Synthesis and first evaluation of new favipiravir analogs based on cyclic amidrazones scaffolds
Abstract
In a context of (re-)emergence of viral infections, there is a strong appeal to propose new therapeutic alternatives which will also help to anticipate the renewal of our armamentarium currently showing limitations in drug resistance. Favipiravir has shown a broad spectrum of activity against a great variety of viruses (West Nile virus, Norovirus, encephalitis viruses, arenaviruses, (ortho)bunya-virus, Ebola virus, coronavirus and influenza viruses). In the course of new generation of efficient antivirals, the design of original nucleos(t)idic inhibitors is crucial and our strategy was inspired by a diversification of the outstanding favipiravir scaffold by taking advantage of the cyclic amidrazone cores as bioisoteric compounds. Our work discloses comparative binding mode studies to evaluate this relevant opportunity of scaffold hopping. Our original strategies allowed the production of two new series of 1,4,5,6-tetrahydro-1,2,4-triazine-6-carboxamides and 5-carboxamide-triazinone analogs. Their first evaluation as anti-influenza candidates was explored and showed a significant effect for one intermediate compound. However, the four final carboxamide compounds did not display the expected activity and might have limitations to afford the corresponding metabolized and active compound. Having in hand attractive building blocks, these new scaffolds should also prompt our scientific community to bring more structural variety within nucleosidic analogs or other drug candidates.
Related
- Design, microwave-assisted domino synthesis, and biological evaluation of novel naphtho[2,3-b]furan-4,9-diones as rigidified combretastatin A-4 analogs inducing G0/G1 cell cycle arrest and apoptosis
- Multigram Synthesis of Heterabicyclo[4.1.1]octanes: Conformationally Restricted Azepane Analogs for Drug Discovery
- Drug-Initiated Synthesis and Processing of Mupirocin–PLGA Conjugates for Biodegradable Antibacterial Scaffolds
- Synthesis of Nitrogen‐Containing Heterocyclic Scaffolds and Applications in Scaffold Hopping: Development of an Aripiprazole Analog
- Binary SiO2-CaO bioactive glass nanoparticles synthesis and colloidal stability investigated via in-situ SAXS for freeze-cast scaffolds
BibTeX
@article{boutin2026synthesis,
title = {{Synthesis and first evaluation of new favipiravir analogs based on cyclic amidrazones scaffolds}},
author = {Margaux Boutin and Jacques Lebreton and Edeildo Ferreira da Silva-Júnior and Andrés Pizzorno and Aurélien Traversier and Manuel Rosa-Calatrava and Arnaud Tessier},
journal = {European Journal of Medicinal Chemistry Reports},
year = {2026},
month = nov,
doi = {10.1016/j.ejmcr.2026.100352},
url = {https://nantes-universite.hal.science/hal-05849451v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Synthesis and first evaluation of new favipiravir analogs based on cyclic amidrazones scaffolds
AU - Margaux Boutin
AU - Jacques Lebreton
AU - Edeildo Ferreira da Silva-Júnior
AU - Andrés Pizzorno
AU - Aurélien Traversier
AU - Manuel Rosa-Calatrava
AU - Arnaud Tessier
PY - 2026
DA - 2026/11/03
JO - European Journal of Medicinal Chemistry Reports
DO - 10.1016/j.ejmcr.2026.100352
UR - https://nantes-universite.hal.science/hal-05849451v1
AB - In a context of (re-)emergence of viral infections, there is a strong appeal to propose new therapeutic alternatives which will also help to anticipate the renewal of our armamentarium currently showing limitations in drug resistance. Favipiravir has shown a broad spectrum of activity against a great variety of viruses (West Nile virus, Norovirus, encephalitis viruses, arenaviruses, (ortho)bunya-virus, Ebola virus, coronavirus and influenza viruses). In the course of new generation of efficient antivirals, the design of original nucleos(t)idic inhibitors is crucial and our strategy was inspired by a diversification of the outstanding favipiravir scaffold by taking advantage of the cyclic amidrazone cores as bioisoteric compounds. Our work discloses comparative binding mode studies to evaluate this relevant opportunity of scaffold hopping. Our original strategies allowed the production of two new series of 1,4,5,6-tetrahydro-1,2,4-triazine-6-carboxamides and 5-carboxamide-triazinone analogs. Their first evaluation as anti-influenza candidates was explored and showed a significant effect for one intermediate compound. However, the four final carboxamide compounds did not display the expected activity and might have limitations to afford the corresponding metabolized and active compound. Having in hand attractive building blocks, these new scaffolds should also prompt our scientific community to bring more structural variety within nucleosidic analogs or other drug candidates.
SN - 2772-4174
ER -