REACTOR FOR GENERATION OF COMPOUND DERIVATIVE LIBRARIES

该计划的目标是开发一种新工艺，用于快速生成具有基于单一生物活性母体化合物结构的化学结构的衍生物混合物（即衍生物库）。所提出的工艺可以快速生产结构独特的衍生物，并且可以生产使用传统化学方法不易从母体化合物中获得的衍生物。该过程有望大大加快药物先导物的优化和开发。在第一阶段，我们通过生产含有50种或更多基于两种母体结构的衍生化合物的化学文库来证明其可行性：咖啡因和黄嘌呤。文库反应是可重复的，并且产生了足够数量的特定化合物，可以进行分离、测试和结构表征。这些文库被证明含有生物活性化合物，适合用于高通量筛选。第二阶段的工作将侧重于通过对新的、化学成分更多样化的文库进行广泛的结构解析来开发这一过程。各种衍生化分子和制备变量的影响将被检查。Bend Research计划基于这项技术开发一项业务，为制药客户生产定制库，并提供进一步的分离和有前途的化合物结构解析服务。该工艺将提供一种新的、廉价的方法来快速生成与具有药物活性的母体化合物密切相关但在直接结构特征上不同的化合物文库。成功实施可以显著减少从母体化合物生成具有药用价值的衍生物所需的时间和精力。由于其速度和形成传统化学方法难以获得的衍生物的潜力，该过程在提高药物发现效率方面具有突破性潜力。

This goal of this program is to develop a new process for rapidly generating mixtures of derivatives (i.e., derivative libraries) with chemical structures that are based on the structure of a single bioactive parent compound. The proposed process makes it possible to produce structurally distinct derivatives rapidly and to produce derivatives not readily accessible from the parent compound using traditional chemical methods. The process promises to greatly accelerate the optimization and development of pharmaceutical leads. In Phase I, we demonstrated feasibility by producing chemical libraries that contained 50 or more derivative compounds based on two parent structures: caffeine and xanthine. The library reactions were reproducible, and specific compounds were produced in sufficient amounts to allow isolation, testing, and structural characterization. These libraries were shown to contain bioactive compounds and were suitable for use with high- throughput screening. Phase II work will focus on development of the process through extensive structural elucidation of new, more chemically diverse libraries. The effects of various derivatizing molecules and preparation variables will be examined. Bend Research plans to develop a business based on this technology that will produce custom libraries for pharmaceutical clients and provide further services of isolation and structural elucidation of promising compounds. PROPOSED COMMERCIAL APPLICATION This process would provide a new, inexpensive method for rapidly generating libraries of compounds that are closely related to pharmaceutically active parent compounds but that differ in a direct structural feature. Successful implementation could significantly reduce the time and effort required to generate pharmaceutically valuable derivatives from parent compounds. Due to its speed and potential for forming classes of derivatives not readily accessible by traditional chemical methods, this process has breakthrough potential for increasing the efficiency of drug discovery.