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W2014201426 abstract "Structural variation of the endothelin A-selective antagonist (S)-3-methoxy-2-(4,6-dimethoxypyrimidin-2-yloxy)-3, 3-diphenylpropionic acid (LU 135252) led to analogues which retain ET(A) 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 ET(A) 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." @default.
W2014201426 created "2016-06-24" @default.
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W2014201426 date "1999-07-24" @default.
W2014201426 modified "2023-09-27" @default.
W2014201426 title "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 ETA/ETB Receptor Antagonist" @default.
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W2014201426 doi "https://doi.org/10.1021/jm9910425" @default.
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