UCD Combinatorial Center - Novel and Diverse Pilot-Scal*

UCD 组合中心 - 新颖多样的 Pilot-Scal*

• 批准号: 7125571
• 负责人: MARK J. KURTH
• 金额: $ 45.33万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-23 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125571
• 关键词: NIH Roadmap Initiative tag; biochemistry; chemical group; chemical registry /resource; chemical synthesis; cheminformatics; combinatorial chemistry; high performance liquid chromatography; mass spectrometry; small molecule

DESCRIPTION (provided by applicant): In response to the RFA-RM-05-014, we plan to use both solid- and solution-phase strategies to synthesize several pilot-scale libraries to be submitted to NIH for subsequent distribution for various biological assays. Our aim is to prepare chemically pure, structurally diverse small-molecule compounds. These small-molecule compounds will be prepared by adaptation of published synthetic routes or, as appropriate, by development of novel synthetic strategies. Diversity-oriented synthesis (DOS) libraries will generally have ~100-200 members each with =90% purity of non-commercial small-molecules. Our plan is to prepare two types of libraries for each scaffold: (i) a small demo library to test the chemistry and validate the procedures, using the IRORI system for compound synthesis and tracking; (ii) a Trident- or IRORI-based library to deliver a focused library of compounds. The output of libraries (i) and (ii) will be combined, archived, and made available for biochemical evaluation. The dinitrodifluorobenzene-based scaffold will be prepared in larger number and quantity. Some of the solid-phase synthesis libraries will be generated with a built-in hydrophilic handle with site-specific functional groups so that these compounds can be subsequently tagged for specific assays while others will be prepared without any handle. Each compound will be analyzed by HPLC for purity and its identity confirmed by mass spectroscopy. If needed, FlashTube advanced flash chromatography will be used for compound purification. The NIH PubChem will be used for management of our various pilot libraries and we plan to set up a UC Davis Combinatorial Chemistry web site with links to PubChem. As required by the RFA, at least 10 mg of each library member will be archived and each will have =90% purity.

描述（由申请人提供）：为了响应 RFA-RM-05-014，我们计划使用固相和溶液相策略来合成几个中试规模的文库，并将其提交给 NIH，以便随后分发用于各种生物测定。我们的目标是制备化学纯、结构多样的小分子化合物。这些小分子化合物将通过调整已发表的合成路线或酌情通过开发新的合成策略来制备。面向多样性的合成 (DOS) 库通常有约 100-200 个成员，每个成员的非商业小分子纯度 = 90%。我们的计划是为每个支架准备两种类型的库：（i）一个小型演示库，用于测试化学并验证程序，使用 IRORI 系统进行化合物合成和跟踪； (ii) 基于 Trident 或 IRORI 的库，用于提供重点化合物库。文库 (i) 和 (ii) 的输出将被合并、存档并可用于生化评估。二硝基二氟苯基支架将大量制备。一些固相合成文库将使用带有位点特异性官能团的内置亲水手柄生成，以便随后可以标记这些化合物用于特定测定，而其他化合物将在没有任何手柄的情况下制备。每种化合物将通过 HPLC 分析纯度，并通过质谱确认其身份。如果需要，FlashTube 先进的快速色谱法将用于化合物纯化。 NIH PubChem 将用于管理我们的各个试点图书馆，我们计划建立一个加州大学戴维斯分校组合化学网站，并提供 PubChem 的链接。根据 RFA 的要求，每个文库成员至少 10 毫克将被存档，并且每个成员的纯度均 = 90%。