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-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.
Peçanha
E P
EP
Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Brazil.
Fraga
C A
CA
Maurício
C
C
de Sant'Anna
R
R
de Miranda
A L
AL
Barreiro
E J
EJ
D000818:Animals; D010743:Phospholipids / Q000138:chemical synthesis* / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis; D011817:Rabbits
D010743:Phospholipids; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors