167403-77-2

Basic information

• Product Name: Morpholine, 4-[4,6-dichloro-5-(2-methoxyphenoxy)-2-pyrimidinyl]-
• CAS NO: 167403-77-2
• Molecular Formula: C15H15Cl2N3O3
• Molecular Weight: 356.208
• Mol File: 167403-77-2.mol
• Article Data: 6

Chemical Properties

• CAS DataBase Reference: Morpholine, 4-[4,6-dichloro-5-(2-methoxyphenoxy)-2-pyrimidinyl]-(CAS DataBase Reference)
• NIST Chemistry Reference: Morpholine, 4-[4,6-dichloro-5-(2-methoxyphenoxy)-2-pyrimidinyl]-(167403-77-2)
• EPA Substance Registry System: Morpholine, 4-[4,6-dichloro-5-(2-methoxyphenoxy)-2-pyrimidinyl]-(167403-77-2)

Safety Data

• Hazardous Substances Data: 167403-77-2(Hazardous Substances Data)

Upstream product

• 167403-76-1 5-(2-methoxy-phenoxy)-2-(morpholin-4-yl)-4,6(1H,5H)-pyrimidinedione 
• 1878-85-9 (2-methoxyphenoxy)acetic acid 
• 150726-89-9 (2-methoxyphenoxy)-malonic acid dimethyl ester 
• 96042-30-7 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 
• 329924-46-1 5-(o-methoxyphenoxy)-4,6-dihydroxy-2-(N-morpholino)-pyrimidine 
• 7087-68-5 N-ethyl-N,N-diisopropylamine 
• 5638-78-8 morpholinoformamidine hydrochloride 
• 20730-58-9 2-(2-Methoxyphenoxy)propanedioic acid diethyl ester 

Downstream Products

• 179400-53-4 5-methyl-pyridine-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-ylamide 
• 167403-79-4 4-tert-Butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-benzenesulfonamide 
• 179400-65-8 5-isopropyl-pyridine-2-sulfonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl-amide 
• 167403-78-3 4-tert.-butyl-N-[6-chloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-benzene sulfonamide 
• 441797-12-2 C₂₈H₃₀BrN₇O₇S 
• 441797-11-1 C₂₄H₂₉N₅O₇S 
• 179400-99-8 5-isopropyl-pyridine-2-sulfonic acid 6-chloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl-amide 
• 179400-98-7 5-methyl-pyridine-2-sulphonic acid 6-chloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-ylamide 
• 179400-71-6 pyridin-2-yl-carbamic acid 2-[6-(5-isopropyl-pyridine-2-sulfonylamino)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yloxy]-ethyl ester 
• 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 
• 556067-15-3 5-isopropyl-pyridine-2-sulfonic acid [6-(3-amino-propoxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-amide 
• 329924-50-7 5-isopropyl-pyridine-2-sulfonic acid [6-(2-amino-ethoxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-amide 
• 329924-87-0 5-methyl-pyridine-2-sulfonic acid [6-(2-amino-ethoxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-amide 

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.

Butyne diol derivatives

The present invention relates to novel butyne diol derivatives of the general formula I and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more compounds of the general formula I and especially their use as endothelin receptor antagonists.

Discovery of Ro 48-5695: A potent mixed endothelin receptor antagonist optimized from Bosentan

Implementation of a pyridylcarbamoyl group and an isopropylpyridylsulfonamide substituent as key components in the scaffold of Bosentan resulted in the identification of the potent orally active endothelin receptor antagonist Ro 48-5695. It shows affinities for ET(A) and ET(B) receptors in the low nanomolar range and high functional antagonistic potency in vitro.