| Design, synthesis, and biological activity of a difluoro-substituted, conformationally rigid vigabatrin analogue as a potent gamma-aminobutyric acid aminotransferase inhibitor. | |
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MedLine Citation:
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PMID: 14640537 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previously it was found that a conformationally rigid analogue (2) of the epilepsy drug vigabatrin (1) did not inactivate gamma-aminobutyric acid aminotransferase (GABA-AT). A cyclic compound with an exocyclic double bond (6) was synthesized and was found to inactivate GABA-AT, but only in the absence of 2-mercaptoethanol. The corresponding difluoro-substituted analogue (14) was synthesized and was shown to be a very potent time-dependent inhibitor, even in the presence of 2-mercaptoethanol. |
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Authors:
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Yue Pan; Jian Qiu; Richard 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: 46 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 2003 Dec |
Date Detail:
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Created Date: 2003-12-03 Completed Date: 2004-01-16 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: 5292-3 Citation Subset: IM |
Affiliation:
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Department of Chemistry, 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*,
chemistry Amino Acids / chemical synthesis*, chemistry Cyclopentanes / chemical synthesis*, chemistry Drug Design Fluorine* Molecular Conformation Structure-Activity Relationship Vigabatrin / analogs & derivatives*, chemical synthesis*, chemistry |
| Grant Support | |
ID/Acronym/Agency:
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NS15703/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/3-amino-4-(difluoromethylidene)cyclopentanecarboxylic acid; 0/Amino Acids; 0/Cyclopentanes; 60643-86-9/Vigabatrin; 7782-41-4/Fluorine; 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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