Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors
- Resource Type
- article
- Authors
- Jing Wu; Bo Feng; Li-Xin Gao; Chun Zhang; Jia Li; Da-Jun Xiang; Yi Zang; Wen-Long Wang
- Source
- Molecules, Vol 27, Iss 10, p 3359 (2022)
- Subject
- COVID-19
Mpro inhibitors
drug design and synthesis
structure-activity relationships (SAR)
Organic chemistry
QD241-441
- Language
- English
- ISSN
- 1420-3049
The COVID-19 pandemic caused by SARS-CoV-2 is a global burden on human health and economy. The 3-Chymotrypsin-like cysteine protease (3CLpro) becomes an attractive target for SARS-CoV-2 due to its important role in viral replication. We synthesized a series of 8H-indeno[1,2-d]thiazole derivatives and evaluated their biochemical activities against SARS-CoV-2 3CLpro. Among them, the representative compound 7a displayed inhibitory activity with an IC50 of 1.28 ± 0.17 μM against SARS-CoV-2 3CLpro. Molecular docking of 7a against 3CLpro was performed and the binding mode was rationalized. These preliminary results provide a unique prototype for the development of novel inhibitors against SARS-CoV-2 3CLpro.