Discovery Based Studies of Medicinally Relevant Pharmacophore Libraries

基于发现的医学相关药效团库研究

• 批准号: 7945926
• 负责人: MATTHEW S SIGMAN
• 金额: $ 36.11万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7945926
• 关键词: Architecture; Biological; Biological Factors; Chemicals; Commit; Communities; Creativeness; Development; Guanidines; Individual; Indoles; Laboratories; Lead; Libraries; Methodology; Mission; Modeling; Preparation; Property; Research; Research Activity; Research Infrastructure; Screening procedure; Structure; Universities; Utah; base; interest; pharmacophore; public health relevance; scaffold; small molecule; small molecule libraries

DESCRIPTION (provided by applicant): This proposal describes our intent to prepare chemical libraries based on important medicinally or natural product inspired scaffolds. We have created a small molecule screening platform to support the University of Utah's commitment to discovery based research activities. We believe that engaging the creativity of individuals within the synthetic community will lead to increased diversity with respect to compound architecture and function. Further this model is supported by individuals with a vested interest in the biological properties of their core architectures, the preparation of which has been inspired by the development of new methodologies. From both internal screening activities and known natural product activities, we have identified several important core structures that are poorly represented in the national screening infrastructure. These architectures are broadly identified as 1) diarylmethines; 2) 2-aminoimidazoles/cyclic guanidines and 3) dimeric indoles. Under the umbrella of these structural classes we have proposed the preparation of 14 chemical libraries to be submitted for screening at the MPLCN. PUBLIC HEALTH RELEVANCE: The proposed research has direct relevance to the mission of the MPLCN. Small molecule libraries will be prepared by the implementation of previously developed chemical methodologies from our individual laboratories. We are committed to delivering -2,500 compounds that will contribute to the fundamental chemical diversity represented in the MLPCN.

描述（由申请人提供）：本提案描述了我们基于重要药物或天然产物启发支架制备化学文库的意图。我们已经创建了一个小分子筛选平台，以支持犹他大学对基于发现的研究活动的承诺。我们相信，在合成社区中融入个人的创造力将增加复合建筑和功能的多样性。此外，该模型得到了对其核心体系结构的生物学特性有既得利益的个人的支持，其准备工作受到新方法发展的启发。从内部筛选活动和已知的天然产物活动中，我们已经确定了几个重要的核心结构，这些结构在国家筛选基础设施中代表性不足。这些结构被广泛地识别为：1)二芳基甲基；2) 2-氨基咪唑/环胍和3)二聚体吲哚。在这些结构类的保护伞下，我们提出了14个化学文库的准备提交给MPLCN筛选。