Synthesis of 2-(4-substitutedbenzyl-[1,4]diazepan-1-yl)-n-(1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides as inotropic agents

Chem Biol Drug Des. 2011 Jan;77(1):98-103. doi: 10.1111/j.1747-0285.2010.01057.x. Epub 2010 Nov 26.

Abstract

In an attempt to search for more potent positive inotropic agents, a series of N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(substitutedbenzyl-[1,4]diazepan-1-yl)acetamides were 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 2-(4-(4-methylbenzyl)-[1,4]-diazepan-1-yl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamide (6m) was the most potent, increasing stroke volume by 8.38±0.16% (milrinone 2.45± 0.06%) at 3 x 10(-5) m. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides* / chemical synthesis
  • Acetamides* / pharmacology
  • Animals
  • Azepines / chemical synthesis*
  • Azepines / pharmacology*
  • Cardiotonic Agents* / chemical synthesis
  • Cardiotonic Agents* / pharmacology
  • Heart / drug effects*
  • Milrinone / pharmacology*
  • Myocardial Contraction / drug effects*
  • Organ Culture Techniques / methods
  • Rabbits
  • Stroke Volume / drug effects*
  • Triazoles / chemical synthesis*
  • Triazoles / pharmacology*

Substances

  • 2-(4-(4-methylbenzyl)-(1,4)diazepan-1-yl)-N-(4,5-dihydro-1-methyl-(1,2,4)triazolo(4,3-a)quinolin-7-yl)acetamide
  • Acetamides
  • Azepines
  • Cardiotonic Agents
  • Triazoles
  • Milrinone