2-(2-chloro-5-nitrophenyl)-1-methylbenzo[ d]imidazole | 1421132-36-6

• 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-(2-chloro-5-nitrophenyl)-1-methylbenzo[ d]imidazole
• 英文别名: 2-(2-Chloro-5-nitrophenyl)-1-methyl-1H-benzimidazole；2-(2-chloro-5-nitrophenyl)-1-methylbenzimidazole
• CAS: 1421132-36-6
• 化学式: C₁₄H₁₀ClN₃O₂
• 分子量: 287.705
• InChiKey: AFTQRXLXBZXWGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  60.96
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-(2-chloro-5-nitrophenyl)-1-methylbenzo[ d]imidazole 在 4-二甲氨基吡啶 、 铁粉 、 氯化铵 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 17.0h， 生成 (R)-N-(4-chloro-3-(1-methyl-1H-benzo[d]imidazol-2-yl)phenyl)-2-((5R,8S)-2,5-dimethyl-5,6,7,8-tetrahydroquinolin-8-yl)-propanamide
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of 2-(2,5-Dimethyl-5,6,7,8-tetrahydroquinolin-8-yl)-N-aryl Propanamides as Novel Smoothened (Smo) Antagonists

  摘要：

  A series of novel Smo antagonists were developed either by directly incorporating the basic skeleton of the natural product artemisinin or by first breaking artemisinin into structurally simpler and stable intermediates and then reconstructing into diversified heterocyclic derivatives, equipped with a Smo-targeting bullet. 2-(2,5-Dimethy1-5,6,7,8-tetrahydroquinolin-8-yl)-N-arylpropanamide 65 was identified as the most potent, with an IC50 value of 9.53 nM against the Hh signaling pathway. Complementary mechanism studies confirmed that 65 inhibits Hh signaling pathway by targeting Smo and shares the same binding site as that of the tool drug cyclopamine. Meanwhile, 65 has a good plasma exposure and an acceptable oral bioavailability. Dose-dependent antiproliferative effects were observed in ptch+/;p53-/- medulloblastoma cells, and significant tumor growth inhibitions were achieved for 65 in the ptch+/-;p53-/- medulloblastoma allograft model.

  DOI：

  10.1021/acs.jmedchem.6b01247
• 作为产物：
  描述：

  N-(2-氨基苯基)-2-氯-5-硝基苯甲酰胺 在 溶剂黄146 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 4.0h， 生成 2-(2-chloro-5-nitrophenyl)-1-methylbenzo[ d]imidazole
  参考文献：
  名称：

  一类含苯并咪唑基团的二芳基酰胺类化合物及 其合成和应用

  摘要：

  本发明涉及一类含苯并咪唑基团的二芳基酰胺类化合物及其合成和应用，属于化学医药领域，所述化合物具有如下通式Ⅰ：其中：R1为氢、卤素、羟基、氨基、C1～C6烷基、C1～C6烷氧基、C1～C6酯基、C1～C6烷胺基或C1～C6酰胺基；R2为氢、卤素、羟基、氨基、C1～C6烷基、C1～C6烷氧基、C1～C6酯基、C1～C6烷胺基或C1～C6酰胺基；R3为氢、卤素、羟基、氨基、C1～C6烷基、C1～C6烷氧基、C1～C6酯基、C1～C6烷胺基、C1～C6酰胺基、苯环或氮杂芳环；R4为H或C1～C6烷基；R5为甲砜基、硝基、三氟甲基或氰基，所述化合物及其药学上可接受的盐在制备抗肿瘤药物中的应用。

  公开号：

  CN104151250B

文献信息

• [EN] N-(3-HETEROARYLARYL)-4-ARYLARYLCARBOXAMTDES AND ANALOGS AS HEDGEHOG PATHWAY INHIBITORS AND USE THEREOF<br/>[FR] N-(3-HÉTÉROARYLARYL)-4-ARYLARYLCARBOXAMIDES ET ANALOGUES COMME INHIBITEURS DE LA VOIE HEDGEHOG ET LEUR UTILISATION
  申请人：IMPACT THERAPEUTICS INC

  公开号：WO2014012511A1

  公开（公告）日：2014-01-23

  Disclosed are novel N-(3-heteroarylaryl)-4-arylarylcarboxamides and analogs thereof, represented by the Formula I: wherein C cyclic group, D1-D4, Q1, Q2, R5 are defined herein. Compounds having Formula (I) are hedgehog pathway inhibitors. Therefore, compounds of the invention may be used to treat clinical conditions that are responsive to the inhibition of hedgehog activity, such as cancer.

  揭示了一种新颖的N-(3-杂环芳基芳基)-4-芳基芳基羧酰胺及其类似物，表示为公式I：其中C是环状基团，D1-D4，Q1，Q2，R5在此定义。具有公式(I)的化合物是刺猬通路抑制剂。因此，本发明的化合物可用于治疗对刺猬活性抑制敏感的临床病况，如癌症。
• N-(3-heteroarylaryl)-4-arylarylcarboxamides and Analogs as Hedgehog Pathway Inhibitors and Use Thereof
  申请人：IMPACT Therapeutics, Inc.

  公开号：US20150191460A1

  公开（公告）日：2015-07-09

  Disclosed are novel N-(3-heteroarylaryl)-4-arylarylcarboxamides and analogs thereof, represented by the Formula I: wherein C cyclic group, D 1 -D 4 , Q 1 , Q 2 , R 5 are defined herein. Compounds having Formula (I) are hedgehog pathway inhibitors. Therefore, compounds of the invention may be used to treat clinical conditions that are responsive to the inhibition of hedgehog activity, such as cancer.

  揭示了一种新型的N-(3-杂环芳基芳基)-4-芳基芳基羧酰胺及其类似物，其化学式如下：其中C为环状基团，D1-D4，Q1，Q2，R5在此处定义。具有化学式(I)的化合物是刺猬途径抑制剂。因此，本发明的化合物可用于治疗对刺猬活性抑制有响应的临床病况，如癌症。
• N-(3-heteroarylaryl)-4-arylarylcarboxamides and analogs as hedgehog pathway inhibitors and use thereof
  申请人：IMPACT Therapeutics, Inc.

  公开号：US10676468B2

  公开（公告）日：2020-06-09

  Disclosed are novel N-(3-heteroarylaryl)-4-arylarylcarboxamides and analogs thereof, represented by the Formula I: wherein C cyclic group, D1-D4, Q1, Q2, R5 are defined herein. Compounds having Formula (I) are hedgehog pathway inhibitors. Therefore, compounds of the invention may be used to treat clinical conditions that are responsive to the inhibition of hedgehog activity, such as cancer.

  公开了新型 N-(3-异芳基)-4-芳基羧酰胺及其类似物，由式 I 表示：其中 C 环基、D1-D4、Q1、Q2、R5 在此定义。具有式（I）的化合物是刺猬通路抑制剂。因此，本发明的化合物可用于治疗对抑制刺猬活性有反应的临床病症，如癌症。
• N-(3-HETEROARYLARYL)-4-ARYLARYLCARBOXAMTDES AND ANALOGS AS HEDGEHOG PATHWAY INHIBITORS AND USE THEREOF
  申请人：Impact Therapeutics, Inc.

  公开号：EP2875005B1

  公开（公告）日：2020-11-11