Synthesis and biological evaluation of 4,5,6,7‐tetrahydrothieno[2,3‐ c ]pyridine–based β‐aminonitriles and their derivatives: β‐amino carboxamides, (thio)ureas, and tetracycles

The preparation and cytotoxic characterization of 4,5,6,7‐tetrahydrothieno[2,3‐ c ]pyridine–based β‐aminonitriles, β‐amino carboxamides, and their (thio)urea and annulated derivatives were accomplished. Following a synthetic route involving Gewald three‐component reactions (G‐3CR) and a Lewis acid–catalyzed iso (thio)cyanate coupling, 30 compounds were prepared for antitumor evaluation. For derivatizations, a catalytic amount of CuOAc 2 (20 mol%) was essential for improving the reactivity of either the C‐2 amino function of thiophene or isocyanates. The synthesized analogues demonstrated a weak to moderate antitumor activity in a low micromolar range against A549 and K562 cancer cell lines.