Kanojia R M, Press J B, Lever O W, Williams L, McNally J J, Tobia A J, Falotico R, Moore J B
Research Laboratories, Ortho Pharmaceutical Corporation, Raritan, New Jersey 08869.
J Med Chem. 1988 Jul;31(7):1363-8. doi: 10.1021/jm00402a020.
A series of isoquinolin-3-ol derivatives (II) was prepared as analogues of the clinical cardiotonic agent bemarinone (ORF 16600, I). Although in many respects the structural requirements for the cardiotonic activity of II are similar to those of bemarinone, certain differences between the series were noted. Our structure-activity studies show that II is less sensitive to alkoxy-substitution effects than is I, and more significantly, 4-substitution of II by alkyl groups, halogen, or alkanecarboxylic acid derivatives enhances cardiotonic activity in II in contrast to I, wherein analogous substitution eliminated activity. A linear correlation between contractile force (CF) increase and cyclic nucleotide phosphodiesterase fraction III (PDE-III) inhibition by the title compounds was determined. The isoquinoline derivatives were characteristically short-acting cardiotonic agents with good potency and selectivity.
制备了一系列异喹啉 -3-醇衍生物（II）作为临床强心剂苄吗啉（ORF 16600，I）的类似物。尽管在许多方面，II的强心活性的结构要求与苄吗啉相似，但注意到这两个系列之间存在某些差异。我们的构效关系研究表明，II对烷氧基取代效应的敏感性低于I，更重要的是，与I相反，II被烷基、卤素或链烷羧酸衍生物进行4-取代可增强其强心活性，而在I中类似取代会消除活性。确定了标题化合物的收缩力（CF）增加与环核苷酸磷酸二酯酶III（PDE -III）抑制之间的线性相关性。异喹啉衍生物是典型的短效强心剂，具有良好的效力和选择性。
