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.

“硼脱氧核糖核苷”关注硼可能取代的两点 脱氧核糖核苷中的碳，以提供具有良好的 成为抗病毒剂的可能性。 首先，合成了3-[1-（2-（2-甲氧基苯基）氨基]-3-甲基-苯并[d]吡啶-2-基]-2-甲基-苯并[d]吡啶-2-基]-2-甲酸酯。 脱氧）核糖基]-6-硼嘧啶。 6-硼嘧啶是 只有硼嘧啶异构体具有硼原子， 稳定的位置 这是一系列重要的化合物测试，因为 只有有限数量的方法可以将嘧啶环 修饰以干扰RNA或DNA的合成。 的合成 在3-位上具有硼取代基的脱氧核糖核苷类似物 还提出了脱氧核糖单元的结构。 它们具有紧密的结构 类似于已知的抗HIV-1药物，如AZT或DDC， 去偶联对核苷酸合成至关重要的酶促磷酸化。 一旦化合物制备完成，样品将提交给 艾滋病病毒的筛查。 还将对样本进行筛选， 抗癌活性以及其它抗病毒活性。 如果无毒 如果发现化合物，它们将被提交到其他地方进行筛选， 用于所提出的10 B中子捕获肿瘤治疗的可能药剂。