| SAR studies of acidic dual γ-secretase/PPARγ modulators. | |
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MedLine Citation:
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PMID: 21873070 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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A novel set of dual γ-secretase/PPARγ modulators characterized by a 2-benzyl hexanoic acid scaffold is presented. Synthetic efforts were focused on the variation of the substitution pattern of the central benzene. Finally, we obtained a new class of 2,5-disubstituted 2-benzylidene hexanoic acid derivatives, which act as dual γ-secretase/PPARγ modulators in the low micromolar range. We have explored broad SAR and successfully improved the dual pharmacological activity and the selectivity profile against potential off-targets such as NOTCH and COX. Compound 17 showed an IC(50) Aβ42=2.4μM and an EC(50) PPARγ=7.2μM and could be a valuable tool to further evaluate the concept of dual γ-secretase/PPARγ modulators in animal models of Alzheimer's disease. |
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Authors:
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Martina Hieke; Julia Ness; Ramona Steri; Christine Greiner; Oliver Werz; Manfred Schubert-Zsilavecz; Sascha Weggen; Heiko Zettl |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-6 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry Volume: - ISSN: 1464-3391 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9413298 Medline TA: Bioorg Med Chem 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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Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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