Thromboxane receptor active analogues based on the 6-oxabicyclo[3.2.1]octane ring system

Article abstract of DOI:10.1016/0223-5234(93)90092-S

Prostanoid analogues with a 6-oxabicyclo[3.2.1]octane ring and 3 different types of ω-chain have been synthesized and evaluated for biological activity on thromboxane A₂ (TXA₂) receptors and prostaglandin I₂ (PGI₂) receptors. The standard ω-chain analogue 34b is a TXA₂ receptor agonist approximately 10-fold less potent than U46619 3, the standard agonist. The O-diphenylmethyloximino-ω'-chain analogue 32 gives a PGI₂-like agonist ~5-fold less active than EP 157, the most active molecule in this class. Conversely, 4-arylsemicarbazone ω-chain analogues 35a and 35b show TXA₂ antagonism comparable to that obtained with bicyclo[2.2.2]octane and bicyclo[2.2.1]heptane systems containing this type of ω-chain (eg EP 092).