Medicinal Chemistry and Lead Development Core

药物化学和铅开发核心(MCLDC)是抗病毒药物发现和开发中心的关键组成部分，为每个单独项目的目标做出贡献。MCLDC将提供Hit-to-Lead分析、合成化学、结构-活性关系(SAR)数据和分析、计算支持以及领先的优化化学，以推进CETR为治疗新出现的病原体开发新的复制抑制剂和其他基础广泛的疗法的目标。在这一角色中，MCLDC将与筛选核心(SC)一起，成为该计划翻译研究部分的中心焦点。随着SC优化由各种研究项目开发的新的分析方法，并随后进行筛选活动，MCLDC的职能将是评估出现的热门化合物的质量，并最终将新的、易处理的Hit转化为具有优化的生物学和生物物理特性的潜在临床有用药物。因此，MCLDC将与自然科学委员会和每个研究项目团队密切合作。由于在铅优化过程中准备了新的化学实体，由于预期的合成吞吐量，SC通常将在初步测试中测试这些类似物，以推动SAR调查。如下文详细描述的那样，适当的化合物还将提供给各个研究项目团队进行深入研究，包括功效、作用机制和其他实验。由SC和Research项目产生的关于这些化合物的结果数据将由MCLDC进行分析，以推动迭代药物发现计划的完成。MCLDC将把自然科学和研究项目团队的主要成员纳入优先次序和决策程序。这一过程的最终结果将是确定适合IND应用的新药。

The Medicinal Chemistry and Lead Development Core (MCLDC) is a key component of the Antiviral Drug Discovery and Development Center, contributing to the goals of each of the individual projects. The MCLDC will provide hit-to-lead analysis, synthetic chemistry, structure-activity relationship (SAR) data and analysis, computational support, and lead optimization chemistry to further the CETR's goal of developing new replication inhibitors and other broad-based therapeutics for the treatment of emerging pathogens. In this role, the MCLDC, in conjunction with the Screening Core (SC), will be the central focus of the translational research component of the program. As the SC optimizes the novel assays developed by various Research Projects, and subsequently prosecutes the screening campaign, it will be the function of the MCLDC to assess the quality ofthe hit compounds that emerge, and ultimately to convert novel, tractable hits into potential clinically useful drugs with optimized biological and biophysical properties. As such, the MCLDC will work closely with both the SC and each of the Research Project teams. As new chemical entities are prepared during the lead optimization process, because of the anticipated synthetic throughput the SC will generally test these analogs in a primary assay in order to drive the SAR investigation. As described in detail below, appropriate compounds will also be provided to the various Research Project teams for advanced studies including efficacy, mechanism of action, and other experiments. The resulting data about these compounds, generated by the SC and Research Projects, will then be analyzed by the MCLDC in order to drive the iterative drug discovery program to completion. The MCLDC will incorporate key members of the SC and Research Project teams into the prioritization and decision making procedures. The end result of this process will be the identification of novel drugs appropriate for IND applications.