1. Academic Validation
  2. Discovery and structure-activity relationships of a series of pyroglutamic acid amide antagonists of the P2X7 receptor

Discovery and structure-activity relationships of a series of pyroglutamic acid amide antagonists of the P2X7 receptor

  • Bioorg Med Chem Lett. 2010 Sep 1;20(17):5080-4. doi: 10.1016/j.bmcl.2010.07.033.
Muna H Abdi 1 Paul J Beswick Andy Billinton Laura J Chambers Andrew Charlton Sue D Collins Katharine L Collis David K Dean Elena Fonfria Robert J Gleave Clarisse L Lejeune David G Livermore Stephen J Medhurst Anton D Michel Andrew P Moses Lee Page Sadhana Patel Shilina A Roman Stefan Senger Brian Slingsby Jon G A Steadman Alexander J Stevens Daryl S Walter
Affiliations

Affiliation

  • 1 Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK.
Abstract

A computational lead-hopping exercise identified compound 4 as a structurally distinct P2X(7) receptor antagonist. Structure-activity relationships (SAR) of a series of pyroglutamic acid amide analogues of 4 were investigated and compound 31 was identified as a potent P2X(7) antagonist with excellent in vivo activity in animal models of pain, and a profile suitable for progression to clinical studies.

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