Synthesis and vasorelaxant evaluation of novel 7-methoxyl-2,3-disubstituted-quinoxaline derivatives

Bioorg Med Chem Lett. 2021 Mar 15:36:127785. doi: 10.1016/j.bmcl.2021.127785. Epub 2021 Jan 12.

Abstract

An array of novel 7-methoxyl-2,3-disubstituted quinoxaline derivatives was designed, synthesized and their potential antihypertensive activities were examined, in an attempt to discover potent small molecules with vasorelaxant effects. The vasoactivities of these compounds on vascular tone, as well as underlying mechanisms were hereby explored. Results showed that five compounds (7s, 7t, 7v, 7w, 7γ) could induce endothelium-independent relaxation in high extracellular K+- and phenylephrine-precontracted C57 mice aortic rings. These five compounds, unlike other commonly used vasodilators, could slowly but effectively inhibit vasoconstriction.

Keywords: 7-Methoxyl-2,3-disubstituted quinoxaline derivatives; Endothelium-independent; Vasorelaxant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / chemical synthesis
  • Antihypertensive Agents / chemistry
  • Antihypertensive Agents / pharmacology*
  • Aorta, Thoracic / drug effects*
  • Aorta, Thoracic / metabolism
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Phenylephrine
  • Quinoxalines / chemical synthesis
  • Quinoxalines / chemistry
  • Quinoxalines / pharmacology*
  • Structure-Activity Relationship
  • Vasodilator Agents / chemical synthesis
  • Vasodilator Agents / chemistry
  • Vasodilator Agents / pharmacology*

Substances

  • Antihypertensive Agents
  • Quinoxalines
  • Vasodilator Agents
  • Phenylephrine