SYNTHESIS OF 1,2-DIACYL-3-NICOTINOYL GLYCEROL DERIVATIVES AND EVALUATION OF THEIR ACUTE EFFECTS ON PLASMA-LIPIDS IN THE RAT

Nicotinic acid (CAS 59-67-6) is the only hypolipidemic agent whose act ivity has been shown both on atherosclerotic lesions and on long term mortality Unfortunately, its use is hindered by the frequent occurrenc e (> 70 %) of adverse reactions (i.e. cutaneous rash, pruritus and mos t significantly, flush). New prodrugs of nicotinic acid have been prep ared by the use of diacylglycerol esters In the rat, after acute oral administration of these products, a significant decrease of the free f atty acid plasma levels was obtained without the dramatic ina ease in nicotinic acid plasma levels observed after the oral administration of an equimolecular dose of nicotinic acid. The most interesting ester, S 16961 ((d, l)-1,2-dipalmitoyl-3-nicotinoyl glycerol, CAS 160555-46-4 ) is undergoing clincial trials.