5-Arylidene-2-imino-4-thiazolidinones: design and synthesis of novel anti-inflammatory agents

Bioorg Med Chem. 2005 Jul 1;13(13):4243-52. doi: 10.1016/j.bmc.2005.04.058.

Abstract

The synthesis and pharmacological activity of 5-arylidene-2-imino-4-thiazolidinones (3a-8a) are described. All derivatives exhibited significant activity levels in models of acute inflammation such as carrageenan-induced paw and pleurisy edema in rats. In particular, 5-(3-methoxyphenylidene)-2-phenylimino-3-propyl-4-thiazolidinone (3a) displayed high levels of carrageenan-induced paw edema inhibition comparable to those of indomethacin. In addition the ability of such a new class of anti-inflammatory agents to inhibit COX isoforms was assessed in murine monocyte/macrophage J774 cell line assay. 5-(4-Methoxyphenylidene)-2-phenylimino-3-propyl-4-thiazolidinone (6a), the most interesting compound in such an experiment, was docked in the known active site of COX-2 protein and showed that its 4-methoxyarylidene moiety can easily occupy the COX-2 secondary pocket considered as the critical interaction for COX-2 selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Binding Sites
  • Carrageenan
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / chemical synthesis
  • Cyclooxygenase Inhibitors / pharmacology
  • Drug Design*
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / pathology
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Peroxidase / metabolism
  • Pleurisy / chemically induced
  • Pleurisy / drug therapy
  • Pleurisy / pathology
  • Prostaglandin-Endoperoxide Synthases / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship
  • Thiazolidinediones / chemical synthesis*
  • Thiazolidinediones / chemistry
  • Thiazolidinediones / pharmacology*

Substances

  • 5-(3-methoxyphenylidene)-2-phenylimino-3-propyl-4-thiazolidinone
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Thiazolidinediones
  • Carrageenan
  • Peroxidase
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases