- CRYSTALLINE FORMS OF A 4-PYRIMIDINESULFAMIDE DERIVATIVE APROCITENTAN
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The present invention concerns novel crystalline forms of {5-(4-bromo-phenyl)-6 [2 (5 bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl}-sulfamide, processes for the preparation thereof, pharmaceutical compositions comprising said crystalline forms, pharmac
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Paragraph 0231
(2020/01/22)
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- COMBINATION OF A 4-PYRIMIDINESULFAMIDE DERIVATIVE WITH AN SGLT-2 INHIBITOR FOR THE TREATMENT OF ENDOTHELIN RELATED DISEASES
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The present invention concerns the compound aprocitentan, {5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl}-sulfamide and its use as endothelin receptor antagonist, in combination with an SGLT-2 inhibitor. The invention further
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Page/Page column 38
(2019/06/17)
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- PROCESS FOR MANUFACTURING PYRIMIDINE SULFAMIDE DERIVATIVES
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The invention relates to a process for manufacturing the compound of formula I wherein R is H, (C1-C6)alkyl or benzyl, or a salt thereof, said process comprising the reaction of the compound of formula I-1 wherein X is Br, Cl or F, or a salt thereof, with the compound of formula I-2 wherein R is H, C1-C6)alkyl or benzyl, or a salt thereof, in the presence of a base, and, when X is Br or Cl, in the presence of tetra-n-butyl ammonium fluoride hydrate or cesium fluoride. The invention further relates to the compound of formula I-1 and uses thereof.
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Page/Page column 44; 45
(2015/09/22)
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- 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
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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.
- 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
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p. 7849 - 7861
(2012/10/29)
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- 4-PYRIMIDINESULFAMIDE DERIVATIVE
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The invention relates to the compound of structural formula (I) and the salts thereof. Said compound is useful as endothelin receptor antagonist. The invention further relates to a process for preparing said compound.
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- 4-PYRIMIDINESULFAMIDE DERIVATIVE
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The invention relates to the compound of structural formula (I) and the salts thereof. Said compound is useful as endothelin receptor antagonist. The invention further relates to a process for preparing said compound.
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Page/Page column 15
(2009/04/25)
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