ChemMedChem, volume 10, issue 10, pages 1629-1634
Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino- and Enteroviruses
Makarov Vadim A.
1
,
Braun Heike
2
,
Richter Martina
2
,
Riabova Olga B
1
,
Kirchmair Johannes
3
,
Kazakova Elena S
1
,
Seidel Nora
2
,
Wutzler P.
2
,
Schmidtke Michaela
2
2
Virology & Antiviral Therapy, Jena University Hospital, Hans-Knöll-Str. 2, 07745 Jena (Germany)
|
3
Center for Bioinformatics, University of Hamburg, Bundesstrasse 43, 20146 Hamburg (Germany)
|
Publication type: Journal Article
Publication date: 2015-08-10
Journal:
ChemMedChem
Quartile SCImago
Q1
Quartile WOS
Q2
Impact factor: 3.4
ISSN: 18607179, 18607187
Organic Chemistry
Drug Discovery
Biochemistry
Pharmacology
Molecular Medicine
General Pharmacology, Toxicology and Pharmaceutics
Abstract
There are currently no drugs available for the treatment of enterovirus (EV)-induced acute and chronic diseases such as the common cold, meningitis, encephalitis, pneumonia, and myocarditis with or without consecutive dilated cardiomyopathy. Here, we report the discovery and characterization of pyrazolopyrimidines, a well-tolerated and potent class of novel EV inhibitors. The compounds inhibit the replication of a broad spectrum of EV in vitro with IC50 values between 0.04 and 0.64 μM for viruses resistant to pleconaril, a known capsid-binding inhibitor, without affecting cytochrome P450 enzyme activity. Using virological and genetics methods, the viral capsid was identified as the target of the most promising, orally bioavailable compound 3-(4-trifluoromethylphenyl)amino-6-phenylpyrazolo[3,4-d]pyrimidine-4-amine (OBR-5-340). Its prophylactic as well as therapeutic application was proved for coxsackievirus B3-induced chronic myocarditis in mice. The favorable pharmacokinetic, toxicological, and pharmacodynamics profile in mice renders OBR-5-340 a highly promising drug candidate, and the regulatory nonclinical program is ongoing.
Citations by journals
Citations by publishers
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9
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Elsevier
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Elsevier
9 publications, 27.27%
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Multidisciplinary Digital Publishing Institute (MDPI)
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Multidisciplinary Digital Publishing Institute (MDPI)
4 publications, 12.12%
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Wiley
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Wiley
3 publications, 9.09%
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Thieme
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Thieme
3 publications, 9.09%
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Frontiers Media S.A.
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Frontiers Media S.A.
2 publications, 6.06%
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Springer Nature
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Springer Nature
2 publications, 6.06%
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American Chemical Society (ACS)
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American Chemical Society (ACS)
1 publication, 3.03%
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Royal Society of Chemistry (RSC)
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Royal Society of Chemistry (RSC)
1 publication, 3.03%
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Pleiades Publishing
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Pleiades Publishing
1 publication, 3.03%
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Taylor & Francis
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Taylor & Francis
1 publication, 3.03%
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Dove Medical Press
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Dove Medical Press
1 publication, 3.03%
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Oxford University Press
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Oxford University Press
1 publication, 3.03%
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Walter de Gruyter
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Walter de Gruyter
1 publication, 3.03%
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Proceedings of the National Academy of Sciences (PNAS)
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Proceedings of the National Academy of Sciences (PNAS)
1 publication, 3.03%
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Saint Petersburg Pasteur Institute
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Saint Petersburg Pasteur Institute, 1, 3.03%
Saint Petersburg Pasteur Institute
1 publication, 3.03%
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Makarov V. A. et al. Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino- and Enteroviruses // ChemMedChem. 2015. Vol. 10. No. 10. pp. 1629-1634.
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Makarov V. A., Braun H., Richter M., Riabova O. B., Kirchmair J., Kazakova E. S., Seidel N., Wutzler P., Schmidtke M. Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino- and Enteroviruses // ChemMedChem. 2015. Vol. 10. No. 10. pp. 1629-1634.
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TY - JOUR
DO - 10.1002/cmdc.201500304
UR - https://doi.org/10.1002%2Fcmdc.201500304
TI - Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino- and Enteroviruses
T2 - ChemMedChem
AU - Braun, Heike
AU - Richter, Martina
AU - Riabova, Olga B
AU - Kazakova, Elena S
AU - Seidel, Nora
AU - Makarov, Vadim A.
AU - Kirchmair, Johannes
AU - Wutzler, P.
AU - Schmidtke, Michaela
PY - 2015
DA - 2015/08/10 00:00:00
PB - Wiley
SP - 1629-1634
IS - 10
VL - 10
SN - 1860-7179
SN - 1860-7187
ER -
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@article{2015_Makarov,
author = {Heike Braun and Martina Richter and Olga B Riabova and Elena S Kazakova and Nora Seidel and Vadim A. Makarov and Johannes Kirchmair and P. Wutzler and Michaela Schmidtke},
title = {Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino- and Enteroviruses},
journal = {ChemMedChem},
year = {2015},
volume = {10},
publisher = {Wiley},
month = {aug},
url = {https://doi.org/10.1002%2Fcmdc.201500304},
number = {10},
pages = {1629--1634},
doi = {10.1002/cmdc.201500304}
}
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Makarov, Vadim A., et al. “Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino- and Enteroviruses.” ChemMedChem, vol. 10, no. 10, Aug. 2015, pp. 1629-1634. https://doi.org/10.1002%2Fcmdc.201500304.
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