Prostaglandin endoperoxide receptor

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. ... 

Mohler ER, Franklin MT, Adam LP. Intracellular signaling by 8-epi-prostaglandin F2 is mediated by dirranboxane A/prostaglandin endoperoxide receptors in porcine carotid arteries. Biochem Biophys Res Commun 1996 25 915-23... 

Ogletree ML, Harris DN, Schumacher WA, Webb ML, Misra RN. Pharmocological profile of BMS 180,291 a potent, long-acting, orally active thromboxane Aj/prostaglandin endoperoxide receptor antagcmist J Pharmacol Exp Ther 1993 264 570-8... 

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. 

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)...

Fitzgerald, D.J., Doran, J., Jackson, E. and FitzGerald, G.A. (1986). Coronary vascular occlusion mediated via thromboxane A2-prostaglandin endoperoxide receptor activation in vivo. ]. Clin. Invest., 77, 496-502... 

Saussy, D., Mais, D., Knapp, D. and Halushka, P. (1985). Thromboxane A2 and prostaglandin endoperoxide receptors in platelets and vascular smooth muscle. Circulation,... 

Fig. (6). Vasoconstrictor mechanism of myricetin. PLA2 phospholipase A2 PL phospholipids AA arachidonic acid COX cyclooxygenase PGG2 prostaglandin G2 PGES prostaglandin endoperoxide synthase PGH2 prostaglandin Hi TXS Thromboxane synthase TXA2 Thromboxane A2 Tp Thromboxane receptor PKC protein kinase C.

Scheurlen M, Kirchner M, Clemens MR, Jaschonek K. Fish oil preparations rich in docosahexaenoic acid modify platelet responsiveness to prostaglandin-endoperoxide/thromboxane A2 172. receptor agonists. Biochem. Pharmacol. 1993 46 245-249. 

Dom II GW, Davis MG, D Angdo DD. Structural determinants for ironist binding affinity to diromboxane/prostaglandin endoperoxide (TP) receptors. JBiolChem 1997 272 12399-405... 

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. 

Armstrong, R.A., Jones, R.L., Leigh, P.J., MacDermot, J. and Wilson, N.H. (1986). Novel prostaglandin endoperoxide analogues which block thromboxane receptors and mimic prostacyclin. Br. ]. Pharmacol, 85, 643p... 

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