2. Academic Validation
  3. 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

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

  • J Med Chem. 2009 Oct 8;52(19):5785-8. doi: 10.1021/jm9009857.
Gerard M P Giblin 1,  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
Affiliations

Affiliation

  • 1 Neurosciences CEDD, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK. ged.m.giblin@gsk.com
PMID: 19743867 DOI: 10.1021/jm9009857
Abstract

We report the synthesis and SAR of a series of novel azaindole CB(2) 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 CB(2) agonist with high CNS penetration. This compound was efficacious in the acute model and the chronic joint pain model.

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