Synthesis and evaluation of nitric oxide-releasing derivatives of 3-n-butylphthalide as anti-platelet agents

Bioorg Med Chem Lett. 2011 Jul 15;21(14):4210-4. doi: 10.1016/j.bmcl.2011.05.082. Epub 2011 May 27.

Abstract

Most ischemic stroke results from brain blood vessel blockage by platelet-mediated thrombus, and anti-platelet therapy has been demonstrated clinical benefits in the treatment of this disease. In the present work, novel nitric oxide (NO)-releasing derivatives of an anti-ischemic stroke drug 3-n-butylphthalide (NBP) were synthesized. Compounds 7a and 7c exhibited more potent anti-platelet activity than NBP and aspirin, and released a moderate amount of NO, which is beneficial in improving cardiovascular and cerebral circulation. These findings provide an alternative approach to the development of drugs more potent than NBP for the intervention of ischemic stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Animals
  • Benzoates / chemical synthesis*
  • Benzoates / chemistry
  • Benzoates / pharmacology
  • Benzofurans / chemical synthesis
  • Benzofurans / chemistry*
  • Benzofurans / pharmacology
  • Blood Platelets / drug effects*
  • Caffeic Acids / chemical synthesis*
  • Caffeic Acids / chemistry
  • Caffeic Acids / pharmacology
  • Nitrates / chemical synthesis*
  • Nitrates / chemistry
  • Nitrates / pharmacology
  • Nitric Oxide / metabolism*
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology
  • Rabbits

Substances

  • Benzoates
  • Benzofurans
  • Caffeic Acids
  • Nitrates
  • Platelet Aggregation Inhibitors
  • Nitric Oxide
  • Adenosine Diphosphate
  • 3-n-butylphthalide