COOPERATIVE DRUG DISCOVERY GROUP--AIDS

一个多机构集团寻求为一个非常成功的 正在进行的协作已经确定了一名临床候选人 治疗HIV-1感染，即U-87201E，一种非核苷类药物 HIV-1逆转录酶(RT)。本建议书包含4个项目， 代表识别、评估和优化的完整、合理的计划 新型艾滋病毒复制抑制剂。 厄普约翰实验室的四个项目将主要寻求 确定并优化其抗病毒和药用性能 HIV基本核糖核酸酶H(RNase H)活性的抑制物 RT.这些项目将相互整合，并使用一种“结构-- “主导药物设计范式”将先导抑制剂开发成药物 候选人。研究RT亚基相互作用及其与 将执行反转录的控制。致力于新的 已经在Upjohn化学物质中确定的RT抑制剂的类别 将对清单进行评估，以确定抑制HIV RT的新机制。 这些项目加在一起代表的是一群研究人才，而不是 在任何一家机构都可以实现。这个群体的经历和 他们在艾滋病研究领域的记录生产力，确保了这一点 该计划将继续取得成功。

A multi-institutional group seeks to renew funding of a very successful ongoing collaboration that has already identified a clinical candidate for treating HIV-1 infection, i.e., U-87201E, a nonnucleoside inhibitor of the HIV-1 reverse transcriptase (RT). This proposal contains 4 projects that represent an integrated, rational plan to identify, evaluate, and optimize novel inhibitors of HIV replication. Four of the project at Upjohn Laboratories will principally seek to identify and optimize the antiviral and pharmaceutical properties of inhibitors of the essential ribonuclease H (RNase H) activity of the HIV RT. These projects will integrate with one another and use a "Structure- Driven Drug Design Paradigm" to develop lead inhibitors into drug candidates. Studies investigating RT subunit interaction as it relates to the control of reverse transcription will be performed. Work on new classes of RT inhibitors already identified in the Upjohn chemical inventory will be evaluated for novel mechanisms of inhibiting the HIV RT. Together these projects represent a group of research talents not attainable at any single institution. The experience of this group and their documented productivity in the AIDS research area, insure this program will continue to be successful.