188025-29-8Relevant academic research and scientific papers
N-Substituted amino acid N′-benzylamides: Synthesis, anticonvulsant, and metabolic activities
Beguin, Cecile,LeTiran, Arnaud,Stables, James P.,Voyksner, Robert D.,Kohn, Harold
, p. 3079 - 3096 (2004)
Amino acid amides (AAA) were prepared and evaluated in seizure models. The AAA displayed moderate-to-excellent activity in the maximal electroshock seizure (MES) test and were devoid of activity in the subcutaneous Metrazol-induced (scMet) seizure test. The AAA anticonvulsant activity was neither strongly influenced by the C(2) substituent nor by the degree of terminal amine substitution. An in vitro metabolism study suggested that the structure-activity relationship pattern was due, in part, to metabolic processes that occurred at the N-terminal amine unit.
The anticonvulsant activities of functionalized N-benzyl 2-acetamidoacetamides. The importance of the 2-acetamido substituent
Choi, Daeock,Stables, James P.,Kohn, Harold
, p. 2105 - 2114 (2007/10/03)
Recent studies have demonstrated that substituted N-benzyl 2-acetamidoacetamides provide significant protection against maximal electroshock (MES)-induced seizures in mice and rats. In this study, we investigated whether the 2-acetamido moiety was necessary for anticonvulsant activity. Ten derivatives of the known anticonvulsant, N-benzyl 2-acetamido-2-phenylacetamide were prepared in which the 2-acetamido group was replaced by hydrogen, methyl, oxygen, and halogen substituents. Evaluation of these compounds in the MES-induced seizure test demonstrated that both the hydroxy and the methoxy compounds provided full protection against MES-induced seizures in mice given ip at 100 mg/g. Moreover, evaluation of the individual stereoisomers for the hydroxy compound showed that the principal activity resided in the (R)-isomer. These findings demonstrated that the 2-acetamido substituent is important but not obligatory for the prevention of MES-induced seizures. Further supporting evidence was provided by comparing the pharmacological activities of N-benzyl 2,3-dimethoxypropionamide with N-benzyl 2-acetamido-3-methoxypropionamide. The ED50 value for the former in the MES test was 3.0 mg/kg (ip), which compared favorably with phenobarbital (ED50=22 mg/kg), but the ED50 value for N-benzyl 2-acetamido-3-methoxypropionamide was 8.3 mg/kg.
