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To improve water solubility and to study structure-activity relationships, we modified the structure of the pyrimidine nucleus of each of a series of potent ET A antagonists, 3a and 4a, at the 2-position. In a previous study, each of these antagonists showed an extremely high affinity for the ET A receptor in porcine aortic membrane (IC 50 3a; < 0.001 nM, 4a; 0.0039...
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