来自三组分Joullié-Ugi合的甘油和二模剂显示有选择性的抗病毒活性
Timothy M Chapman1, Ieuan G Davies, Baohua Gu
1Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford UK, OX1 3TA.
Journal of the American Chemical Society
|January 13, 2005
概括
研究人员合成了一系列的imino糖和peptidomimetics. 这个图书馆显示了高希尔的强烈抑制.
科学领域:
- 有机合成 有机合成
- 药品化学 药品化学 是一个
- 葡萄糖科学 (Glycoscience) 是一种科学.
背景情况:
- 聚氧化罗利丁是药物化学中有价值的支架.
- 开发高效的合成路径到这些化合物的各种图书馆对于药物发现至关重要.
研究的目的:
- 为了开发一个平行合成的策略,为多氧化罗利丁.
- 创建一个伊米诺糖 (糖仿制剂) 和二基酸 (仿制剂) 的图书馆.
- 针对各种目标,评估合成图书馆的生物活动.
主要方法:
- 化 - 消除化学 化学
- 三组分的朱利埃-乌吉反应
- 易于去除保护的方法
- 平行合成并行合成
- 对15个目标进行生物查.
主要成果:
- 实现了对多基化罗利丁的图书馆的有效访问.
- 观察到葡萄糖胺合成酶 (高氏病酶) 的强有力和选择性抑制.
- 证实了人类型肝炎病毒 (HCV) 和牛腹病毒 (BVDV) 的初级病原体模型的抑制.
- 他们注意到HCV模型对乙型肝炎病毒的选择性和低毒性.
结论:
- 开发的合成方法提供了一个多功能平台,用于生成各种图书馆的imino糖和peptidomimetics.
- 合成的图书馆显示出有前途的治疗潜力,特别是对于高氏病和像HCV这样的病毒感染.
- 观察到的选择性和低毒性表明,已识别的抑制剂具有一种新的作用机制.
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