Indolin-2-ones with high in vivo efficacy in a model for multiple sclerosis.

Abstract

The known KDR inhibitor SU5416 and several analogues of the indolin-2-one family were surprisingly found to be highly efficacious in the EAE model, an established model for multiple sclerosis. The high in vivo effect could be correlated to in vitro inhibition of the pro-inflammatory cytokine IL-2. Activity following po administration was obtained with several analogues and via the use of prodrugs.

• Authors: Laëtitia Bouérat, Jef Fensholdt, Xifu Liang, Sophie Havez, Simon F Nielsen, Jens R Hansen, Simon Bolvig, Christina Andersson
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 48 Issue 17 Pg. 5412-4 (Aug 25 2005) ISSN: 0022-2623 [Print] United States
• PMID: 16107139 (Publication Type: Journal Article)

Chemical References

• Indoles
• Interleukin-2
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Animals
• Encephalomyelitis, Autoimmune, Experimental (drug therapy, metabolism)
• In Vitro Techniques
• Indoles (chemical synthesis, chemistry, pharmacology)
• Interleukin-2 (antagonists & inhibitors, biosynthesis)
• Leukocytes, Mononuclear (drug effects, metabolism)
• Mice
• Multiple Sclerosis (drug therapy, metabolism)
• Structure-Activity Relationship
• Vascular Endothelial Growth Factor Receptor-2 (antagonists & inhibitors)