4-chloro-2-(5-nitro-1H-benzo[d]imidazol-2-yl)phenol

• 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: 4-chloro-2-(5-nitro-1H-benzo[d]imidazol-2-yl)phenol
• 英文别名: 4-chloro-2-(6-nitro-1H-benzimidazol-2-yl)phenol
• 化学式: C₁₃H₈ClN₃O₃
• 分子量: 289.678
• InChiKey: CXIOJCBUFHEXSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  94.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-2-(5-nitro-1H-benzo[d]imidazol-2-yl)phenol 、 乙醚 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以71%的产率得到2,2-Dimethyl-propionic acid 2-(5-nitro-1H-benzimidazol-2-yl)-4-chloro-phenyl ester
  参考文献：
  名称：

  Ester derivatives of dimethylpropionic acid and pharmaceutical compositions containing them

  摘要：

  本发明涉及具有通式（I）的2,2-二甲基丙酸酯或其药理学上可接受的盐，以及含有该化合物并具有弹性蛋白酶抑制活性的药物组合物。

  公开号：

  EP1132381A1
• 作为产物：
  描述：

  4-硝基邻苯二胺 、 5-氯代水杨醛 在 sodium metabisulfite 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 4-chloro-2-(5-nitro-1H-benzo[d]imidazol-2-yl)phenol
  参考文献：
  名称：

  新型苯并咪唑类化合物在三阴性乳腺癌中对Wnt /β-catenin信号的优先抑制

  摘要：

  与其他乳腺癌亚型和正常组织相比，三阴性乳腺癌（TNBC）中的Wnt /β-catenin信号上调。目前的Wnt /β-catenin抑制剂（例如niclosamide）非特异性地靶向该途径，并且在体内表现出较差的药代动力学/药效学。Niclosamide靶向其他途径，包括mTOR，STAT3和Notch。已开发出新型苯并咪唑以更高的特异性抑制Wnt /β-catenin信号传导。发现化合物SRI33576和SRI35889在TNBC细胞系中比在非癌细胞中产生更大的细胞毒性。这些药物还下调了Wnt /β-catenin信号传导介质LRP6，cyclin D1，survivin和核活性β-catenin。此外，SRI33576不会影响TNBC和非癌细胞中的mTOR，STAT3和Notch信号传导。SRI35889在非癌细胞中抑制mTOR信号的能力比在癌细胞中抑制作用小，但不影响STAT3和No

  DOI：

  10.3390/ijms19051524

文献信息

• CHEMICAL MODULATORS OF IMMUNE CHECKPOINTS AND THERAPEUTIC USE
  申请人：Duke University

  公开号：US20170190675A1

  公开（公告）日：2017-07-06

  Compounds and pharmaceutical compositions that down-regulate immune checkpoints such as PD-1, PD-L1 and CTLA-4 are provided. Also provided are methods of treating a disease by down-regulating immune checkpoints such as PD-1, PD-L1 and CTLA-4. The methods are useful for treating cancer and viral infection in a subject.

  提供了下调免疫检查点如PD-1、PD-L1和CTLA-4的化合物和药物组合物。还提供了通过下调免疫检查点如PD-1、PD-L1和CTLA-4来治疗疾病的方法。这些方法对于治疗受试者的癌症和病毒感染是有用的。
• Chemical modulators of immune checkpoints and therapeutic use
  申请人：Duke University

  公开号：US10189797B2

  公开（公告）日：2019-01-29

  Compounds and pharmaceutical compositions that down-regulate immune checkpoints such as PD-1, PD-L1 and CTLA-4 are provided. Also provided are methods of treating a disease by down-regulating immune checkpoints such as PD-1, PD-L1 and CTLA-4. The methods are useful for treating cancer and viral infection in a subject.

  提供了下调免疫检查点如 PD-1、PD-L1 和 CTLA-4 的化合物和药物组合物。还提供了通过下调免疫检查点如 PD-1、PD-L1 和 CTLA-4 来治疗疾病的方法。这些方法可用于治疗受试者的癌症和病毒感染。
• 6,7-Dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives as selective inhibitors of PI3Kα
  作者：Yong Yin、Yan-Qing Zhang、Biao Jin、Shao Sha、Xun Wu、Chetan B. Sangani、She-Feng Wang、Fang Qiao、Ai-Min Lu、Peng-Cheng Lv、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2015.01.052

