329924-27-8

Upstream product

• 370105-26-3 C₁₄H₁₄N₂O₄ 
• 1878-85-9 (2-methoxyphenoxy)acetic acid 
• 150726-89-9 (2-methoxyphenoxy)-malonic acid dimethyl ester 
• 150727-02-9 rac-2-cyclopropyl-5-(2-methoxy-phenoxy)-1H-pyrimidine-4,6-dione 

Downstream Products

• 150726-47-9 4-tert-butyl-N-[2-cyclopropyl-6-(2-hydroxy-ethoxy)-5-(2-methoxyphenoxy)-pyrimidin-4-yl]-benzenesulfonamide 
• 556066-74-1 5-methyl-pyridine-2-sulfonic acid [6-chloro-2-cyclopropyl-5-(2-methoxy-phenoxy)-pyrimidin-4-yl]-amide 
• 150727-73-4 4-tert-butyl-N-[6-chloro-2-cyclopropyl-5-(2-methoxy-phenoxy)-pyrimidin-4-yl]-benzenesulfonamide 
• 329924-30-3 5-i-propyl-N-[6-chloro-5-(o-methoxyphenoxy)-2-cyclopropyl-pyrimidin-4-yl]-pyridine-2-sulfonamide 
• 441795-96-6 C₂₃H₂₆N₄O₆S 
• 441797-53-1 C₂₁H₂₁ClN₄O₄S 
• 167402-15-5 pyridin-2-ylcarbamic acid 2-[6-(4-tert-butyl-phenylsulfonylamino)-2-cyclopropyl-5-(2-methoxy-phenoxy)-pyrimidin-4-yloxy]-ethyl ester 
• 329925-15-7 N-[6-(3-amino-propoxy)-2-cyclopropyl-5-(2-methoxy-phenoxy)-pyrimidin-4-yl]-4-tert-butyl-benzenesulfonamide 
• 329925-26-0 5-isopropyl-pyridine-2-sulfonic acid [6-(3-amino-propoxy)-2-cyclopropyl-5-(2-methoxy-phenoxy)-pyrimidin-4-yl]-amide 

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.

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.

SULFONAMIDES

The novel sulfonamides of formula I, STR1 in which the symbols R. sup.1-R 9, R a, R b, X, Y and n have the significance given in the description and salts thereof can be used for the treatment of circulatory disorders, especially hypertension, ischemia, vasopasms and angina pectoris.