SYSTEM FOR THE LARGE SCALE SYNTHESIS OF ANTI-AIDS DRUGS

抗艾滋病药物大规模合成系统

• 批准号: 2185180
• 负责人: NORMAN G ANDERSON
• 金额: $ 25万
• 依托单位: LARGE SCALE BIOLOGY CORPORATION
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2185180
• 关键词: antiAIDS agent; antisense nucleic acid; centrifugation; chemical synthesis; drug design /synthesis /production; nucleic acid chemical synthesis; thiophosphate

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.

特定序列药物的大规模固相合成， 包括反义药物、适配子、核酶、核酶和其他形式 一系列尚未完全解决的问题。台架秤 这些化合物的合成是例行公事，就像在 所谓的“大规模”合成器。芳香族化合物的研究进展 这一类药物最初需要小规模的合成 毒物学和生物制品的筛选、中试合成 药理研究，并逐步扩大生产，以获得更多 更广泛的动物研究和临床试验。规模的大幅增长 如果一种药物最终获得批准，就需要进行生产。现有 商用合成器，最初单独使用，然后用于电池供电 不断地，并已使公司达到I期临床试验 大多数药物，并达到充分生产的药物，其利用 都会很小。然而，对于需要在 每年几十公斤到公吨的范围内，一直没有路径 弥合现有的克级系统和预计的大型系统之间的差距 规模化生产。这项建议描述了一种灵活的发展 固相合成系统，其每个组分都可以放大到 产品的千克范围、结构和测试 小规模的组件，以及系统的设计计划， 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。这个 开发专有和高效的新的合成方法 以及前景看好的药物类别--这项研究的潜在产品-- 将有助于保持这一领导地位。