Synthesis and cardiotonic activity of 2-substituted 5-cyano-1,6-dihydro-6-oxo-3-pyridinecarboxylic acids and their methyl or ethyl esters

Farmaco. 1992 Apr;47(4):427-37.

Abstract

The synthesis of ethyl or methyl esters of 5-cyano-1,6-dihydro-6-oxo-3- pyridinecarboxylic acids carrying as 2-substituent a polar group such as CO2C2H5, (CH2)2CO2CH3, (CH2)3CO2C2H5, CH2OCH3, or CF3 group is described. Also 2-[5-cyano-1,6-dihydro-2-(1,1-dimethylethyl)-6-oxo-3-pyridyl]-2- oxoacetic acid and 2,5,6,8-tetrahydro-2,5-dioxo-1H-thiopyrano[3,4-b]pyridine-3-carbon itrile were prepared. Nearly all the above esters gave routinely the corresponding carboxylic acids by alkaline hydrolysis followed by acidification. As milrinone analogues, the above compounds were tested on contractile activity and frequency rate of spontaneously beating atria from reserpine-treated guinea-pigs. 5-Cyano-2-trifluoromethyl-1,6- dihydro-6-oxo-3-pyridinecarboxylic acid and, in a lesser degree, the relative ethyl ester showed an appreciable positive inotropic activity, although inferior to that of milrinone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiotonic Agents / chemical synthesis*
  • Cardiotonic Agents / pharmacology
  • Guinea Pigs
  • Heart / drug effects
  • In Vitro Techniques
  • Male
  • Milrinone
  • Myocardial Contraction / drug effects
  • Nicotinic Acids / chemical synthesis*
  • Nicotinic Acids / pharmacology
  • Pyridones / pharmacology
  • Reserpine / pharmacology

Substances

  • Cardiotonic Agents
  • Nicotinic Acids
  • Pyridones
  • Reserpine
  • Milrinone