NEW SYNTHETIC METHODS FOR ANTICANCER RESEARCH

抗癌研究的新合成方法

• 批准号: 6137431
• 负责人: LANNY S LIEBESKIND
• 金额: $ 24.92万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-20 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6137431
• 关键词: antineoplastics; chemical synthesis; cycloalkene; drug design /synthesis /production; organometallic compounds; porphyrins; quinones

DESCRIPTION: (Principal Investigator's) The broad, long-term objectives of thi proposal are: (1) to develop new synthetic methods of use in the design and development of anticancer, antibiotic, and possibly antiviral drugs, and (2) to develop novel methods for the delivery and in vivo activation of anticancer drugs. The facile and controlled introduction of varied substituents about an aromati or heteroaromatic core during structure-activity relationship studies is a recurring problem encountered in the development of many new medicinal agents that are based on small organic molecules. This remains an important factor in drug development even with the advent of combinatorial chemistry, which identifies but does not optimize drug leads. To accomplish this important goal new methods are proposed that are based upon "biominetic" cross-coupling using coenzyme A and coenzyme M mimics. Cyclobutenedione-based synthetic methods have matured to the point that they now are ready for incorporation into challenging, non-methodological problems. Using cyclobutenedione methodology as a seminal component of each system, metallaquinones and porphyrin quinones are being developed as novel anticancer agents.

描述：（主要研究者）广泛的长期目标 这些建议是： (1)开发新的合成方法，用于设计和开发 抗癌、抗生素和可能的抗病毒药物，以及（2）开发 用于抗癌药物的递送和体内活化的新方法。 本文介绍了一种简便、可控地引入各种取代基的方法， 构效关系中的芳香或杂芳核 研究是一个经常性的问题，在许多新的发展中遇到的， 基于小有机分子的药剂。 这依然是一项 药物开发中的重要因素，即使随着组合药物的出现， 化学，它识别但不优化药物线索。 完成 这一重要目标提出了新的方法， 使用辅酶A和辅酶M模拟物的“生物动力学”交叉偶联。 基于环丁烯二酮的合成方法已经成熟到这样的程度， 现在已经准备好纳入具有挑战性的，非方法论的， 问题 使用环丁烯二酮方法作为每种方法的种子成分， 系统，金属醌和卟啉醌被开发为新的 抗癌剂。