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

Authors :: Abdi MH
Beswick PJ
Billinton A
Chambers LJ
Charlton A
Collins SD
Collis KL
Dean DK
Fonfria E
Gleave RJ
Lejeune CL
Livermore DG
Medhurst SJ
Michel AD
Moses AP
Page L
Patel S
Roman SA
Senger S
Slingsby B
Steadman JG
Stevens AJ
Walter DS
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Sep 01; Vol. 20 (17), pp. 5080-4. Date of Electronic Publication: 2010 Jul 14.
Publication Year :: 2010
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.<br /> (Copyright 2010 Elsevier Ltd. All rights reserved.)

Subjects :: Amides chemistry
Drug Discovery
Models, Molecular
Purinergic P2 Receptor Antagonists chemistry
Structure-Activity Relationship
Amides pharmacology
Purinergic P2 Receptor Antagonists pharmacology
Pyrrolidonecarboxylic Acid chemistry
Receptors, Purinergic P2X7 drug effects

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