2-(2,5-dimethylbenzyloxy)-4-nitroaniline | 930797-62-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(2,5-dimethylbenzyloxy)-4-nitroaniline
• 英文别名: 2-(3',6'-dimethylbenzyloxy)-4-nitroaniline；Benzenamine, 2-[(2,5-dimethylphenyl)methoxy]-4-nitro-；2-[(2,5-dimethylphenyl)methoxy]-4-nitroaniline
• CAS: 930797-62-9
• 化学式: C₁₅H₁₆N₂O₃
• 分子量: 272.304
• InChiKey: LTWHKOMPBNVASZ-UHFFFAOYSA-N

物化性质

• 熔点：
  160-161 °C
• 沸点：
  482.6±40.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  81.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2,5-dimethylbenzyloxy)-4-nitroaniline 在 iron(III) chloride 、 sodium hydride 、 potassium carbonate 、 Ammonium hydroxide 、 三乙胺 、 锌 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(4-(N-(6-aminohexyl)methylsulfonamido)-3-((2,5-dimethylbenzyl)oxy)phenyl)cyclohexanecarboxamide
  参考文献：
  名称：

  COX-2抑制剂尼美舒利类似物JCC76生物素化探针的设计与合成

  摘要：

  JCC76是环氧合酶2（COX-2）选择性抑制剂尼美舒利的衍生物，具有强大的抗乳腺癌活性。它选择性地诱导Her2阳性乳腺癌细胞凋亡。但是，JCC76的特定分子靶标仍然不清楚，这大大撤消了JCC76的进一步药物开发。为了鉴定JCC76的分子靶标，设计并合成了六碳接头和生物素共轭的JCC76探针。评价了探针及其类似物的抗增殖活性。

  DOI：

  10.1016/j.bmcl.2011.07.025
• 作为产物：
  描述：

  2,5-二甲基苄氯 、 2-氨基-5-硝基苯酚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-(2,5-dimethylbenzyloxy)-4-nitroaniline
  参考文献：
  名称：

  AMIDE DERIVATIVES OF BENZENE-SULFONANILIDE, PHARMACEUTICAL COMPOSITION THEREOF AND METHOD FOR CANCER TREATMENT USING THE SAME

  摘要：

  该发明提供了一种式(I)的化合物，其药物组成物，用于治疗癌症的药物制备方法，以及治疗癌症的方法。该发明展示了针对癌症的优点，如在更广泛的癌症范围内具有显着更高的效力和有效性。在式(I)中，R是含有烷基和/或烷氧基的苄基；R被选自H和烷基；Rf是烷基；而R3被选自取代苯基、杂环基，以及其中Rc被选自融合环、融合环和任何二价环状基团。

  公开号：

  US20120095092A1

文献信息

• Novel sulfonanilide analogs as selective aromatase modulators (SAMs)
  申请人：Brueggemeier W. Robert

  公开号：US20080045598A1

  公开（公告）日：2008-02-21

  Compounds and methods suppressing aromatase activity expression in cancer cells. Provided are compounds are those of formula I: wherein R 1 may be alkyl, cycloalkyl, haloalkyl, aryl, substituted aryl, haloaryl, alkoxy, alkylaryl, and arylalkyl; R 2 is H, alkyl, aryl, alkylaryl, arylalkyl, and cycloalkyl; R 3 , with the base nitrogen, forms an amide or sulfonamide; R 4 is selected from nitro, amine, amide, and benzamide; or a pharmaceutically acceptable salts thereof Also provided are small molecule selective aromatase inhibitors having a molecular weight of less 500 g/mol. In some embodiments, the small molecule selective aromatase inhibitors described herein have a molecular weight of less than 450 g/mol. Also provided are methods for suppressing aromatase activity expression in cancer cells comprising the step of administering a pharmaceutically effective amount of a small molecule aromatase inhibitor to a subject in need of such treatment. In one embodiment, the cancer cells are breast cancer cells.

  抑制癌细胞中芳香化酶活性表达的化合物和方法。提供的化合物是公式I中的化合物：其中R1可能是烷基，环烷基，卤代烷基，芳基，取代芳基，卤代芳基，烷氧基，烷基芳基和芳基烷基；R2是H，烷基，芳基，烷基芳基，芳基烷基和环烷基；R3与碱性氮形成酰胺或磺酰胺；R4从硝基，胺基，酰胺和苯甲酰中选择；或其药学上可接受的盐。还提供了分子量小于500 g/mol的小分子选择性芳香化酶抑制剂。在某些实施例中，本文所述的小分子选择性芳香化酶抑制剂的分子量小于450 g/mol。还提供了一种方法，用于抑制癌细胞中芳香化酶活性表达，包括向需要这种治疗的受试者施用药学有效量的小分子芳香化酶抑制剂。在一种实施例中，癌细胞是乳腺癌细胞。
• From COX-2 inhibitor nimesulide to potent anti-cancer agent: Synthesis, in vitro, in vivo and pharmacokinetic evaluation
  作者：Bo Zhong、Xiaohan Cai、Snigdha Chennamaneni、Xin Yi、Lili Liu、John J. Pink、Afshin Dowlati、Yan Xu、Aimin Zhou、Bin Su

