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.
|
Authors | Muna H Abdi, 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 |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 20
Issue 17
Pg. 5080-4
(Sep 01 2010)
ISSN: 1464-3405 [Electronic] England |
PMID | 20673717
(Publication Type: Journal Article)
|
Copyright | Copyright 2010 Elsevier Ltd. All rights reserved. |
Chemical References |
- Amides
- Purinergic P2 Receptor Antagonists
- Receptors, Purinergic P2X7
- Pyrrolidonecarboxylic Acid
|
Topics |
- Amides
(chemistry, pharmacology)
- Drug Discovery
- Models, Molecular
- Purinergic P2 Receptor Antagonists
(chemistry, pharmacology)
- Pyrrolidonecarboxylic Acid
(chemistry)
- Receptors, Purinergic P2X7
(drug effects)
- Structure-Activity Relationship
|