8-SUBSTITUTED PURINE DERIVATIVES - A NEW CLASS OF LIPID-LOWERING AGENTS

A series of purine derivatives have been prepared and their in vivo ab ilities to lower plasma total cholesterol and triglyceride levels, and to elevate high density lipoprotein (HDL) cholesterol levels in hyper lipemic rats have been tested. Some compounds, among which [(p-isobuto xycarbonyl)phenoxy]propylthio}adenosine 31, 8-{3-[(p-isobutoxy carbony l)phenoxy]-2-oxopropylthio} adenosine 33 and arbonyl)phenoxy]-2-hydraz onecarboxamidepropylthio} adenosine 36 appear to be the most interesti ng, have been found to have both the desired profile of activity and n o hepatotoxicity, when administered po at 50, 100 or 300 mg/kg. Compou nds 31, 33 and 36, orally tested at the same doses in the 15-d test, l ower triglyceride and VLDL/LDL (very low density lipoprotein/low densi ty lipoprotein) cholesterol levels by 10-33% and 13-46%, respectively, and increase HDL-associated cholesterol levels by 10-32%. These molec ules have been chosen for further pharmacological and toxicological ev aluations.