N-(2-氯苄基)-4-甲氧基-2-硝基苯胺 | 1036530-84-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(2-氯苄基)-4-甲氧基-2-硝基苯胺
• 英文名称: N-(2-chlorobenzyl)-4-methoxy-2-nitroaniline
• 英文别名: N-[(2-chlorophenyl)methyl]-4-methoxy-2-nitroaniline
• CAS: 1036530-84-3
• 化学式: C₁₄H₁₃ClN₂O₃
• 分子量: 292.722
• InChiKey: AKRCGRWIDZTQKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  67.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-氯苄基)-4-甲氧基-2-硝基苯胺 在 tin(II) chloride dihdyrate 、 氢溴酸 、 四丁基碘化铵 、 caesium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 2-[({1-(2-chlorobenzyl)-2-[1-(4-isobutylphenyl)ethyl]-1H-benzimidazol-5-yl}oxy)methyl]quinoline
  参考文献：
  名称：

  Identification of novel benzimidazole derivatives as inhibitors of leukotriene biosynthesis by virtual screening targeting 5-lipoxygenase-activating protein (FLAP)

  摘要：

  Pharmacological suppression of leukotriene biosynthesis by 5-lipoxygenase (5-LO)-activating protein (FLAP) inhibitors is a promising strategy to intervene with inflammatory, allergic and cardiovascular diseases. Virtual screening targeting FLAP based on a combined ligand-and structure-based pharmacophore model led to the identification of 1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-1H-benzimidazole (7) as developable candidate. Compound 7 potently suppressed leukotriene formation in intact neutrophils (IC50 = 0.31 mu M) but essentially failed to directly inhibit 5-LO suggesting that interaction with FLAP causes inhibition of leukotriene synthesis. For structural optimization, a series of 46 benzimidazole-based derivatives of 7 were synthesized leading to more potent analogues (70-72, 82) with IC50 = 0.12-0.19 mu M in intact neutrophils. Together, our results disclose the benzimidazole scaffold bearing an ibuprofen fingerprint as a new chemotype for further development of anti-leukotriene agents. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.048
• 作为产物：
  描述：

  2-氯苄溴 、 2-硝基-4-甲氧基苯胺 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(2-氯苄基)-4-甲氧基-2-硝基苯胺
  参考文献：
  名称：

  白三烯生物合成抑制剂BRP-7的C（5）取代衍生物的合成和生物学评估。

  摘要：

  用5-脂氧合酶（5-LO）途径进行药理干预可抑制白三烯（LT）生物合成，这是经临床验证的策略，可用于治疗呼吸道和心血管疾病，例如哮喘和动脉粥样硬化。在这里我们描述了先前描述的5-LO激活蛋白（FLAP）抑制剂BRP-7（IC50 = 0.31μM）的一系列C（5）取代类似物的合成，以探讨在C（5 ）-苯并咪唑（BI）环作为增加针对FLAP介导的5-LO产物形成的效力的策略。在BI核的C（5）位置上掺入极性取代基，例如具有C（5）-腈取代基的化合物11，可显着增强抑制人类嗜中性粒细胞中5-LO产物合成的能力（IC50 = 0.07μM ）和单核细胞（IC50 = 0.026μM）。

  DOI：

  10.1016/j.ejmech.2016.07.004

文献信息

• [EN] COMPOUNDS AND METHODS FOR TREATMENT OF HEDGEHOG PATHWAY ASSOCIATED CONDITIONS<br/>[FR] COMPOSÉS ET MÉTHODES POUR LE TRAITEMENT D'AFFECTIONS ASSOCIÉES À LA VOIE HEDGEHOG
  申请人：SUZHOU MEDNES PHARMA TECH CO LTD

  公开号：WO2020003119A1

  公开（公告）日：2020-01-02

  Provided herein is novel compounds of formula (I), (II), (III), (IV), and (V) as described in the specification, and pharmaceutically acceptable salts, solvates, and prodrugs and compositions thereof, and methods of measuring hedgehog pathway activation in tumor cells, examining tumor cell proliferation, differentiation and apoptosis and using the compounds and pharmaceutical compositions disclosed for treatment of diseases and disorders associated with the hedgehog signaling pathway.

