Pilot Scale Libraries Based on Biologically Active Scaffolds

描述（由申请人提供）：在本申请中，我们拟合成基于以下支架的文库：tropinones， hydroxy脯氨酸，2(1H)-pyridone环体系和1,5- dioxaoctahydroinines。选择这些支架有多种原因，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用方法。在每个拟议的库的合成中，将采取的一般方法是从一个可以合成足够数量的支架开始，以确保对起始核心的访问不会限制库的合成能力。（dysiherbaine核心的合成更为复杂，因此围绕这个支架将合成更小的文库。）因此，我们保证能够提供我们提出的文库，每个核心都有具有正交反应性的官能团，可以通过可靠的化学方法附着在药效团上。为了确保文库具有所需的物理性质，如溶解度和稳定性，所选择的支架都被发现具有生物活性。此外，我们还与md安德森癌症中心的张树星博士合作，为各种图书馆的设计提供计算支持。

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.