Macitentan , ≥97% , 441798-33-0
Synonym(s):
ACT 064992;ACT064992;ACT-064992;Actelion-1;N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N′-propyl-sulfamide
CAS NO.：441798-33-0
Empirical Formula: C19H20Br2N6O4S
Molecular Weight: 588.27
MDL number: MFCD17167076
EINECS: 1308068-626-2
| Pack Size | Price | Stock | Quantity |
| 5MG | RMB159.20 | In Stock |
|
| 1g | RMB184.80 | In Stock |
|
| 25MG | RMB479.20 | In Stock |
|
| 100MG | RMB1359.20 | In Stock |
|
| others | Enquire |
PRODUCT Properties
| Boiling point: | 692.4±65.0 °C(Predicted) |
| Density | 1.675 |
| storage temp. | Store at -20°C |
| solubility | ≥24.4 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
| form | solid |
| pka | 4.99±0.50(Predicted) |
| color | White to off-white |
| InChI | 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) |
| InChIKey | JGCMEBMXRHSZKX-UHFFFAOYSA-N |
| SMILES | S(NC1C(C2=CC=C(Br)C=C2)=C(OCCOC2=NC=C(Br)C=N2)N=CN=1)(NCCC)(=O)=O |
Description and Uses
Macitentan (also known as ACT-064992) received US FDA approval in October 2013 for the treatment of pulmonary arterial hypertension (PAH) (WHO group I) to delay disease progression. Treatment options include phosphodiesterase type 5 inhibitors, prostacyclins, and the endothelin receptor antagonists bosentan and ambrisentan. Macitentan was discovered through SAR studies starting with the bosentan structure with three main goals: (1) to increase potency for both endothelin receptor A and B (ETA and ETB) subtypes; (2) to improve tissue distribution to reach the target receptors; and (3) to avoid bile salt transport inhibition. Starting with the bosentan sulfonamido-pyrimidinyl central core, potency was increased 10-fold via incorporation of a bromopyrimidinyl ethylene glycol ether, as found in the clinical endothelin antagonist, T-0201. An aryl ether in bosentan was replaced with the bromophenyl group in macitentan, and a substituent on the 2-position of the central pyrimidine was replaced with hydrogen. Several sulfonamides and alkyl sulfamates were explored, with the propylsulfamate providing the best combination of in vitro potency, especially for ETB antagonism, and in vivo efficacy.
Macitentan is an endothelin receptor antagonist that is used in the therapy of pulmonary arterial hypertension (PAH). It also reduced hospitalization for PAH. Macitentan was approved for PAH by the United States Food and Drug Administration (FDA) in 2013. Macitentan has been associated with a low rate of serum enzyme elevations during therapy, but has yet to be implicated in cases of clinically apparent acute liver injury.
