BIOMOLECULES & ANALOGUES AS ANTIVIRAL/ANTITUMOR AGENTS

生物分子

• 批准号: 3175658
• 负责人: CARL RANDOLPH JOHNSON
• 金额: $ 12.48万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-05-01 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3175658
• 关键词: 2'3' dideoxynucleoside; antiAIDS agent; antineoplastics; antiviral agents; cyclopentane; drug design /synthesis /production; enzyme inhibitors; nucleoside analog; nucleotide analog; prostaglandins

The thrust of the program is the synthesis of compounds which are known or have potential as antitumor/antiviral agents with appropriate followup biological screening. The overall objectives are: (i) Development of efficient methods for the synthesis of several unusual, naturally occurring nucleosides analogues which have antitumor and/or antiviral activity. (ii) Synthesis and screening of novel nucleoside analogues designed as possible antitumor/antiviral agents by analogy with known bioactive substances or on the basis of known or probable enzymatic pathways. (iii) Synthesis and screening for antitumor activity of a variety of analogues of prostanoids and prostanoids metabolites. (iv) Development of efficient methods for the production of optically pure starting materials, particularly dialkoxycyclopentenones, which should be widely useful in enantiospecific syntheses of a variety of bioactive substances. (v) Development of new synthetic methods of general interest for organic synthesis. (vi) Further demonstration of the applicability of the materials and methods developed by synthesis of a selection of additional targets of biological interest. Targets of priority include carbocylic nucleoside analogues based on the carbocycle of neplanocin A, novel nucleosides designed to be inhibitors of methyltransferases, novel variations of the chain terminator nucleosides drugs azidothymidine and dideoxycytodine of current interest in AIDS therapy, the recently discovered antiviral nucleoside oxetanocin and a variety of electrophilic cyclopentenones related to prostanoids and designed to serve as DNA polymerase inhibitors.

该程序的推力是化合物的合成 已知或具有抗肿瘤/抗病毒剂的潜力 适当的后续生物学筛查。 总体目标 是： （i）开发有效方法来合成几种 异常的，天然存在的核苷类似物 抗肿瘤和/或抗病毒活性。 （ii）新型核苷类似物的合成和筛选 通过类似 已知的生物活性物质或根据已知或可能的 酶促途径。 （iii）合成和筛选各种抗肿瘤活性 前列腺素和前列腺素代谢产物的类似物。 （iv）开发有效的方法来生产 光学上纯的起始材料，特别是 Dialkoxyclopentenones，应在 各种生物活性物质的对映体合成。 （v）开发新的合成方法的普遍关注 有机合成。 （vi）进一步证明材料的适用性 以及通过合成其他其他选择而开发的方法 生物学兴趣的目标。 优先级的目标包括基于碳纤维核苷类似物 在本质基金A的碳纤维上，新型核苷设计为 是甲基转移酶的抑制剂，链的新变化 终结剂核苷药物叠氮噻嗪和二氧基霉素 目前对艾滋病治疗的兴趣，最近发现的 抗病毒核苷氧甲烷和多种亲电的 与前列腺素有关的环戊烯酮，旨在用作 DNA聚合酶抑制剂。