[PAF-antagonists with phospholipid structure. 3. Phospholipids with heterocyclane head groups and variations of the...

A series of 13 PAF-analogues with heterocyclane head groups and variation of the P-N-distance on the C-3-position of the backbone were synthesized. The proaggregatory and inhibitory potencies on rabbit and human blood platelets in vitro was evaluated. Investigations of structure-activity relationship revealed that the PAF-inhibitory potency is strongly influenced by the distance between phosphate and onium center and the structure of the heterocyclane. Derivatives with a P-N-distance of 4 or more methylene groups emerged effective inhibitors. The best activity was observed by chinuclidine- and N-methylpiperidine analogues with a chain length of 6 methylene groups (KB = 1.1 to 2.3 mumol/l).