TY - JOUR
T1 - 2,6-difluorophenol as a bioisostere of a carboxylic acid
T2 - Bioisosteric analogues of γ-aminobutyric acid
AU - Qiu, Jian
AU - Stevenson, Scott H.
AU - O'Beirne, Michael J.
AU - Silverman, Richard B.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
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U2 - 10.1021/jm980435l
DO - 10.1021/jm980435l
M3 - Article
C2 - 9925739
AN - SCOPUS:0032927808
VL - 42
SP - 329
EP - 332
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 2
ER -