3'4'-ALKYL NUCLEOSIDES--PROSPECTS FOR AIDS THERAPY

34-烷基核苷——艾滋病治疗的前景

• 批准号: 2069933
• 负责人: CARL RANDOLPH JOHNSON
• 金额: $ 12.33万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-12-01 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2069933
• 关键词: AIDS therapy; antiAIDS agent; carbohydrates; chemical structure function; chemical synthesis; drug design /synthesis /production; nucleoside analog

The overall objective of the program is the development of novel compounds that exhibit biological activity of interest in the treatment of AIDS. The specific aims of the program are: (i) The development of efficient and innovative chemistry for the synthesis of modified sugars related to ribose and deoxyribose. (ii) The utilization of these modified sugars in the synthesis of novel nucleoside analog as potential anti-AIDS drugs. (ii) To increase the understanding of the relationship between structure and biological activity in nucleoside analog which exhibit such activity by functioning as reverse transcriptase inhibitors and/or chain terminators during viral DNA synthesis. In some cases the syntheses will begin with common sugars or their derivatives such as diacetone glucose, in other cases the starting material will be cyclopentadiene and the syntheses will incorporate enzymatic asymmetrizations of meso derivatives. Many of the novel compounds proposed are derivatives of branched-chain sugars with methyl, trifluoroethyl and other alkyl groups strategically placed. Methods for the production of 4-C-alkyl ribose derivatives, especially 4-C-methyl and 4-C-trifluoroethyl derivatives are stressed. Application of trifluoroethyl-trimethylsilane for the introduction of trifluoroethyl groups in appropriate carbohydrate derivatives will be explored. Nucleoside derivatives of the ribo, 2-deoxyribo- and 2,3-dideoxyribo classes will be prepared and submitted for screening.

该计划的总体目的是发展新颖 在治疗中表现出生物学活性的化合物 艾滋病。 该计划的具体目的是：（i）开发 用于合成改良糖的高效和创新化学 与核糖和脱氧核糖有关。 （ii）这些利用 在新型核苷类似物合成中的改性糖作为电势 抗艾滋病药物。 （ii）增加对关系的理解 在核苷类似物中的结构和生物学活性之间 通过用作逆转录酶抑制剂来表现这种活性 在病毒DNA合成过程中，和/或链终止剂。 在某些情况下 合成将从普通糖或其衍生物（例如 二座葡萄糖，在其他情况下，起始材料将是 环戊二烯和合成将结合酶促 内索衍生物的不对称化。 许多新颖的化合物 提出的是用甲基的分支链糖的衍生物， 三氟乙基和其他烷基策略性放置。 方法 产生4-烷基核糖衍生物，尤其是4-C-甲基和 4-C-三氟乙基衍生物受到压力。 应用 三氟乙基三甲基硅烷，用于引入三氟乙基 将探索适当的碳水化合物衍生物中的组。 Ribo的核苷衍生物，2-脱氧纤维和2,3-二氧基鸟 课程将准备并提交筛查。