The identification of potent, selective and CNS penetrant furan-based inhibitors of B-Raf kinase.

Abstract

Modification of the potent imidazole-based B-Raf inhibitor SB-590885 resulted in the identification of a series of furan-based derivatives with enhanced CNS penetration. One such compound, SB-699393 (17), was examined in vivo to challenge the hypothesis that selective B-Raf inhibitors may be of value in the treatment of stroke.

• Authors: Andrew K Takle, Mark J Bamford, Susannah Davies, Robert P Davis, David K Dean, Alessandra Gaiba, Elaine A Irving, Frank D King, Antoinette Naylor, Christopher A Parr, Alison M Ray, Alastair D Reith, Beverley B Smith, Penelope C Staton, Jon G A Steadman, Tania O Stean, David M Wilson
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 18 Issue 15 Pg. 4373-6 (Aug 01 2008) ISSN: 1464-3405 [Electronic] England
• PMID: 18621524 (Publication Type: Journal Article)

Chemical References

• Furans
• Imidazoles
• Indans
• L-779,450
• Pyridines
• SB-590885
• SB-699393
• Proto-Oncogene Proteins B-raf

Topics

• Animals
• Central Nervous System (drug effects)
• Furans (chemical synthesis, chemistry, pharmacology)
• Imidazoles (chemistry, pharmacology)
• Indans (chemical synthesis, chemistry, pharmacology)
• Molecular Structure
• Proto-Oncogene Proteins B-raf (antagonists & inhibitors)
• Pyridines (chemistry, pharmacology)
• Rats
• Stroke (drug therapy)
• Structure-Activity Relationship