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.

体内和体外的大量研究表明，化合物 维生素 A 组、其衍生物或类似物（统称为 称为类视黄醇）可以预防或逆转致癌物诱发的恶性肿瘤。 尽管在开发类视黄醇方面已经取得了很大进展 癌症的化学预防，具有改进化学预防作用的新型维A酸 活性、较低的毒性和优异的药代动力学特性必须 发现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，必须开发具有不同结构的新类维生素A 合成用于评估化学预防活性、药理学 调查和生化研究。 为了进一步探索 结构修饰对化学预防活性的影响，这 新类视黄醇的合成程序由 (1) 的衍生物组成 具有已知活性的类视黄醇和（2）新型类视黄醇结构。 一些新的类维生素A将是视黄醇和视黄酸的衍生物 酸。 一些新型类视黄醇的结构将在以下位置进行修改： 或接近极性端基。 其他组的新类视黄醇将 环己烯基被修饰，并且在一些环己烯基中 被替换。