| Discovery of 4-aminomethylphenylacetic acids as γ-secretase modulators via a scaffold design approach. | |
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MedLine Citation:
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PMID: 22061640 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Starting from literature examples of nonsteroidal anti-inflammatory drugs (NSAIDs)-type carboxylic acid γ-secretase modulators (GSMs) and using a scaffold design approach, we identified 4-aminomethylphenylacetic acid 4 with a desirable γ-secretase modulation profile. Scaffold optimization led to the discovery of a novel chemical series, represented by 6b, having improved brain penetration. Further SAR studies provided analog 6q that exhibited a good pharmacological profile. Oral administration of 6q significantly reduced brain Aβ42 levels in mice and rats. |
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Authors:
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Zhili Xin; Hairuo Peng; Andrew Zhang; Tina Talreja; Gnanasambandam Kumaravel; Lin Xu; Ellen Rohde; Mi-Yong Jung; Melanie N Shackett; David Kocisko; Sowmya Chollate; Anthone W Dunah; Pamela A Snodgrass-Belt; H Moore Arnold; Arthur G Taveras; Kenneth J Rhodes; Robert H Scannevin |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-19 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: - ISSN: 1464-3405 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-11-8 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 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Medicinal Chemistry, Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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