N-methylisoindoline-2-carboxamide | 6765-53-3

• 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: N-methylisoindoline-2-carboxamide
• 英文别名: N-methyl-2,3-dihydro-1H-isoindole-2-carboxamide；N-methyl-1,3-dihydroisoindole-2-carboxamide
• CAS: 6765-53-3
• 化学式: C₁₀H₁₂N₂O
• 分子量: 176.218
• InChiKey: MJVZHYANAWGLMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  1

文献信息

• NAMPT AND ROCK INHIBITORS
  申请人：Curtin Michael L.

  公开号：US20120122842A1

  公开（公告）日：2012-05-17

  Disclosed are compounds which inhibit the activity of NAMPT, compositions containing the compounds and methods of treating diseases during which NAMPT is expressed. Disclosed are compounds which inhibit the activity of ROCK, compositions containing the compounds and methods of treating diseases during which ROCK is expressed.

  公开了一种抑制NAMPT活性的化合物，包含该化合物的组合物和治疗NAMPT表达疾病的方法。公开了一种抑制ROCK活性的化合物，包含该化合物的组合物和治疗ROCK表达疾病的方法。
• Nampt and Rock Inhibitors
  申请人：AbbVie Inc.

  公开号：US20160031880A1

  公开（公告）日：2016-02-04

  Disclosed are compounds which inhibit the activity of NAMPT, compositions containing the compounds and methods of treating diseases during which NAMPT is expressed. Disclosed are compounds which inhibit the activity of ROCK, compositions containing the compounds and methods of treating diseases during which ROCK is expressed.

  本发明涉及抑制NAMPT活性的化合物、含有该化合物的组合物以及治疗表达NAMPT的疾病的方法。本发明还涉及抑制ROCK活性的化合物、含有该化合物的组合物以及治疗表达ROCK的疾病的方法。
• 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。
• C20' Urea Derivatives of Vinca Alkaloids
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：US20150291610A1

  公开（公告）日：2015-10-15

  A vinca alkaloid compound that is substituted at the 20′-position with a urea or thiourea group is disclosed. The urea's proximal nitrogen atom bonded to the 20′-position carbon atom is secondary, whereas the distal nitrogen atom can be unsubstituted only when the compound contains an optionally present 10′-fluoro substituent, and is otherwise preferably mono- or di-substituted. Methods of preparing the compounds are disclosed as are compositions for their use and methods of treatment using a compound.
• ULTRA-POTENT VINA ALKALOIDS: ADDED MOLECULAR COMPLEXITY FURTHER DISRUPTS THE TUBLIN DIMER-DIMER INTERFACE
  申请人：The Scripps Research Institute

  公开号：US20200317696A1

  公开（公告）日：2020-10-08

  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 (IC 50 '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.