Cardiotonic Agents. 1-Methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3 (2H)-isoquinolinones and Related Compounds. Synthesis and Activity

J Med Chem. 1989 Feb;32(2):351-7. doi: 10.1021/jm00122a012.

Abstract

A series of 1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and related compounds were synthesized and evaluated for positive inotropic activity. Most members of this series exerted a dose-dependent increase in myocardial contractility in the dog acute heart failure model, whereas they caused only slight changes in heart rate and blood pressure. Several derivatives, especially those with cyano, acetyl, and ethyl substituents at the 4-position, were more potent than milrinone, which was used as a reference. 4-Acetyl-1-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinone (MS-857) is one of the most potent positive inotropic agents in this series.

MeSH terms

  • Animals
  • Cardiotonic Agents / chemical synthesis*
  • Cardiotonic Agents / pharmacology
  • Dogs
  • Female
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / pharmacology
  • Male
  • Myocardial Contraction / drug effects
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology
  • Structure-Activity Relationship

Substances

  • Cardiotonic Agents
  • Isoquinolines
  • Pyridines