Antilipidemic agents, Part IV : Synthesis and antilipidemic testing of some heterocyclic derivatives of hexadecyl and cyclohexyl hemisuccinate esters

Two main classes of novel esters containing a hexadecyl or cyclohexyl group and various heterocyclic rings, like quinazolines, triazoles, thiadiazoles and pyrazoles have been synthesized. The first class involves the synthesis of the hexadecyl ester derivatives; namely 3-substituted-2-(hexadecyloxycarbonylpropionylthio)-4(3H)-quinazol inones 4a-c; 4-substituted-3-(4-pyridyl)-5-(hexadecyloxycarbonylpropionylthio)- 4H- 1,2,4-triazoles 6a-c; 5-substituted-2-(hexadecyloxycarbonylpropionylamino)-1,3,4-thiadia zoles 8a-c, 4-[4-(hexadecyloxycarbonyl)phenyl]azo-5-hydroxy-3-methyl-1-phen ylpyrazole 16; and 1-[4-(hexadecyloxycarbonyl) phenyl]-3-methyl-2-pyrazolin-5-one 19. The second class comprises the synthesis of the cyclohexyl ester derivatives; namely 3-substituted-2-(cyclohexyloxycarbonylpropionylthio)-4(3H)-quinazo linones 11a, b, 4-substituted-3-(4-pyridyl)-5-(cyclohexyloxycarbonylpropionylthio) -4 H-1,2,4-triazoles 12a, b and 5-isopropylthio-2-(cyclohexyloxycarbonylpropionylamino)-1,3, 4-thiadiazole 13. The antihypercholesterolemic as well as antihyperlipidemic activities of representative compounds have been studied. All the compounds tested resulted in a decrease in the lipid indices (cholesterol, LDL-cholesterol, HDL-cholesterol and serum triglycerides levels) studied in mice. Compounds 4b, 11a and 12a showed the highest antihyperlipidemic activity; their activities were almost equal to that of beta-sitosterol which was used as a standard.