Heterocyclic compounds derived from cyclohexane-1,4-dione: synthesis of tetrahydro-4H-chromene and tetrahydrobenzo[d]thiazole derivatives as target SARS-CoV-2 main protease (Mpro) and potential anti-Covid-19

Tetrahydro-4H-chromene-3-carbonitrile derivatives 4a-c where prepared from the reaction of 1,4-cyclohexane dione (1), malononitrile (2) and either benzaldehyde (3a), 2-chlorobenzaldehyde (3b) or 4-methoxybenzaldehyde (3c) in ethanol containing triethylamine. Compound 4b was used to prepare pyrazole, pyrimidine thiazole derivatives. Moreover, tetrahydrobenzo[d]thiazole derivative 18 (1) with elemental sulfur followed by phenyl isothiocyanate (12) absolute The latter compound reacted ethyl orthoformate cyanoacetate 1,4-dioxane presence triethylamine produce 9-ethoxy-2H-chromeno[6,5-d]thiazole 20a,b. In addition, fused thiophene pyran were synthesized starting 18. screened compounds designed as mimics transition state RNA2’-O-methylation against several viral RNA 2’-OMTases SARS-CoV (nsp10/nsp16 complex), Zika, West Nile, dengue, vaccinia (VP39) viruses. At same time, tested human N7-MTase (hRNMT) selected N7-MTases such nsp14 D1-D12 complex evaluate their specificity. Compounds 4a, 4b, 6b, 6c, 6e, 9a, 9b, 15, 16, 21b, 23b showed high % inhibitions SARs-Cov nsp 14 values 93.42, 87.49, 98.23, 88.15, 89.24, 96.31, 93.28, 89.25, 89.20, 87.24, 94.49, respectively.