Discovery of 1-[4-(3-Chlorophenylamino)-1-methyl-1 H-pyrrolo [3, 2-c] pyridin-7-yl]-1-morpholin-4-ylmethanone (GSK554418A), a Brain Penetrant 5-Azaindole CB2 …

…, NM Clayton, AJ Eatherton, P Goldsmith…

文献索引：Giblin, Gerard M. P.; Billinton, Andrew; Briggs, Michael; Brown, Andrew J.; Chessell, Iain P.; Clayton, Nick M.; Eatherton, Andrew J.; Goldsmith, Paul; Haslam, Carl; Johnson, Matthew R.; Mitchell, William L.; Naylor, Alan; Perboni, Alcide; Slingsby, Brian P.; Wilson, Alex W. Journal of Medicinal Chemistry, 2009 , vol. 52, # 19 p. 5785 - 5788

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被引用次数: 40

摘要

We report the synthesis and SAR of a series of novel azaindole CB2 agonists. 6-Azaindole 18 showed activity in an acute pain model but was inactive in a chronic model. 18 is a Pgp substrate with low brain penetration. The template was redesigned, and the resulting 5- azaindole 36 was a potent CB2 agonist with high CNS penetration. This compound was efficacious in the acute model and the chronic joint pain model.