Macitentan-d4

Macitentan-d4 is intended for use as an internal standard for the quantification of macitentan (Cay-23304) by GC- or LC-MS. 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-1,1,2,2-d4]-4-pyrimidinyl]-N'-propyl-sulfamide. CAS Number: 1258428-05-5. Synonyms: ACT-064992-d4. Molecular Formula: C19H16Br2D4N6O4S. Formula Weight: 592.3. Purity: >99% deuterated forms (d1-d4). Formulation: (Request formulation change), A solid. Solubility: DMSO: slightly soluble, Methanol: slightly, heated. SMILES: BrC1=CC=C(C2=C(OC([2H])([2H])C([2H])([2H])OC3=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)/i8D2,9D2. InChi Key: JGCMEBMXRHSZKX-LZMSFWOYSA-N.