  日期：2015.3

  Twenty eight 6,7-dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4] oxazepine derivatives were synthesized and evaluated their biological activities as PI3K inhibitors. Biological evaluation against four human tumor cell lines revealed that most target compounds showed impressively better antiproliferative activities than that of LY294002. Among these compounds, compound 25 exhibited the most potent and selective activity for PI3K alpha, with the IC50 value of 0.016 mu M, an approximately 30-fold increase in comparison with LY294002, it also has an increased potency of approximately 11-fold for PI3K beta. It indicated the potential of developing 6,7-dihydrobenzo[f] benzo[4,5]imidazo[1,2-d][1,4] oxazepine derivatives as the new PI3K alpha selective inhibitors for tumor treatment. (C) 2015 Elsevier Ltd. All rights reserved.
• Benzimidazole inhibitors from the Niclosamide chemotype inhibit Wnt/β-catenin signaling with selectivity over effects on ATP homeostasis
  作者：Robert A. Mook、Xiu-Rong Ren、Jiangbo Wang、Hailan Piao、Larry S. Barak、H. Kim Lyerly、Wei Chen

  DOI：10.1016/j.bmc.2017.01.046

  日期：2017.3

  The Wnt signaling pathway plays a key role in organ and tissue homeostasis, and when dysregulated, can become a major underlying mechanism of disease, particularly cancer. We reported previously that the anthelmintic drug Niclosamide inhibits Wnt/beta-catenin signaling and suppresses colon cancer cell growth in vitro and in vivo. To define Niclosamide's mechanism of Wnt/beta-catenin inhibition, and to improve its selectivity and pharmacokinetic properties as an anticancer treatment, we designed a novel class of benzimidazole inhibitors of Wnt/beta-catenin signaling based on SAR studies of the Niclosamide salicylanilide chemotype. Niclosamide has multiple biological activities. To address selectivity in our design, we interrogated a protonophore SAR model and used the principle of conformational restriction to identify novel Wnt/beta-catenin inhibitors with less effect on ATP cellular homeostasis. These studies led to the identification of 4-chloro-2-(5-(trifluoromethyl)-1H-benzo[d]imidazol-2-y1) phenol ((4) under bar) and related derivatives with greater selectivity for Wnt/beta-catenin signaling inhibition vs. differential effects on cellular ATP homeostasis. This is the first report that the Wnt signaling inhibitory activity of Niclosamide can be translated into a new chemical class and to show that its effects on ATP homeostasis can be separated from its inhibitory effects on Wnt signaling. These compounds could be useful tools to elucidate the mechanism of Niclosamide's inhibition of Wnt signaling, and aid the discovery of inhibitors with improved pharmacologic properties to treat cancer and diseases in which Niclosamide has important biological activity. (C) 2017 Elsevier Ltd. All rights reserved.
• 6-Nitrobenzimidazole derivatives: Potential phosphodiesterase inhibitors: Synthesis and structure–activity relationship
  作者：K.M. Khan、Zarbad Shah、V.U. Ahmad、N. Ambreen、M. Khan、M. Taha、F. Rahim、S. Noreen、S. Perveen、M.I. Choudhary、W. Voelter

  DOI：10.1016/j.bmc.2011.12.041

  日期：2012.2

  6-Nitrobenzimidazole derivatives (1-30) synthesized and their phosphodiesterase inhibitory activities determined. Out of thirty tested compounds, ten showed a varying degrees of phosphodiesterase inhibition with IC50 values between 1.5 +/- 0.043 and 294.0 +/- 16.7 mu M. Compounds 30 (IC50 = 1.5 +/- 0.043 mu M), 1 (IC50 = 2.4 +/- 0.049 mu M), 11 (IC50 = 5.7 +/- 0.113 mu M), 13 (IC50 = 6.4 +/- 0.148 mu M), 14 (IC50 = 10.5 +/- 0.51 mu M), 9 (IC50 = 11.49 +/- 0.08 mu M), 3 (IC50 = 63.1 +/- 1.48 mu M), 10 (IC50 = 120.0 +/- 4.47 mu M), and 6 (IC50 = 153.2 +/- 5.6 mu M) showed excellent phosphodiesterase inhibitory activity, much superior to the standard EDTA (IC50 = 274 +/- 0.007 mu M), and thus are potential molecules for the development of a new class of phosphodiesterase inhibitors. Astructure-activity relationship is evaluated. All compounds are characterized by spectroscopic parameters (C) 2011 Elsevier Ltd. All rights reserved.