Novel Heterocyclic Libraries

新型杂环文库

• 批准号: 7925160
• 负责人: Peter Wipf
• 金额: $ 29.12万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-05 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7925160
• 关键词: 3-Dimensional; Accounting; Architecture; Automation; Azoles; Biological; Biological Assay; Biological Factors; Chemical Structure; Chemicals; Collaborations; Communities; DNA Sequence Rearrangement; Dimensions; Diversity Library; Ethers; Funding; Generations; Goals; Hybrids; Laboratories; Libraries; Methodology; Molecular Bank; Muscle Rigidity; Pharmaceutical Chemistry; Pharmaceutical Preparations; Preparation; Protocols documentation; Provider; Pyrimidine; Pyrimidines; Reaction; Research; Sampling; Screening procedure; Shapes; Shipping; Ships; Steroids; Structure; System; Techniques; United States National Institutes of Health; base; chemical synthesis; combinatorial; enol; follow-up; high throughput screening; member; milligram; nonane; novel; programs; scaffold; small molecule libraries; stereochemistry

DESCRIPTION (provided by applicant): The purpose of this application for support from the NIH Molecular Libraries Roadmap program on the topic of "Accelerated Approaches to Hetero- and Carbocyclic Scaffolds" is to exploit new methodologies previously discovered in the PI's laboratories for the efficient synthesis of chemically diverse Pilot-Scale Libraries for High-Throughput Screening. We propose to generate 4 small molecule libraries of 100-1,000 distinct chemical compounds each, for a total of 2,100 samples, to be submitted to the MLSMR over a period of 3 years. We exclusively target scaffolds that are far underrepresented in the MLSMR. The proposed 3 heterocyclic as well as 1 bridged carbobicyclic ring systems have a high likelihood of modulating the function of biomacro-molecules due to their similarity to natural products or heterocyclic drugs, but contain novel or exceedingly rare core structures. Specifically, we intend to pursue the following goals: 1. Preparation of libraries based on the 5,6-dihydro-2H-1,2,6-thiadiazine 1,1-dioxide heterocyclic chemotype. 2. Preparation of libraries based on the 4H-pyrimido[1,2-a]pyrimidine heterocyclic chemotype. 3. Preparation of libraries based on the 5-sulfonyl-pyrimidine-2,4(1H,3H)-dione heterocyclic chemotype. 4. Preparation of libraries based on the bicyclo[3.3.1]nonane carbobicyclic chemotype. 5. Efficient follow up on the synthesis of 2nd generation libraries for any hits identified in MLPCN HTS campaigns, in close collaboration with the MLPCN and the assay providers. The major strengths of this application are (a) the medicinal chemistry relevance of the proposed scaffolds, which include both heterocyclic, carbobicyclic, and natural product-like structures that currently are poorly if at all represented in the MLSMR, as well as, (b) the track record of the PI in the successful parallel synthesis of libraries of 50-500 members of well characterized organic compounds on multi-milligram scale, including the shipping and handling of these samples to the screening community and the proactive interactions with multiple biological collaborators.

描述（由申请人提供）：本申请申请的目的是NIH分子库路线图计划的“加速方法的加速方法和碳环环脚手架”的主题是利用先前在PI的实验室中发现的新方法，以有效地综合化学的飞行员图书馆库，以供化学多样化的库库来进行较高的群体。我们建议在3年内生成4个小分子文库，分别为100-1,000种不同的化合物，总共2,100个样品，将其提交给MLSMR。我们专门针对 MLSMR中人数不足的脚手架。提出的3个杂环以及1个桥接的碳环状环系统具有很高的可能性，因为它们与天然产物或杂环药物相似，因此可以调节生物分子的功能，但包含新颖或极为罕见的核心结构。具体而言，我们打算追求以下目标：1。基于5,6-二氢-2H-1,2,6-噻嗪1,1-二氧化物杂环化学型制备库的准备。 2。基于4H-吡啶不[1,2-A]嘧啶杂环化学型的库制备。 3。基于5-磺酰基 - 吡啶胺-2,4（1H，3H）-Dione杂环化学型的库制备。 4。基于bicyclo [3.3.1]非甲烷碳环状化学型的库制备。 5。与MLPCN和分析提供商密切合作，在MLPCN HTS广告系列中确定的任何命中的第二代库的合成有效随访。 The major strengths of this application are (a) the medicinal chemistry relevance of the proposed scaffolds, which include both heterocyclic, carbobicyclic, and natural product-like structures that currently are poorly if at all represented in the MLSMR, as well as, (b) the track record of the PI in the successful parallel synthesis of libraries of 50-500 members of well characterized organic compounds on multi-milligram规模，包括将这些样品运送到筛选社区以及与多个生物合作者的积极互动。