NEW APPROACH TO ANTIVIRAL NUCLEOSIDE ANALOGUES

抗病毒核苷类似物的新方法

• 批准号: 3915855
• 负责人: PETER SCHEINER
• 金额: --
• 依托单位: YORK COLLEGE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3915855
• 关键词: acyclovir; antiviral agents; benzodiazepines; chemical structure function; deoxyguanosine; drug design /synthesis /production; drug screening /evaluation; heterocyclic compounds; nuclear magnetic resonance spectroscopy; nucleosides; polyvinyls

Michael addition of heterocyclic bases to acceptor molecules is a versatile new method for nucleoside synthesis. Experimental simplicity, efficiency and potential for asymmetric synthesis distinguish it from conventional routes. The proposed research will explore and refine the sequence, and apply it to the preparation of candidate antiviral nucleoside analogues. Equilibrium constants of model systems will be determined (NMR) to define optimal reaction conditions. Asymmetric inductions affording nucleosides with the R configuration at C1' will be attempted with chiral catalysts. The scope of the method will be explored with selective acceptors, and a homologous series of C1'- branched acyclic nucleosides will be prepared and tested to clarify antiherpetic structure-activity relationships. Unsaturated nucleosides of a new type (vinyl) will be obtained, as well as acyclic and carbocyclic derivatives of neplanocin A. A 2'- deoxyguanosine analogue (26), structurally closer to the natural substrate than either acylovir or DHPG, will be synthesized and evaluated for antiviral activity. Student researchers will be exposed to a wide range of modern experimental techniques and concepts. Participants will be involved in significant frontline research in medicinal chemistry. The experience should serve to stimulate students to pursue graduate study and careers in biomedical science.

迈克尔在受体分子中添加了杂环碱基是一个 核苷合成的多功能新方法。 实验 简单，效率和不对称合成的潜力 将其与常规路线区分开。 拟议的研究 将探索和完善序列，并将其应用于 候选抗病毒核苷类似物的制备。 将确定模型系统的平衡常数（NMR） 定义最佳反应条件。 不对称诱导 在C1'处使用R构型提供核苷 尝试使用手性催化剂。 该方法的范围将是 与选择性受体一起探索，以及一系列同源的C1'- 将准备并测试分支的无环核苷以澄清 抗脊髓性结构活性关系。 不饱和 将获得一种新型（乙烯基）的核苷，以及 Nedranocin A的无环和碳环衍生物A。A2'-- 脱氧鸟苷类似物（26），结构上更靠近自然 底物比酰胺维尔或DHPG合成，并将合成 评估抗病毒活性。 学生研究人员将暴露于广泛的现代 实验技术和概念。 参与者会 参与药物化学方面的重要一线研究。 经验应该刺激学生追求 生物医学科学研究生研究和职业。