Function and Informatics Driven Assembly of New Pilot Scale Libraries

功能和信息学驱动的新中试规模文库的组装

• 批准号: 8116699
• 负责人: SERGEY A KOZMIN
• 金额: $ 33.6万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8116699
• 关键词: Benzodiazepines; Biological; Biological Factors; Biological Process; Biomedical Research; Chemicals; Collection; Computer Analysis; Databases; Development; Guanidines; Informatics; Libraries; Molecular Bank; Parents; Property; Protocols documentation; PubChem; Pyrrolidinones; Screening procedure; Series; Therapeutic Agents; United States National Institutes of Health; base; design; novel therapeutics; public health relevance; repository; research and development; scaffold; small molecule; small molecule libraries; tool

DESCRIPTION (provided by applicant): The objective of this project is to assemble a series of pilot-scale heterocyclic libraries to enable the discovery of new bioactive chemotypes by accessing the regions of chemical diversity space, which are not represented in the PubChem database and absent in the NIH Molecular Libraries Small-Molecule Repository (MLSMR). The design of such libraries will be guided by three main considerations, including (a) validated biological activity of closely related chemotypes; (b) rigorous computational analysis of favorable physicochemical properties; and (c) development of concise, parallel synthetic protocols to enable efficient assembly of parent libraries, resupply of active compounds and construction of focused libraries. The project is divided into four specific aims, including (a) construction of libraries based on dihydroquinolone and quassinoids; (b) assembly of scaffold-diversified pyrrolidinone libraries; (c) synthesis of tricyclic benzodiazepine-fused library; and (d) assembly of polycyclic amino guanidine-based libraries. We will prepare seven heterocyclic libraries (3,600 new compounds), which are designed to expand the MLSMR collection with sophisticated, natural product-like compounds in order to enable identification of new small- molecule modulators of diverse biological functions. PUBLIC HEALTH RELEVANCE: The objective of this project is to assemble a series of chemical libraries which are not represented in the PubChem database and absent in the NIH Molecular Libraries Small-Molecule Repository. Subsequent high-throughput biological screening of such compound libraries will produce new chemical tools, large amount of publicly accessible information, and will facilitate basic biomedical research and development of new therapeutic agents.

描述（由申请人提供）：该项目的目的是组装一系列试验尺度的杂环库，以通过访问化学多样性空间的区域来发现新的生物活性化学型，这些区域在PubChem数据库中并未表示，而在NIH分子图书馆中没有代表。此类文库的设计将以三个主要考虑因素为指导，包括（a）密切相关化学型的验证生物学活性； （b）有利物理化学特性的严格计算分析； （c）开发简明的并行合成协议，以有效地组装父库，补充活性化合物和集中库的构建。该项目分为四个特定的目标，包括（a）基于二氢喹诺酮和Quassinoids的图书馆的构建； （b）脚手架变化的吡咯烷酮库的组装； （c）三环苯二氮卓融合的库的合成； （d）基于多环氨基鸟嘌呤的库的组装。我们将准备七个杂环库（3,600种新化合物），旨在扩大具有复杂的天然产物样化合物的MLSMR收集，以便鉴定出多种生物学功能的新小分子调节剂。 公共卫生相关性：该项目的目的是组装一系列化学库，这些化学库在PubChem数据库中未代表，而在NIH分子库中不存在小分子存储库中。随后对此类化合物库的高通量生物学筛查将产生新的化学工具，大量公共信息，并促进新的治疗剂的基本生物医学研究和开发。