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）：本项目的目的是组装一系列中试规模的杂环文库，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数据库中不存在，并且在NIH分子文库小分子库（MLSMR）中不存在。此类文库的设计将由三个主要考虑因素指导，包括（a）密切相关化学型的经验证的生物活性;（B）有利物理化学性质的严格计算分析;以及（c）开发简明、平行的合成方案，以使得能够有效组装亲本文库、再供应活性化合物和构建聚焦文库。该项目分为四个具体目标，包括（a）构建基于二氢喹诺酮和苦木素的文库;（B）组装支架多样化的吡咯烷酮文库;（c）合成三环苯并二氮杂卓融合文库;以及（d）组装基于多环氨基胍的文库。我们将准备七个杂环库（3，600种新化合物），其旨在用复杂的天然产物样化合物扩展MLSMR集合，以便能够鉴定具有不同生物功能的新小分子调节剂。 公共卫生相关性：本项目的目的是组装一系列的化学库，这些库在PubChem数据库中没有，在NIH分子库小分子库中也没有。随后对这些化合物库的高通量生物筛选将产生新的化学工具，大量的公众可获得的信息，并将促进基础生物医学研究和新治疗剂的开发。