SYNTHESIS AND ANTICONVULSANT ACTIVITY OF 2 CARBETHOXYMETHYL ANILINES

2-二甲氧甲基苯胺的合成及其抗惊厥活性

• 批准号: 6344877
• 负责人: COSMAS O OKORO
• 金额: $ 3.38万
• 依托单位: UNIVERSITY OF ARKANSAS AT PINE BLUFF
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6344877
• 关键词: aniline; anticonvulsants; brain disorder chemotherapy; chemical structure function; chemical substitution; drug design /synthesis /production; drug screening /evaluation; epilepsy; myoclonus epilepsy; pharmacokinetics

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).

虽然有几种抗癫痫药物用于治疗 癫痫，许多患者未能体验到令人满意的控制与这些 毒品那些进入完全缓解的人是以牺牲 严重的副作用。到目前为止，还没有普遍的理论。 接受，这将解释上述差异。的目的 建议是设计，合成和药理学评价的一些 2-作为抗惊厥剂的乙氧羰基甲基苯胺衍生物。这些 化合物在结构上类似于加巴喷丁（1-氨基甲基 环己烷乙酸）。所提出的化合物中的乙氧羰基甲基部分 系列将用作体内羧酸替代物。我们将介绍 取代基如甲基、乙基、丙基、环戊基、苄基和 在分子的乙酰氧基部分的碳2处取代的苄基。的 引入这些取代基是必要的， 亲脂性并改变分子中的电子分布。 这些因素反过来又会对 分子的药理学特征。 这项调查的重点将主要是在开发一个简易的 合成无毒和高选择性抗- 治疗部分性和全身性癫痫患者的惊厥药， 强直阵挛性发作 将测试合成的化合物对最大 电击诱发的癫痫初步的药理测试 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项目癫痫分支 神经系统疾病和中风（NINDS）。