Prostacyclin receptors agonists

M. Takasuka, M. Kishi, M. Yamakawa, FTIR spectral study of intramolecular hydrogen bonding in thromboxane A2 receptor agonist (U-46619), prostaglandin (PG)E2, PGD2, PGF2.alpha., prostacyclin receptor agonist (carbacyclin) and their related compounds in dilute carbon tetrachloride solution Structure-activity relationships, J. Med. Chem. 37 (1994) 47. 

Hoch M, Darpo B, Remenova T et al (2014) A thorough QT study in the context of an uptitration regimen with selexipag, a selective oral prostacyclin receptor agonist. Drug Des Devel Ther 9 175-185... 

C.S. Chang, M. Negishi, T. Nakano, Y. Morizawa, Y. Matsumura, A. Ichikawa, 7,7-Difluoroprostacyclin derivative, AFP-07, a highly selective and potent agonist for the prostacyclin receptor. Prostaglandins 53 (1997) 83-90. 

Cibenzoline [ban, inn] (clfenllne [usan]) is a cyclopropyl-imidazole derivative, a hypoglycaemic acting as a pancreatic p-cell potassium-channel blocker. It also is a cardiac depressant and can be used as an ANTIARRHYTHMIC (class la with some class III and class IV properties), cicaprost [inn] is a prostacyclin analogue, an (IP) prostanoid receptor agonist, with platelet aggregation INHIBITOR and vasodilator activity, ciclacillin [ban, inn.ian] (cyclacillin [usan]) is a semisynthetic (penicillin) ANTIBIOTIC. It can be used as an ANTIBACTERIAL to treat certain infections. 

U 53217 Flolan ) is a natural prostaglandin (prostacyclin) present in the walls of blood vessels. It is an (IP) prostanoid RECEPTOR agonist. When administered therapeutically by intravenous infusion, it has PLATELET AGGREGATION INHIBITOR and ANTITHROMBOTIC activity, and is a potent VASODILATOR. 

Tapazole methimazole. taprostene [inn] (CG 4203) is a prostaglandin and synthetic analogue of prostacyclin (PGI2). It is a prostanoid RECEPTOR AGONIST that iS a PLATELET AGGREGATION INHIBITOR and claimed to be cardioprotective. 

In order to determine the physiological roles of various prostanoid receptors a number of knockout mice have been developed [18]. These studies indicate that prostacyclin receptors are involved in at least some types of pain responses, EP3 receptors are involved in the development of fever, EP2 and EP4 function in allergy and bone resorption, and EPl receptors are involved in chemically induced colon cancer. The availability of cloned prostanoid receptors provides a rational and the appropriate technology to search for receptor agonists and antagonists that might provide some specificity beyond the currently available COX inhibitors, which prevent broadly the synthesis of all PGs. 

The Schollkopf reaction has found considerable use in the preparation of eompounds containing 4,5-disubstituted oxazoles. 4,5-Disubstituted oxazole 30 served as a key intermediate in DuPont s synthesis of benzamidine 31, a Factor Xa inhibitor. The Sehdllkopf reaetion has similarly found use in the preparation of 4,5-disubstituted oxazoles for P3-adrenergie receptor agonist," Fe(II)-form-selective E. coli methionine aminopeptidase inhibitor," and prostacyclin receptor antagonist programs. The robustness of this synthetic methodology has also led to the use of the Schollkopf oxazole synthesis as a test reaction in the evaluation of a number of flow-reactor systems. ... 

Prostacyclin receptors (IP) mediate the effects of prostacyclin, although this is the least selective of the prostanoid receptors. Agonists, in order of relative binding affinity strength, include PGE PGF, = PGD. The effects of prostacyclin are numerous (e.g. vasodilator, hyperalgesic, inhibits platelet aggregation). The IP receptor is most closely related in sequence to the DP receptor, and most evidence indicates that IP signals via a stimulation of cAMP (Breyer et al, 2001 Ullrich et al, 2001). 

All agonist-induced platelet responses, including shape change, aggregation, adhesion and secretion are inhibited by increased intracellular cAMP levels (1). Synthesis of cAMP in the platelet is stimulated by the binding of mediators, such as prostacyclin and adenosine, to cell surfece receptors ( ) coupled to GTP binding proteins (Fig. 1). 

Binding of agonists to receptors linked to Gs proteins increases cAMP production. Such receptors include those for catecholamines (beta), dopamine (Dj), glucagon, histamine (H2), prostacyclin, and some serotonin subtypes.-... 

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