In silico assessment and sonochemical synthesis of 2-alkynyl 3-chloropyrazines as prospective ligands for SARS-CoV-2.
J Mol Struct
; 1231: 129981, 2021 May 05.
Article
in English
| MEDLINE | ID: covidwho-1046204
ABSTRACT
The recent global pandemic caused by COVID-19 has triggered an intense effort worldwide towards the development of an effective cure for this disease. In our effort we have explored the 2-alkynyl substituted 3-chloropyrazine framework as a potential template for the design of molecules for this purpose. Our strategy was supported by the in silico studies of representative compounds to assess their binding affinities via docking into the N-terminal RNA-binding domain (NTD) of N-protein of SARS-CoV-2. Thus we created a small library of molecules based on the aforementioned template via an environmentally safer method that involved the rapid synthesis of 2-alkynyl 3-chloropyrazine derivatives under Cu-catalysis assisted by ultrasound. The reactions proceeded via the coupling of 2,3-dichloropyrazine with commercially available terminal alkynes in the presence of CuI, PPh3 and K2CO3 in PEG-400. Further molecular modelling studies helped in establishing a virtual SAR (Structure Activity Relationship) within the series and identification of three potential hits. The desirable ADME was also predicted for these three molecules suggesting their prospective medicinal value.
Full text:
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Collection:
International databases
Database:
MEDLINE
Type of study:
Observational study
/
Prognostic study
Language:
English
Journal:
J Mol Struct
Year:
2021
Document Type:
Article
Affiliation country:
J.molstruc.2021.129981
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