SYNTHESIS AND ANTICONVULSANT ACTIVITY OF 2 CARBETHOXYMETHYL ANILINES

虽然有几种抗癫痫药物被用于治疗 癫痫，许多患者未能体验到令人满意的控制 毒品。那些进入完全缓解状态的人这样做的代价是 严重的副作用。到目前为止，还没有得到任何普遍的理论 接受，这将解释上述差异。这样做的目的是 建议是一些化合物的设计、合成和药理评价 2-甲氧基苯胺衍生物作为抗惊厥剂。这些 化合物结构类似于加巴喷丁(1-氨基甲基 环己烷乙酸)。建议中的甲乙氧基甲基部分 该系列将作为体内羧酸替代品。我们将介绍 取代基，如甲基、乙基、丙基、环戊基、苯基和 在分子的乙酰氧基部分的碳2处取代的苄基。这个 有必要引入这些取代基来增加 亲油性和改变分子中的电子分布。 这些因素将反过来对 这些分子的药理学特征。 这项调查的重点将主要是开发一种便利的 一种无毒、高选择性抗氧剂的合成方法 惊厥药物治疗部分性和全身性- 强直性阵挛发作。 合成的化合物将进行活性测试，以对抗最大 电击导致的癫痫发作。初步药理试验 将由抗癫痫药物开发(ADD)计划进行， 美国国立卫生研究院神经疾病计划癫痫学部 神经功能障碍和中风(NINDS)。

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).