1: Arch Pharm (Weinheim)  2001 Oct;334(10):323-31

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

Usifoh CO, Lambert DM, Wouters J, Scriba GK.

Department of Pharmaceutical Chemistry, University of Jena, Philosophenweg 14,
07743 Jena, Germany.

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
taltrimide on the seizure-antagonizing activity glycine, beta-alanine and
gamma-aminobutyric acid (GABA) derivatives were synthesized. The corresponding
taurine derivatives were also included. Generally, the glycine-derived amides
showed a higher activity than the beta-alanine and GABA derivatives in the
maximal electroshock seizure (MES) test in mice upon intraperitoneal
administration. The activity was comparable to the respective taurine
derivatives. 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 pentylene-tetrazole. The ED50 of
N,N-phthaloyl-glycine ethyl amide (4b) in the MES test upon intraperitoneal
administration to mice was 19.1 mg/kg. On a molar basis this activity is
comparable to the activity of phenytoin with little toxicity in the rotorod
test. In conclusion, N,N-phthaloyl-glycine amides might represent promising
antiepileptic drugs.

PMID: 11759171 [PubMed - in process]