5-(Dimethylamino)-1,3-dihydroisoindole-2-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 5-(Dimethylamino)-1,3-dihydroisoindole-2-carboxylic acid
• 英文别名: 5-(dimethylamino)-1,3-dihydroisoindole-2-carboxylic acid
• 化学式: C₁₁H₁₄N₂O₂
• 分子量: 206.24
• InChiKey: CROGXQXBAQWTSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  3

文献信息

• Ultra-potent vinca alkaloids: added molecular complexity further disrupts the tublin dimer-dimer interface
  申请人：The Scripps Research Institute

  公开号：US10975101B2

  公开（公告）日：2021-04-13

  Synthetically-derived and previously inaccessible modifications of 20′-hydroxy-vinca derivative compounds such as vinblastine, vincristine or vindesine are disclosed that are a stunning 100-fold more active than the natural product (IC50's 50-75 pM vs 7 nM, HCT116), and are now accessible as a result of advances in the total synthesis of the natural product. Illustrative new ultra-potent vinblastines bind tubulin with much higher affinity and likely further disrupt the tubulin head-to-tail α/β dimer-dimer interaction by virtue of the strategic placement of an added conformationally well-defined, rigid and extended C20′-urea along the adjacent protein-protein interface. Added molecular complexity was used to markedly enhance target binding and functional biological activity, and represents a general approach to improving the properties of other natural products targeting a protein-protein interaction. A pharmaceutical composition containing an ultra-potent 20′-hydroxy-vinca derivative compound and a method of treating cancerous cells with such a compound are also disclosed.

  本研究揭示了 20′-羟基长春新碱衍生物化合物（如长春新碱、长春新碱或长春新碱）的合成衍生物和以前无法获得的修饰物，其活性比天然产物高出 100 倍（IC50 为 50-75 pM 对 7 nM，HCT116），由于天然产物全合成技术的进步，现在可以获得这些修饰物。举例说明的新型超强长春新碱能以更高的亲和力与微管蛋白结合，并可能进一步破坏微管蛋白头尾α/β二聚体之间的相互作用，这是因为在相邻的蛋白质-蛋白质界面上战略性地放置了一个构象明确、刚性和延伸的C20′-脲。增加的分子复杂性可显著增强目标结合力和功能性生物活性，是改善其他天然产品针对蛋白质-蛋白质相互作用特性的通用方法。此外，还公开了一种含有超强 20′-羟基长春花衍生物化合物的药物组合物，以及用这种化合物治疗癌细胞的方法。
• ULTRA-POTENT VINA ALKALOIDS: ADDED MOLECULAR COMPLEXITY FURTHER DISRUPTS THE TUBLIN DIMER-DIMER INTERFACE
  申请人：The Scripps Research Institute

  公开号：EP3464289A1

  公开（公告）日：2019-04-10
• ULTRA-POTENT VINCA ALKALOIDS: ADDED MOLECULAR COMPLEXITY FURTHER DISRUPTS THE TUBULIN DIMER-DIMER INTERFACE
  申请人：The Scripps Research Institute

  公开号：EP3464289B1

  公开（公告）日：2021-04-21