9,11-Epoxy-9-homo-14-oxaprosta-5-enoic acid derivatives. Novel inhibitors of fatty acid cyclooxygenase.
A novel bicyclic prostaglandin analogue, [1R-[l alpha,2 beta (5Z),3 beta,4 alpha]]-7-[3-[(hexyloxy)methyl]- 7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (1), and cogeners were found to be potent inhibitors of fatty acid cyclooxygenase. Compound 1 was the only stereoisomer out of eight possible structures that was active. Ether 1 was 20 times more potent than indomethacin (IND) in inhibiting arachidonic acid (AA) induced aggregation of human platelet-rich plasma. Compound 1 was also more potent than IND in several in vivo assays, AA-induced sudden death in the conscious mouse (2 times) and AA-induced bronchoconstriction in the anesthetized guinea pig (16-45 times).
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008968:Molecular Conformation; D010974:Platelet Aggregation / Q000187:drug effects; D011465:Prostaglandins, Synthetic / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D011465:Prostaglandins, Synthetic; D016718:Arachidonic Acid; D007213:Indomethacin