Core B Medicinal Chemistry

摘要 药物化学(MedChem)的核心已经形成，以满足对新技术的迫切需求 抗菌剂。MedChem核心将与项目团队和其他核心无缝合作，以推动 以高威胁性细菌为靶标的新型先导化合物的发现和开发 感染。对其使命至关重要的是其在工业和学术药物化学方面的能力， 化学信息学和结构生物学，这两个学科都有几十年的经验 相关细菌剂的基础生物学。MedChem Core将帮助确认命中 通过计算或实验筛选发现，将这些演变为早期并随后优化的线索 遵循已定义的工作流程，在流程中的每个阶段使用分子的定量度量。这个 MedChem Core将在专注于发现和开发A)间苯三酚的项目上进行合作 和Myxopyronin抗菌药，B)利福霉素和恶唑烷酮类药物抗脓肿分枝杆菌，C) 针对细胞壁生物合成或呼吸作用的抗结核药物，D)挖掘生物合成的抗生素 基因簇和E)细菌细胞膜生物发生抑制剂预防革兰氏阴性菌多药耐药 抵抗力感染。

Abstract The Medicinal Chemistry (MedChem) Core has been formed to address the urgent need for novel antibacterial agents. The MedChem Core will work seamlessly with the Project Teams and other Cores to drive the time- and cost-efficient discovery and development of novel lead compounds to target high-threat bacterial infections. Critical to its mission are its competencies in industrial and academic medicinal chemistry, cheminformatics, and structural biology, which are complemented by decades of experiences with the fundamental biology of the relevant bacterial agents. The MedChem Core will aid in the confirmation of hits discovered through computation or experimental screens, evolve these to early and then optimized leads following a defined workflow with quantitative metrics for molecules at each stage in the process. The MedChem Core will collaborate on projects focused on the discovery and development of A) phloroglucinol and myxopyronin antibacterials, B) rifamycin and oxazolidinone agents against Mycobacterium abscessus, C) antituberculars targeting cell wall biosynthesis or respiration, D) antibiotics suggested by mining of biosynthetic gene clusters, and E) bacterial cell envelope biogenesis inhibitors to prevent Gram-negative multi-drug resistant infections.