HETEROCYCLIC COMPOUNDS AS SELECTIVE INHIBITORS OF HUMAN CYTOMEGALOVIRUS

杂环化合物作为人类巨细胞病毒的选择性抑制剂

• 批准号: 6099541
• 负责人: LEROY B. TOWNSEND
• 金额: $ 17.23万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6099541
• 关键词: antiviral agents; benzimidazoles; cytomegalovirus; drug design /synthesis /production; imidazole; nucleoside analog; nucleosides; pyrimidine nucleosides; tubercidin

This proposal outlines several specific areas for the development of an agent to specifically treat HCMV infections. The target compounds will be elected on the basis of the structure activity relationships which have already been established from current and previous studies in our laboratory. Several areas of research are proposed and the specific aims for the next five years include the following: the synthesis of some polysubstituted benzimidazoles and imidazoles and their corresponding nucleosides and nucleoside analogs based on structure activity relationships derived from structurally related compounds. The synthesize of a few select 5-bromotubercidin and thiosangivamycin analogs is proposed. Synthesis of selected polysubstituted benzimidazole carbamates, unrelated to the above polysubstituted benzimidazoles, using a compound discovered through our very limited screen involving compounds selected at random from our previous synthetic investigations, as our focal point. The in vitro evaluations from Professors Drach, Lopatin and Kern's laboratories will be used to direct the chemical modifications in each new area of potential agents. All of these studies should provide some insights into the modifications which will effect an increase in the selectivity of these compounds against HCMV.

该提案概述了制定一项 特异性治疗HCMV感染的药剂。 目标化合物将是 选择的基础上的结构活性关系， 已经建立了从目前和以前的研究，在我们的 实验室 提出了几个研究领域和具体目标， 包括以下内容： 多取代的苯并咪唑和咪唑及其相应的 基于结构活性的核苷和核苷类似物 结构相关的化合物的关系。 本发明合成 提出了一些选择的5-溴杀结核菌素和硫代桑吉霉素类似物。 选择的多取代苯并咪唑氨基甲酸酯的合成，无关 涉及上述多取代的苯并咪唑， 通过我们非常有限的筛选，包括随机选择的化合物， 我们之前的合成研究作为我们的焦点 体外 来自Drach教授、洛帕廷教授和克恩教授实验室的评估将是 用于指导每个新的潜在领域的化学修饰 剂. 所有这些研究都应该提供一些见解， 这些修饰将影响这些化合物的选择性的增加， 抗HCMV的化合物。