Nitric oxide releasing morpholine derivatives as hypolipidemic and antioxidant agents

J Med Chem. 2002 Nov 21;45(24):5406-9. doi: 10.1021/jm011062i.

Abstract

The synthesis and evaluation of activity of some nitric acid esters of substituted morpholines are presented. All compounds inhibit lipid peroxidation and reduce cholesterol (20-63%) and triglyceride (37-85%) plasma levels. The more potent NO donors 14 and 17 specifically reduce low-density lipoprotein (LDL). These data indicate that proper structural modifications to the hypolipidemic and antioxidant morpholines enabling NO production, besides preserving or enhancing the above activities, offer a remarkable reduction of LDL, considered advantageous for antiatheromatic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemical synthesis*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Cholesterol / blood
  • Hypolipidemic Agents / chemical synthesis*
  • Hypolipidemic Agents / chemistry
  • Hypolipidemic Agents / pharmacology
  • In Vitro Techniques
  • Lipid Peroxidation / drug effects
  • Lipoproteins, LDL / blood
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Morpholines / chemical synthesis*
  • Morpholines / chemistry
  • Morpholines / pharmacology
  • Nitrates / chemical synthesis*
  • Nitrates / chemistry
  • Nitrates / pharmacology
  • Nitric Oxide Donors / chemical synthesis*
  • Nitric Oxide Donors / chemistry
  • Nitric Oxide Donors / pharmacology
  • Rats
  • Structure-Activity Relationship
  • Triglycerides / blood

Substances

  • Antioxidants
  • Hypolipidemic Agents
  • Lipoproteins, LDL
  • Morpholines
  • Nitrates
  • Nitric Oxide Donors
  • Triglycerides
  • Cholesterol