TARGETING DRUGS TO CENTRAL NERVOUS SYSTEM--AIDS TESTING

抗病毒药物的改良被确定为有效对抗 通过NIAID的筛选工作进行体外HTLV-III/LAV/HIV，或 国家合作药物发现小组的治疗 艾滋病（NCDDG-艾滋病）可能需要允许交付 中枢神经系统（CNS）的药物。 因此， 该拟议项目旨在确保现在将努力 发展必要的专业知识，将药物输送到CNS。 NIAID与美国陆军研究所合作， 发展指挥部，已经建立了一个快速，在体外筛选 评估潜在HTLV有效性的计划- III/LAV/艾滋病毒药物。 NIAID今年将发挥主导作用， 与NCI合作，将科学家组织成小组， 专注于发现治疗艾滋病的新药 （NCDDG-艾滋病）。 通过这些努力和其他独立的 努力，药物，将防止逆转录病毒的复制， 将由艾滋病项目确定和开发。 预防HTLV-III/LAV/HIV复制的药物可能会通过 血脑屏障并有效地达到治疗水平， 很差或者根本没有。 最近的报告显示， 制备核苷的二氢吡啶衍生物， 通过酯键连接化学载体。 这些 修饰的药物（称为前药）在其 穿越血脑屏障的能力。 成功 制定更好的方法， 中枢神经系统的有效药物将特别有益于停止 疾病的发展，感染的扩散， 控制病毒的储存库 本次征集的目的是 两方面：第一，修改已知的抗逆转录病毒药物， 他们穿越血脑屏障的能力;第二，鼓励 开发创新的药物靶向方法， 中枢神经系统

The modification of antiviral drugs identified as effective against HTLV-III/LAV/HIV in vitro by the screening efforts of NIAID or National Cooperative Drug Discovery Groups for the Treatment of AIDS (NCDDG-AIDS) may be required to allow the delivery of drugs to the central nervous system (CNS). Thus, the objective of this proposed project is to ensure that efforts will be made now to develop the expertise necessary to deliver drugs to the CNS. NIAID, in collaboration with the United States Army Research Development Command, has established a rapid, in vitro screening program to evaluate the effectiveness of potential HTLV- III/LAV/HIV drugs. NIAID will undertake the lead role this year, in collaboration with NCI, in organizing scientists into groups focused on the discovery of novel drugs for the treatment of AIDS (NCDDG-AIDS). Through these efforts and other independent efforts, drugs which will prevent the replication of retroviruses will be identified and developed by the AIDS Program. Drugs which prevent HTLV-III/LAV/HIV replication may cross the blood brain barrier and achieve therapeutic levels efficiently, poorly or not at all. Recent reports have shown the ability to make dihydropyridine derivatives of nucleosides by the attachment of a chemical carrier through an ester linkage. These modified drugs (termed prodrugs) are greatly enhanced in their ability to cross the blood brain barrier. The successful development of improved methods for delivery and targeting of effective agents to the CNS will be especially beneficial to halt the progression of the disease, the spread of the infection and control a reservoir of the virus. The purpose of this solicitation is two-fold: first, to modify known antiretroviral drugs to increase their ability to cross the blood brain barrier; second, to encourage the development of innovative approaches for targeting drugs to the central nervous system.