Synthesis and inotropic evaluation of 1-substituted-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)piperidine-4-carboxamides

Bioorg Med Chem Lett. 2009 May 1;19(9):2392-5. doi: 10.1016/j.bmcl.2009.03.089. Epub 2009 Mar 26.

Abstract

A series of 1-substituted-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl) piperidine-4-carboxamides has been synthesized and evaluated for positive inotropic activity by measuring left atrium stroke volume in isolated rabbit-heart preparations. Some of these derivatives exhibited favorable activity compared with the standard drug, milrinone, among which 1-(2-fluorobenzyl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)piperidine-4-carboxamide 6a was the most potent, increasing stroke volume by 11.92+/-0.35% (milrinone: 6.36+/-0.13%) at 1x10(-4)M.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiotonic Agents / chemical synthesis
  • Cardiotonic Agents / pharmacology
  • Chemistry, Organic / methods*
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Heart / drug effects*
  • Isonipecotic Acids / chemistry
  • Milrinone / chemical synthesis
  • Milrinone / pharmacology
  • Models, Chemical
  • Myocardium / metabolism
  • Piperidines / chemistry*
  • Quinolines / chemistry*
  • Rabbits

Substances

  • Cardiotonic Agents
  • Isonipecotic Acids
  • Piperidines
  • Quinolines
  • piperidine
  • Milrinone