7-Oxabicycloheptane analogs: modulators of the arachidonate cascade

Small structural changes in a series of 7-oxabicyclo[2.2.1]heptyl acids have produced four types of agents that modify the actions of TXA2 and PG. We showed that SQ 26,655 is a TXA2 receptor agonist, SQ 28,668 and SQ 29,548 are TXA2 receptor antagonists, SQ 28,852 is a CO inhibitor, and SQ 27,986 is a PGI2/PGD2 agonist. SQ 30,077 bound reversibly with high affinity to one site in human platelet membranes. The specific binding of SQ 30,077 is competitively inhibited by the identified TXA2 receptor agonists and antagonists with an order of affinity that correlates well with their functional potencies. SQ 27,986, PDG2 and SQ 28,852 show marginal affinity, indicating that their biological actions are not mediated via the TXA2 receptor.