Pilot Scale Libraries Based on Biologically Active Scaffolds

基于生物活性支架的中试规模文库

• 批准号: 8076724
• 负责人: SCOTT R GILBERTSON
• 金额: $ 36.46万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8076724
• 关键词: 3-tropinone; Biology; Biomedical Research; Cancer Center; Chemistry; Collaborations; Communities; Doctor of Medicine; Ensure; Hydroxyproline; Libraries; Methods; Molecular Bank; Pyridones; Research; Solubility; System; United States; United States National Institutes of Health; Work; analog; base; design; dysiherbaine; functional group; pharmacophore; physical property; public health relevance; scaffold; small molecule; tool

DESCRIPTION (provided by applicant): In this application we propose to synthesize libraries based on the following scaffolds, tropinones, hydroxyprolines, 2(1H)-pyridone ring systems and 1,5-dioxaoctahydroindenes. These scaffolds were chosen for a variety of reasons, including their inherent activity, stability, availability and common methods that can be used in the synthesis of analogs. The general approach that will be taken in the synthesis of each of the libraries proposed is to start with a scaffold that can be synthesized in sufficient quantities to ensure that access to the starting core will not limit the ability to synthesize libraries. (The synthesis of the dysiherbaine core is more complicated and consequently smaller libraries will be synthesized around this scaffold.) So that we are assured to being able to provide the libraries we propose, each core has functional groups with orthogonal reactivity that allows for the attachment of pharmacophores by reliable chemistry. To help ensure that the libraries have the desired physical properties such as solubility and stability the scaffolds that have been chosen have all been found to be biologically active. Additionally, we have entered in to a collaboration with Dr. Shuxing Zhang from M.D. Anderson Cancer Center to provide computational support in the design of diverse libraries. PUBLIC HEALTH RELEVANCE: The compounds synthesized during the project period will be used to support the National Institutes of Health Molecular Libraries initiative and the National Small Molecule Repertory. The proposed work will create valuable research tools to study biology and support the biomedical research community in the United States.

描述（由申请人提供）：在本申请中，我们建议根据以下支架，肌动蛋白，羟基丙啉，2（1H） - 吡啶酮环系统和1,5-二氧化碳的2（1h）二氧化碳。由于多种原因选择了这些脚手架，包括它们固有的活性，稳定性，可用性和可用于合成类似物的常见方法。提出的每个库的合成中将采用的一般方法是从可以用足够数量合成的脚手架开始，以确保访问开始核心不会限制合成库的能力。 （放置障碍核心的合成更为复杂，因此较小的库将在该脚手架周围合成。）这样我们就可以确保能够提供我们提出的库，每个核心具有正交反应性，可以通过可靠的化学来连接药物学。为了帮助确保库具有所需的物理特性，例如溶解度和稳定性，已发现所选择的脚手架都被发现具有生物活性。此外，我们已经与M.D. Anderson Cancer Center的Shuxing Zhang博士进行了合作，以在不同图书馆的设计中提供计算支持。 公共卫生相关性：项目期间合成的化合物将用于支持美国国立卫生学院分子图书馆计划和国家小分子库。拟议的工作将创建有价值的研究工具，以研究生物学并支持美国的生物医学研究界。