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

Abstract

In order to study the influence of the length of the amino acid chain of N,N‐phthaloylamino acid amides as analogues of the former anticonvulsant taltrimide on the seizureantagonizing activity glycine, β‐alanine and γ‐aminobutyric acid (GABA) derivatives were synthesized. The corresponding taurine derivatives were also included. Generally, the glycine‐derived amides showed a higher activity than the β‐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 pentylenetetrazole. 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.

β-Lactam and penicillin substituted mesoionic metal carbene complexes

“…Compounds 9 , 7 d 10b , 13 10c , 19 11 , 20 and 18 21 were prepared according to previously described procedures. Benzyloxyacetyl chloride 10a and penicillin G potassium salt were obtained from commercial sources and used without further purification.…”

Taurine Analogues; A New Class of Therapeutics: Retrospect and Prospects

“…Analogues like phosphonates, guanidine derivatives, and trimethyltaurine were evaluated for neuroprotection against mpp + induced neurotoxicity in coronal slices from rat brain. It is assumed that the activity is mediated via an extra cellular mechanism [62].…”

High‐performance liquid chromatographic separation of stereoisomers of N‐phthaloyl‐protected amino acids and dipeptidomimetics

“…These protecting groups have found many applications in organic and peptide synthesis. More recently, several phthaloyl-protected amino acids have been reported to exhibit interesting biological activities [2,3]. Although a number of relatively mild methods are available for the cleavage of the protecting group, a general method for its introduction is still lacking.…”