Synthesis by the Thorpe–Ziegler Reaction and In Silico Prediction of the Biological Activity of 3-Amino-4-aryl-6-oxo-4,5,6,7-tetrahydrothieno[2,3-b]pyridines

Abstract

Morpholinium (N-methylmorpholinium) 4-aryl-6-oxo-3-cyano-1,4,5,6-tetrahydropyridine-2-thiolates obtained by the reaction of cyanothioacetamide and aromatic aldehydes with Meldrum’s acid in the presence of a base undergo a tandem S-alkylation–Thorpe–Ziegler heterocyclization reaction upon treatment with α-halo carbonyl compounds in the presence of excess KOH. Predictive in silico analysis and molecular docking were performed for the newly synthesized 3-amino-4-aryl-6-oxo-4,5,6,7-tetrahydrothieno[2,3-b]pyridines to identify bioavailability parameters and potential protein targets. In laboratory experiments on sunflower seedlings, some of the compounds exhibited a pronounced safening effect against the herbicide 2,4-D (2,4-dichlorophenoxyacetic acid).