Novel delta2-isoxazolines as group II phospholipase A2 inhibitors

Bioorg Med Chem Lett. 2004 Jul 16;14(14):3679-81. doi: 10.1016/j.bmcl.2004.05.012.

Abstract

The synthesized imidazolyl substituted delta2-isoxazolines were subjected to Phospholipase A(2) (PLA(2)) enzyme inhibitory activity against snake venom source and their structure-activity relationship with respect to different groups attached to this moiety is reported for the first time. The crystal structure of the compound 2-butyl-5-chloro-3H-imidazolyl-4-carbaldehyde oxime 2, an intermediate for the construction of isoxazolines is reported. These compounds exerted a significant PLA(2) enzyme inhibitory activity against group II PLA(2). The in vivo activity on mice of selected compounds 3bI and 3bIV shows the comparable anti-inflammatory activity with the known standard ursolic acid.

Publication types

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

MeSH terms

  • Aldehydes / chemistry
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Imidazoles / chemistry
  • Isoxazoles / chemistry
  • Isoxazoles / pharmacology*
  • Mice
  • Models, Molecular
  • Oximes / chemistry
  • Phospholipases A / antagonists & inhibitors*
  • Phospholipases A / metabolism
  • Phospholipases A2
  • Snake Venoms / enzymology*
  • Structure-Activity Relationship
  • Triterpenes / chemistry
  • Ursolic Acid

Substances

  • Aldehydes
  • Anti-Inflammatory Agents
  • Enzyme Inhibitors
  • Imidazoles
  • Isoxazoles
  • Oximes
  • Snake Venoms
  • Triterpenes
  • Phospholipases A
  • Phospholipases A2