SYNTHESIS OF NEW 2(1H) QUINOLONE ANTICONVULSANT DRUGS

描述：（改编自申请人摘要）PI建议 设计并合成了几种新的3，4-二氢-2（1H）-喹诺酮类化合物， 潜在的抗惊厥候选药物，基于观察到的 抗惊厥活性的两个先导化合物，表现出良好的抗惊厥活性， MES（有效对抗电诱导癫痫发作）和抗PTZ（有效 对抗戊四唑诱导的癫痫发作）活性。 期 研究中，PI建议通过以下方式测试增强的可行性： 适当的结构操作和合理的合成， 新的3-取代和3，3-二取代的3，4- 二氢-2（1H）-喹诺酮。 他计划利用独特而方便的新 合成方法，基于生成和区域选择性 由3，4-二氢-2（1H）-喹诺酮衍生的N，C3-二价阴离子， 他声称这代表了新的化学技术。 拟定商业应用： 由于癫痫患者的数量众多， 以及有限数量的批准的治疗剂可用于 治疗，迫切需要追求新的发展 新一代抗癫痫药物（AEDs）， 抗癫痫，神经毒性低，毒副作用少 方面的影响.正如本STTR第一阶段提案中最初概述的那样 项目，我们目前正在准备一些衍生物的3，4- 二氢-2（1H）-喹诺酮，以评估其作为 抗惊厥候选药物。这些化合物的生物筛选 预计将提供一个更清晰的了解结构 其抗惊厥特性的必要要求，以及 它们的作用机制的可能线索反过来，这将使更多 明确定义我们的合成目标，为第二阶段的调查，这 新型潜在抗癫痫药物我们设计的合成方法 提供了低成本，随时获得这些喹诺酮衍生物的任何 生产规模从毫克到公斤，使这项技术适用于 商业生产。如果这些新颖的，结构简单， 改性化合物被证明是有效的，潜在的商业 申请将包括对该工艺的专利考虑， 毒品本身，以及它们的大规模生产。

DESCRIPTION: (adapted from applicant's abstract) The PI proposes to design and synthesize several new 3,4-dihydro-2(1H)-quinolones as potential anticonvulsant drug candidates, based upon the observed anticonvulsant activity of two lead compounds, which exhibit good anti- MES (active against electrically-induced seizures) and anti-PTZ (active against pentylenetetrazol-induced seizures) activities. In the Phase studies, the PI proposes to test the feasibility of enhancing, by appropriate structural manipulation and rational synthesis, the anticonvulsant activity of new 3-substituted and 3,3-disubstituted 3,4- dihydro-2(1H)-quinolones. He plans to utilize unique and convenient new synthetic methodology, based upon the generation and regioselective reaction of N,C3-dianions derived from 3,4-dihydro-2(1H)-quinolones, which he claims represents new chemical technology. PROPOSED COMMERCIAL APPLICATION: In light of the significant number of people affected by epilepsy as well as the limited number of approved therapeutic agents available for treatment, there is an urgent need to pursue the development of new generation antiepileptic drugs (AEDs) which exhibit greater efficacy against seizures, lower neurotoxicity and fewer deleterious side effects. As originally outlined in the proposal for this STTR Phase I project, we are currently preparing a number of derivatives of 3,4- dihydro-2(1H)-quinolone in order to evaluate their potential as anticonvulsant drug candidates. Biological screening of these compounds is expected to provide a clearer understanding of the structural requirements necessary for their anticonvulsant properties, as well as possible clues to their mechanism of action. This, in turn, will more sharply define our synthetic goals for Phase II investigations of this new class of potential AEDs. The synthetic methodology we have devised provides low-cost, ready access to these quinolone derivatives on any production scale, from mg to kg, making this technology amenable to commercial production. If these novel, structurally simple, and readily modified compounds prove to be efficacious, potential commercial applications would include patent considerations for the process and the drugs themselves, as well as their large-scale manufacture.