TECHNOLOGY FOR GENERATION OF DRUG CANDIDATE LIBRARIES

描述(改编自申请人摘要)：本报告的目标 该计划是开发一种用于生物产生的新技术 用于药物高通量筛选的活性化合物文库 发现号。这种新的合成方法将使创造 大量具有不同结构的候选药物-- 其中许多是很难或不可能使用其他 文库合成方法。在第一阶段，计划生产八个 化合物的资料库。每个库都将由反应物创建 与两个靶标受体的配体结构相似-- 大麻素和K阿片受体--以及由此产生的化合物将 筛选与这些受体的结合。可行性将是 如果每1000个筛选中至少有1个显示结合，则会显示 化合物。这将代表着比 目前使用组合化学获得的“命中率” 技巧。第二阶段的目标是将命中率提高到至少 每100种化合物中就有1种是通过结构解析和受体研究得出的 结合条件与合成条件。这项技术也将是 扩展到其他配体/受体系统以展示广泛的 适用性。由于市场需求旺盛，产品质量得到改善 与高通量筛选技术一起使用的技术，我们 期待一条通向商业化的直通之路。 建议的商业应用：不可用

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