BORADEOXYRIBONUCLEOSIDES

硼脱氧核糖核苷

• 批准号: 3304371
• 负责人: DONALD S MATTESON
• 金额: $ 9.81万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-06-05 至 1993-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3304371
• 关键词: antiAIDS agent; antineoplastics; antiviral agents; boron; chemical structure function; deoxyribonucleosides; drug design /synthesis /production; drug screening /evaluation; nucleic acid chemical synthesis; nucleoside analog

"Boradeoxyribonucleosides" focuses on two points where boron may replace carbon in deoxyribonucleosides to provide novel compounds which have a good chance of being antiviral agents. First, syntheses of 3-[1-(2- deoxy)ribosyl]-6-borapyrimidines are proposed. 6-Borapyrimidines are the only borapyrimidine isomers which have the boron atom in a hydrolytically stable position. This is a significant series of compounds to test because there are only a limited number of ways in which the pyrimidine ring can be modified so as to interfere with RNA or DNA synthesis. Syntheses of deoxyribonucleoside analogues having boron substituents in the 3-position of the deoxyribose unit are also proposed. These bear a close structural analogy to known anti-HIV-1 agents such as AZT or DDC and would be likely to decouple the crucial enzymatic phosphorylation for nucleotide synthesis. ONce the compounds have been prepared, samples will be submitted for screening against the AIDS virus. Samples will also be screened for anticancer activity, as well as for other antiviral activity. If nontoxic compounds are found, they will be submitted elsewhere for screening as possible agents for the proposed 10B neutron capture tumor therapy.

《硼氧基核糖核苷》聚焦两点：硼可能被取代 碳在脱氧核糖核苷中提供的新型化合物具有良好的 成为抗病毒药物的机会。3-[1-(2-)]的合成 提出了脱氧核糖基]-6-冰片嘧啶类化合物。6-冰片嘧啶类化合物 只有水解态中含硼原子的硼嘧啶异构体 位置稳定。这是一系列需要测试的重要化合物，因为 只有有限的几种方法可以将嘧啶环 被修改以干扰RNA或DNA的合成。几种有机化合物的合成 3-位含硼取代的脱氧核糖核苷类似物 还提出了脱氧核糖单元的结构。它们承受着紧密的结构 类似于已知的抗HIV-1药物，如AZT或DDC，很可能 去偶联核苷酸合成的关键酶的磷酸化。 一旦化合物制备完成，样品将被提交用于 对艾滋病病毒进行筛查。样本也将进行筛选，以确定 抗癌活性，以及其他抗病毒活性。如果无毒 发现化合物，它们将被提交到其他地方进行筛选，作为 建议的10B中子俘获肿瘤治疗的可能试剂。