[PAF-antagonists with a phospholipid structure. 1. Phospholipids with hetero-arene head groups: synthesis,...

A series of analogues of platelet-activating factor (PAF) with heteroarene head groups have been synthesized, and tested for biological activities on blood platelets in vitro. In comparison with PAF most of the structural modifications exerted weak proaggregatory effects. The 4-(dimethylamino)pyridinium compound did not activate platelets but inhibited selectively PAF-induced platelet responses. These results point to a crucial role of the distance between the phosphoryl group and polar head for expression of PAF-antagonistic properties. Structural features of PAF-antagonist have been investigated by two-dimensional proton NMR spectroscopy, and proposed a model with three-dimensional structure.