Yoshino K, Goto K, Yoshiizumi K, Morita T, Tsukamoto G
Pharmaceuticals Research Center, Kanebo Ltd., Osaka, Japan.
J Med Chem. 1990 Aug;33(8):2192-6. doi: 10.1021/jm00170a024.
Structural modifications of the calcium antagonist fostedil (KB-944) and their coronary vasodilator activity are described. Amidophosphonates 4a-m, lactam amidophosphonates 7a-1, and diamide dilactam 10 were prepared, and their coronary vasodilator activity was assessed in dogs. Many compounds exhibited coronary vasodilator activity superior to that of fostedil. Among them, the 2-oxopyrrolidine derivative 7a was the most effective compound. Its action as a coronary vasodilator was 3 and 2 times more potent than that of fostedil and diltiazem hydrochloride, respectively.
描述了钙拮抗剂福司地尔（KB-944）的结构修饰及其冠状血管舒张活性。制备了氨基膦酸酯4a-m、内酰胺氨基膦酸酯7a-1和二酰胺二内酰胺10，并在犬身上评估了它们的冠状血管舒张活性。许多化合物表现出优于福司地尔的冠状血管舒张活性。其中，2-氧代吡咯烷衍生物7a是最有效的化合物。其作为冠状血管舒张剂的作用分别比福司地尔和盐酸地尔硫䓬强3倍和2倍。
