NEW DRUGS FOR MYCOBACTERIAL INFECTIONS IN AIDS PATIENTS

描述：(改编自申请人摘要)。总的目标是 这一应用是为了开发治疗分枝杆菌的新药 艾滋病患者的感染，特别是禽类分枝杆菌和结核分枝杆菌 (MTB)。目标是分枝杆菌细胞壁，它与 两种病原体，但它包含一种独特的化学结构，没有 哺乳动物细胞中的对应物。这是一个全面的计划，以优化 已经开发的化合物的活性，并从更多的 最近的合成研究。下列类别的化合物为 潜在抗分枝杆菌药物的设计与合成(1) 低聚糖同属于生物合成的天然底物 可作为底物和双底物抑制剂的酶 阿拉伯半乳糖的生物合成；(2)基于 天然阿拉伯糖供体，beta-D-arabinofuranose-1-monophosphodecaprenol (DPA)，脂联阿拉伯糖供体；和(3)过渡态和 将作为多糖抑制剂的双底物类似物 精加工，尤其是霉酚化。合成化合物将是 针对一组MAC和MTB菌株进行了筛选。

DESCRIPTION: (Adapted from Applicant's Abstract). The overall objective of this application is to develop new drugs for treatment of mycobacterial infections in AIDS patients, especially M. avium (MAC) and M. tuberculosis (MTB). The target is the mycobacterial cell wall which is quite similar in both pathogens, but which contains a unique chemical structure with no counterpart in mammalian cells. This is a comprehensive program to optimize activity of compounds already developed and pursue emerging leads from more recent synthetic studies. Compounds of the following classes are to be designed and synthesized as potential antimycobacterial agents (1) Oligosaccharides congeneric to the natural substrates of the biosynthetic enzymes that can act as substrate- and bisubstrate-based inhibitors of the biosynthesis of arabinogalactan; (2) Transferase inhibitors based on the natural arabinose donor, beta-D-arabinofuranose-1-monophosphodecaprenol (DPA), a lipid conjugated arabinose donor; and (3) Transition state and bisubstrate analogs that will act as inhibitors of polysaccharide elaboration, particularly mycolylation. Synthetic compounds are to be screened against a panel of MAC and MTB strains.