2-(difluoromethyl)-4-ethoxy-1H-benzimidazole | 1188914-96-6

• 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: 2-(difluoromethyl)-4-ethoxy-1H-benzimidazole
• 英文别名: 2-difluoromethyl-4-ethoxy-1H-benzimidazole；1H-Benzimidazole, 2-(difluoromethyl)-7-ethoxy-
• CAS: 1188914-96-6
• 化学式: C₁₀H₁₀F₂N₂O
• 分子量: 212.199
• InChiKey: MYUPIPHPVSJVDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  37.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(difluoromethyl)-4-ethoxy-1H-benzimidazole 在 potassium carbonate 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-ethoxy-1H-benzimidazole
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Analogues of the Pan Class I Phosphatidylinositol 3-Kinase (PI3K) Inhibitor 2-(Difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474)

  摘要：

  A structure activity relationship (SAR) study of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474) identified substitution at the 4 and 6 positions of the benzimidazole ring as having significant effects on the potency of substituted derivatives. The 6-amino-4-methoxy analogue displayed a greater than 1000-fold potency enhancement over the corresponding 6-aza-4-methoxy analogue against all three class Ia PI 3-kinase enzymes (p110 alpha, p110 beta, and p110 delta) and also displayed significant potency against two mutant forms of the p110 alpha isoform (H1047R and E545K). This compound was also evaluated in vivo against a U87MG human glioblastoma tumor xenograft model in Ragl(-/-) mice, and at a dose of 50 mg/kg given by ip injection at a qd x 10 dosing schedule it dramatically reduced cancer growth by 81% compared to untreated controls.

  DOI：

  10.1021/jm200688y
• 作为产物：
  描述：

  2-ethoxy-6-nitroaniline 在 盐酸 、 5%-palladium/activated carbon 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 生成 2-(difluoromethyl)-4-ethoxy-1H-benzimidazole
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Analogues of the Pan Class I Phosphatidylinositol 3-Kinase (PI3K) Inhibitor 2-(Difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474)

  摘要：

  A structure activity relationship (SAR) study of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474) identified substitution at the 4 and 6 positions of the benzimidazole ring as having significant effects on the potency of substituted derivatives. The 6-amino-4-methoxy analogue displayed a greater than 1000-fold potency enhancement over the corresponding 6-aza-4-methoxy analogue against all three class Ia PI 3-kinase enzymes (p110 alpha, p110 beta, and p110 delta) and also displayed significant potency against two mutant forms of the p110 alpha isoform (H1047R and E545K). This compound was also evaluated in vivo against a U87MG human glioblastoma tumor xenograft model in Ragl(-/-) mice, and at a dose of 50 mg/kg given by ip injection at a qd x 10 dosing schedule it dramatically reduced cancer growth by 81% compared to untreated controls.

  DOI：

  10.1021/jm200688y

文献信息

• HETEROCYCLIC COMPOUND
  申请人：Astellas Pharma Inc.

  公开号：US20130150364A1

  公开（公告）日：2013-06-13

  [Problem] A novel and excellent compound which is useful as an agent for preventing and/or treating rejection reactions in various organ transplantations, allergy diseases, autoimmune diseases, and hematologic tumor, and based on a PI3Kδ selective inhibitory action and/or an IL-2 production inhibitory action and/or a B cell proliferation inhibitory action (including an activation inhibitory action). [Means for Solution] The present inventors have investigated a compound having a PI3Kδ selective inhibitory action and/or an IL-2 production inhibitory action and/or a B cell proliferation inhibitory action (including an activation inhibitory action), and have found that the heterocyclic compound of the present invention has a PI3Kδ selective inhibitory action and/or and IL-2 production inhibitory action and/or a B cell proliferation inhibitory action (including an activation inhibitory action), thereby completing the present invention.

  一种新颖且优秀的化合物，可用作预防和/或治疗各种器官移植排斥反应、过敏疾病、自身免疫疾病和血液肿瘤的药剂，基于PI3Kδ选择性抑制作用和/或IL-2产生抑制作用和/或B细胞增殖抑制作用（包括激活抑制作用）。 解决方案是，本发明者研究了一种具有PI3Kδ选择性抑制作用和/或IL-2产生抑制作用和/或B细胞增殖抑制作用（包括激活抑制作用）的化合物，发现本发明的杂环化合物具有PI3Kδ选择性抑制作用和/或IL-2产生抑制作用和/或B细胞增殖抑制作用（包括激活抑制作用），从而完成了本发明。
• SUBSTITUTED PYRIMIDINES AND TRIAZINES AND THEIR USE IN CANCER THERAPY
  申请人：Rewcastle Gordon William

  公开号：US20110053907A1

  公开（公告）日：2011-03-03

  Provided herein are substituted pyrimidine and triazine derivatives, including bicyclic pyrimidine derivatives, their pharmaceutical compositions, their preparation, and their use as agents or drugs for cancer therapy, either alone or in combination with radiation and/or other anticancer drugs. In one embodiment, the pyrimidine and triazine derivatives are morpholino-pyrimidine, morpholino-triazine, pyridyl-pyrimidine, and pyridyl-triazine derivatives which are selective irreversible inhibitors of the p110α isoform of PI3K.

  本文提供了替代嘧啶和三嗪衍生物，包括双环嘧啶衍生物，它们的药物组合物，其制备以及它们作为单独的癌症治疗剂或药物的用途，或与放射线和/或其他抗癌药物组合使用。在一种实施例中，嘧啶和三嗪衍生物是吗啡啶基嘧啶，吗啡啶基三嗪，吡啶基嘧啶和吡啶基三嗪衍生物，它们是PI3K的p110α亚型的选择性不可逆抑制剂。
• Heterocyclic compound
  申请人：Astellas Pharma Inc.

  公开号：US08912180B2

  公开（公告）日：2014-12-16

  Provided is a novel compound which is an agent for treating rejection reactions in various organ transplantations, allergy diseases, autoimmune diseases, and hematologic tumor, and based on a PI3Kδ selective inhibitory action and/or an IL-2 production inhibitory action and/or a B cell proliferation inhibitory action (including an activation inhibitory action). The provided compound has a PI3Kδ selective inhibitory action, an IL-2 production inhibitory action, and/or a B cell proliferation inhibitory action, including an activation inhibitory action.

  提供的是一种新型化合物，它是一种治疗各种器官移植的排斥反应、过敏性疾病、自身免疫性疾病和血液肿瘤的药物，基于PI3Kδ选择性抑制作用和/或IL-2产生抑制作用和/或B细胞增殖抑制作用（包括激活抑制作用）。所提供的化合物具有PI3Kδ选择性抑制作用、IL-2产生抑制作用和/或B细胞增殖抑制作用，包括激活抑制作用。
• [EN] SUBSTITUTED PYRIMIDINES AND TRIAZINES AND THEIR USE IN CANCER THERAPY<br/>[FR] PYRIMIDINES ET TRIAZINES SUBSTITUÉES, ET LEUR UTILISATION EN THÉRAPIE ANTICANCÉREUSE
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2009120094A3

  公开（公告）日：2010-01-28
• HETERO RING COMPOUND
  申请人：Astellas Pharma Inc.

  公开号：EP2604601B1

  公开（公告）日：2016-02-24