TCS/ZnCl2 as a controlled reagent for the Michael addition and heterocyclic cyclization based on the phenyl pyrazolone scaffold with docking validation as a Covid-19 protease inhibitor

Abstract

TCS/ZnCl2 is presented as a new catalyst for achieving the Michael addition adduct 5a-g by the reaction of phenyl pyrazolone 4 as the Michael donor and arylidene derivatives 3a-g as the Michael acceptor. The one-pot multi-component reaction of the same fragments' scaffolds as aldehydes 1a-g, malononitrile (2), and phenyl pyrazolone 4 with the same catalyst gives pyrano[2,3-c]pyrazole derivatives 6a-g as final products. The prepared compounds undergo docking validation as COVID-19 protease inhibitors and are compared with hydroxychloroquine as a reference drug. KEY WORDS: Pyranopyrazole, multi-component reactions, TCS/ZnCl2 catalyst, COVID-19, the energy score, hydroxychloroquine Bull. Chem. Soc. Ethiop. 2024, 38(4), 1119-1127.                                                       DOI: https://dx.doi.org/10.4314/bcse.v38i4.24