TUMOR INHIBITORS AND RELATED SUBSTANCES

肿瘤抑制剂及相关物质

• 批准号: 3482129
• 负责人: PAUL A GRIECO
• 金额: $ 28.22万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-06-01 至 1997-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3482129
• 关键词: antineoplastics; cardenolides; cardiac glycoside aglycone; chemical structure function; drug adverse effect; drug design /synthesis /production; drug metabolism; drug screening /evaluation; medicinal plants; neoplasm /cancer pharmacology; plant extracts

This proposal focuses on the synthesis of antineoplastic agents. In the quassinoid area major emphasis will be placed on completing syntheses of quassimarin, bruceantin, and glaucarubinone. As a result of the lower toxicity in in vivo systems of 4beta-hydroxy withanolide E relative to cardenolides and bufadienolides, a synthetic program centered around 4beta-hydroxy withanolide E has been initiated in an effort to uncover an analog possessing a reasonable therapeutic index. Part III of this proposal focuses on a convergent total synthesis of the potent cytotoxic cyclodepsidpeptide, jaspamide. In addition a number of analogs will be prepared in order to examine the structural requirements for biological activity.

这项建议的重点是抗肿瘤药物的合成。 在类星体领域，主要重点将放在完成 拟马豆素、布鲁西丁和蓝豆草酮的合成。作为一名 4-β-羟基在体内系统毒性较低的结果 与花内酯E和二烯内酯相比，a 以4β-羟基为中心的合成程序 是为了发现一种拥有 合理的治疗指标。这项提案的第三部分侧重于 关于高效细胞毒药物的一种收敛全合成 环磷酰胺，茉莉酰胺。此外，还有一些类似物 将做好准备，以便检查结构要求 用于生物活动。