Medicinal Chemistry Core

药物化学核心

基本信息

批准号：
8655936
负责人：
Joel Stephen Freundlich
金额：
$ 50.63万
依托单位：
RBHS-NEW JERSEY MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8655936
关键词：
Academia Address Animal Testing Anti-Bacterial Agents Area Bacterial Infections Binding Biological Biological Assay Chemicals Chemistry Clinical Complement Complex Computer Simulation Computing Methodologies Consult Cyclization Data Doctor of Philosophy Drug Industry Drug Kinetics Enzymes Evaluation Evolution Family Foundations Generations Human Resources Individual Industry Lead Learning Libraries Metabolic Methods Mind Mycobacterium tuberculosis Paper Peptides Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacologic Substance Pharmacology Plant Resins Postdoctoral Fellow Process Program Research Project Grants Property RNA Polymerase Inhibitor Research Resources S Phase Scientist Solid Source Structure Techniques Therapeutic Time Toxic effect Translating Translations Validation Vision analog chemical resource cheminformatics cost design drug candidate drug discovery experience follow-up global health inhibitor/antagonist insight interest member novel programs screening skills small molecule structural biology

项目摘要

The Medicinal Chemistry Core (MCC; Core D) will provide chemistry resources complementary to those existing within the respective project teams. The MCC resource will distinguish itself by relying on extensive pharmaceutical medicinal chemistry experience melded with an academic foundation in antibacterials. Critically, the MCC staff have demonstrated in the pharmaceutical industry setting their ability to discover drug candidates by evolving small molecules to address a wide range of problems encountered during the process. This experience will be essential to: Project 1) the optimization of small molecules ofthe arylpropionyl trialkylphloroglucinol family as antibacterials. Project 2) the evolution of small molecule inhibitors of essential metabolic enzymes, such Pks13, in M. tuberculosis. Project 4) the solid-phase synthesis of non-ribosomally encoded peptides with significant potential as antibacterials, and Project 5) the discovery and optimization of small molecule antibacterials leveraging Bayesian computational models. These projects necessitate experience with a diverse range of chemistries as found in the description of each MCC member's background. Overall, the spectrum and depth ofthe MCC staffs chemistry background will prove critical to their ability to translate basic scientific discoveries within the individual projects to small molecules with significant potential for positively impacting the antibacterial clinical landscape to address the global health crisis.

药物化学核心（MCC；核心 D）将提供与各自项目团队中现有资源互补的化学资源。 MCC 资源将凭借丰富的药物化学经验与抗菌药物的学术基础相结合而脱颖而出。至关重要的是，MCC 工作人员在制药行业展示了他们通过开发小分子来发现候选药物的能力，以解决在此过程中遇到的各种问题。这一经验对于以下项目至关重要：项目 1) 芳基丙酰基三烷基间苯三酚家族小分子作为抗菌剂的优化。项目 2) 结核分枝杆菌中必需代谢酶（例如 Pks13）的小分子抑制剂的进化。项目 4）具有作为抗菌药物的巨大潜力的非核糖体编码肽的固相合成，项目 5）利用贝叶斯计算模型发现和优化小分子抗菌药物。这些项目需要具有各种化学方面的经验，每个 MCC 成员的背景描述中都可以找到这些经验。总体而言，MCC 员工化学背景的广度和深度对于他们将各个项目中的基本科学发现转化为小分子的能力至关重要，这些小分子具有对抗菌临床景观产生积极影响以应对全球健康危机的巨大潜力。