2-pyridin-2-yl-3H-benzimidazol-5-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-pyridin-2-yl-3H-benzimidazol-5-ol
• 化学式: C₁₂H₉N₃O
• 分子量: 211.22
• InChiKey: FRXPNZAFIBJXOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  3

文献信息

• INHIBITORS OF INV(16) LEUKEMIA
  申请人：The University of Virginia Patent Foundation

  公开号：EP3670509A1

  公开（公告）日：2020-06-24

  This invention describes the development of targeted small molecule inhibitors of the inv(16) fusion, the causative agent in ∼12% of acute myeloid leukemia (AML). The inv(16) fusion results in expression of the CBFβ-SMMHC fusion protein in the blood cells of afflicted patients. The present invention provides compounds which inhibit the function of both CBFβ and the CBFβ-SMMHC fusion. These compounds block the growth of an inv(16) leukemia cell line as well as increase its apoptosis, while showing minimal effects against non inv(16) cell lines. As a mechanism to develop inhibitors with selectivity for the CBFβ-SMMHC fusion protein, the present invention further provides dimeric derivatives of these compounds which show both increased potency as well as selectivity for CBFβ-SMMHC. These compounds show potent inhibition of an inv(16) leukemia cell line with minimal effects on non inv(16) cell lines. Analysis of the pharmacokinetics of the developed compounds has made it possible to improve the lifetime of the compound in the plasma of mice to a level commensurate with long-term treatment.

  本发明描述了 inv(16) 融合的靶向小分子抑制剂的开发，inv(16) 融合是 12% 的急性髓性白血病（AML）的致病因子。inv（16）融合会导致患者血细胞中表达 CBFβ-SMMHC 融合蛋白。本发明提供了抑制 CBFβ 和 CBFβ-SMMHC 融合蛋白功能的化合物。这些化合物能阻断inv(16)白血病细胞系的生长，并增加其凋亡，同时对非inv(16)细胞系的影响极小。作为开发对 CBFβ-SMMHC 融合蛋白具有选择性的抑制剂的机制，本发明进一步提供了这些化合物的二聚衍生物，它们对 CBFβ-SMMHC 具有更高的效力和选择性。这些化合物对 inv(16) 白血病细胞系具有强效抑制作用，而对非 inv(16) 细胞系的影响极小。通过对所开发化合物的药代动力学分析，可以将化合物在小鼠血浆中的存活时间延长到与长期治疗相称的水平。
• US8748618B2
  申请人：——

  公开号：US8748618B2

  公开（公告）日：2014-06-10
• US9221764B2
  申请人：——

  公开号：US9221764B2

  公开（公告）日：2015-12-29
• US9926290B2
  申请人：——

  公开号：US9926290B2

  公开（公告）日：2018-03-27
• [EN] INHIBITORS OF INV(16) LEUKEMIA<br/>[FR] INHIBITEURS DE LEUCÉMIE INV(16)
  申请人：UNIV VIRGINIA

  公开号：WO2010132684A2

  公开（公告）日：2010-11-18

  This invention describes the development of targeted small molecule inhibitors of the inv(16) fusion, the causative agent in ~12% of acute myeloid leukemia (AML). The inv(16) fusion results in expression of the CBFβ-SMMHC fusion protein in the blood cells of afflicted patients. The present invention provides compounds which inhibit the function of both CBFβ and the CBFβ-SMMHC fusion. These compounds block the growth of an inv(16) leukemia cell line as well as increase its apoptosis, while showing minimal effects against non inv(16) cell lines. As a mechanism to develop inhibitors with selectivity for the CBFβ-SMMHC fusion protein, the present invention further provides dimeric derivatives of these compounds which show both increased potency as well as selectivity for CBFβ-SMMHC. These compounds show potent inhibition of an inv(16) leukemia cell line with minimal effects on non inv(16) cell lines. Analysis of the pharmacokinetics of the developed compounds has made it possible to improve the lifetime of the compound in the plasma of mice to a level commensurate with long-term treatment.