PRODRUGS FOR ADENOVIRAL EYE INFECTIONS

用于腺病毒眼部感染的前药

• 批准号: 6073929
• 负责人: CHARLES E MCKENNA
• 金额: $ 11.53万
• 依托单位: MAST THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6073929
• 关键词: Adenoviridae; chemical conjugate; chemical synthesis; cidofovir; dipeptides; drug design /synthesis /production; eye agent; eye infections; high performance liquid chromatography; keratoconjunctivitis; nuclear magnetic resonance spectroscopy; prodrugs; topical drug application

The long-term goal of the project is to develop drugs for the prevention and treatment of adenoviral ocular disease. Although usually acute, they can become chronic and impair vision. Cidofovir is a nucleoside analog with activity against adenovirus, but is taken up poorly by cells. The focus of the application is to demonstrate the feasibility of optimizing the conjunctival uptake of cidofovir through derivitization into prodrugs that are substrates for the dipeptide transporter. This research will demonstrate the feasibility of improving the ocular absorption of topically applied polar drugs of low molecular weight via amino acid ester prodrug derivitization. By shifting the pathway of absorption from paracellular to transcellular, it will be possible to increase the probability of drug exposure of corneal and conjunctival epithelial cells. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

该项目的长期目标是开发药物， 预防和治疗腺病毒性眼病。虽然通常是急性的， 它们会变成慢性病并损害视力。西多福韦是核苷类似物 具有抗腺病毒的活性，但被细胞吸收较差。的焦点 应用是为了证明优化的可行性， 西多福韦通过衍生为前药的结膜摄取， 二肽转运蛋白的底物。这项研究将证明， 提高局部施用的极性药物的眼部吸收的可行性 通过氨基酸酯前体药物衍生化的低分子量。通过 将吸收途径从细胞旁转移到跨细胞， 有可能增加角膜药物暴露的概率， 结膜上皮细胞 拟议商业应用：不可用