Small molecule Nociceptin Receptor Agonists to Treat Cocaine Abuse

项目总监/首席投资人(最后第一，伊利德尔)：班尼斯特，托马斯，D核心A 项目总结(见说明)： 核心A.药物化学核心，托马斯·班尼斯特主任。博士学位。 摘要： 我们之前已经发现了NOP激动剂具有非常高的选择性，目前还超过了任何配体 报道，并为它们的制备开发了有效的合成路线。核心A将提供药物 为所有其他核心提供化学支持。A芯的化学家将进一步优化势能的制备 多克尺度的探针，为其他 根据需要配置核心。此外，我们将使用体外分析化合物的性质，以确定适当的 其他岩心动物给药用的化合物和适当的盐形式和配方。这个核心是 负责向所有项目成员分发化合物，并被认为是所有项目的必要核心 团队进行他们的研究。项目团队将在执行之前从核心请求化合物 他们的评估。核心将保存至少1克重要化合物(SR-8323、SR-8993、 SR-9279等)准备好快速合成任何其他必要的化合物，如果他们 因此，没有一个项目团队无法完成他们的工作。 相关性(请参阅说明)： NOP受体激动剂已被提出作为潜在的探针来调节与 可卡因成瘾。核心A，提供药物化学支持和化合物的体外评价 属性，是该计划的组合目标的核心，只有可靠的 并及时向其他岩心提供探测候选者。概述了四个目标，包括扩大研究， 候选探针的交付、盐形态评估和探针性能的体外评估。

Program Director/Principal Invesligator (Last. First, IVIiddle): Bannister, ThomaS, D Core A PROJECT SUMMARY (See instmctions): Core A. Medicinal Chemistry Core, Director Thomas Bannister. Ph.D. Abstract: We have previously identified NOP agonists with very high selectivity, surpassing those of any ligands yet reported, and have developed efficient synthetic routes for their preparation. Core A will provide medicinal chemistry support for all other cores. The chemists in Core A will further optimize the preparation of potential probes of a multigram scale, providing probe candidates and literature comparison compounds to other cores as needed. In addition, we will use in vitro analysis of compound properties to identify appropriate compounds and suitable salt forms and formulations for animal dosing by other cores. This core is responsible for giving out compounds to all project members and is deemed a necessary core for all project teams to perform their research. The project teams will request compound from the core prior to performing their assessments. The core will keep a minimum of 1 gram of important compounds (SR-8323, SR-8993, SR-9279, etc.) on hand, and be prepared to quickly synthesize any other necessary compounds, should they be needed, so that no project team is unable to perform their work. RELEVANCE (See instructions): Agonists of the NOP receptor have been proposed as potential probes to modulate behavior associated with cocaine addiction. Core A, providing medicinal chemistry support and in vitro assessment of compound properties, is central to the combined objectives of the program, which can only succeed with a dependable and timely supply of probe candidates to the other cores. Four aims are outlined, including scale-up studies, delivery of probe candidates, salt form evaluation, and in vitro assessment of probe properties.