Cardiotonic agents. 2. Synthesis and structure-activity relationships in a new class of 6-, 7-, and 8-pyridyl-2(1H)-quinolone derivatives

J Med Chem. 1986 Dec;29(12):2433-8. doi: 10.1021/jm00162a003.

Abstract

A series of 6-, 7-, and 8-pyridyl-2(1H)-quinolone derivatives with various quinolone substitutents (CH3, Cl, OH, OCH3) was prepared by arylation of pyridine with quinolone via a diazotized aminoquinolone for positive inotropic activity. Several derivatives, especially those with a pyridyl ring in the 6-position, were from 28 to 50 times more potent on left guinea pig atria than ARL-115 and milrinone used as references. Intrinsic activities of the derivatives were almost equivalent to that of ARL-115. These results indicate that pyridyl-2(1H)-quinolone derivatives are a potent new class of positive inotropic agents.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Atrial Function
  • Cardiotonic Agents / chemical synthesis*
  • Female
  • Guinea Pigs
  • Heart Atria / drug effects
  • In Vitro Techniques
  • Indicators and Reagents
  • Male
  • Myocardial Contraction / drug effects
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology
  • Structure-Activity Relationship

Substances

  • Cardiotonic Agents
  • Indicators and Reagents
  • Pyridines
  • Quinolines