Antilipidemic agents, Part IV: Synthesis and antilipidemic testing of someheterocyclic 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 synthesi s of the hexadecyl ester derivatives: namely 3-substituted-2-(hexadecyloxyc arbonylpropionylthio)-4(3H)-quinazolinones 4a-c; 4-substituted-3-(4-pyridyl )-5-(hexadecyloxycarbonylpropionylthio)-4H-1,2,4-trizoles 6a-c; 5-substitut ed-2-(hexadecyloxycarbonylpropionylamino)-1,3,4-thiadiazoles 8a-c, 4-[4-(he xadecyloxycarbonyl)phenyl]azo-5-hydrixt-3-methyl-1-phenylpyrazole 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)-quinazolinones 1 1a, b, 4-substituted-3-(4-pyridyl)-5-(cyclohexyloxycarbonylpropionylthio)-4 H-1,2,4-triazoles 12a,b and 5-isopropylthio-2-(cyclohexyloxycarbonylpropion ylamino)-1,3,4-thiadiazole 13. The antihypercholesterolemic as well as anti hyperlipidemic activities of representative compounds have been studied. Al l the compounds tested resulted in a decrease in the lipid indices (cholest erol, LDL-cholesterol, HDL-cholesterol and serum triglycerides levels) stud ied in mice. Compounds 4b, 11a and 12a showed the highest antihyperlipidemi c activity; their activities were almost equal to that of beta-sitosterol w hich was used as a standard.