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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 注：这一信息见以往报告核心D项下。 基于HTS实验室的命中，Core C已经支持了两个具有药物化学专业知识的项目，并制备了许多命中化合物的类似物。 一个项目集中于合成一个库的蛋氨酸氨基肽酶抑制剂作为潜在的抗癌，抗菌和抗真菌剂。 该酶与取代的糠酸共结晶，糠酸成为进一步研究的先导化合物。为了实现这一目标，我们开发了一种捕捉-铃木-释放策略来生成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的吡啶羧酸的实验条件。 此外，正在进行使用Irori Accutag？方案进行简易组合-分选-切割方法的研究，以生成上述联芳基化合物。 第二个项目涉及MurA，一种细菌细胞壁合成酶。 酶的抑制导致抗菌活性。 通过HTS鉴定MurA抑制剂，并且一种命中化合物与酶共结晶。 这些初步数据用于提交NIH RO 3申请，并制定了结构-活性关系研究计划。 继续购置大型合成设备和分析仪器，以提高核心C实验室的能力。 核心C人员一直积极参与NIPTE（国家制药技术和教育研究所）的成立，该组织的目标是制造更安全，更便宜的药物，并保持美国在药物制造方面的优势。 核心C继续与核心A合作举办专题讨论会、讲习班和研讨会。 核心C还为HTS实验室采购了化合物。 我们预计在下一个财政年度启动1-2个新的药物化学项目。