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
  • 1. Neurosciences CEDD, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK. [email protected]
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.