SYNTHESIS AND EVALUATION OF ANTIHIV NUCELOSIDES

描述：(改编自申请者摘要)：本建议书是 继续开展核苷领域的药物发现工作 佐治亚大学和埃默里大学/退伍军人医学中心。这 续展申请与新近的化学和生物有关 出现了L-核苷，并正在寻找新的抗艾滋病毒药物 不会与现有的核苷类抗艾滋病毒药物产生交叉耐药性。 最近，包括3TC、FTC、L-FddC、L-Fmau在内的几个L核苷 已被发现是很有前途的抗HIV/抗乙肝药物。建议的L- 核苷将联合或作为单一药物进行研究。 具有抗药性的病毒株。此外，核苷磷酸二聚体 将被调查以寻找能抑制病毒的抗HIV药物 特异酶、整合酶。以下四类核苷是 建议用于合成以及用于生物和生化评估： (1)D-和L-2‘，3’-二脱氧-和2‘，3’-二氢-2‘，3’-双脱氧- (2)D-和L-碳环核苷；(3)L-C-核苷； (4)核苷磷酸二聚体。此应用程序的长期目标是 是开发临床上有用的新型抗艾滋病毒核苷，它不会 与现有的抗艾滋病毒药物产生交叉耐药性。

DESCRIPTION: (Adapted from Applicant's Abstract): This proposal is a continuation of the drug discovery efforts in the area of nucleosides at the University of Georgia and Emory University/VA Medical Center. This renewal application is concerned with the chemistry and biology of newly emerged L-nucleosides andis in search of novel anti-HIV agents which do not confer cross-resistance with existing nucleoside anti-HIV modalities. Recently, several L-nucleosides including 3TC, FTC, L-FddC, L-FMAU have been discovered as promising anti-HIV/anti-HBV agents. The proposed L- nucleosides will be studied in combination or as single agents against drug-resistant viral strains. Additionally, nucleoside phosphate dimers will be investigated in search of anti-HIV agents which inhibit a viral specific enzyme, integrase. The following four classes of nucleosides are proposed for synthesis and for biological and biochemical evaluation: (1) D- and L-2',3'-dideoxy- and 2',3'-didehydro-2',3'-dideoxy- nucleosides; (2) D- and L-carbocyclic nucleosides; (3) L-C-nucleosides; (4) nucleoside phosphate dimers. The long-term goal of this application is to develop novel clinically useful anti-HIV nucleosides which do not confer cross resistance with the existing anti-HIV modalities.