16216-94-7Relevant 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
Bolli, Martin H.,Boss, Christoph,Binkert, Christoph,Buchmann, Stephan,Bur, Daniel,Hess, Patrick,Iglarz, Marc,Meyer, Solange,Rein, Josiane,Rey, Markus,Treiber, Alexander,Clozel, Martine,Fischli, Walter,Weller, Thomas
supporting information, p. 7849 - 7861 (2012/10/29)
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.
DEFLUORINATION REACTIONS OF gem-DIFLUORO- AND MONOFLUOROOLEFINS. NOVEL METHODS FOR ONE-CARBON HOMOLOGATIONS OF CARBONYL COMPOUNDS LEADING TO ALDEHYDES, CARBOXYLIC ACIDS, AND ESTERS
Hayashi, Sei-ichi,Nakai, Takeshi,Ishikawa, Nobuo
, p. 651 - 654 (2007/10/02)
Defluorinative hydrolysis (or alcoholysis) of gem-difluoroolefins (1) easily prepared via the facile difluoromethylenation of carbonyl compounds afforded the carboxylic acids (or esters).The homologation method was applied to the synthesis of anti-inflammatory ibuprofen.Furthermore, defluorinative hydrolysis of monofluoroolefins obtained via the reduction of 1 gave the aldehydes.
