TSUKAMOTO (JOHNS HOPKINS UNIVERSITY) MCSP - LEAD OPTIMIZATION CHEMISTRY

这项研究是NIH帮助结束长期成瘾（HEAL）计划的一部分，旨在加速科学解决方案，以了解疼痛的基础并加强临床疼痛管理。 国家神经疾病和中风研究所（NINDS）和NIH蓝图 神经治疗学网络（BPN）http://neuroscienceblueprint.nih.gov/bpdrugs/index.htm有需求 药物化学支持计划（MCSP）提供全方位服务的设施和工作人员， 支持从铅优化化学阶段开始的药物化学发现计划， 开展构效关系（SAR）分析与设计、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）和化合物的储存和运输物流，以支持贡献者 冢本（约翰霍普金斯大学）开发一种新的治疗有效的疼痛。这将是 通过利用其小分子杂环起始化合物的SAR/SPR来实现 检测和体外ADMET，以鉴定靶酶的新型选择性抑制剂， 痛苦我们的药物发现方法将是合成基于杂环骨架的新型配体 是有效的抑制剂。候选分子将接受分析以评估具体相关的标准 涉及化合物在治疗环境中的物理化学性质，包括酶选择性和 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 关于临床前候选者的识别的项目进行/不进行决定）。由此产生的数据 合同将由NINDS、贡献者或申办的研究者使用，以支持研究性新 药物（IND）申请指导临床前活动。这份合同的努力结果将是 推进临床前候选化合物进一步开发的基础，即，高级PK和 IND申报材料制备中的毒理学评价

This study is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to understand the basis of pain and enhance clinical pain management. The National Institute on Neurological Disorders and Stroke (NINDS) and the NIH Blueprint Neurotherapeutics Network (BPN) http://neuroscienceblueprint.nih.gov/bpdrugs/index.htm have a need for the Medicinal Chemistry Support Program (MCSP) to provide a full-service facility and staff who would support a medicinal chemistry discovery program beginning at the Lead Optimization 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 Tsukamoto (John Hopkins University) to develop a novel therapeutic effective in pain. 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 pain. 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 on identification of a preclinical candidate). The data generated from this contract will be used by NINDS, contributors or sponsored investigators in support of Investigational New Drug (IND) application directed preclinical activities. The results of the efforts of this contract will be the basis to advance preclinical candidate compounds for further development i.e., advanced PK and toxicological evaluation in preparation of IND filings