SYNTHESIS AND EVALUATION OF ANTIHIV NUCELOSIDES

描述：（改编自申请人摘要）：本提案是一项 继续在核苷领域的药物发现努力， 格鲁吉亚大学和埃默里大学/退伍军人医疗中心。这 更新申请涉及新的化学和生物学 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HIV药物产生交叉耐药性。 近年来，包括3 TC、FTC、L-FddC、L-FMAU在内的几种L-核苷类化合物已被广泛应用于临床。 被发现是有前途的抗HIV/抗HBV药物。 建议的L- 核苷将被研究在组合或作为单一的药物， 耐药病毒株。 此外，核苷磷酸二聚体 将进行研究，以寻找抗艾滋病毒药物， 特异性酶整合酶。以下四类核苷是 建议用于合成以及生物学和生物化学评价： (1)D-和L-2 '，3'-二脱氧-和2 '，3'-二巯基-2 '，3'-二脱氧- 核苷;（2）D-和L-碳环核苷;（3）L-C-核苷; (4)核苷磷酸二聚体。 这个应用程序的长期目标是 是开发新的临床上有用的抗HIV核苷， 与现有的抗HIV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.