  DOI：10.1016/j.ejmech.2011.11.012

  日期：2012.1

  Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. In the presented study, a series of new nimesulide analogs were synthesized based on the structure function analysis generated previously. Some of them displayed very potent anti-cancer activity with IC(50)s around 100 nM-200 nM to inhibit SKBR-3 breast cancer cell growth. CSUOH0901 (NSC751382) from the compound library also inhibits the growth of the 60 cancer cell lines used at National Cancer Institute Developmental therapeutics Program (NCIDTP) with IC(50)s around 100 nM-500 nM. Intraperitoneal injection with a dosage of 5 mg/kg/d of CSUOH0901 to nude mice suppresses HT29 colorectal xenograft growth. Pharmacokinetic studies demonstrate the good bioavailability of the compound. Published by Elsevier Masson SAS.
• Synthesis and Biological Evaluation of Selective Aromatase Expression Regulators in Breast Cancer Cells
  作者：Bin Su、Serena Landini、Danyetta D. Davis、Robert W. Brueggemeier

  DOI：10.1021/jm061133j

  日期：2007.4.1

  Aromatase converts androgens to estrogens and is a particularly attractive target in the treatment of estrogen receptor positive breast cancer. The enzyme is encoded by the CYP19 gene, which is expressed in a tissue-specific manner. Prostaglandin E-2 (PGE(2)), the major product of cyclooxygenase-2 (COX-2), stimulates aromatase gene expression via protein kinase A and C signaling pathways. Our previous study demonstrated that COX-2 selective inhibitor nimesulide decreased aromatase activity from the transcriptional level in breast cancer cells. In this manuscript, the synthesis and biological evaluation of a series of nimesulide analogues as potential selective aromatase expression regulators are described. Several novel sulfonanilide compounds demonstrate IC50 values from 0.33 to 2.68 mu M in suppressing aromatase enzyme activity in SK-BR-3 breast cancer cells and are 10- to 80-fold more active than nimesulide. Also, the sulfonanilide compounds selectively decrease aromatase gene expression in breast cancer cells, without exhibiting cytotoxic or apoptotic effects at low micromole concentrations.
• Synthesis and Anticancer Mechanism Investigation of Dual Hsp27 and Tubulin Inhibitors
  作者：Bo Zhong、Snigdha Chennamaneni、Rati Lama、Xin Yi、Werner J. Geldenhuys、John J. Pink、Afshin Dowlati、Yan Xu、Aimin Zhou、Bin Su

  DOI：10.1021/jm4004736

  日期：2013.7.11

  Heat shock protein 27 (Hsp27) is a chaperone protein, and its expression is increased in response to various stress stimuli including anticancer chemotherapy, which allows the cells to survive and causes drug resistance. We previously identified lead compounds that bound to Hsp27 and tubulin via proteomic approaches. Systematic ligand based optimization in the current study significantly increased the cell growth inhibition and apoptosis inducing activities of the compounds. Compared to the lead compounds, one of the new derivatives exhibited much better potency to inhibit tubulin polymerization but a decreased activity to inhibit Hsp27 chaperone function, suggesting that the structural modification dissected the dual targeting effects of the compound. The most potent compounds 20 and 22 exhibited strong cell proliferation inhibitory activities at subnanomolar concentration against 60 human cancer cell lines conducted by Developmental Therapeutic Program at the National Cancer Institute and represented promising candidates for anticancer drug development.
• Identification of a Class of Novel Tubulin Inhibitors
  作者：Xin Yi、Bo Zhong、Kerri M. Smith、Werner J. Geldenhuys、Ye Feng、John J. Pink、Afshin Dowlati、Yan Xu、Aimin Zhou、Bin Su

  DOI：10.1021/jm300100d

  日期：2012.4.12

  We previously developed a series of anticancer agents based on cyclooxygenase-2 (COX-2) inhibitor nimesulide as a lead compound. However, the molecular targets of these agents still remain unclear. In this study, we synthesized a biotinylated probe based on a representative molecule of the compound library and performed protein pull-down assays to purify the anticancer targets of the compound. Via proteomic approaches, the major proteins bound to the probe were identified to be tubulin and heat shock protein 27 (Hsp27), and the compound inhibited tubulin polymerization by binding at the colchicine domain. However, the tubulin inhibitory effect of the compound activated the Hsp27 phosphorylation and possibly overrode the direct Hsp27 inhibitory effects, which made it difficult to solely validate the Hsp27 target. Taken together, the compound was a dual ligand of tubulin and Hsp27, inhibited tubulin polymerization, and had the potential to be a class of new chemotherapeutic agents.