Synthesis and pharmacological activities of ethyl 5-cyano-1,6-dihydro-6-oxo-2-(2,3,4-pyridyl)-3-pyridinecarboxylates and derivatives

Farmaco. 1994 Sep;49(9):559-66.

Abstract

The synthesis of ethyl esters of 5-cyano-1,6-dihydro-6-oxo-3-pyridinecarboxylic acids carrying as 2-substituent the 2-,3- or 4-pyridyl group is described. By alkaline hydrolysis followed by acidification, these esters gave the corresponding carboxylic acids, which were decarboxylated to 1,2-dihydro-2-oxo-6-(2,3,4-pyridyl)-3-pyridinecarbonitriles. As milrinone analogues, the above compounds were tested on contractile activity and frequency rate of spontaneously beating atria from reserpine-treated guinea-pigs. Ethyl 5-cyano-1,6-dihydro-6-oxo-2-(2-pyridyl)-3-pyridinecarboxylate showed an appreciable positive inotropic activity, although inferior to that of milrinone; moreover, some other compounds bearing the above 2-substitution pattern showed interesting antiinflammatory, analgesic and hypotensive activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / chemical synthesis*
  • Analgesics / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antihypertensive Agents / chemical synthesis*
  • Antihypertensive Agents / pharmacology
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / pharmacology
  • Guinea Pigs
  • Heart Atria / drug effects
  • In Vitro Techniques
  • Male
  • Myocardial Contraction / drug effects
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / pharmacology
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology

Substances

  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antihypertensive Agents
  • Carboxylic Acids
  • Platelet Aggregation Inhibitors
  • Pyridines