Cardiotonic agents. 1-Methyl-7-(4-pyridyl)-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and related compounds. Synthesis and activity

• Published in: Journal of medicinal chemistry Vol. 32; no. 2; pp. 351 - 357
• Main Authors: Kaiho, Tatsuo, Sannohe, Kunio, Kajiya, Seitaro, Suzuki, Tsuneji, Otsuka, Kengo, Ito, Toshihiko, Kamiya, Joji, Maruyama, Masahiko
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.02.1989
• Subjects: Animals; Cardiotonic Agents - chemical synthesis; Cardiotonic Agents - pharmacology; Chemistry; Dogs; Exact sciences and technology; Female; heart; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; inotropism; Isoquinolines - chemical synthesis; Isoquinolines - pharmacology; Male; Myocardial Contraction - drug effects; Organic chemistry; Preparations and properties; Pyridines - chemical synthesis; Pyridines - pharmacology; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00122a012

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.