@article{Bardiot_D-2022_65317,
title = {Synthesis, Structure–Activity Relationships, and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs as Inhibitors of SARS-CoV-2 Replication},
author = {Bardiot, D. and Vangeel, L. and Koukni, M. and Arzel, P. and Zwaagstra, M. and Lyoo, H. and Wanningen, P. and Ahmad, S. and Zhang, L. and Sun, X. and Delpal, A. and Eydoux, C. and Guillemot, J. and Lescrinier, E. and Klaassen, H. and Leyssen, P. and Jochmans, D. and Castermans, K. and Hilgenfeld, R. and Robinson, C. and Decroly, E. and Canard, B. and Snijder, E. and van Hemert, M. and van Kuppeveld, F. and Chaltin, P. and Neyts, J. and De Jonghe, S. and Marchand, A.},
month = {feb},
year = {2022},
abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to a pandemic, that continues to be a huge public health burden. Despite the availability of vaccines, there is still a need for small-molecule antiviral drugs. In an effort to identify novel and drug-like hit matter that can be used for subsequent hit-to-lead optimization campaigns, we conducted a high-throughput screening of a 160 K compound library against SARS-CoV-2, yielding a 1-heteroaryl-2-alkoxyphenyl analog as a promising hit. Antiviral profiling revealed this compound was active against various beta-coronaviruses and preliminary mode-of-action experi-ments demonstrated that it interfered with viral entry. A systematic structure–activity relationship (SAR) study demonstrated that a 3-or 4-pyridyl moiety on the oxadiazole moiety is optimal, whereas the oxadiazole can be replaced by various other heteroaromatic cycles. In addition, the alkoxy group tolerates some structural diversity.},
volume = {27},
issue = {3},
journal = {Molecules},
publisher = {MDPI},
url = {https://doi.org/10.3390/molecules27031052},
}
