Medicinal Chemistry Core

药物化学与放射化学核心摘要 药物化学和放射化学(MCRC)核心代表着这一活动的中心枢纽 U19中心。MCRC核心的最初重点是使用新的硅胶方法来识别 用于开发α-突触核蛋白(ASYN)和4R-tau的PET放射性示踪剂的先导化合物。这 铅化合物鉴定方法具有很高的创新性，因为它在此之前从未被应用过 在PET放射性示踪剂开发领域。一旦进入硅胶，点击率已被确认为真正的铅 在项目1和2中进行的放射性配基结合研究的化合物，MCRC核心将是 负责进行结构-活性关系(SAR)研究，以确定具有 用于放射性标记的适当性质以及附加的体外和活体表征。这个 放射标记研究将由MCRC核心的放射化学部分进行。 华盛顿宾夕法尼亚大学的MCRC核心项目涉及四个不同的地点 圣彼得堡大学Louis、匹兹堡大学和合同研究机构MedChem 成像。核心联席董事是宾夕法尼亚大学的罗伯特·H·马赫博士和E·詹姆斯·彼得森博士；每个网站 还将有一个网站P.I.(C.Mathis，皮特；Z.Tu，华盛顿大学；Neil Vasdev，MedChem成像)。网站P.I.S 将担任执行指导委员会成员，该委员会将通过视频电话会议 每两周一次。执行指导委员会的目标是监测硅胶技术的进展情况 筛选方法和体外结合研究，以及应分配给哪一组的确定 由此产生的合成孔径雷达研究了真正的先导化合物。MCRC核心的另一个目标是进行 体外试验，以确定有希望的化合物是否为P-糖蛋白的底物。的最后一个功能 MCRC的核心是对成像所需的前体和标准进行放大合成 由临床影像中心进行的研究。

MEDICINAL CHEMISTRY AND RADIOCHEMISTRY CORE ABSTRACT The Medicinal Chemistry and Radiochemistry (MCRC) Core represents the central hub of activity of this U19 Center. The initial focus of the MCRC Core is the use of novel in silico methods for the identification of lead compounds for PET radiotracer development for alpha synuclein (Asyn) and 4R tau. This approach to lead compound identification is highly innovative since it has never been applied prior to this in the field of PET radiotracer development. Once in silico hits have been confirmed as true lead compounds from the radioligand binding studies conducted in Projects 1 and 2, the MCRC Core will be responsible for conducting structure-activity relationship (SAR) studies to identify compounds having the appropriate properties for radiolabeling and additional in vitro and in vivo characterization. The radiolabeling studies will be conducted by the radiochemistry component of the MCRC Core. There are four different sites involved in the MCRC Core, the University of Pennsylvania, Washington University-St. Louis, the University of Pittsburgh, and the contract research organization, MedChem Imaging. The Core Co-Directors are Drs. Robert H. Mach and E. James Petersson of Penn; each site will also have a site P.I. (C. Mathis, Pitt; Z. Tu, Wash U; Neil Vasdev, MedChem Imaging). The site P.I.s will serve as members of the Executive Steering Committee, who will meet via video teleconference on a bi-weekly basis. The goal of the Executive Steering Committee is to monitor progress of the in silico screening methods and in vitro binding studies, and the determination of which group should be assigned the resultant SAR studies on the true lead compounds. Another goal of the MCRC Core is to conduct an in vitro assay to determine if promising compounds are substrates for P-glycoprotein. A final function of the MCRC Core is to conduct scale-up synthesis of precursors and standards required for the imaging studies conducted by the Clinical Imaging Core.