| Design, synthesis, and in vivo characterization of a novel series of tetralin amino imidazoles as γ-secretase inhibitors: Discovery of PF-3084014. | |
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MedLine Citation:
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PMID: 21269827 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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A novel series of tetralin containing amino imidazoles, derived from modification of the corresponding phenyl acetic acid derivatives is described. Replacement of the amide led to identification of a potent series of tetralin-amino imidazoles with robust central efficacy. The reduction of brain Aβ in guinea pigs in the absence of changes in B-cells suggested a potential therapeutic index with respect to APP processing compared with biomarkers of notch related toxicity. Optimization of the FTOC to plasma concentrations at the brain Aβ EC(50) lead to the identification of compound 14f (PF-3084014) which was selected for clinical development. |
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Authors:
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Michael A Brodney; David D Auperin; Stacey L Becker; Brian S Bronk; Tracy M Brown; Karen J Coffman; James E Finley; Carol D Hicks; Michael J Karmilowicz; Thomas A Lanz; Dane Liston; Xingrong Liu; Barbara-Anne Martin; Robert B Nelson; Charles E Nolan; Christine E Oborski; Christine P Parker; Karl E G Richter; Nikolay Pozdnyakov; Barbara G Sahagan; Joel B Schachter; Sharon A Sokolowski; Barbara Tate; Douglas E Wood; Kathleen M Wood; Jeffrey W Van Deusen; Lei Zhang |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2010-12-30 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: - ISSN: 1464-3405 ISO Abbreviation: - Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2011-1-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Ltd. |
Affiliation:
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Neuroscience Medicinal Chemistry, Pfizer PharmaTherapeutics Research and Development, Eastern Point Road, Groton, CT 06340, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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