5,6-dimethoxy-2-(pyridin-2-yl)-1H-benzo[d]imidazole | 1256094-28-6

• 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: 5,6-dimethoxy-2-(pyridin-2-yl)-1H-benzo[d]imidazole
• 英文别名: 5,6-dimethoxy-2-pyridin-2-yl-1H-benzimidazole
• CAS: 1256094-28-6
• 化学式: C₁₄H₁₃N₃O₂
• 分子量: 255.276
• InChiKey: SQAPVUBRWDCDNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  60
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  iodonium ethynylphenyl triflate 、 5,6-dimethoxy-2-(pyridin-2-yl)-1H-benzo[d]imidazole 以 甲苯 为溶剂， 反应 16.0h， 以51%的产率得到10,11-dimethoxybenzo[4,5]imidazo[1,2-a]pyrido[2,1-c]pyrazin-5-ium triflate
  参考文献：
  名称：

  N-炔基吡啶鎓盐：高亲电性炔-吡啶共轭物作为阳离子氮嵌入多环芳烃的前体

  摘要：

  我们通过吡啶与炔基-λ3-碘反应，首次合成了 N-炔基吡啶鎓盐。N-炔基吡啶鎓表现出高度的电子接受特性，并具有扩展的 π 共轭。亲电炔基很容易受到迈克尔加成和 1,3-偶极环加成的影响，得到各种 N-烯基吡啶鎓。稠环吡啶鎓是通过分子内环化合成的，证明了 N-炔基吡啶鎓可用于设计具有独特光学和电化学性质的各种缺电子阳离子氮嵌入多环芳烃。

  DOI：

  10.1021/jacs.8b00356
• 作为产物：
  描述：

  吡啶-2-甲醛 、 4,5-二甲氧基-1,2-苯二胺 在 氧气 作用下， 以 N-甲基吡咯烷酮 、 甲醇 为溶剂， 反应 96.0h， 以61.5%的产率得到5,6-dimethoxy-2-(pyridin-2-yl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Structure-Based Design of New Dihydrofolate Reductase Antibacterial Agents: 7-(Benzimidazol-1-yl)-2,4-diaminoquinazolines

  摘要：

  A new series of dihydrofolate reductase (DHFR) inhibitors, the 7-(benzimidazol-1-yl)-2,4-diaminoquinazolines, were designed and optimized for antibacterial potency and enzyme selectivity. The most potent inhibitors in this series contained a five-membered heterocycle at the 2-position of, the benzimidazole, leading to highly potent and selective compounds that exploit the differences in the size of a binding pocket adjacent to the NADPH cofactor between the bacterial and human DHFR enzymes. Typical of these compounds is 74(2-thiazol-2-yObenzimidazol-1-yl)-2,4 diaminoquinazoline, which is a potent inhibitor of S. aureus DHFR (K-i = 0.002 nM) with 46700-fold selectivity over human DHFR. This compound also has high antibacterial potency on Gram-positive bacteria with an MIC versus wild type S. aureus of 0.0125 mu g/mL and a MIC versus trimethoprim-resistant S. aureus of 0.25 mu g/mL. In vivo efficacy versus a S. aureus septicemia was demonstrated, highlighting the potential of this new series.

  DOI：

  10.1021/jm401204g

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.