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

在执行本任务指令项下的工作时，承包商应提供全套服务设施 和支持药物化学发现计划的工作人员，从Hit-toLead（HTL）化学阶段开始，开发结构活性关系（SAR）分析， 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 物流的存储和运输，以支持贡献者Ganesh在开发一个新的 有效治疗癫痫发作后认知缺陷。为实现这些目标将 利用其小分子杂环起始化合物的SAR/SPR， 试验和体外ADMET，以鉴定靶酶的新型选择性抑制剂， 旨在治疗癫痫发作后认知缺陷。我们的药物发现方法将是 合成基于杂环骨架的新型配体，它们是有效的抑制剂。 将对候选分子进行分析，以评估与所述分子特异性相关的标准。 化合物在治疗环境中的物理化学性质，包括酶的选择性 和测试以确定与关键代谢酶系统的潜在相互作用。目标是 推进项目进行/不进行决策，以推进可选销售线索 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.