THE ANALYTICAL CHEMISTRY OF ANTI-AIDS AGENTS

抗艾滋病药物的分析化学

• 批准号: 3752319
• 负责人: J A KELLEY
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 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/3752319
• 关键词: 2'3' dideoxynucleoside; adenosine deaminase; analytical chemistry; analytical method; antiAIDS agent; antiviral agents; chemical structure function; drug design /synthesis /production; drug metabolism; drug quality /standard; high performance liquid chromatography; mass spectrometry; method development; pharmacokinetics; pharmacology

The objective of this project is the research and development of suitable bioanalytical methods to: (1) establish the structure and purity of potential anti-AIDS agents and new antiviral drugs, (2) determine physical, chemical and biochemical properties, including octanol-water partition coefficients, of these compounds and their metabolites, and (3) measure these drugs and their metabolites in biological samples to elucidate pharmacology and to determine pharmacokinetics. High- performance liquid chromatography and mass spectrometry are emphasized techniques. Sugar-fluorinated dideoxynucleosides, including 2'-F-ddA and prodrugs of 2'-F-ddI and the modified cyclodextran sulfate m-CDS71 are currently the compounds of primary interest. A high sensitivity HPLC assay involving direct fluorogenic derivatization of biological samples has been developed for the analysis of F-ddA. The role of adenosine deaminase in prodrug activation is also under investigation.

该项目的目的是研究和开发合适的 生物分析方法：（1）建立 潜在的抗AID剂和新的抗病毒药物，（2）确定 物理，化学和生化特性，包括辛醇水 这些化合物及其代谢物的分区系数，以及（3） 在生物样品中测量这些药物及其代谢物 阐明药理学并确定药代动力学。 高的- 强调性能液相色谱和质谱法 技术。 糖氟二乙氧基核苷，包括2'-f-dda和 2'-F-DDI的前药和修饰的环糊精M-CDS71为 目前，主要兴趣的化合物。 高灵敏度HPLC 涉及生物样品的直接荧光衍生化的测定 已开发用于F-DDA的分析。 腺苷的作用 前药激活中的脱氨酶也正在研究中。