Prostaglandin endoperoxide receptor antagonist

Amino-3-fluorobenzoic acid is an important intermediate in the synthesis of derivatives of indole, such as the potent and selective thromboxane/prostaglandin endoperoxide receptor antagonist L-670,596 or the anti-inflammatory agent Etodolac. Compounds of this type have therapeutic applications. 2-Amino-3-fluoro-benzoic add is aiso an important precursor for the synthesis of fluoroacridines, which can be converted to interesting tridentate ligands, such as Acriphos. ... 

Figure 6.3 Effect of two structurally distinct thromboxane A2/prostaglandin endoperoxide receptor antagonists, L636,499 and SQ29,548, on the time to coronary occlusion in the canine model of coronary thrombosis following electrically-induced endothelial injury...

Figure 6.5 Percent change in thromboxane A2 and prostacyclin biosynthesis, measured as excretion of their urinary metabolites, 2,3-dinor-thromboxane (Tx) 82 and 2,3-dinor-6-keto-prostaglandin (PG) respectively, in response to a thromboxane A2/prostaglandin endoperoxide receptor antagonist (L636,499) alone and in combination with a thromboxane synthase inhibitor (U63,557A) in the chronic canine model of coronary thrombosis. (Note that occlusion did not occur in dogs treated with the combination therapy)...

In addition, since these compounds are competitive antagonists, the degree of antagonism of the thromboxane A2/prostaglandin endoperoxide receptor required to achieve a biological response will depend on the amount of agonist formed. Thus, a lack of a response to these compounds would not preclude a role for thromboxane A2 in a particular clinical setting. 

As well as the apparent pathological role that thromboxane A2 plays in unstable angina, it also seems to be involved in the transient ischaemic attacks that occur in stroke patients. Aspirin is recommended by the FDA for treating these patients. The evaluation of thromboxane synthase inhibitors and prostaglandin endoperoxide-thromboxane A2 receptor antagonists in the clinical setting will doubtless reveal pathological roles for thromboxane A2 in other human diseases. 

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