150727-28-9

Upstream product

• 202288-10-6 5-(3-methoxyphenoxy)-1H-pyrimidin-4,6-dione 
• 2088-24-6 3-methoxyphenoxyacetic acid 
• 150727-91-6 C₁₁H₁₀N₂O₄ 
• 189574-46-7 m-methoxyphenoldimethyl 3-methoxyphenoxymalonate 
• 150-19-6 O-methylresorcine 

Downstream Products

• 202288-13-9 4-chloro-6-[3-(5,5-dimethyl-1,3-dioxinan-2-yl)propoxy]-5-(3-methoxyphenoxy)pyrimidin 
• 1393813-56-3 C₂₄H₂₃BrN₆O₆S 
• 202288-11-7 4-tert-butyl-N-[6-(4-hydroxybutoxy)-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide 
• 202287-80-7 4-tert-butyl-N-[5-(3-methoxy-phenoxy)-6-(4-oxo-butoxy)-pyrimidin-4-yl]-benzenesulfonamide 

Relevant academic research and scientific papers

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.

Synthesis and structure-activity relationships of potent and orally active sulfonamide ETB selective antagonists

The synthesis and structure-activity relationships of a series of N-pyrimidinyl benzenesulfonamides as ETB selective antagonists are described. N-Isoxazolyl benzenesulfonamide 1a, previously reported, was selected as a lead compound, and isosteric replacement of the isoxazole ring of 1a with a pyrimidine ring led to the discovery of the highly potent ETB selective antagonist 6e with oral bioavailability. Modification of the terminal aldehyde group at the 6-position of the pyrimidine ring was investigated, and malonate 15b and acylhydrazone 16f were found to be equipped to aldehyde 6e. Compound 6e showed ETB antagonistic activity on in vivo evaluation. Copyright