Synthesis of lysophosphatidylethanolamine analogs that inhibit renin activity

Article abstract of DOI:10.1021/jm00246a003

A series of lysophosphatidylethanolamine analogs containing saturated and methylene interrupted cis olefinic fatty chains was synthesized by phosphorylation and phosphonylation of respective fatty alcohols. Arachidonyl and linolenyl phosphoryl ethanolamines, arachidonyl (2 phthalimidoethyl)phosphonate and arachidonyl (2 aminoethyl)phosphonate were found to be effective inhibitors of the renin renin substrate reaction in vitro; lysophosphatidylethanolamine analogs of lesser unsaturation were either weakly active or inactive. In a preliminary study, intramuscular administration of 25 mg/kg/day of arachidonyl (2 aminoethyl)phosphonate to the hypertensive rat caused pronounced reduction (50 mm) in blood pressure within 3 days; upon continued dosage (15 mg/kg/day) for an additional 4 days, plasma renin activity was found to be 16 ng/0.1 ml/15 hr as compared with 69 ng/0.1 ml/15 hr before initial drug administration. Arachidonic acid, arachidonyl alcohol, and several corresponding tetraenoid ester, amide, mesylate, and glyceryl ether derivatives, that are not phosphate or phosphonates esters, were found to exhibit negligible or modest inhibition of renin activity in vitro.