| 2,6-Difluorophenol as a bioisostere of a carboxylic acid: bioisosteric analogues of gamma-aminobutyric acid. | |
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MedLine Citation:
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PMID: 9925739 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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3-(Aminomethyl)-2,6-difluorophenol (6) and 4-(aminomethyl)-2, 6-difluorophenol (7) were synthesized in eight and four steps, respectively, starting from 2,6-difluorophenol, to test the potential of the 2,6-difluorophenol moiety to act as a lipophilic bioisostere of a carboxylic acid. Compounds 6 and 7 are potential bioisosteric analogues of gamma-aminobutyric acid (GABA). Substrate studies and inhibition studies were carried out with pig brain gamma-aminobutyric acid aminotransferase; 6 and 7 are very poor substrates, but both inhibit the enzyme, indicating that the 2, 6-difluorophenol moiety appears to be able to substitute for a carboxylic acid to increase the lipophilicity of drug candidates. |
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Authors:
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J Qiu; S H Stevenson; M J O'Beirne; R B Silverman |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 42 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 1999 Jan |
Date Detail:
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Created Date: 1999-03-04 Completed Date: 1999-03-04 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 329-32 Citation Subset: IM |
Affiliation:
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Departments of Chemistry and of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208-3113, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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4-Aminobutyrate Transaminase
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antagonists & inhibitors Animals Brain / enzymology Carboxylic Acids / chemistry* Enzyme Inhibitors / pharmacology Magnetic Resonance Spectroscopy Mass Spectrometry Phenols / chemistry, pharmacology* Swine gamma-Aminobutyric Acid / analogs & derivatives* |
| Grant Support | |
ID/Acronym/Agency:
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NS15703/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carboxylic Acids; 0/Enzyme Inhibitors; 0/Phenols; 28177-48-2/2,6-difluorophenol; 56-12-2/gamma-Aminobutyric Acid; EC 2.6.1.19/4-Aminobutyrate Transaminase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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