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.

Abstract

Regioselective cyclocondensation of 2,4-diacetyl-5-hydroxy-5-methyl-3-(3-nitrophenyl/4-nitrophenyl)cyclohexanones 1a,b 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(2H)-thiones 2a,b. Reaction of compounds 2a,b with ethyl iodide, 2-chloroacetamide (4a), or its N-aryl derivatives 4b–e in the presence of sodium acetate trihydrate gave 3-ethylthio-5,6,7,8-tetrahydroisoquinoline 3 and (5,6,7,8-tetrahydroisoquinolin-3-ylthio)acetamides 5a–i, respectively. Cyclization of compounds 5b–d,f,g into their isomeric 1-amino-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carboxamides 6b–d,f,g 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 5d 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.