Tezosentan

• CAT Number: R053967
• CAS Number: 180384-57-0
• Molecular Formula: C27H27N9O6S
• Molecular Weight: 605.63
• Purity: ≥95%
• Synonyms: N-[6-(2-Hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2H-tetrazol-5-yl)-4-pyridinyl]-4-pyrimidinyl]-5-(1-methylethyl)-2-pyridinesulfonamide
• Target: ETA and ETB receptor antagonist
• Storage: 3 years -20C powder
• IUPAC Name: N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2H-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-5-propan-2-ylpyridine-2-sulfonamide
• InChI: InChI=1S/C27H27N9O6S/c1-16(2)18-8-9-22(29-15-18)43(38,39)34-26-23(42-21-7-5-4-6-20(21)40-3)27(41-13-12-37)31-24(30-26)17-10-11-28-19(14-17)25-32-35-36-33-25/h4-11,14-16,37H,12-13H2,1-3H3,(H,30,31,34)(H,32,33,35,36)
• InChIKey: TUYWTLTWNJOZNY-UHFFFAOYSA-N
• SMILES: CC(C)C1=CN=C(C=C1)S(=O)(=O)NC2=C(C(=NC(=N2)C3=CC(=NC=C3)C4=NNN=N4)OCCO)OC5=CC=CC=C5OC

Tezosentan is a non-selective ETA and ETB receptor antagonist. It acts as a vasodilator and was designed as a therapy for patients with acute heart failure. Tezosentan inhibits uptake of proinflammatory endothelin-1 in stenotic aortic valves. Tezosentan increases nitric oxide signaling via enhanced hydrogen peroxide generation in lambs with surgically induced acute increases in pulmonary blood flow. Tezosentan reduces the renal injury induced by abdominal aortic ischemia-reperfusion in rats.

Reference

1:Measurement of troponin and natriuretic peptides shortly after admission in patients with heart failure-does it add useful prognostic information? An analysis of the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Studies (VERITAS). Cleland JG, Teerlink JR, Davison BA, Shoaib A, Metra M, Senger S, Milo O, Cotter G, Bourge RC, Parker JD, Jondeau G, Krum H, O/’Connor CM, Torre-Amione G, van Veldhuisen DJ, McMurray JJ; VERITAS Investigators..Eur J Heart Fail. 2017 Mar 10. doi: 10.1002/ejhf.786. [Epub ahead of print] PMID: 28296139 2:Cardiopulmonary bypass is associated with altered vascular reactivity of isolated pulmonary artery in a porcine model: therapeutic potential of inhaled tezosentan. Mommerot A, Denault AY, Dupuis J, Carrier M, Perrault LP.J Cardiothorac Vasc Anesth. 2014 Jun;28(3):698-708. doi: 10.1053/j.jvca.2013.12.013. PMID: 24917060 3:Tezosentan and right ventricular failure in patients with pulmonary hypertension undergoing cardiac surgery: the TACTICS trial. Denault AY, Pearl RG, Michler RE, Rao V, Tsui SS, Seitelberger R, Cromie M, Lindberg E, D/’Armini AM.J Cardiothorac Vasc Anesth. 2013 Dec;27(6):1212-7. doi: 10.1053/j.jvca.2013.01.023. Epub 2013 Mar 21. PMID: 23523254 4:Tezosentan increases nitric oxide signaling via enhanced hydrogen peroxide generation in lambs with surgically induced acute increases in pulmonary blood flow. Kumar S, Oishi PE, Rafikov R, Aggarwal S, Hou Y, Datar SA, Sharma S, Azakie A, Fineman JR, Black SM.J Cell Biochem. 2013 Feb;114(2):435-47. doi: 10.1002/jcb.24383. PMID: 22961736 Free PMC Article5:Tezosentan inhibits uptake of proinflammatory endothelin-1 in stenotic aortic valves. Leskelä HV, Vuolteenaho O, Koivula MK, Taskinen P, Ruskoaho H, Peltonen T, Lehenkari P.J Heart Valve Dis. 2012 Jan;21(1):23-30. PMID: 22474738 6:Haemodynamic and neuroendocrine effects of tezosentan in chronic experimental pulmonary hypertension. Lourenço AP, Vasques-Nóvoa F, Oliveira-Pinto J, Fontoura D, Roncon-Albuquerque R Jr, Leite-Moreira AF.Intensive Care Med. 2012 Jun;38(6):1050-60. doi: 10.1007/s00134-012-2484-5. Epub 2012 Feb 14. PMID: 22349420 7:Effect of the endothelin receptor antagonist tezosentan on alpha-naphthylthiourea-induced lung injury in rats. Atalay F, Yurdakan G, Yilmaz-Sipahi E.Kaohsiung J Med Sci. 2012 Feb;28(2):72-8. doi: 10.1016/j.kjms.2011.10.019. Epub 2012 Jan 14. PMID: 22313533 Free Article8:Hemodynamics and pharmacokinetics of tezosentan, a dual endothelin receptor antagonist, in patients with cirrhosis. Lebrec D, Bosch J, Jalan R, Dudley FJ, Jessic R, Moreau R, Garcia-Pagan JC, Mookerjee RP, Chiossi E, Van Giersbergen PL, Kusic-Pajic A, Dingemanse J.Eur J Clin Pharmacol. 2012 May;68(5):533-41. doi: 10.1007/s00228-011-1157-6. Epub 2011 Nov 20. PMID: 22101624 9:Dual endothelin receptor blockade with tezosentan markedly attenuates hypoxia-induced pulmonary vasoconstriction in a porcine model. Hedelin P, Kylhammar D, Rådegran G.Acta Physiol (Oxf). 2012 Mar;204(3):419-34. doi: 10.1111/j.1748-1716.2011.02339.x. Epub 2011 Aug 12. PMID: 21726419 10:Effect of clazosentan, a selective endothelin A receptor antagonist, and tezosentan, a dual endothelin A/B antagonist, on pulsatile shear stress induced constriction of the iliac in the anaesthetized pig. Ruane-O/’Hora T, Rae MG, Markos F.Clin Exp Pharmacol Physiol. 2011 Aug;38(8):515-20. doi: 10.1111/j.1440-1681.2011.05540.x. PMID: 21575033