Yoshino K, Kohno T, Uno T, Morita T, Tsukamoto G
J Med Chem. 1986 May;29(5):820-5. doi: 10.1021/jm00155a037.
A series of 4-(benzothiazol-2-yl)benzylphosphonic acid dialkyl ester derivatives were synthesized and evaluated for coronary vasodilatory activity by Langendorff's method in the isolated guinea pig heart. Many of the phosphonic acid dialkyl esters exhibited vasodilatory activity and calcium antagonism comparable with those of diltiazem hydrochloride, whereas phosphonic acid 1b and its nonphosphonated precursor 7a were inactive. These results indicate the necessity of the diethoxyphosphinyl moiety for vasodilatory activity. Substitution of the benzothiazole ring with a variety of substituents did not significantly enhance the activity of the unsubstituted compound. Compound 10b (KB-944) was chosen for detailed pharmacological evaluation.
合成了一系列4-(苯并噻唑-2-基)苄基膦酸二烷基酯衍生物，并通过Langendorff法在离体豚鼠心脏中评估其冠状血管舒张活性。许多膦酸二烷基酯表现出与盐酸地尔硫卓相当的血管舒张活性和钙拮抗作用，而膦酸1b及其未膦酸化的前体7a没有活性。这些结果表明二乙氧基膦酰基部分对于血管舒张活性是必需的。用各种取代基取代苯并噻唑环并没有显著提高未取代化合物的活性。选择化合物10b(KB-944)进行详细的药理学评估。
