Summit Plc(1), 91 Milton Park, Abingdon, Oxon, OX14 4RY, UK.
Drug Discov Today. 2011 Feb;16(3-4):107-18. doi: 10.1016/j.drudis.2010.08.017. Epub 2010 Sep 21.
Iminosugars comprise the most attractive class of carbohydrate mimetics reported to date and are ideally positioned to take advantage of our increasing understanding of glycobiology in the search for new medicines. First-generation iminosugar drugs suffered from lack of adequate selectivity, resulting in considerable side-effects in the clinic. Current efforts directed towards second-generation compounds, encompassing a much greater range of structures and addressing a wider selection of biochemical targets, are enabling the identification and development of suitable candidates that benefit from improved activity and selectivity. Furthermore, second-generation compounds can address a variety of established targets that have previously proved refractory to other compound classes. This review focuses on the breadth of opportunities provided by second-generation leads from iminosugars (Seglins™).
亚胺糖包含了迄今为止报道的最有吸引力的一类碳水化合物类似物，并且非常适合利用我们对糖生物学的日益深入了解来寻找新药。第一代亚胺糖药物由于缺乏足够的选择性，在临床上产生了相当大的副作用。目前针对第二代化合物的研究，涵盖了更广泛的结构范围，并针对更广泛的生化靶点，使人们能够识别和开发具有改善活性和选择性的合适候选药物。此外，第二代化合物可以解决以前对其他化合物类别具有抗药性的各种已确立的靶标。本综述重点介绍了亚胺糖（SeglinsTM）的第二代先导化合物所提供的广泛机会。
