179401-12-8

Basic information

• Product Name: Pyrimidine, 4,6-dichloro-5-(2-methoxyphenoxy)-2-(methylthio)-
• CAS NO: 179401-12-8
• Molecular Formula: C12H10Cl2N2O2S
• Molecular Weight: 317.196
• Mol File: 179401-12-8.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: Pyrimidine, 4,6-dichloro-5-(2-methoxyphenoxy)-2-(methylthio)-(CAS DataBase Reference)
• NIST Chemistry Reference: Pyrimidine, 4,6-dichloro-5-(2-methoxyphenoxy)-2-(methylthio)-(179401-12-8)
• EPA Substance Registry System: Pyrimidine, 4,6-dichloro-5-(2-methoxyphenoxy)-2-(methylthio)-(179401-12-8)

Safety Data

• Hazardous Substances Data: 179401-12-8(Hazardous Substances Data)

Upstream product

• 329924-14-3 5-(o-methoxyphenoxy)-2-thioxo-dihydro-pyrimidine-4,6-dione 
• 1878-85-9 (2-methoxyphenoxy)acetic acid 
• 150726-89-9 (2-methoxyphenoxy)-malonic acid dimethyl ester 
• 20730-58-9 2-(2-Methoxyphenoxy)propanedioic acid diethyl ester 
• 184779-24-6 4,6-dihydroxy-5-(2-methoxyphenoxy)-2-methylthiopyrimidine 

Downstream Products

• 1393813-55-2 C₂₇H₂₉BrN₆O₈S 
• 1393813-68-7 N-(6-(2-hydroxyethoxy)-2-(2-methoxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl)-N'-benzylsulfamide 
• 441797-10-0 N-(6-(2-hydroxyethoxy)-2-methylsulfonyl-5-(2-methoxyphenoxy)pyrimidin-4-yl)-N'-benzylsulfamide 
• 441797-09-7 N-(6-(2-hydroxyethoxy)-2-methylsulfanyl-5-(2-methoxyphenoxy)pyrimidin-4-yl)-N'-benzylsulfamide 
• 441797-86-0 N-(6-chloro-2-methylsulfanyl-5-(2-methoxyphenoxy)pyrimidin-4-yl)-N'-benzylsulfamide 
• 184779-25-7 4-tert-butyl-N-[6-chloro-5-(o-methoxyphenoxy)-2-methylsulfanyl-pyrimidin-4-yl]-benzenesulfonamide 
• 184779-27-9 N-{6-[2-(5-bromopyrimidin-2-yloxy)ethoxy]-5-(2-methoxy-phenoxy)-2-methylsulfonylpyrimidin-4-yl}-4-tert-butylbenzenesulfonamide 
• 184778-95-8 N-{6-[2-(5-bromopyrimidin-2-yloxy)ethoxy]-5-(2-methoxyphenoxy)-2-methylthiopyrimidin-4-yl}-4-tert-butylbenzene-sulfonamide 
• 184779-26-8 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-methylthiopyrimidin-4-yl]-benzenesulfonamide 

Relevant articles and documents

The discovery of N -[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy] ethoxy]-4-pyrimidinyl]- N ′-propylsulfamide (macitentan), an orally active, potent dual endothelin receptor antagonist

Starting from the structure of bosentan (1), we embarked on a medicinal chemistry program aiming at the identification of novel potent dual endothelin receptor antagonists with high oral efficacy. This led to the discovery of a novel series of alkyl sulfamide substituted pyrimidines. Among these, compound 17 (macitentan, ACT-064992) emerged as particularly interesting as it is a potent inhibitor of ETA with significant affinity for the ET B receptor and shows excellent pharmacokinetic properties and high in vivo efficacy in hypertensive Dahl salt-sensitive rats. Compound 17 successfully completed a long-term phase III clinical trial for pulmonary arterial hypertension.

Modifications and structure-activity relationships at the 2-position of 4-sulfonamidopyrimidine derivatives as potent endothelin antagonists

To improve water solubility and to study structure-activity relationships, we modified the structure of the pyrimidine nucleus of each of a series of potent ETA antagonists, 3a and 4a, at the 2-position. In a previous study, each of these antag