New developments on thromboxane and prostacyclin modulators part I: thromboxane modulators.
The pathogenesis of numerous cardiovascular, pulmonary, inflammatory, and thromboembolic diseases can be related to arachidonic acid (AA) metabolites. One of these bioactive metabolites of particular importance is thromboxane A(2) (TXA(2)). It is produced by the action of thromboxane synthase on the prostaglandin endoperoxide H(2)(PGH(2)), which results from the enzymatic degradation of AA by the cyclooxygenases. TXA(2) is a potent inducer of platelet aggregation, vasoconstriction and bronchoconstriction. It is involved in a series of major pathophysiological states such as asthma, myocardial ischemia, pulmonary hypertension, and thromboembolic disorders. Therefore, TXA(2) receptor antagonists, thromboxane synthase inhibitors and drugs combining both properties have been developed by several pharmaceutical companies since the early 1980s. Several compounds have been launched on the market and others are under clinical evaluation. Moreover, the recent literature reported the interest of thromboxane modulators, which combine another pharmacological activity such as, platelet activating factor antagonism, angiotensin II antagonism, or 5-lipoxygenase inhibition. In this review, we will propose a description of the recently described thromboxane modulators of major interest from both a pharmacological and a chemical point of view.
Dogné
Jean-Michel
JM
Natural and Synthetic Drug Research Center, Medicinal Chemistry, University of Liège, 1, av. de l'Hôpital, B-4000 Liège, Belgium. Jean-Michel.Dogne@ulg.ac.be
de Leval
Xavier
X
Hanson
Julien
J
Frederich
Michel
M
Lambermont
Bernard
B
Ghuysen
Alexandre
A
Casini
Angela
A
Masereel
Bernard
B
Ruan
Ke-He
KH
Pirotte
Bernard
B
Kolh
Philippe
P
D016718:Arachidonic Acid / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D044262:Prostaglandin H2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013931:Thromboxanes; D016718:Arachidonic Acid; D044262:Prostaglandin H2; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase