TO TARGET DRUGS TO THE CENTRAL NERVOUS SYSTEM FOR AIDS T

经鉴定有效的抗病毒药物的改良 NIAID OR筛选HTLV-III/LAV/HIV的体外研究 用于治疗的国家合作药物发现小组 可能需要艾滋病(NCDDG-AIDS)才能交付 中枢神经系统(CNS)的药物。因此，目标是 这项拟议的项目是为了确保现在将努力 发展向中枢神经系统运送药物所需的专业知识。 NIAID，与美国陆军研究中心合作 开发司令部，已经建立了一种快速的体外筛选 评估潜在HTLV有效性的计划- III/LAV/HIV药物。NIAID将在今年担任领导角色， 与NCI合作，将科学家组织成小组 专注于艾滋病治疗新药的发现 (非传染性疾病--艾滋病)。通过这些努力和其他独立的 防止逆转录病毒复制的努力、药物 将由艾滋病计划署确定和开发。 防止HTLV-III/LAV/HIV复制的药物可能会跨越 血脑屏障并有效地达到治疗水平， 很差，或者根本不是。最近的报告表明，有能力 核苷二氢吡啶类化合物的制备 通过酯键连接化学载体。这些 经修饰的药物(称为前药物)在其 穿越血脑屏障的能力。成功者 改进的给药和靶向方法的开发 有效的中枢神经系统毒剂将特别有益于停止 疾病的发展，感染的传播和 控制病毒的蓄水池。本次征集的目的是 双重：首先，修改已知的抗逆转录病毒药物以增加 他们跨越血脑屏障的能力；第二，鼓励 开发针对药物的创新方法以 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.