of viral diseases, we initiated a discovery research program aimed at identifying novel nucleos(t)ide inhibitors for emerging diseases like Dengue and Chikungunya. Based on the previously reported 2'-spiro-oxetane uridine derivatives active against Hepatitis C Virus (HCV), we envisaged its sulfur analogue as an interesting congener both from a synthetic as well as biological point of view. Surprisingly, we found the 2'-spirothietane uridine derivatives not only to be active against HCV and Dengue virus (DENV), viruses belonging to the flavivirus family, but also to demonstrate activity against alphaviruses like Chikungunya virus (CHIKV) and Sindbis virus (SINV). Competing Interests: The authors declare no competing financial interest. (© 2022 American Chemical Society.)
Databáze:	MEDLINE
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