Ambrisentan

• CAT Number: A001124
• CAS Number: 177036-94-1
• Molecular Formula: C22H22N2O4
• Molecular Weight: 378.42
• Purity: ≥95%
• Target: Dopamine Receptor
• Solubility: Soluble in DMSO > 10 mM
• Storage: 3 years -20C powder
• InChI: InChI=1S/C22H22N2O4/c1-15-14-16(2)24-21(23-15)28-19(20(25)26)22(27-3,17-10-6-4-7-11-17)18-12-8-5-9-13-18/h4-14,19H,1-3H3,(H,25,26)/t19-/m1/s1
• InChIKey: OUJTZYPIHDYQMC-LJQANCHMSA-N
• SMILES: O=C(O)[C@@H](OC1=NC(C)=CC(C)=N1)C(C2=CC=CC=C2)(OC)C3=CC=CC=C3

Ambrisentan, also known as BSF-208075 and LU-208075, is a drug indicated for use in the treatment of pulmonary hypertension. Ambrisentan, which relaxes those muscles, is an endothelin receptor antagonist, and is selective for the type A endothelin receptor (ETA). Ambrisentan significantly improved exercise capacity (6-minute walk distance) compared with placebo in two double-blind, multicenter trials (ARIES-1 and ARIES-2). Ambrisentan was approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency, and designated an orphan drug, for the treatment of pulmonary hypertension.

Reference

1:Clinical and hemodynamic improvements after adding ambrisentan to background PDE5i therapy in patients with pulmonary arterial hypertension exhibiting a suboptimal therapeutic response (ATHENA-1). Shapiro S, Torres F, Feldman J, Keogh A, Allard M, Blair C, Gillies H, Tislow J, Oudiz RJ.Respir Med. 2017 May;126:84-92. doi: 10.1016/j.rmed.2017.03.025. Epub 2017 Mar 29. PMID: 28427554 2:Ambrisentan: a review of its use in pulmonary arterial hypertension. Rivera-Lebron BN, Risbano MG.Ther Adv Respir Dis. 2017 Apr 1:1753465817696040. doi: 10.1177/1753465817696040. [Epub ahead of print] PMID: 28425346 3:Functional estimation of endothelin-1 receptor antagonism by bosentan, macitentan and ambrisentan in human pulmonary and radial arteries in vitro. Angus JA, Soeding PF, Hughes RJA, Wright CE.Eur J Pharmacol. 2017 Jun 5;804:111-116. doi: 10.1016/j.ejphar.2017.03.014. Epub 2017 Mar 11. PMID: 28300593 4:Combined approach using capillary electrophoresis, NMR and molecular modeling for ambrisentan related substances analysis: Investigation of intermolecular affinities, complexation and separation mechanism. Pasquini B, Melani F, Caprini C, Del Bubba M, Pinzauti S, Orlandini S, Furlanetto S.J Pharm Biomed Anal. 2017 Jan 21. pii: S0731-7085(17)30175-9. doi: 10.1016/j.jpba.2017.01.038. [Epub ahead of print] PMID: 28131522 5:Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial. Coghlan JG, Galiè N, Barberà JA, Frost AE, Ghofrani HA, Hoeper MM, Kuwana M, McLaughlin VV, Peacock AJ, Simonneau G, Vachiéry JL, Blair C, Gillies H, Miller KL, Harris JH, Langley J, Rubin LJ; AMBITION investigators..Ann Rheum Dis. 2016 Dec 30. pii: annrheumdis-2016-210236. doi: 10.1136/annrheumdis-2016-210236. [Epub ahead of print] PMID: 28039187 Free Article6:Initial combination therapy with ambrisentan and tadalafil and mortality in patients with pulmonary arterial hypertension: a secondary analysis of the results from the randomised, controlled AMBITION study. Hoeper MM, McLaughlin VV, Barberá JA, Frost AE, Ghofrani HA, Peacock AJ, Simonneau G, Rosenkranz S, Oudiz RJ, White RJ, Miller KL, Langley J, Harris JHN, Blair C, Rubin LJ, Vachiery JL.Lancet Respir Med. 2016 Nov;4(11):894-901. doi: 10.1016/S2213-2600(16)30307-1. Epub 2016 Oct 11. PMID: 27745818 7:Evaluation of efficacy, safety and tolerability of Ambrisentan in Chinese adults with pulmonary arterial hypertension: a prospective open label cohort study. Huo Y, Jing ZC, Zeng XF, Liu JM, Yu ZX, Zhang GC, Li Y, Wang Y, Ji QS, Zhu P, Wu BX, Zheng Y, Wang PP, Li J.BMC Cardiovasc Disord. 2016 Oct 22;16(1):201. PMID: 27770771 Free PMC Article8:Antifibrotic effects of ambrisentan, an endothelin-A receptor antagonist, in a non-alcoholic steatohepatitis mouse model. Okamoto T, Koda M, Miyoshi K, Onoyama T, Kishina M, Matono T, Sugihara T, Hosho K, Okano J, Isomoto H, Murawaki Y.World J Hepatol. 2016 Aug 8;8(22):933-41. doi: 10.4254/wjh.v8.i22.933. PMID: 27574547 Free PMC Article9:Ambrisentan response in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) – A subgroup analysis of the ARIES-E clinical trial. Fischer A, Denton CP, Matucci-Cerinic M, Gillies H, Blair C, Tislow J, Nathan SD.Respir Med. 2016 Aug;117:254-63. doi: 10.1016/j.rmed.2016.06.018. Epub 2016 Jun 29. PMID: 27492539 10:Enantioseparation and impurity determination of ambrisentan using cyclodextrin-modified micellar electrokinetic chromatography: Visualizing the design space within quality by design framework. Orlandini S, Pasquini B, Caprini C, Del Bubba M, Douša M, Pinzauti S, Furlanetto S.J Chromatogr A. 2016 Oct 7;1467:363-371. doi: 10.1016/j.chroma.2016.06.082. Epub 2016 Jul 1. PMID: 27425759