title: New developments on thromboxane and prostacyclin modulators part I: thromboxane modulators.
abstract: 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.
authors.affiliation: 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
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dogné
authors.forename: Xavier
authors.initials: X
authors.lastname: de Leval
authors.forename: Julien
authors.initials: J
authors.lastname: Hanson
authors.forename: Michel
authors.initials: M
authors.lastname: Frederich
authors.forename: Bernard
authors.initials: B
authors.lastname: Lambermont
authors.forename: Alexandre
authors.initials: A
authors.lastname: Ghuysen
authors.forename: Angela
authors.initials: A
authors.lastname: Casini
authors.forename: Bernard
authors.initials: B
authors.lastname: Masereel
authors.forename: Ke-He
authors.initials: KH
authors.lastname: Ruan
authors.forename: Bernard
authors.initials: B
authors.lastname: Pirotte
authors.forename: Philippe
authors.initials: P
authors.lastname: Kolh
mesh_terms: 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
chemical_list: 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