5-(difluoromethoxy)-2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfonyl)-1H-benzo[d]imidazole

• 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-(difluoromethoxy)-2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfonyl)-1H-benzo[d]imidazole
• 英文别名: 2-{[4-(3-methoxy-propoxy)-3-methylpyridine-2-yl]-methyl-sulfonyl}-1H-5-difluoromethoxyl-benzimidazole；6-(difluoromethoxy)-2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfonyl]-1H-benzimidazole
• 化学式: C₁₉H₂₁F₂N₃O₅S
• 分子量: 441.456
• InChiKey: ABIHYABOYVXRDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-(difluoromethoxy)-2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfonyl)-1H-benzo[d]imidazole 在 lithium hydroxide 作用下， 以 水 为溶剂， 生成 2-{[4-(3-methoxy-propoxy)-3-methylpyridine-2-yl]-methyl-sulfonyl}-1H-5-difluoromethoxy benzimidazole lithium salt
  参考文献：
  名称：

  NEW PRAZOLE COMPOUND AND THE USE THEREOF

  摘要：

  本发明涉及化合物（式（I）或（II））及其盐的衍生物，其中R1代表较低烷基或被卤素原子取代的较低烷基，R2代表含有1-4个碳原子的直链或支链烷基，R3代表氢原子或碱金属如锂、钠、钾或碱土金属如镁和钙。在本发明中，具有式（I）或（II）的化合物及其衍生物或药学和药理学上可接受的盐可以显著提高抗溃疡在消化道中的有效性，微弱抑制胃酸分泌，降低患胃癌的风险，并具有优异的生物利用度和其他体内药代动力学特性。

  公开号：

  EP1795195A1
• 作为产物：
  描述：

  2-羟甲基-4-甲氧基丙氧基-3-甲基吡啶 在 sodium hypochlorite 、 氯化亚砜 、 碳酸氢钠 、 间氯过氧苯甲酸 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 2.5h， 生成 5-(difluoromethoxy)-2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfonyl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Proton pump inhibitors selectively suppress MLL rearranged leukemia cells via disrupting MLL1-WDR5 protein-protein interaction

  摘要：

  Genetic rearrangements of the mixed lineage leukemia (MLL) leading to oncogenic MLL-fusion proteins (MLL-FPs). MLL-FPs occur in about 10% of acute leukemias and are associated with dismal prognosis and treatment outcomes which emphasized the need for new therapeutic strategies. In present study, by a cell-based screening in-house compound collection, we disclosed that Rabeprazole specially inhibited the proliferation of leukemia cells harboring MLL-FPs with little toxicity to non-MLL cells. Mechanism study showed Rabeprazole down-regulated the transcription of MLL-FPs related Hox and Meis1 genes and effectively inhibited MLL1 H3K4 methyltransferase (HMT) activity in MV4-11 cells bearing MLL-AF4 fusion protein. Displacement of MLL1 probe from WDR5 protein suggested that Rabeprazole may inhibit MLL1 HMT activity through disturbing MLL1-WDR5 protein-protein interaction. Moreover, other proton pump inhibitors (PPIs) also indicated the inhibition activity of MLL1-WDR5. Preliminary SARs showed the structural characteristics of PPIs were also essential for the activities of MLL1-WDR5 inhibition. Our results indicated the drug reposition of PPIs for MLL-rearranged leukemias and provided new insight for further optimization of targeting MLL1 methyltransferase activity, the MLL1-WDR5 interaction or WDR5. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.112027

文献信息

• CXCL10 Inhibitors
  申请人：LAPKO INC, dba AFECTA PHARMACEUTICALS

  公开号：US20210338650A1

  公开（公告）日：2021-11-04

  Provided herein are compounds and compositions effective for inhibiting CXCL10 gene expression, production, and secretion in mammalian cells, tissues and organs, as well as ameliorating its biological activity, along with a method for treatment of one or more disorders associated with an increase in CXCL10 gene expression, production, and secretion.
• NEW PRAZOLE COMPOUND AND THE USE THEREOF
  申请人：Jiangsu Hansen Pharmaceutical Co., Ltd.

  公开号：EP1795195A1

  公开（公告）日：2007-06-13

  The present invention relates to derivatives of compounds (formula (I) or (II)) and their salts, wherein R1 represents lower alkyl or the lower alkyl substituted by halogen atoms, R2 represents straight-chain or branched-chain alkyl containing 1-4 carbon atoms and R3 represents hydrogen atom or alkali metals such as lithium, sodium, potassium or alkaline-earth metals such as magnesium and calcium. In the present invention, compounds with formula (I) or (II) and their derivatives or salts thereof acceptable in pharmacy and pharmacology can remarkably improve the effectiveness of anti-ulcer in alimentary tract, weakly inhibit gastric acid secretion, reduce the risk of stomach cancer and have excellent bio-availability and other in-vive pharmacokinetic characteristics.

  本发明涉及化合物（式（I）或（II））及其盐的衍生物，其中R1代表较低烷基或被卤素原子取代的较低烷基，R2代表含有1-4个碳原子的直链或支链烷基，R3代表氢原子或碱金属如锂、钠、钾或碱土金属如镁和钙。在本发明中，具有式（I）或（II）的化合物及其衍生物或药学和药理学上可接受的盐可以显著提高抗溃疡在消化道中的有效性，微弱抑制胃酸分泌，降低患胃癌的风险，并具有优异的生物利用度和其他体内药代动力学特性。
• Proton pump inhibitors selectively suppress MLL rearranged leukemia cells via disrupting MLL1-WDR5 protein-protein interaction
  作者：Wei-Lin Chen、Dong-Dong Li、Xin Chen、Ying-Zhe Wang、Jun-Jie Xu、Zheng-Yu Jiang、Qi-Dong You、Xiao-Ke Guo

  DOI：10.1016/j.ejmech.2019.112027

  日期：2020.2

  Genetic rearrangements of the mixed lineage leukemia (MLL) leading to oncogenic MLL-fusion proteins (MLL-FPs). MLL-FPs occur in about 10% of acute leukemias and are associated with dismal prognosis and treatment outcomes which emphasized the need for new therapeutic strategies. In present study, by a cell-based screening in-house compound collection, we disclosed that Rabeprazole specially inhibited the proliferation of leukemia cells harboring MLL-FPs with little toxicity to non-MLL cells. Mechanism study showed Rabeprazole down-regulated the transcription of MLL-FPs related Hox and Meis1 genes and effectively inhibited MLL1 H3K4 methyltransferase (HMT) activity in MV4-11 cells bearing MLL-AF4 fusion protein. Displacement of MLL1 probe from WDR5 protein suggested that Rabeprazole may inhibit MLL1 HMT activity through disturbing MLL1-WDR5 protein-protein interaction. Moreover, other proton pump inhibitors (PPIs) also indicated the inhibition activity of MLL1-WDR5. Preliminary SARs showed the structural characteristics of PPIs were also essential for the activities of MLL1-WDR5 inhibition. Our results indicated the drug reposition of PPIs for MLL-rearranged leukemias and provided new insight for further optimization of targeting MLL1 methyltransferase activity, the MLL1-WDR5 interaction or WDR5. (C) 2020 Elsevier Masson SAS. All rights reserved.