• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Chemistry: A European journal >A Tryptoline Ring-Distortion Strategy Leads to Complex and Diverse Biologically Active Molecules from the Indole Alkaloid Yohimbine
【24h】

A Tryptoline Ring-Distortion Strategy Leads to Complex and Diverse Biologically Active Molecules from the Indole Alkaloid Yohimbine

机译：试色罗内戒断策略导致来自吲哚生物碱的复杂和不同的生物活性分子来自吲哚生物碱yohimbine

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

High-throughput screening (HTS) is the primary driver to current drug-discovery efforts. New therapeutic agents that enter the market are a direct reflection of the structurally simple compounds that make up screening libraries. Unlike medically relevant natural products (e.g., morphine), small molecules currently being screened have a low fraction of sp~3 character and few, if any, stereogenic centers. Although simple compounds have been useful in drugging certain biological targets (e.g., protein kinases), more sophisticated targets (e.g., transcription factors) have largely evaded the discovery of new clinical agents from screening collections. Herein, a tryptoline ring-distortion strategy is described that enables the rapid synthesis of 70 complex and diverse compounds from yohimbine (1); an indole alkaloid. The compounds that were synthesized had architecturally complex and unique scaffolds, unlike 1 and other scaffolds. These compounds were subjected to phenotypic screens and reporter gene assays, leading to the identification of new compounds that possessed various biological activities, including antiproliferative activities against cancer cells with functional hypoxia-inducible factors, nitric oxide inhibition, and inhibition and activation of the antioxidant response element. This tryptoline ring-distortion strategy can begin to address diversity problems in screening libraries, while occupying biologically relevant chemical space in areas critical to human health.
机译：高通量筛选（HTS）是当前药物发现努力的主要驾驶员。进入市场的新治疗剂是直接反映构成筛查库的结构简单的化合物。与医学相关的天然产物不同（例如，吗啡），目前被筛选的小分子具有低〜3个特征的低分数，很少，如果有的话，则是少量的。尽管简单的化合物可用于吸毒某些生物靶标（例如，蛋白激酶），但在很大程度上逃离了从筛选收集的新临床药物的发现发现了更复杂的靶标（例如，转录因子）。在此，描述了一种从育亨宾（1）的70种复合物和各种化合物的快速合成的季节性环形失真策略;吲哚生物碱。合成的化合物具有架构复杂和独特的支架，与1和其他支架不同。将这些化合物进行表型筛选和报告基因测定，导致鉴定具有各种生物活性的新化合物，包括针对癌细胞的抗增殖活动，具有功能性缺氧诱导因素，一氧化氮抑制和抗氧化剂反应的抑制和活化元素。这种TryPoline环形失真策略可以开始解决筛查库中的多样性问题，同时在对人体健康至关重要的地区占据生物相关的化学空间。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号