Synthesis and pharmacological evaluation of a new class of bicyclic phospholipids, designed as platelet activating factor antagonists

• Published in: Farmaco (Società chimica italiana : 1989) 1998-05, Vol.53 (5), p.327-336
• Main Authors: Peçanha, Emerson Poley, Fraga, Carlos Alberto Manssour, Sant'Anna, Carlos Maurício Rabello de, de Miranda, Ana Luisa Palhares, Barreiro, Eliezer Jesus
• Format: Article
• Language: English
• Subjects: 2-Oxabicyclo[3.3.0]octane system; Animals; Antithrombotic activity; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Medical sciences; Pharmacology. Drug treatments; Phospholipids - chemical synthesis; Phospholipids - pharmacology; Platelet activating factor (PAF) antagonists; Platelet Activating Factor - antagonists & inhibitors; Platelet Aggregation Inhibitors - chemical synthesis; Rabbits
• ISSN: 0014-827X; 1879-0569
• DOI: 10.1016/S0014-827X(98)00027-5

(±)-3-Alkoxymethyl-(2-oxabicyclo[3.3.0]octane)-5-yl-methyl-phosphoryl-ethyl-pyridinium [alkyl chain=methyl ( 5a) and ( 5b), allyl ( 6a) and ( 6b), n-propyl ( 7a) and ( 7b) and n-hexyl ( 8a) and (8b)] derivatives, structurally designed as conformationally restricted platelet activating factor (PAF) antagonists were synthesized in 12–26% overall yield, using ethyl (±)-3-hydroxymethyl-5-(2-oxabicyclo[3.3.0] octane) carboxylate ( 13a,b) as key intermediate. The anti-platelet profile of the new derivatives was evaluated in a PAF-induced aggregation model in rabbit platelet-rich plasma; only compound 8a exhibited a modest activity.