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

E P Peçanha; C A Fraga; C Maurício; R de Sant'Anna; A L de Miranda; E J Barreiro

doi:10.1016/s0014-827x(98)00027-5

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

Farmaco. 1998 May 30;53(5):327-36. doi: 10.1016/s0014-827x(98)00027-5.

Authors

E P Peçanha¹, C A Fraga, C Maurício, R de Sant'Anna, A L de Miranda, E J Barreiro

Affiliation

¹ Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Brazil.

PMID: 9679282
DOI: 10.1016/s0014-827x(98)00027-5

Abstract

(+/-)-3-Alkoxymethyl-(2-oxabicyclo[3.3.0]octane)-5-yl-methyl-phosp horyl- 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Phospholipids / chemical synthesis*
Phospholipids / pharmacology
Platelet Activating Factor / antagonists & inhibitors*
Platelet Aggregation Inhibitors / chemical synthesis
Rabbits

Substances

Phospholipids
Platelet Activating Factor
Platelet Aggregation Inhibitors