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

M. P. Giblin, Gerard; 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.

doi:10.1021/jm9009857.s001

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

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posted on 2009-10-08, 00:00 authored by Gerard M. P. Giblin, Andrew Billinton, Michael Briggs, Andrew J. Brown, Iain P. Chessell, Nick M. Clayton, Andrew J. Eatherton, Paul Goldsmith, Carl Haslam, Matthew R. Johnson, William L. Mitchell, Alan Naylor, Alcide Perboni, Brian P. Slingsby, Alex W. Wilson

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.

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GSK 554418A Chronic PainWe report CNS Azaindole penetration pain model SAR CB 2 agonist novel azaindole CB 2 agonists

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

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