  本文提供了规范中描述的式(I)、(II)、(III)、(IV)和(V)的新化合物，以及其药学上可接受的盐、溶剂化合物、前药和组合物，以及测量肿瘤细胞中刺猬途径激活、检查肿瘤细胞增殖、分化和凋亡的方法，以及使用所披露的化合物和药物组合物治疗与刺猬信号通路相关的疾病和疾病的方法。
• COMPOUNDS AND METHODS FOR TREATMENT OF HEDGEHOG PATHWAY ASSOCIATED CONDITIONS
  申请人：Suzhou Mednes Pharma Tech Co., Ltd.

  公开号：EP3810573A1

  公开（公告）日：2021-04-28
• Identification of novel benzimidazole derivatives as inhibitors of leukotriene biosynthesis by virtual screening targeting 5-lipoxygenase-activating protein (FLAP)
  作者：Erden Banoglu、Burcu Çalışkan、Susann Luderer、Gökçen Eren、Yagmur Özkan、Wolfram Altenhofen、Christina Weinigel、Dagmar Barz、Jana Gerstmeier、Carlo Pergola、Oliver Werz

  DOI：10.1016/j.bmc.2012.04.048

  日期：2012.6

  Pharmacological suppression of leukotriene biosynthesis by 5-lipoxygenase (5-LO)-activating protein (FLAP) inhibitors is a promising strategy to intervene with inflammatory, allergic and cardiovascular diseases. Virtual screening targeting FLAP based on a combined ligand-and structure-based pharmacophore model led to the identification of 1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl)ethyl)-1H-benzimidazole (7) as developable candidate. Compound 7 potently suppressed leukotriene formation in intact neutrophils (IC50 = 0.31 mu M) but essentially failed to directly inhibit 5-LO suggesting that interaction with FLAP causes inhibition of leukotriene synthesis. For structural optimization, a series of 46 benzimidazole-based derivatives of 7 were synthesized leading to more potent analogues (70-72, 82) with IC50 = 0.12-0.19 mu M in intact neutrophils. Together, our results disclose the benzimidazole scaffold bearing an ibuprofen fingerprint as a new chemotype for further development of anti-leukotriene agents. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of C(5)-substituted derivatives of leukotriene biosynthesis inhibitor BRP-7
  作者：Serkan Levent、Jana Gerstmeier、Abdurrahman Olgaç、Felix Nikels、Ulrike Garscha、Andrea Carotti、Antonio Macchiarulo、Oliver Werz、Erden Banoglu、Burcu Çalışkan

  DOI：10.1016/j.ejmech.2016.07.004

  日期：2016.10

  atherosclerosis. Here we describe the synthesis of a series of C(5)-substituted analogues of the previously described 5-LO-activating protein (FLAP) inhibitor BRP-7 (IC50 = 0.31 muM) to explore the effects of substitution at the C(5)-benzimidazole (BI) ring as a strategy to increase the potency against FLAP-mediated 5-LO product formation. Incorporation of polar substituents on the C(5) position of the BI core

  用5-脂氧合酶（5-LO）途径进行药理干预可抑制白三烯（LT）生物合成，这是经临床验证的策略，可用于治疗呼吸道和心血管疾病，例如哮喘和动脉粥样硬化。在这里我们描述了先前描述的5-LO激活蛋白（FLAP）抑制剂BRP-7（IC50 = 0.31μM）的一系列C（5）取代类似物的合成，以探讨在C（5 ）-苯并咪唑（BI）环作为增加针对FLAP介导的5-LO产物形成的效力的策略。在BI核的C（5）位置上掺入极性取代基，例如具有C（5）-腈取代基的化合物11，可显着增强抑制人类嗜中性粒细胞中5-LO产物合成的能力（IC50 = 0.07μM ）和单核细胞（IC50 = 0.026μM）。