MEDICINAL CHEMISTRY, CHEMICAL SYNTHESIS, AND MASS SPECTROMETRY

药物化学、化学合成和质谱分析

• 批准号: 8168768
• 负责人: Paul R Carlier
• 金额: $ 0.01万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-10 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168768
• 关键词: Acetylcholinesterase Inhibitors; Africa South of the Sahara; Alkylation; Alzheimer' s Disease; Anopheles gambiae; Area; Benzodiazepines; Chemistry; Computer Retrieval of Information on Scientific Projects Database; Culicidae; Funding; Grant; Insecticides; Institution; Interest Group; Malaria; Mass Spectrum Analysis; Methods; Multinuclear NMR; NMR Spectroscopy; Organic Synthesis; Pathway interactions; Pharmaceutical Chemistry; Reaction; Reagent; Research; Research Personnel; Resources; Route; SSRI-resistant depression; Source; Structure; United States National Institutes of Health; Work; base; beta secretase; beta-site APP cleaving enzyme 1; chemical synthesis; inhibitor/antagonist; interest; novel; prevent; reuptake; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Medicinal Chemistry. The Carlier group's interests in Medicinal Chemistry encompass three areas. First, they prepare species-selective inhibitors of acetylcholinesterase (AChE) targeting the malaria mosquito (Anopheles gambiae). Such compounds could be deployed on insecticide treated nets to prevent malaria transmission in sub-Saharan Africa. Second, they use click-chemistry based discovery methods to identify BACE1 (beta-secretase) inhibitors; such compounds could be to useful to prevent Alzheimer's disease. Finally, they prepare novel triple reuptake inhibitors to treat SSRI-resistant depression. Enantioselective Synthetic Methods. Organolithium reagents are ubiquitous in organic synthesis. The Carlier group is interested in developing new stereoselective reactions of organolithium compounds and enolates, and in using computation and multinuclear NMR spectroscopy to determine structures and reaction pathways. Recently they developed an enantioselective alkylation route to a new class of (so-called "quaternary") benzodiazepines. A key feature of this work is the intermediacy of transiently non-racemic ("dynamically chiral") intermediates.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 药物化学。卡利尔集团对药物化学的兴趣涵盖三个领域。首先，他们制备了针对疟疾蚊子（冈比亚按蚊）的物种选择性乙酰胆碱酯酶（AChE）抑制剂。此类化合物可用于经过杀虫剂处理的蚊帐，以防止撒哈拉以南非洲地区的疟疾传播。其次，他们使用基于点击化学的发现方法来鉴定 BACE1（β 分泌酶）抑制剂；此类化合物可能有助于预防阿尔茨海默病。最后，他们制备了新型三重再摄取抑制剂来治疗 SSRI 耐药性抑郁症。 对映选择性合成方法。有机锂试剂在有机合成中普遍存在。 Carlier 小组有兴趣开发有机锂化合物和烯醇化物的新立体选择性反应，以及使用计算和多核核磁共振波谱来确定结构和反应途径。最近，他们开发了一种对映选择性烷基化路线，用于生产一类新的（所谓的“季”）苯二氮卓类药物。这项工作的一个关键特征是瞬时非外消旋（“动态手性”）中间体的中间体。