NEW SYNTHETIC METHODS FOR ANTICANCER RESEARCH

描述：(首席调查员)的广泛、长期目标 这些建议包括： (1)开发用于设计和开发的新的合成方法 抗癌，抗生素，可能还有抗病毒药物，以及(2)开发 抗癌药物给药和体内激活的新方法。 关于AN的各种取代基的简便和可控的引入 构效关系中的芳香族或杂芳族核心 学习是一个反复遇到的问题，在许多新的开发中 以有机小分子为基础的药物制剂。这仍然是一个 药物开发中的重要因素，即使是在组合药物出现的情况下 化学，它识别但不优化药物先导。要完成 基于这一重要目标，提出了一些新的方法 利用辅酶A和辅酶M模拟的“生物动力学”交叉偶联。 基于环丁二酮的合成方法已经成熟到它们 现在已经准备好融入到具有挑战性的、非方法论的 有问题。使用环丁二酮方法作为每个 体系、金属对苯二酚和卟啉对苯二酚正被开发为新的 抗癌剂。

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.