SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF A NEW CLASS OF BICYCLIC PHOSPHOLIPIDS, DESIGNED AS PLATELET-ACTIVATING-FACTOR ANTAGONISTS

(+/-)-3-Alkoxymethyl-(2-oxabicyclo[3.3.0] octane)-5-yl-methyl-phosphor yl-ethyl-pyridinium [alkyl chain = methyl (5a) and (5b), allyl (6a) an d (6b), n-propyl (7a) and (7b) and n-hexyl (8a) and (8b)] derivatives, structurally designed as conformationally restricted platelet activat ing factor (PAF) antagonists were synthesized in 12-26% overall yield, using ethyl (+/-)-3-hydroxymethyl-5-(2-oxabicyclo[3.3.0] octane) carb oxylate (13a,b) as key intermediate. The anti-platelet profile of the new derivatives was evaluated in a PAF-induced aggregation model in ra bbit platelet-rich plasma; only compound 8a exhibited a modest activit y. (C) 1998 Elsevier Science S.A. All rights reserved.