GANESH (EMORY UNIVERSITY) - MCSP - HIT TO LEAD CHEMISTRY

在执行本任务单项下的工作时，承包商应提供全方位服务设施 以及支持从Hit-Tolad(HTL)化学阶段开始的药物化学发现计划的工作人员，以开发结构活性关系(SAR)分析和 设计、合成、体外吸收、分布、代谢、排泄和毒理学 (ADMET)、计算化学/计算机辅助药物发现(CADD)和化合物 存储和运输物流，以支持贡献者Ganesh开发一种新的 对癫痫后认知功能障碍的治疗效果。这将通过以下方式实现 利用它们的小分子杂环起始化合物提高其SAR/SPR 检测和体外ADMET以确定目标酶的新的、选择性的抑制剂 旨在治疗癫痫发作后的认知缺陷。我们的药物发现方法将是 合成基于杂环支架的新型配体，这些都是有效的抑制剂。 候选分子将接受简档分析，以评估与 治疗环境中化合物的物理化学性质，包括酶的选择性 以及测试以确定与关键代谢酶系统的潜在相互作用。我们的目标是 要推进项目进行/不进行有关进展到可选领导的决策 优化阶段。

In performance of work under this Task Order, the Contractor shall provide a full service facility and staff who shall support a medicinal chemistry discovery program beginning at the Hit-toLead (HTL) Chemistry phase to develop structure activity relationship (SAR) analysis and design, synthesis, in vitro absorption, distribution, metabolism, excretion and toxicology (ADMET), computational chemistry/Computer Aided Drug Discovery (CADD), and compound logistics of storage and shipping to support the Contributor Ganesh in developing a novel therapeutic effective in treating post-seizure cognitive deficits. This will be achieved by advancing the SAR/SPR of their small molecule heterocyclic starting compound utilizing their assays and in vitro ADMET to identify novel, selective inhibitors of the target enzyme that are directed at treating post-seizure cognitive deficits. Our drug discovery approach will be to synthesize novel ligands based on the heterocyclic scaffold that are potent inhibitors. Candidate molecules will undergo profiling to assess criteria specifically related to the physicochemical properties of compounds in a therapeutic setting, including enzyme selectivity and tests to determine potential interactions with key metabolic enzyme systems. The goal is to advance the project to go/no go decisions with regard to progressing to the optional Lead Optimization phase.