Methylphenidate Analogs as Medications for Cocaine Abuse

哌醋甲酯类似物作为可卡因滥用药物

• 批准号: 6463295
• 负责人: HUW M DAVIES
• 金额: $ 31.69万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6463295
• 关键词: analog; attention deficit disorder; bioimaging /biomedical imaging; biological products; cocaine; dopamine transporter; drug abuse chemotherapy; drug addiction; drug design /synthesis /production; methylphenidate; norepinephrine; positron emission tomography; protein binding; protein structure function; radiotracer; serotonin transporter

DESCRIPTION (provided by applicant): The central goal of this project is to synthesize novel methylphenidate analogs and evaluate their potential as medications for the treatment of cocaine addiction and as precursors to novel neuroimaging agents. Even though a reasonably wide range of methylphenidate analogs have been explored in the past, a major shortcoming with the previous studies in this area was the limitations associated with the traditional method used for the synthesis of these analogs. Having developed a very powerful two-step asymmetric synthesis of threo-methylphenidate, this enabling technology will be used for the synthesis of a wide array of methylphenidate analogs. The specific synthetic targets of the project are the following: naphthyl analogs of threo- and erythro-methylphenidate, heterocyclic analogs of threo-methylphenidate, oxa and carba analogs of threo-methylphenidate, piperidine ring-modified analogs, and polycyclic derivatives. All compounds will be initially screened for their binding to the dopamine, serotonin and norepinephrine transporters. Classes of compounds that display interesting biological properties will be extended into a more extensive series. Further in vitro and in vivo evaluation of promising compounds will be conducted. Initial studies will also be carried out to determine if useful PET radioligands can be made from any potent and selective analogs that are discovered during these studies.

描述（由申请人提供）：本项目的中心目标是 合成新哌甲酯类似物并评价它们作为 用于治疗可卡因成瘾和作为新的可卡因成瘾的前体的药物 神经成像剂尽管哌醋甲酯的剂量范围很大 过去已经探索了类似物，这是以前的主要缺点。 这一领域的研究是与传统方法相关的局限性 用于合成这些类似物。开发了一种非常强大的 苏型哌甲酯的两步不对称合成，这使得 该技术将用于多种哌甲酯的合成 类似物 本项目的具体合成目标如下： 苏型和赤型哌甲酯的类似物， 苏型-哌甲酯，苏型-哌甲酯的OXA和CABA类似物， 哌啶环修饰的类似物和多环衍生物。所有化合物 将首先筛选它们与多巴胺，血清素和 去甲肾上腺素转运蛋白化合物的种类， 生物学特性将扩展到更广泛的系列。进一步 将对有前景的化合物进行体外和体内评价。 初步研究也将进行，以确定是否有用的PET 放射性配体可以由任何有效的和选择性的类似物制成， 在这些研究中发现。