NEW SYNTHETIC METHODS FOR ANTICANCER RESEARCH

抗癌研究的新合成方法

• 批准号: 6341881
• 负责人: LANNY S LIEBESKIND
• 金额: $ 25.24万
• 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 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6341881
• 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：(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。

项目成果

A mild, nonbasic synthesis of thioethers. The copper-catalyzed coupling of boronic acids with N-thio(alkyl, aryl, heteroaryl)imides.

• DOI: 10.1021/ol026948a
• 发表时间: 2002-11
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: C. Savarin;J. Šrogl;L. S. Liebeskind

3-Cyclobutenyl-1,2-dione-substituted porphyrins. A general and efficient entry to porphyrin-quinone and quinone-porphyrin-quinone architectures.

• DOI: 10.1021/jo9912799
• 发表时间: 2000-02
• 期刊: The Journal of organic chemistry
• 作者: X. Shi;S. R. Amin;L. S. Liebeskind

Nonbasic, room temperature, palladium-catalyzed coupling of aryl and alkenyl iodides with boronic acids mediated by copper(I) thiophene-2-carboxylate (CuTC).

• DOI: 10.1021/ol010060p
• 发表时间: 2001-06
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: C. Savarin;L. S. Liebeskind

Substituted alkyne synthesis under nonbasic conditions: copper carboxylate-mediated, palladium-catalyzed thioalkyne-boronic acid cross-coupling.

• DOI: 10.1021/ol006807d
• 发表时间: 2001-01
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: C. Savarin;J. Šrogl;L. S. Liebeskind

3-Cyclobutenyl-1,2-dione-substituted porphyrins. 2. A simple and general entry to quinone-porphyrin-porphyrin-quinone tetrads and related molecules.

3-环丁烯基-1,2-二酮取代的卟啉。

• DOI: 10.1021/jo991382y
• 发表时间: 2000
• 期刊: The Journal of organic chemistry
• 作者: Shi,X;Liebeskind,LS
• 通讯作者: Liebeskind,LS