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 …
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 ETB receptor and ...
