Darusentan

• CAT Number: M128036
• CAS Number: 171714-84-4
• Molecular Formula: C22H22N2O6
• Molecular Weight: 410.426
• Purity: ≥95%
• Storage: -20°C
• IUPAC Name: (2S)-2-(4,6-dimethoxypyrimidin-2-yl)oxy-3-methoxy-3,3-diphenylpropanoic acid
• InChI: InChI=1S/C22H22N2O6/c1-27-17-14-18(28-2)24-21(23-17)30-19(20(25)26)22(29-3,15-10-6-4-7-11-15)16-12-8-5-9-13-16/h4-14,19H,1-3H3,(H,25,26)/t19-/m1/s1
• InChIKey: FEJVSJIALLTFRP-LJQANCHMSA-N
• SMILES: COC1=CC(=NC(=N1)OC(C(=O)O)C(C2=CC=CC=C2)(C3=CC=CC=C3)OC)OC

Darusentan, also known as Lu 135252 and HMR-4005, is anEndothelin-1 receptor A inhibitor for the potential treatment of uncontrolled hypertension and cancer. Darusentan is a potent inhibitor of endothelin signaling and function in both large and small arteries. Endothelin ETA receptor blockade with darusentan increases sodium and potassium excretion in aging rats.

Reference

1:Endothelin-1 receptor A blocker darusentan decreases hepatic changes and improves liver repopulation after cell transplantation in rats. Bahde R, Kapoor S, Viswanathan P, Spiegel HU, Gupta S.Hepatology. 2014 Mar;59(3):1107-17. doi: 10.1002/hep.26766. Epub 2014 Jan 16. PMID: 24114775 Free PMC Article2:Physiology of endothelin in producing myocardial perfusion heterogeneity: a mechanistic study using darusentan and positron emission tomography. Johnson NP, Gould KL.J Nucl Cardiol. 2013 Oct;20(5):835-44. doi: 10.1007/s12350-013-9756-5. Epub 2013 Jul 11. PMID: 23842710 Free PMC Article3:Determination of darusentan enantiomers in rat plasma by enantioselective liquid chromatography with tandem mass spectrometry using cellulose-based chiral stationary phase. Gu J, Shi X, Du Y, Wang W, Du X, Zhang L.J Sep Sci. 2011 Oct;34(19):2680-5. doi: 10.1002/jssc.201100433. Epub 2011 Aug 8. PMID: 21823235 4:Divergent results using clinic and ambulatory blood pressures: report of a darusentan-resistant hypertension trial. Bakris GL, Lindholm LH, Black HR, Krum H, Linas S, Linseman JV, Arterburn S, Sager P, Weber M.Hypertension. 2010 Nov;56(5):824-30. doi: 10.1161/HYPERTENSIONAHA.110.156976. Epub 2010 Oct 4. PMID: 20921430 Free Article5:Darusentan is a potent inhibitor of endothelin signaling and function in both large and small arteries. Liang F, Glascock CB, Schafer DL, Sandoval J, Cable L, Melvin L Jr, Hartman JC, Pitts KR.Can J Physiol Pharmacol. 2010 Aug;88(8):840-9. doi: 10.1139/Y10-061. PMID: 20725142 Free Article6:Darusentan, a selective endothelin A receptor antagonist, for the oral treatment of resistant hypertension. Enseleit F, Lüscher TF, Ruschitzka F.Ther Adv Cardiovasc Dis. 2010 Aug;4(4):231-40. doi: 10.1177/1753944710373785. Epub 2010 Jul 26. Review. PMID: 20660536 7:Evaluation of the endothelin receptor antagonists ambrisentan, darusentan, bosentan, and sitaxsentan as substrates and inhibitors of hepatobiliary transporters in sandwich-cultured human hepatocytes. Hartman JC, Brouwer K, Mandagere A, Melvin L, Gorczynski R.Can J Physiol Pharmacol. 2010 Jun;88(6):682-91. doi: 10.1139/Y10-060. PMID: 20628435 Free Article8:Darusentan in resistant hypertension: lost in translation. Enseleit F, Ruschitzka F.Curr Hypertens Rep. 2010 Feb;12(1):1-3. doi: 10.1007/s11906-009-0081-y. No abstract available. PMID: 20425150 9:Dietary alkalinization and darusentan for prevention of decline in glomerular filtration rate in rats fed a casein diet. Bakker SJ, Gans RO, Navis G.Kidney Int. 2008 Dec;74(12):1625-6; author reply 1626-7. doi: 10.1038/ki.2008.434. No abstract available. PMID: 19034308 Free Article10:Darusentan: a new perspective for treatment of resistant hypertension? Enseleit F, Lüscher TF, Ruschitzka F.Expert Opin Investig Drugs. 2008 Aug;17(8):1255-63. doi: 10.1517/13543784.17.8.1255 . Review. PMID: 18616421