TECHNOLOGY FOR GENERATION OF DRUG CANDIDATE LIBRARIES

候选药物库生成技术

• 批准号: 2651281
• 负责人: James B. West
• 金额: $ 10万
• 依托单位: BEND RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2651281
• 关键词: cannabinoid receptor; chemical registry /resource; drug design /synthesis /production; high performance liquid chromatography; method development; narcotic antagonists; opioid receptor; receptor binding

DESCRIPTION (Adapted from Applicant's Abstract): The goal of this program is to develop a new technology for generating biologically active libraries of compounds for high-throughput screening in drug discovery. This new synthesis method will make it possible to create large numbers of drug-candidate compounds with diverse structures -- many of which are difficult or impossible to produce using other library-synthesis methods. In Phase I, (they) plan to produce eight libraries of compounds. Each library will be created from reactants with structural similarities to ligands for two target receptors -- cannabinoid and K-opioid receptors --and the resulting compounds will be screened for binding to these receptors. Feasibility will be demonstrated if binding is demonstrated in at least 1 in 1000 screened compounds. This would represent an order-of-magnitude improvement over the current "hit rates" achieved using combinatorial-chemistry techniques. Phase II would be aimed at improving hit rates to at least 1 in 100 compounds through structural elucidation and study of receptor binding versus synthetic conditions. The technology would also be extended to other ligand/receptor systems to demonstrate broad applicability. Due to the strong market demand for improved technologies for use with high-throughput screening techniques, we anticipate a straightforward pathway to commercialization. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述（改编自申请人的摘要）：本发明的目标是 一个项目是开发一种新的技术， 用于药物高通量筛选的活性化合物库 的发现 这种新的合成方法将有可能创造 大量具有不同结构的候选药物化合物-- 其中许多是很难或不可能使用其它方法生产的 图书馆综合方法第一阶段计划生产八个， 化合物库。 每一个库都将由反应物 与两种靶受体的配体结构相似-- 大麻素和K-阿片受体-产生的化合物将 筛选与这些受体的结合。可行性将是 如果在筛选的1000例中至少1例中证实结合，则证实 化合物. 这将是一个数量级的改进， 目前使用组合化学实现的“命中率” 技术. 第二阶段的目标是提高命中率， 1/100化合物通过结构解析和受体研究 结合与合成条件。 这项技术还将 扩展到其他配体/受体系统，以证明广泛的 适用性 由于市场需求旺盛， 与高通量筛选技术一起使用的技术，我们 这是一条直接通向商业化的道路。 拟议商业应用：不可用