Synthesis and Reactions of Some Heterocyclic Candidates Based on 2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene Moiety as Anti-Arrhythmic Agents

In continuation of our previous work, a series of novel thiophene derivatives 4, 5, 6, 8, 9, 9a, 9b, 9c, 9d, 9e, 10, 10a, 10b, 10c, 10d, 10e, 11, 12, 13, 14, 15, 16 were synthesized by the reaction of ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (1) or 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (2) with different organic reagents. Fusion of 1 with ethylcyanoacetate or maleic anhydride afforded the corresponding thienooxazinone derivative 4 and N-thienylmalimide derivative 5, respectively. Acylation of 1 with chloroacetylchloride afforded the amide 6, which was cyclized with ammonium thiocyanate to give the corresponding N-theinylthiazole derivative 8. On the other hand, reaction of 1 with substituted aroylisothiocyanate derivatives gave the corresponding thiourea derivatives 9a, 9b, 9c, 9d, 9e, which were cyclized by the action of sodium ethoxide to afford the corresponding N-substituted thiopyrimidine derivatives 10a, 10b, 10c, 10d, 10e. Condensation of 2 with acid anhydrides in refluxing acetic acid afforded the corresponding imide carbonitrile derivatives 11, 12, 13. Similarly, condensation of 1 with the previous acid anhydride yielded the corresponding imide ethyl ester derivatives 14, 15, 16, respectively. The structures of newly synthesized compounds were confirmed by IR, 1H NMR, 13C NMR, MS spectral data, and elemental analysis. The detailed synthesis, spectroscopic data, LD50, and pharmacological activities of the synthesized compounds are reported.