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.

“ Boradeoxyroxyoxyrobonucleosides”重点是硼可能取代的两个点 脱氧核糖核苷中的碳可提供具有好的新型化合物 成为抗病毒剂的机会。 首先，3- [1-（2-）的合成 提出了脱氧）核糖基] -6-硼嘧啶。 6-硼二酰亚胺是 只有硼吡啶胺异构体，该异构体在水解中具有硼原子 稳定的位置。 这是一系列重要的化合物，因为 只有有限数量的嘧啶环可以是 修饰以干扰RNA或DNA合成。 合成 在3位中具有硼取代基的脱氧核苷类似物 还提出了脱氧核糖单元的。 这些带有紧密的结构 类似于已知的抗HIV-1药物，例如AZT或DDC，很可能 将至关重要的酶促磷酸化解脱用于核苷酸合成。 准备化合物后，将提交样品 针对艾滋病病毒进行筛查。 样本也将筛选 抗癌活性以及其他抗病毒活性。 如果无毒 发现化合物，它们将在其他地方提交以进行筛查 拟议的10B中子捕获肿瘤疗法的可能药物。