4,7-disubstituted 7h-pyrrolo[2,3-d]pyrimidines and their analogs as antiviral agents against zika virus

Ruben Soto-Acosta; Eunkyung Jung; Li Qiu; Daniel J. Wilson; Robert J. Geraghty; Liqiang Chen

doi:10.3390/molecules26133779

4,7-disubstituted 7h-pyrrolo[2,3-d]pyrimidines and their analogs as antiviral agents against zika virus

Ruben Soto-Acosta, Eunkyung Jung, Li Qiu, Daniel J. Wilson, Robert J. Geraghty, Liqiang Chen

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Discovery of compound 1 as a Zika virus (ZIKV) inhibitor has prompted us to investigate its 7H-pyrrolo[2,3-d]pyrimidine scaffold, revealing structural features that elicit antiviral activity. Furthermore, we have demonstrated that 9H-purine or 1H-pyrazolo[3,4-d]pyrimidine can serve as an alternative core structure. Overall, we have identified 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs including compounds 1, 8 and 11 as promising antiviral agents against flaviviruses ZIKV and dengue virus (DENV). While the molecular target of these compounds is yet to be elucidated, 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs are new chemotypes in the design of small molecules against flaviviruses, an important group of human pathogens.

Original language	English (US)
Article number	3779
Journal	Molecules
Volume	26
Issue number	13
DOIs	https://doi.org/10.3390/molecules26133779
State	Published - Jul 1 2021

Bibliographical note

Funding Information:
Funding: This research was funded by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, grant number R21AI151427 (to LC) and a University of Minnesota Academic Health Center Faculty Research Development Grant (to RJG).

Funding Information:
This research was funded by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, grant number R21AI151427 (to LC) and a University of Minnesota Academic Health Center Faculty Research Development Grant (to RJG). Acknowledgments: We thank Paul D. Robbins and Fernando Santiago from the UMN Department of Biochemistry, Molecular Biology and Biophysics for the use of the Cytation One imaging system.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Antiviral agents
Dengue virus
Flavivirus
Zika virus

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/molecules26133779

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abstract = "Discovery of compound 1 as a Zika virus (ZIKV) inhibitor has prompted us to investigate its 7H-pyrrolo[2,3-d]pyrimidine scaffold, revealing structural features that elicit antiviral activity. Furthermore, we have demonstrated that 9H-purine or 1H-pyrazolo[3,4-d]pyrimidine can serve as an alternative core structure. Overall, we have identified 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs including compounds 1, 8 and 11 as promising antiviral agents against flaviviruses ZIKV and dengue virus (DENV). While the molecular target of these compounds is yet to be elucidated, 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs are new chemotypes in the design of small molecules against flaviviruses, an important group of human pathogens.",

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author = "Ruben Soto-Acosta and Eunkyung Jung and Li Qiu and Wilson, {Daniel J.} and Geraghty, {Robert J.} and Liqiang Chen",

note = "Funding Information: Funding: This research was funded by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, grant number R21AI151427 (to LC) and a University of Minnesota Academic Health Center Faculty Research Development Grant (to RJG). Funding Information: This research was funded by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, grant number R21AI151427 (to LC) and a University of Minnesota Academic Health Center Faculty Research Development Grant (to RJG). Acknowledgments: We thank Paul D. Robbins and Fernando Santiago from the UMN Department of Biochemistry, Molecular Biology and Biophysics for the use of the Cytation One imaging system. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Wilson, Daniel J.

AU - Geraghty, Robert J.

AU - Chen, Liqiang

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N2 - Discovery of compound 1 as a Zika virus (ZIKV) inhibitor has prompted us to investigate its 7H-pyrrolo[2,3-d]pyrimidine scaffold, revealing structural features that elicit antiviral activity. Furthermore, we have demonstrated that 9H-purine or 1H-pyrazolo[3,4-d]pyrimidine can serve as an alternative core structure. Overall, we have identified 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs including compounds 1, 8 and 11 as promising antiviral agents against flaviviruses ZIKV and dengue virus (DENV). While the molecular target of these compounds is yet to be elucidated, 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs are new chemotypes in the design of small molecules against flaviviruses, an important group of human pathogens.

AB - Discovery of compound 1 as a Zika virus (ZIKV) inhibitor has prompted us to investigate its 7H-pyrrolo[2,3-d]pyrimidine scaffold, revealing structural features that elicit antiviral activity. Furthermore, we have demonstrated that 9H-purine or 1H-pyrazolo[3,4-d]pyrimidine can serve as an alternative core structure. Overall, we have identified 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs including compounds 1, 8 and 11 as promising antiviral agents against flaviviruses ZIKV and dengue virus (DENV). While the molecular target of these compounds is yet to be elucidated, 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs are new chemotypes in the design of small molecules against flaviviruses, an important group of human pathogens.

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4,7-disubstituted 7h-pyrrolo[2,3-d]pyrimidines and their analogs as antiviral agents against zika virus

Abstract

Bibliographical note

Keywords

UN SDGs

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