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Updated: May 5, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Phosphorus GABA Analogues as Potential Prodrugs
1Department of Medicinal Chemistry, College of Pharmacy, University of Houston, University Park, Houston, Texas, 77004.
Abstract:
Analogues of γ-aminobutyric acid (GABA), wherein a P=O moiety is separated by three carbon atoms from an amino group, were incorporated into Schiff bases as potential acid-labile carrier molecules. These include 3-aminophenylphosphonic acid, its dimethyl ester and its previously unreported N,N'-diisopropylphosphonodiamide. A benzophenone derivative of GABA was also synthesized.A study of the degrees of in vitro hydrolysis of four Schiff bases indicated that lability of the C=N bond is determined by electronic influences of ring substituents.All new products were tested for abilities to inhibit maximal electroshock- and subcutaneous pentylenetetrazol (Metrazol)-induced seizures in mice.Activity was found only in the former system with moderate inhibition displayed by two dimethyl ester and the GABA Schiff bases.
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