COBRE: UKS: CORE C: MEDICINAL CHEMISTRY

COBRE：UKS：核心 C：药物化学

• 批准号: 7609706
• 负责人: Lester A. Mitscher
• 金额: $ 37.56万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609706
• 关键词: Acids; Anti-Bacterial Agents; Antifungal Agents; Carboxylic Acids; Cell Wall; Cleaved cell; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Condition; Data; Education; Educational workshop; Enzyme Inhibition; Enzymes; Equipment; Funding; Furans; Generations; Goals; Grant; Human Resources; Institutes; Institution; Investigation; Laboratories; Lead; Libraries; Methionine; Methodology; Numbers; Participant; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmaceutical Technology; Protease Inhibitor; Protocols documentation; Reporting; Research; Research Personnel; Resources; Sorting - Cell Movement; Source; Structure-Activity Relationship; Thiophene; Thiophenes; United States National Institutes of Health; analog; base; furan; inhibitor/antagonist; instrumentation; pyridine; symposium

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. Note: This information was found under Core D in previous reports. Based on hits from the HTS laboratory, Core C has supported two projects with medicinal chemistry expertise and has prepared a number of analogues of the hit compounds. One project focuses on the synthesis of a library of methionine amino peptidase inhibitors as potential anticancer, antibacterial, and antifungal agents. The enzyme was co-crystallized with a substituted furoic acid, which became the lead compound for further study. Towards this goal, we have developed a catch-Suzuki-release strategy to generate various aryl substituted furan and thiophene carboxylic acid. Current efforts are aimed at optimizing experimental conditions for related pyridine carboxylic acids. In addition, investigations using Irori Accutag¿ protocols for facile combine-sort-cleave methodology are being pursued for the generation of the aforementioned biaryl compounds. The second project concerns MurA, a bacterial cell wall synthesis enzyme. Inhibition of the enzyme leads to antibacterial activity. MurA inhibitors were identified by HTS and one hit compound was co-crystallized with the enzyme. These preliminary data were used to submit an NIH RO3 application and a plan for structure-activity relationship studies was developed. The acquisition of large-scale synthesis equipment and analytical instrumentation was continued to enhance the capabilities of the Core C laboratory. Core C personnel have been active participants in the formation of NIPTE (National Institute for Pharmaceutical Technology and Education), an organization that has as its goal making safer, cheaper drugs and to preserve the U.S. advantage in drug manufacturing. Core C continued to organize symposia, workshops and seminars in collaboration with Core A. Core C also and made acquisition of compounds for the HTS laboratory. We expect to initiate 1-2 new medicinal chemistry projects in the coming fiscal year.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 注意：此信息是在先前报告中的核心D下找到的。 根据HTS实验室的命中，Core C支持了两个具有药物化学专业知识的项目，并准备了许多热门化合物的类似物。一个项目的重点是将蛋氨酸氨基肽抑制剂库的合成作为潜在的抗癌，抗菌和抗真菌剂。将酶与取代的呋喃酸共结晶，这成为进一步研究的铅化合物。为了实现这一目标，我们已经开发了一种捕获的苏木释放策略，以产生各种芳基取代的呋喃和噻吩羧酸。目前的努力旨在优化相关吡啶羧酸的实验条件。此外，正在为Priore Biaryl化合物的生成使用IRORI ACCUTAG知识方案进行简便的组合裂缝方法。第二个项目涉及一种细菌细胞壁合成酶Mura。抑制酶会导致抗菌活性。通过HTS鉴定Mura抑制剂，并与酶共结晶。这些初步数据用于提交NIH RO3应用程序，并进行结构活动关系研究的计划，获取大规模合成设备，并继续进行分析仪器，以增强核心C实验室的能力。核心C人员一直是NIPTE（国家药物技术与教育研究所）的成立的积极参与者，该组织的目标是使其目标更安全，廉价的药物并保持美国在药品制造方面的优势。 Core C继续与A Core A合作组织符号，研讨会和下水道，并为HTS实验室收购化合物。我们预计将在未来财政年度开始1-2个新的医学化学项目。