3'-DEOXYNUCLEOSIDE ANALOGS AS POTENTIAL ANTIVIRAL AGENTS

3-脱氧核苷类似物作为潜在的抗病毒剂

• 批准号: 3144251
• 负责人: TAI-SHUN LIN
• 金额: $ 12.54万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-03-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3144251
• 关键词: 2'3' dideoxynucleoside; antiAIDS agent; antiviral agents; azacitidine; chemical structure function; cytomegalovirus; cytosine; cytosine arabinoside; cytotoxicity; drug adverse effect; drug design /synthesis /production; drug metabolism; drug screening /evaluation; human immunodeficiency virus; mass spectrometry; nuclear magnetic resonance spectroscopy; nucleoside analog; nucleoside triphosphate; tissue /cell culture

This investigation has as its goal the design and synthesis of a series of 3'-deoxy pyrimidine and purine nucleoside analogs, and some of their nucleotide addition, the 2', 3'-unsaturated, 2', 3'-dideoxy-ara-C derivatives of 3-deazacytidine will be synthesized and evaluated as potential anti-HIV and anti-CMV agents. The approaches to be employed include the development of methodology mass spectrum, and other spectroscopic techniques, and the determination of their biological and biochemical effects. Recently, a lead compound, 1-(3-deoxy-B-D-threopentofuranosyl) cytosine (3'-deoxy-ara-C), has been synthesized and evaluated for its antiviral activity in this laboratory. Our preliminary studies have shown that 3'- deoxy-ara-C not only has potent anti-HCMV activity (ED50 = 0.31 ug/mL vs ED50 = 0.92 ug/mL for DHPG), but also is structurally different from DHPG. Based on these findings, the 5'-mono- and triphosphates of 3'-deoxy-ara-C will be prepared for biochemical studies. The understanding of the mechanism of action of 3'-deoxy-ara-C may lead to the design and synthesis of new antiviral agents with a better therapeutic index.

本研究的目标是设计和合成一系列的