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

Autor:	Andrew Charlton, Stephen J. Medhurst, Laura J. Chambers, Livermore David, Brian Peter Slingsby, Andy Billinton, Lee William Page, Anton D. Michel, Daryl S. Walter, Jon Graham Anthony Steadman, Shilina Roman, Sadhana Patel, Elena Fonfria, Robert Gleave, Stefan Senger, Katharine Laura Collis, Andrew P. Moses, Sue D. Collins, Muna H. Abdi, Paul John Beswick, Clarisse L. Lejeune, David Kenneth Dean, Alexander J. Stevens
Rok vydání:	2010
Předmět:	Models Molecular Stereochemistry medicine.drug_class Clinical Biochemistry Pharmaceutical Science Biochemistry Structure-Activity Relationship chemistry.chemical_compound In vivo Amide Drug Discovery Purinergic P2 Receptor Antagonists medicine Structure–activity relationship Receptor Molecular Biology Drug discovery Organic Chemistry Antagonist Receptor antagonist Amides Pyrrolidonecarboxylic Acid chemistry Molecular Medicine Receptors Purinergic P2X7 Pyroglutamic acid
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 20:5080-5084
ISSN:	0960-894X
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9a3ff37009bb76b9bfd50c27c623c06d https://doi.org/10.1016/j.bmcl.2010.07.033 Zobrazit plný text záznamu Full Text from ScienceDirect