Methylphenidate Analogs as Medications for Cocaine Abuse

哌甲酯类似物作为可卡因滥用药物

• 批准号: 6866448
• 负责人: HUW M DAVIES
• 金额: $ 30.49万
• 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/6866448
• 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