Inositol phosphatide ester derivs. - with antilipaemic, anti-atherosclerotic, platelet aggregation reducing and peripheral blood flow increasing activity

摘要

New inositol phosphatide derivs. are of formula (I): In (I), R1 and R2 are opt. unsatd. 5-23C alkyl (pref. residues derived from natural fatty acids). R3 is H and/or (a) an opt. unsatd 1-23C alkylcarboxylic acid residue opt. substd. by one or more halogen atoms, OH or alkoxy gps. or aromatic, hydroaromatic or heterocyclic rings (which in turn may be substd. by halogen, OH or alkoxy), (b) an opt. unsatd. 1-6C dicarboxylic acid residue opt. carrying 1 or more substituents, (e.g. halogen, OH, alkyl or alkoxy) or (c) a gp. -CO-CYX1X2 in which X1 and X2 are H, 1-5C alkyl, OH, CN halogen, p-chlorophenoxy or p-chloorophenylthio, and Y is a residue of formula (Ia)-(If) in which X3 is halogen, H, 1-5C alkyl, CF3 or OH, and Z is O,S or SO2, at least one residue R3 being other than H. (I) have antilipaemic and antiathenosclerotic activity. They reduce platelet aggregation and increase peripheral blood flow. Toxicity is low (mouse acute LD50 5000 mg/kg p.o. rat LDo (7 days) 5000 mg/kg p.o). Specific cpds. (I) include monophsophoinostide pentanicotinate. In an example, this is prepd. by reacting monophosphoinositide with nicotinic acid chloride in CHCl3 in the presence of Na2CO3. The product is isolated in the form of its calcium salt.