Macitentan

Macitentan is a dual antagonist of the endothelin (ET) receptors type A and B (IC50s = 0.5 and 391 nM in a radioligand binding assay using recombinant ETA and ETB, respectively). Macitentan inhibits intracellular Ca2+ increases induced by the endothelin isoform ET-1 in human pulmonary arterial smooth muscle cells (HPASMCs, IC50 = 0.9 nM), contractions of isolated rat aortic rings (pA2 = 7.6 for ETA), and sarafotoxin S6c-induced contractions of isolated rat tracheal rings (pA2 = 5.9 for ETB). Macitentan increases plasma ET-1 concentrations in normotensive rats and decreases mean arterial blood pressure in DOCA-salt hypertensive rats (ED50 = 1 mg/kg). Oral administration (30 mg/kg per day) prevents development of pulmonary hypertension and right ventricle hypertrophy in a rat model of hypertension induced by monocrotaline (Cay-16666). It also decreases the number of vascular and tubule-interstitial lesions and amount of glomerular damage in a rat model of diabetes induced by streptozotocin (Cay-13104). Formulations containing macitentan have been used for the treatment of pulmonary arterial hypertension.Formal Name: N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-propyl-sulfamide. CAS Number: 441798-33-0. Synonyms: ACT-064992, Actelion-1. Molecular Formula: C19H20Br2N6O4S. Formula Weight: 588.3. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 33 mg/ml, DMF:PBS (pH 7.2), (1:7): 0.12 mg/ml, DMSO: 33 mg/ml. lambdamax: 215 nm. SMILES: BrC1=CC=C(C2=C(OCCOC3=NC=C(Br)C=N3)N=CN=C2NS(NCCC)(=O)=O)C=C1. InChi Code: InChI=1S/C19H20Br2N6O4S/c1-2-7-26-32(28,29)27-17-16(13-3-5-14(20)6-4-13)18(25-12-24-17)30-8-9-31-19-22-10-15(21)11-23-19/h3-6,10-12,26H,2,7-9H2,1H3,(H,24,25,27). InChi Key: JGCMEBMXRHSZKX-UHFFFAOYSA-N.