478490-01-6Relevant articles and documents
Synthesis, Structure–Activity Relationships, and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs as Inhibitors of SARS-CoV-2 Replication
Ahmad, Shamshad,Arzel, Philippe,Bardiot, Dorothée,Canard, Bruno,Castermans, Karolien,Chaltin, Patrick,De Jonghe, Steven,Decroly, Etienne,Delpal, Adrien,Eydoux, Cecilia,Guillemot, Jean-Claude,Hilgenfeld, Rolf,Jochmans, Dirk,Klaassen, Hugo,Koukni, Mohamed,Lescrinier, Eveline,Leyssen, Pieter,Lyoo, Heyrhyoung,Marchand, Arnaud,Neyts, Johan,Robinson, Colin,Snijder, Eric J.,Sun, Xinyuanyuan,Vangeel, Laura,Wanningen, Patrick,Zhang, Linlin,Zwaagstra, Marleen,van Hemert, Martijn J.,van Kuppeveld, Frank
, (2022/02/11)
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.
