329924-46-1

Basic information

• Product Name: 5-(o-methoxyphenoxy)-4,6-dihydroxy-2-(N-morpholino)-pyrimidine
• Synonyms: 5-(o-methoxyphenoxy)-4,6-dihydroxy-2-(N-morpholino)-pyrimidine
• CAS NO: 329924-46-1
• Molecular Weight: 0
• Mol File: 329924-46-1.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: 5-(o-methoxyphenoxy)-4,6-dihydroxy-2-(N-morpholino)-pyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(o-methoxyphenoxy)-4,6-dihydroxy-2-(N-morpholino)-pyrimidine(329924-46-1)
• EPA Substance Registry System: 5-(o-methoxyphenoxy)-4,6-dihydroxy-2-(N-morpholino)-pyrimidine(329924-46-1)

Safety Data

• Hazardous Substances Data: 329924-46-1(Hazardous Substances Data)

Upstream product

• 20730-58-9 2-(2-Methoxyphenoxy)propanedioic acid diethyl ester 
• 5638-78-8 morpholinoformamidine hydrochloride 
• 38768-62-6 methyl (2-methoxyphenoxy) ethanoate 
• 157415-17-3 Morpholine-4-carboxamidine; hydrobromide 
• 150726-89-9 (2-methoxyphenoxy)-malonic acid dimethyl ester 
• 1878-85-9 (2-methoxyphenoxy)acetic acid 

Downstream Products

• 167403-77-2 4,6-dichloro-5-(2-methoxy-phenoxy)-2-(morpholin-4-yl)pyrimidine 
• 167403-78-3 4-tert.-butyl-N-[6-chloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-benzene sulfonamide 
• 346671-60-1 4-tert.-butyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-benzene sulfonamide 

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.

6 alkoxy-4-pyrimidinyl bis-sulfonamides

The present invention relates to novel bis-sulfonamides represented, for example, by formula I below and a pure diastereomer, a mixture of diastereomers, a diastereomeric racemate, a mixture of diastereomeric racemates and meso-forms and a pharmaceutically acceptable salt thereof, wherein R1represents aryl; aryl-lower alkyl; aryl-lower alkenyl; heteroaryl; or heteroaryl-lower alkyl; and R2represents lower alkyl; trifluoromethyl; lower alkoxy-lower alkyl; lower alkenyl; lower alkynyl; aryl; aryl-lower alkyl; aryl-lower alkenyl; heterocyclyl; heterocyclyl-lower alkyl; heteroaryl; heteroaryl-lower alkyl; cycloalkyl; or cycloalkyl-lower alkyl. The present invention also relates to a process for manufacturing those compounds, pharmaceutical compositions containing one or more of those compounds as endothelin antagonists, and a method of treating a subject having a disorder involving endothelin with the compounds of the invention.