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 …

MH Bolli, C Boss, C Binkert, S Buchmann…

Index: 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 Journal of Medicinal Chemistry, 2012 , vol. 55, # 17 p. 7849 - 7861

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Citation Number: 115

Abstract

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 ...