| N-Substituted carbazolyloxyacetic acids modulate Alzheimer associated gamma-secretase. | |
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MedLine Citation:
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PMID: 17035010 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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N-Sulfonylated and N-alkylated carbazolyloxyacetic acids were investigated for the inhibition and modulation of the Alzheimer's disease associated gamma-secretase. The introduction of a lipophilic substituent, which may vary from arylsulfone to alkyl, turned 2-carbazolyloxyacetic acids into potent gamma-secretase modulators. This resulted in the selective reduction of Abeta(42) and an increase of the less aggregatory Abeta(38) fragment by several compounds (e.g., 7d and 8c). Introduction of an electron donating group at position 6 and 8 of N-substituted carbazolyloxyacetic acids either decreased the activity or inversed modulation. The most active compounds displayed activity on amyloid precursor protein (APP) overexpressing cell lines in the low micromolar range and little or no effect on the gamma-secretase cleavage at the epsilon-site. |
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Authors:
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Rajeshwar Narlawar; Blanca I Pérez Revuelta; Karlheinz Baumann; Robert Schubenel; Christian Haass; Harald Steiner; Boris Schmidt |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-10-10 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 17 ISSN: 0960-894X ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2007 Jan |
Date Detail:
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Created Date: 2006-12-25 Completed Date: 2007-04-24 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: 176-82 Citation Subset: IM |
Affiliation:
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Clemens Schöpf-Institute of Chemistry and Biochemistry, Darmstadt University of Technology, Petersenstr. 22, D-64287 Darmstadt, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetic Acids
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chemistry*,
pharmacology* Alzheimer Disease / enzymology* Amyloid Precursor Protein Secretases / drug effects* Amyloid beta-Protein Precursor / antagonists & inhibitors* Humans |
| Chemical | |
Reg. No./Substance:
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0/Acetic Acids; 0/Amyloid beta-Protein Precursor; EC 3.4.-/Amyloid Precursor Protein Secretases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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