Synthesis and anticonvulsant activity of N,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.

Synthesis and Anticonvulsant Screening of Some Novel Derivatives of Substituted Benzofuran

“…In recent years, the field of antiepileptic drug development (ADD) has become quite dynamic, affording many promising research opportunities, and there is a continuing demand for new anticonvulsant agents as it has not been possible to control every kind of seizure with currently available antiepileptic drugs. The amides are a class of compounds presenting a wide range of biological applications and anticonvulsant activity [12][13][14] . This prompted us to synthesize and study anticonvulsant activity of compounds incorporating both these moieties i.e., Benzofuran and amides.…”

An environmentally compatible synthesis of polyesters derived from 5‐(2‐phthalimidoethanesulfonamido) isophthalic acid as a novel diacid monomer

“…After further washing with water, the crude product was air dried overnight. The resultant was recrystallized from ethylene chloride, yielding 1.7 g (77%) of product (Scheme , step 2), melting at 160–161°C, (lit: 160–161°C20 and 159–162°C21).…”

Synthesis, characterization, and soil biodegradation study of polyamides derived from the novel bioactive diacid monomer 5‐(2‐phthalimidoethanesulfonamido) isophthalic acid

“…The preparation of compound 3 was reported in the literature 17, 18. Here, the synthesis of this compound is reported briefly, and its characterization is reported in detail.…”