Document Detail


Orally active C-6 heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]pyridine acid pump antagonists (APAs).
MedLine Citation:
PMID:  19467868     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acid pump antagonists (APAs) such as the imidazo[1,2-a]pyridine AZD-0865 2 have proven efficacious at low oral doses in acid related gastric disorders. Herein we describe some of the broader SAR in this class of molecule and detail the discovery of an imidazo[1,2-a]pyridine 15 which has excellent efficacy in animal models of gastric acid secretion following oral administration, as well as a good overall developability profile. The discovery strategy focuses on use of heteroaryl and heterocyclic substituents at the C-6 position and optimization of developability characteristics through modulation of global physico-chemical properties.
Authors:
Nick Bailey; Mark J Bamford; Delphine Brissy; Joanna Brookfield; Emmanuel Demont; Richard Elliott; Neil Garton; Irene Farre-Gutierrez; Thomas Hayhow; Gail Hutley; Antoinette Naylor; Terry A Panchal; Hui-Xian Seow; David Spalding; Andrew K Takle
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Publication Detail:
Type:  Journal Article     Date:  2009-05-03
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  19     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-09     Completed Date:  2009-09-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  3602-6     Citation Subset:  IM    
Affiliation:
Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Dogs
H(+)-K(+)-Exchanging ATPase / antagonists & inhibitors*,  metabolism
Humans
Hydrogen-Ion Concentration
Proton Pump Inhibitors / chemical synthesis,  chemistry*,  pharmacology
Pyridines / chemical synthesis,  chemistry*,  pharmacology
Rats
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Proton Pump Inhibitors; 0/Pyridines; 274-76-0/imidazo(1,2-a)pyridine; EC 3.6.1.10/H(+)-K(+)-Exchanging ATPase

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