Synthesis, Structure, and Analgesic Activity of 4-(5-Cyano-{4-(fur-2-yl)-1,4-dihydropyridin-3-yl}carboxamido)benzoic Acids Ethyl Esters

A series of new hybrid molecules containing fragments of anestesin and 4-(2-furyl)-1,4-dihydronicotinonitrile have been obtained starting from diketene, ethyl 4-aminobenzoate, cyanothioacetamide, and furfural. The obtained compounds have been investigated for the analgesic activity in vivo (rats) in the orofacial trigeminal pain and acetic acid induced writhing tests. The compounds exhibiting analgesic effect superior to that of the reference drug (metamizole sodium) have been revealed. Molecular docking has been performed for the considered compounds with respect to a wide range of protein targets, including cyclooxygenases COX-1 and COX-2.

Automated summary

New hybrid molecules derived from anestesin and 4-(2-furyl)-1,4-dihydronicotinonitrile have shown superior analgesic effects compared to metamizole sodium in pain relief experiments. Molecular docking studies suggest that these compounds can target a variety of proteins, including cyclooxygenases COX-1 and COX-2.