European Journal of Medicinal Chemistry, volume 188, pages 112007
Novel pleconaril derivatives: Influence of substituents in the isoxazole and phenyl rings on the antiviral activity against enteroviruses
Egorova Anna E.
1
,
Kazakova Elena
1
,
Jahn Birgit
2
,
Ekins Sean
3
,
Makarov Vadim A.
1
,
Schmidtke Michaela
2
2
Jena University Hospital, Department of Medical Microbiology, Section Experimental Virology, Hans-Knöll-Strasse 2, Jena, 07745, Germany.
|
3
Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, NC27606, USA.
|
Publication type: Journal Article
Publication date: 2020-02-01
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 6.7
ISSN: 02235234, 17683254
Organic Chemistry
Drug Discovery
General Medicine
Pharmacology
Abstract
Today, there are no medicines to treat enterovirus and rhinovirus infections. In the present study, a series of novel pleconaril derivatives with substitutions in the isoxazole and phenyl rings was synthesized and evaluated for their antiviral activity against a panel of pleconaril-sensitive and -resistant enteroviruses. Studies of the structure-activity relationship demonstrate the crucial role of the N,N-dimethylcarbamoyl group in the isoxazole ring for antiviral activity against pleconaril-resistant viruses. In addition, one or two substituents in the phenyl ring directly impact on the spectrum of antienteroviral activity. The 3-(3-methyl-4-(3-(3-N,N-dimethylcarbamoyl-isoxazol-5-yl)propoxy)phenyl)-5-trifluoromethyl-1,2,4-oxadiazole 10g was among the compounds exhibiting the strongest activity against pleconaril-resistant as well as pleconaril-susceptible enteroviruses with IC50 values from 0.02 to 5.25 μM in this series. Compound 10g demonstrated markedly less CYP3A4 induction than pleconaril, was non-mutagenic, and was bioavailable after intragastric administration in mice. These results highlight compound 10g as a promising potential candidate as a broad spectrum enterovirus and rhinovirus inhibitor for further preclinical investigations.
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- We do not take into account publications that without a DOI.
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Egorova A. E. et al. Novel pleconaril derivatives: Influence of substituents in the isoxazole and phenyl rings on the antiviral activity against enteroviruses // European Journal of Medicinal Chemistry. 2020. Vol. 188. p. 112007.
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Egorova A. E., Kazakova E., Jahn B., Ekins S., Makarov V. A., Schmidtke M. Novel pleconaril derivatives: Influence of substituents in the isoxazole and phenyl rings on the antiviral activity against enteroviruses // European Journal of Medicinal Chemistry. 2020. Vol. 188. p. 112007.
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TY - JOUR
DO - 10.1016/j.ejmech.2019.112007
UR - https://doi.org/10.1016%2Fj.ejmech.2019.112007
TI - Novel pleconaril derivatives: Influence of substituents in the isoxazole and phenyl rings on the antiviral activity against enteroviruses
T2 - European Journal of Medicinal Chemistry
AU - Egorova, Anna E.
AU - Kazakova, Elena
AU - Jahn, Birgit
AU - Ekins, Sean
AU - Makarov, Vadim A.
AU - Schmidtke, Michaela
PY - 2020
DA - 2020/02/01 00:00:00
PB - Elsevier
SP - 112007
VL - 188
SN - 0223-5234
SN - 1768-3254
ER -
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@article{2020_Egorova,
author = {Anna E. Egorova and Elena Kazakova and Birgit Jahn and Sean Ekins and Vadim A. Makarov and Michaela Schmidtke},
title = {Novel pleconaril derivatives: Influence of substituents in the isoxazole and phenyl rings on the antiviral activity against enteroviruses},
journal = {European Journal of Medicinal Chemistry},
year = {2020},
volume = {188},
publisher = {Elsevier},
month = {feb},
url = {https://doi.org/10.1016%2Fj.ejmech.2019.112007},
pages = {112007},
doi = {10.1016/j.ejmech.2019.112007}
}
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