Macitentan

Base Information

• Chemical Name: Macitentan
• CAS No.: 441798-33-0
• Molecular Formula: C19H20Br2N6O4S
• Molecular Weight: 588.27
• European Community (EC) Number: 810-007-8
• UNII: Z9K9Y9WMVL
• ChEMBL ID: CHEMBL2103873
• DSSTox Substance ID: DTXSID50196063
• Metabolomics Workbench ID: 152011
• NCI Thesaurus Code: C87728
• Nikkaji Number: J2.832.870B
• Pharos Ligand ID: RCSNMFR4CQSF
• RXCUI: 1442132
• Wikidata: Q6724151
• Wikipedia: Macitentan
• Mol file: 441798-33-0.mol

Synonyms:ACT 064992;ACT-064992;ACT064992;Actelion-1;macitentan;N-(5-(4-bromophenyl)-6-(2-(5-bromopyrimidin-2-yloxy)ethoxy)pyrimidin-4-yl)-N'-propylaminosulfonamide;opsumit

Chemical Property of Macitentan

Chemical Property:

• Boiling Point: 692.397 °C at 760 mmHg
• PKA: 4.99±0.50(Predicted)
• Flash Point: 372.548 °C
• PSA: 159.84000
• Density: 1.675 g/cm³
• LogP: 5.37240
• Solubility.: ≥24.4 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
• XLogP3: 3.7
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 11
• Exact Mass: 587.96130
• Heavy Atom Count: 32
• Complexity: 642

Purity/Quality:

99% ^*data from raw suppliers

Macitentan ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Pulmonary Arterial Hypertension Agents
• Canonical SMILES: CCCNS(=O)(=O)NC1=C(C(=NC=N1)OCCOC2=NC=C(C=N2)Br)C3=CC=C(C=C3)Br
• Recent ClinicalTrials: Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
• Recent EU Clinical Trials: A Prospective, Open-label, Platform Study for Long-term Follow-up of Participants Using Study Intervention in Pulmonary Hypertension Parent Studies
• Recent NIPH Clinical Trials: A Study of Macitentan in Japanese Pediatric Participants with Pulmonary Arterial Hypertension
• Description: 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.
• Uses: 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.
• Clinical Use: Endothelin receptor antagonist: Treatment of pulmonary arterial hypertension
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration reduced by rifampicin - avoid. Antidepressants: avoid with St John’s wort. Antiepileptics: avoid with carbamazepine, fosphenytoin and phenytoin.