1027289-66-2Relevant articles and documents
Discovery and synthesis of (S)-3-[2-(3,4-dimethoxyphenyl)ethoxy]-2(4,6- dimethylpyrimidin-2-yloxy)-3,3-diphenylpropionic acid (LU 302872), a novel orally active mixed ET(A)/ET(B) receptor antagonist
Amberg, Willi,Hergenr?der, Stefan,Hillen, Heinz,Jansen, Rolf,Kettschau, Georg,Kling, Andreas,Klinge, Dagmar,Raschack, Manfred,Riechers, Hartmut,Unger, Liliane
, p. 3026 - 3032 (2007/10/03)
Structural variation of the endothelin A-selective antagonist (S)-3- methoxy-2-(4,6-dimethoxy-pyrimidin-2-yloxy)-3,3-diphenylpropionic acid (LU 135252) led to analogues which retain ETA affinity but exhibit substantial ET(B) affinity as well. The most active derivative obtained is (S)-3-[2- (3,4-dimethoxyphenyl)ethoxy]-2-(4,6-dimethylpyrimidin-2-yloxy)-3,3- diphenylpropionic acid (LU 302872), which can be prepared in enantiomerically pure form in eight steps via an acid-catalyzed transetherification. It has a K(i) = 2.15 nM for binding to the ETA receptor and a K(i) = 4.75 nM for binding to the ET(B) receptor, is orally available, and antagonizes the big ET-induced blood pressure increase in rats and the big ET-induced bronchospasm in guinea pigs each time at a dose of 10 mg/kg.
