Sircar I, Gregor E K, Anderson K R, Haleen S J, Shih Y H, Weishaar R E, Steffen R P, Pugsley T A, Taylor M D
Department of Chemistry, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
J Med Chem. 1991 Jul;34(7):2248-60. doi: 10.1021/jm00111a047.
The synthesis and pharmacological evaluation of a series of 2-[(arylsulfonyl)methyl]-4-aryl-5-cyano-1,4-dihydropyridine-3-carboxylic acid esters and analogues are described. These compounds possess a unique profile namely, calcium channel blocking and positive inotropic activities in vitro. Compound 54 was selected as the best compound in the series and was studied in detail. The synthesis and biological profiles of enantiomers of 54 are also reported. The data indicate that although the calcium channel blocking property of 54 is stereospecific the positive inotropic activity is not. Examples of 3- and 6-cyano and other closely related 1,4-dihydropyridine derivatives are described and evaluated for comparison and were found to be devoid of dual activities mentioned above.
本文描述了一系列2-[(芳基磺酰基)甲基]-4-芳基-5-氰基-1,4-二氢吡啶-3-羧酸酯及其类似物的合成与药理评价。这些化合物具有独特的特性，即在体外具有钙通道阻滞和正性肌力活性。化合物54被选为该系列中的最佳化合物并进行了详细研究。还报道了54对映体的合成和生物学特性。数据表明，虽然54的钙通道阻滞特性具有立体特异性，但正性肌力活性并非如此。描述并评估了3-和6-氰基以及其他密切相关的1,4-二氢吡啶衍生物的实例以作比较，发现它们没有上述双重活性。
