SYNTHESIS AND ANTICONVULSANT ACTIVITY OF 2 CARBETHOXYMETHYL ANILINES

虽然有几种抗癫痫药物用于治疗

Although several anti-epileptic drugs are used in the treatment of epilepsy, many patients fail to experience satisfactory control with those drugs. Those who go into complete remission do so at the expense of significant side effects. As of date no general theories have gained acceptance, which would explain the above disparity. The objective of this proposal is the design, synthesis and pharmacological evaluation of some 2-carbethoxymethyl aniline derivatives as anti-convulsant agents. These compounds are structurally similar to Gabapentin (1-aminomethyl cyclohexaneacetic acid). The carbethoxymethyl moiety in the proposed series will serve as in vivo carboxylic acid surrogate. We will introduce substituents such as methyl, ethyl, propyl, cyclopentyl, benzyl and substituted benzyl at carbon 2 of the acetoxy portion of the molecule. The introduction of these substituents is necessary to increase the lipophilicity and change the electronic distribution in the molecule. These factors will in turn have a corresponding effect on the pharmacological profile of the molecules. The focus of this investigation will be primarily in developing a facile method for the synthesis of non-toxic and highly selective anti- convulsants for the treatment of patients with partial and generalized- tonic clonic seizures. The synthesized compounds will be tested for activity against maximal electroshock-induced seizures. The preliminary pharmacological testing will be conducted by the Anti-epileptic Drug Development (ADD) Program, Epilepsy Branch, Neurological Disorders Program, national Institute of Neurological Disorders and Stroke (NINDS).