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.

A series of phosphorus compounds, designed as analogues of gamma-aminobutyric acid (GABA) in that they possess a P = O moiety separated by three atoms from an amino or acetamido group, was synthesized and tested by using in vitro GABAA and GABAB receptor binding, GABA uptake assays, and was examined for anticonvulsant activity. Weak GABAB receptor affinity was noted for one agent, whereas six compounds displayed moderate to high potencies as inhibitors of electroshock- and pentylenetetrazol-induced seizures. The best anticonvulsant effect was found with the (m-aminophenyl) phosphinic acid compounds, with members of this class selected for further study.

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