Document Detail

2,6-Difluorophenol as a bioisostere of a carboxylic acid: bioisosteric analogues of gamma-aminobutyric acid.
MedLine Citation:
PMID:  9925739     Owner:  NLM     Status:  MEDLINE    
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.
J Qiu; S H Stevenson; M J O'Beirne; R B Silverman
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  42     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-03-04     Completed Date:  1999-03-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  329-32     Citation Subset:  IM    
Departments of Chemistry and of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208-3113, USA.
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MeSH Terms
4-Aminobutyrate Transaminase / antagonists & inhibitors
Brain / enzymology
Carboxylic Acids / chemistry*
Enzyme Inhibitors / pharmacology
Magnetic Resonance Spectroscopy
Mass Spectrometry
Phenols / chemistry,  pharmacology*
gamma-Aminobutyric Acid / analogs & derivatives*
Grant Support
Reg. No./Substance:
0/Carboxylic Acids; 0/Enzyme Inhibitors; 0/Phenols; 28177-48-2/2,6-difluorophenol; 56-12-2/gamma-Aminobutyric Acid; EC Transaminase

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