Prostacyclin (PGI2) is a potent vasorelaxant and inhibitor of platelet aggregation. It mediates its actions by binding to a specific G protein-coupled receptor, the IP receptor, on the surface of endothelial cells, arterial smooth muscle, and platelets.The IP receptor also participates in signal transduction of the pain response, cardioprotection, and inflammation.MRE-269 is the active form of the prodrug NS-304. It is a potent and selective agonist for the human IP receptor with a Ki value of 20 nM. In contrast to PGI2, which has a half-life of 30 seconds to a few minutes in vivo, plasma concentrations of MRE-269 remain near peak levels for more than eight hours in rats and dogs.Unlike the PGI2 analogues, beraprost and iloprost, MRE-269 lacks high affinity for the EP3 receptor.As a result, MRE-269 induces vasodilation equally in large and small pulmonary arteries, whereas vasodilation of small arteries by beraprost and iloprost is reduced via EP3-mediated vasoconstriction.Aristoff, P.A., Johnson, P.D., and Harrison, A.W. Synthesis of 9-substituted carbacyclin analogues. J Org Chem 48 5341-5348 (1983). Murata, T., Ushikubi, F., Matsuoka, T., et al. Altered pain perception and inflammatory response in mice lacking prostacyclin receptor. Nature 388 678-682 (1997). Cheng, Y., Austin, S.C., Rocca, B., et al. Role of prostacyclin in the cardiovascular response to thromboxane A2. Science 296 539-541 (2002). Cui, Y., Kataoka, Y., Satoh, T., et al. Protective effect of prostaglandin I2 analogs on ischemic delayed neuronal damage in gerbils. Biochem Biophys Res Commun 265 301-304 (1999). McLaughlin, V.V., Genthner, D.E., Panella, M.M., et al. Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N Engl J Med 338 273-277 (1998). Kuwano, K., Hashino, A., Asaki, T., et al. 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther 322(3) 1181-1188 (2007).Kuwano, K., Hashino, A., Noda, K., et al. A long-acting and highly selective prostacyclin receptor agonist prodrug, 2-{4-[5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide (NS-304), ameliorates rat pulmonary hypertension with unique relaxant responses of its active form, {4-[5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}acetic acid (MRE-269), on rat pulmonary artery. J Pharmacol Exp Ther 326(3) 691-699 (2008).

June 21, 2017

prudect name : Prostacyclin (PGI2) is a potent vasorelaxant and inhibitor of platelet aggregation. It mediates its actions by binding to a specific G protein-coupled receptor, the IP receptor, on the surface of endothelial cells, arterial smooth muscle, and platelets.The IP receptor also participates in signal transduction of the pain response, cardioprotection, and inflammation.MRE-269 is the active form of the prodrug NS-304. It is a potent and selective agonist for the human IP receptor with a Ki value of 20 nM. In contrast to PGI2, which has a half-life of 30 seconds to a few minutes in vivo, plasma concentrations of MRE-269 remain near peak levels for more than eight hours in rats and dogs.Unlike the PGI2 analogues, beraprost and iloprost, MRE-269 lacks high affinity for the EP3 receptor.As a result, MRE-269 induces vasodilation equally in large and small pulmonary arteries, whereas vasodilation of small arteries by beraprost and iloprost is reduced via EP3-mediated vasoconstriction.Aristoff, P.A., Johnson, P.D., and Harrison, A.W. Synthesis of 9-substituted carbacyclin analogues. J Org Chem 48 5341-5348 (1983). Murata, T., Ushikubi, F., Matsuoka, T., et al. Altered pain perception and inflammatory response in mice lacking prostacyclin receptor. Nature 388 678-682 (1997). Cheng, Y., Austin, S.C., Rocca, B., et al. Role of prostacyclin in the cardiovascular response to thromboxane A2. Science 296 539-541 (2002). Cui, Y., Kataoka, Y., Satoh, T., et al. Protective effect of prostaglandin I2 analogs on ischemic delayed neuronal damage in gerbils. Biochem Biophys Res Commun 265 301-304 (1999). McLaughlin, V.V., Genthner, D.E., Panella, M.M., et al. Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N Engl J Med 338 273-277 (1998). Kuwano, K., Hashino, A., Asaki, T., et al. 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther 322(3) 1181-1188 (2007).Kuwano, K., Hashino, A., Noda, K., et al. A long-acting and highly selective prostacyclin receptor agonist prodrug, 2-{4-[5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide (NS-304), ameliorates rat pulmonary hypertension with unique relaxant responses of its active form, {4-[5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}acetic acid (MRE-269), on rat pulmonary artery. J Pharmacol Exp Ther 326(3) 691-699 (2008).
MRE-269

Synonyms: CAS NO: 475085-57-5Molecular Formula: C25H29N3O3Molecular Weight: 419.5Purity: 98% minSolubility: In DMSOStorage: −20°C


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References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/18528812