Nitrophenyl-Group-Containing Heterocycles. I. Synthesis, Characterization, Crystal Structure, Anticancer Activity, and Antioxidant Properties of Some New 5,6,7,8-Tetrahydroisoquinolines Bearing 3(4)-Nitrophenyl Group.

Regioselective cyclocondensation of 2,4-diacetyl-5-hydroxy-5-methyl-3-(3-nitrophenyl/4-nitrophenyl)cyclohexanones , with cyanothioacetamide afforded the corresponding 7-acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8-(3- and -4-nitrophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2)-thiones ,. Reaction of compounds , with ethyl iodide, 2-chloroacetamide (), or its -aryl derivatives - in the presence of sodium acetate trihydrate gave 3-ethylthio-5,6,7,8-tetrahydroisoquinoline and (5,6,7,8-tetrahydroisoquinolin-3-ylthio)acetamides -, respectively. Cyclization of compounds -,, into their isomeric 1-amino-6,7,8,9-tetrahydrothieno[2,3-]isoquinoline-2-carboxamides -,, was achieved by heating in ethanol containing a catalytic amount of sodium carbonate. Structures of all synthesized compounds were characterized on the basis of their elemental analyses and spectroscopic data. The crystal structure of 5,6,7,8-tetrahydroisoquinoline was determined by X-ray diffraction analysis. In addition, the biological evaluation of some synthesized compounds as anticancer agents was performed, and only six compounds showed moderate to strong activity against PACA2 (pancreatic cancer cell line) and A549 (lung carcinoma cell line). Moreover, the antioxidant properties of most synthesized compounds were examined. The results revealed high antioxidant activity for the most tested compounds.