Synthesis and positive inotropic activity of N-(4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(piperazin-1-yl)acetamide derivatives

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4606-9. doi: 10.1016/j.bmcl.2008.07.026. Epub 2008 Jul 12.

Abstract

A series of N-(4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(piperazin-1-yl)acetamide derivatives were synthesized and their positive inotropic activity was evaluated by measuring left atrium stroke volume on isolated rabbit heart preparations. Several compounds showed favorable activity compared with the standard drug, milrinone, among which N-(1-benzyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(4-benzylpiperazin-1-yl)acetamide 6j was found to be the most potent with the 13.2% increased stroke volume (milrinone 4.7%) at concentration of 3x10(-5) M in our in vitro study. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemical synthesis*
  • Acetamides / pharmacology
  • Animals
  • Cardiotonic Agents / chemical synthesis
  • Cardiotonic Agents / pharmacology
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Heart / drug effects*
  • Heart Atria / drug effects
  • Heart Rate / drug effects
  • Milrinone / pharmacology
  • Models, Chemical
  • Myocardium / metabolism*
  • Oxazolidinones / pharmacology
  • Rabbits
  • Stroke Volume / drug effects
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / pharmacology

Substances

  • Acetamides
  • Cardiotonic Agents
  • Oxazolidinones
  • Triazoles
  • Milrinone