| Orally active C-6 heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]pyridine acid pump antagonists (APAs). | |
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MedLine Citation:
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PMID: 19467868 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article Date: 2009-05-03 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 19 ISSN: 1464-3405 ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-09 Completed Date: 2009-09-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 3602-6 Citation Subset: IM |
Affiliation:
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Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Proton Pump Inhibitors; 0/Pyridines; 274-76-0/imidazo(1,2-a)pyridine; EC 3.6.1.10/H(+)-K(+)-Exchanging ATPase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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