NON OLIGONUCLEOTIDE ANALOGS AS ANTI HBV AGENTS

作为抗 HBV 药物的非寡核苷酸类似物

• 批准号: 6016859
• 负责人: THOMAS C HARVEY
• 金额: $ 21.62万
• 依托单位: SCRIPTGEN PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6016859
• 关键词: antiviral agents; carbazoles; chemical models; chemical structure function; combinatorial chemistry; drug design /synthesis /production; hepatitis B virus group; intermolecular interaction; model design /development; nucleic acid sequence; quinoline analog; triazines; virus RNA

DESCRIPTION (Adapted from the application): Development of antihepatitis B viral drugs (anti-HBV drugs) with enhanced potency, efficacy, bioavailability, and a broad therapeutic index is proposed. Using SCAN technology, four classes of lead molecules were identified by a high-throughput screen as small molecule ligands of virus-specific HBV epsilon RNA. All four classes of lead molecules will be subjected to structure-activity studies. In the first phase of the project, a series of small molecule analogs of the lead molecules will be synthesized with various positions substituted by electron-donating, electron withdrawing, hydrophilic, or sterically demanding groups. Other specific tasks include screening compounds for ability to bind to viral RNA and evaluating activity data to gain information about structure-activity correlations. PROPOSED COMMERCIAL APPLICATION: There are few effective antiviral therapeutic. It is estimated, for example, that over 200 million people are infected with Hepatitis B virus (HBV). This virus can cause chronic infections of the liver, leading to cirrhosis, cancer, and death. at present, there is not fully efficacious treatment for the disease. Novel small molecule therapeutics that reduce the morbidity and mortality of such infections can be identified by the proposed research program and would therefore have tremendous commercial potential.

描述（根据应用程序改编）：抗肝炎B的发展 病毒药物（抗HBV药物）具有增强的效力，功效，生物利用度， 并提出了广泛的治疗指数。使用扫描技术，四个类 通过高通量屏幕鉴定出铅分子的小分子 病毒特异性HBV Epsilon RNA的配体。所有四类铅分子 将接受结构活性研究。在第一阶段 项目，铅分子的一系列小分子类似物将是 由用电子，电子代替的各种位置合成 撤回，亲水性或在空间要求的群体。其他特定任务 包括筛选化合物，以结合病毒RNA并评估 活动数据以获取有关结构活动相关性的信息。 拟议的商业应用： 有效的抗病毒治疗很少。例如，估计有200多个 百万人感染了丙型肝炎病毒（HBV）。该病毒会引起慢性 肝脏的感染，导致肝硬化，癌症和死亡。目前，没有完全 对该疾病的有效治疗。新颖的小分子疗法，减少 拟议的研究可以确定这种感染的发病率和死亡率 计划，因此具有巨大的商业潜力。