2,6-difluorophenol as a bioisostere of a carboxylic acid: Bioisosteric analogues of γ-aminobutyric acid

Jian Qiu, Scott H. Stevenson, Michael J. O'Beirne, Richard B. Silverman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

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 γ- aminobutyric acid (GABA). Substrate studies and inhibition studies were carried out with pig brain γ-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.

Original languageEnglish (US)
Pages (from-to)329-332
Number of pages4
JournalJournal of Medicinal Chemistry
Volume42
Issue number2
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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