Derivatives of 2-methylenepropane-1,3-diol as new antagonists of platelet activating factor

Article abstract of DOI:10.1021/jm00401a017

Two new achiral platelet activating factor (PAF) antagonists, N-[5-[[2-methylene-3-[[(octadecylamino)carbonyl]oxy]propoxy]carbonyl]p2 entyl]pyridinium bromide (9) and 3-[6-[[2-methylene-3-[[(octadecylamino)carbonyl]oxy]propoxy]carbonyl]h2 exyl]thiazolium bromide (10) were synthesized from 2-methylenepropane-1,3-diol (5). Platelet aggregation in platelet-rich plasma from rabbits, induced by racemic C₁₆-PAF, was competitively antagonized by 9 or 10. At concentrations ≤ 10^-4 M, neither compound 9 nor compound 10 caused platelet aggregation, nor did they inhibit platelet aggregation induced by collagen or adenosine diphosphate. Bronchoconstriction in the guinea pig and hypotension in the rat, induced by racemic C₁₆-PAF, were also effectively antagonized by 9 and 10. Both appear to be more potent as PAF antagonists than Takeda's CV-3988.