TSUKAMOTO (JOHNS HOPKINS UNIVERSITY) MCSP - LEAD OPTIMIZATION CHEMISTRY

这项研究是NIH帮助结束成瘾长期(Hear)倡议的一部分，该倡议旨在加快科学解决方案，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)和美国国立卫生研究院的蓝图 神经治疗网络(BPN)http://neuroscienceblueprint.nih.gov/bpdrugs/index.htm有需求 为药物化学支持计划(MCSP)提供全方位服务的设施和工作人员 从领先优化化学阶段开始支持药物化学发现计划，以 发展构效关系(SAR)分析和设计、合成、体外吸收、 分布、新陈代谢、排泄和毒理学(ADMET)、计算化学/计算机辅助 药物发现(CADD)和储存和运输的复合物流，以支持贡献者 Tsukamoto(约翰·霍普金斯大学)开发出一种新的治疗疼痛的有效方法。这将是 通过提高它们的小分子杂环起始化合物的SAR/SPR来实现 检测和体外ADMET，以确定新的，选择性的靶酶抑制剂 疼痛。我们的药物发现途径将是合成基于杂环支架的新型配体 这些都是有效的抑制物。候选分子将接受分析以评估具体相关的标准 在治疗环境中化合物的物理化学性质，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。我们的目标是推进 关于确定临床前候选人的项目进行/不进行的决定)。由此产生的数据 合同将由NINDS、贡献者或受赞助的调查人员用于支持调查新闻 药物(IND)应用指导临床前活动。这份合同的努力成果将是 促进临床前候选化合物进一步开发的基础，即先进的PK和 IND备案准备过程中的毒理学评价

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