SYSTEM FOR THE LARGE SCALE SYNTHESIS OF ANTI-AIDS DRUGS

特定序列药物的大规模固相合成， 包括反义药物、适体、核酶、nexamers等， 一系列尚未完全解决的问题。 实验室规模 这些化合物的合成是常规的， 所谓的“大规模”合成器。 化合物的开发 这类药物需要最初的小规模合成， 筛选、毒理学和 药理学研究，并逐步扩大生产， 动物实验和临床试验。 规模的大幅度增加 如果一种药物最终获得批准，就需要进行生产。 现有 商业合成器，最初单独使用，然后在电池运行 并使公司能够进入I期临床试验 大多数药物，并达到充分生产的药物， 会很小。 然而，对于需要在 从每年几十公斤到公吨的范围， 弥合现有克级系统和预计的大型 规模生产。 该提案描述了灵活的 固相合成系统，其每个组件可以按比例放大到 公斤的产品范围，建设和测试的 小规模的组件，以及设计的系统计划， 评估和生产一系列越来越大的系统。 拟议的商业应用：保持世界领先地位， 新药的生产对美国经济很重要。 的 开发专有和有效的方法来合成新的 和有前途的药物类别-这项研究的潜在产品- 将有助于保持这种领导地位。

The large scale solid phase synthesis of specific-sequence drugs, including antisense drugs, aptamers, ribozymes, nexamers, and others pose a series of problems which are not completely solved. Bench scale synthesis of these compounds is routine, as is gram-scale production in so-called "large scale" synthesizers. The development of compounds of this class as pharmaceuticals requires initially small scale synthesis for screening, intermediate scale synthesis for toxicological and pharmacological studies, and progressively larger production for more extended animal studies, and clinical trials. A large increment in scale of production is required if a drug is finally approved. Existing commercial synthesizers, used initially alone and then in batteries run continuously, and have allowed companies to reach Phase I clinical trials for most drugs, and to reach full production for drugs whose utilization will be small. However, for compounds which will require production in the range of tens of kilos to metric tons per year, there has been no path to bridge the gap between existing gram scale systems and projected large scale production. This proposal describes the development of a flexible solid phase synthesis system, each component of which can be scaled up to the kilogram-of-product range, the construction and testing of the components on a small scale, and a systematic plan for designing, evaluating, and producing a series of increasingly larger systems. PROPOSED COMMERCIAL APPLICATION: Maintaining world leadership in the production of new pharmaceuticals is important to the U.S. economy. The development of proprietary and efficient methods for the synthesis of new and promising classes of drugs - a potential product of this research - will assist in maintaining that leadership.