DEVELOPMENT OF CHEMOPREVENTIVE RETINOIDS

化学预防性维A酸的开发

• 批准号: 3093602
• 负责人: Donald L. Hill
• 金额: $ 79.29万
• 依托单位: SOUTHERN RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3093602
• 关键词: cancer prevention; chemical synthesis

Numerous studies in vivo, as well as in vitro, have shown that compounds of the vitamin A group, their derivatives, or their analogs (collectively called retinoids) may prevent or reverse carcinogen-induced malignacy. Although much progress has already been made in developing retinoids for the chemoprevention of cancer, new retinoids with improved chemopreventive activity, lower toxicity, and superior pharmacokinetic properties must be found in order to make chemoprevention a more effective method of cancer control. For these reasons, new retinoids of diverse structures must be synthesized for evaluations of chemopreventive activity, pharmacological investigations, and biochemical studies. In order to explore further the effects of structural modification on chemopreventive activity, this program of synthesis of new retinoids is comprised (1) of derivatives of retinoids with known activity and (2) of new types of retinoid structures. Some of the new retinoids will be derivatives of retinol and retinoic acid. Some of the new types of retinoids will be modified in structure at, or near, the polar, terminal group. Other groups of new retinoids will be modified in the cyclohexenyl group, and in some the cyclohexenyl group will be replaced.

体内和体外研究的大量研究表明， 维生素A组，它们的衍生物或它们的类似物（统称 称为类维生素类似）可以预防或反向致癌物诱导的恶性肿瘤。 尽管在开发类维生素类似方面已经取得了很多进展 癌症的化学预防，具有改进化学预防的新类维生素 活性，较低的毒性和优质的药代动力学必须是 为了使化学预防成为更有效的癌症方法 控制。 由于这些原因，不同结构的新类视角必须是 合成用于化学预防活性的评估药理 研究和生化研究。 为了进一步探索 结构修饰对化学预防活性的影响，这 新类维生素类似的合成程序包括（1）的（1） 具有已知活性的类视视视网索性和（2）种类型的类类视感结构。 一些新的类视网膜类似是视黄醇和视网膜的衍生物 酸。 某些新类型的类维生素类型将在结构上修改 或附近，极性终端组。 其他新类视网膜类似组将是 在环己烯基组中进行了修饰，在某些环己烯基组中将 被替换。