Synthesis and anticonvulsant activity of N,N-phthaloyl derivatives of central nervous system inhibitory amino acids

In order to study the influence of the length of the amino acid chain of N, N-phthaloyl-amino acid amides as analogues of the former anticonvulsant tal trimide on the seizure-antagonizing activity glycine, beta -alanine and gam ma -aminobutyric acid (GABA) derivatives were synthesized. The correspondin g taurine derivatives were also included. Generally, the glycine-derived am ides showed a higher activity than the beta -alanine and GABA derivatives i n the maximal electroshock seizure (MES) test in mice upon intraperitoneal administration. The activity was comparable to the respective taurine deriv atives. The N,N-phthaloyl-glycine, amides were also active in the MES test upon oral administration to rats. No significant activity was noted in the seizure threshold test with subcutaneous pentylenetetrazole. The ED50 of N, N-phthaloyl-glycine ethyl amide (4b) in the MES test upon intraperitoneal a dministration to mice was 19.1 mg/kg. On a molar basis this activity is com parable to the activity of phenytoin with little toxicity in the rotorod te st. In conclusion, N,N-phthaloyl-glycine amides might represent promising a ntiepileptic drugs.