N-(2-benzyIoxy-4-nitrophenyl)-methanesulfonamide | 622843-25-8

• 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: N-(2-benzyIoxy-4-nitrophenyl)-methanesulfonamide
• 英文别名: N-(4-nitro-2-phenylmethoxyphenyl)methanesulfonamide
• CAS: 622843-25-8
• 化学式: C₁₄H₁₄N₂O₅S
• 分子量: 322.342
• InChiKey: XDQFGDRBMTXPFY-UHFFFAOYSA-N

物化性质

• 熔点：
  129-132 °C
• 沸点：
  516.6±60.0 °C(Predicted)
• 密度：
  1.423±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(2-benzyIoxy-4-nitrophenyl)-methanesulfonamide 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以28%的产率得到N-(2-benzyloxy-4-nitro-phenyl)-N-isopropyl-methane-sulfonamide
  参考文献：
  名称：

  WO2007/120379

  摘要：

  公开号：
• 作为产物：
  描述：

  2-氨基-5-硝基苯酚 在 sodium hydroxide 、 水 、 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 8.0h， 生成 N-(2-benzyIoxy-4-nitrophenyl)-methanesulfonamide
  参考文献：
  名称：

  WO2007/120379

  摘要：

  公开号：

文献信息

• Novel Sulfonanilide Analogs Decrease Aromatase Activity in Breast Cancer Cells: Synthesis, Biological Evaluation, and Ligand-Based Pharmacophore Identification
  作者：Bin Su、Ran Tian、Michael V. Darby、Robert W. Brueggemeier

  DOI：10.1021/jm701107h

  日期：2008.3.13

  selective inhibitor nimesulide and analogs decreased aromatase expression and enzyme activity independent of COX-2 inhibition. In this manuscript, a combinatorial approach was used to generate diversely substituted novel sulfonanilides by parallel synthesis. Their pharmacological evaluation as agents for suppression of aromatase activity in SK-BR-3 breast cancer cells was extensively explored. A ligand-based

  芳香酶将雄激素转化为雌激素，是治疗雌激素受体阳性乳腺癌的一个特别有吸引力的靶点。以前，COX-2 选择性抑制剂尼美舒利和类似物降低了芳香酶表达和酶活性，而与 COX-2 抑制无关。在这份手稿中，使用组合方法通过平行合成生成不同取代的新型磺酰苯胺。广泛探索了它们作为抑制 SK-BR-3 乳腺癌细胞中芳香酶活性的药物的药理学评价。使用 Catalyst HipHop 算法详细阐述了基于配体的药效团模型，用于选择性芳香酶调节 (SAM)。最好的定性模型由四个特征组成：一个芳香环、两个氢键受体和一个疏水功能。几种先导化合物也在芳香酶转染的 MCF-7 细胞中进行了测试，它们显着抑制了细胞芳香酶活性。结果表明，这些化合物的基因组和非基因组机制均涉及芳香酶抑制作用。
• 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。
• Radiosynthesis of New Carbon-11-labeled Nimesulide Analogs as Potential PET SAER Tracers for Imaging of Aromatase Expression in Breast Cancer
  作者：Min Wang、Mingzhang Gao、Kathy D. Miller、George W. Sledge、Gary D. Hutchins、Qi-Huang Zheng

  DOI：10.1080/00397910903013747

  日期：2010.2.12

  Carbon-11-labeled nimesulide analogs, N-[11C]methyl-N-(2-benzyloxy-4-nitrophenyl)methanesulfonamide ([11C]4a), N-[11C]methyl-N-[2-(4'-methylbenzyloxy)-4-nitrophenyl]methanesulfonamide ([11C]4b), N-[11C]methyl-N-[2-(4'-fluorobenzyloxy)-4-nitrophenyl]methanesulfonamide ([11C]4c), N-[11C]methyl-N-[2-(4'-nitrobenzyloxy)-4-nitrophenyl]methanesulfonamide ([11C]8a), N-[11C]methyl-N-[2-(-naphthylmethoxy)-4-nitrophenyl]methanesulfonamide ([11C]8b), and N-[11C]methyl-N-[2-(2'-phenylbenzyloxy)-4-nitrophenyl]methanesulfonamide ([11C]8c), have been synthesized as new potential positron emission tomography (PET) selective aromatase expression regulator (SAER) radiotracers for imaging of aromatase expression in breast cancer. The target tracers were prepared by N-[11C]methylation of their corresponding precursors using [11C]CH3OTf under basic conditions (NaH) and isolated by reversed-phase high-pressure liquid chromatography (HPLC) method in 30-50% radiochemical yields decay corrected to end of bombardment (EOB) with 25-30min overall synthesis time and 111-148 GBq/mol specific activity at end of synthesis (EOS).
• 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.
• SULFONANILIDE ANALOGS AS SELECTIVE AROMATASE MODULATORS
  申请人：THE OHIO STATE UNIVERSITY RESEARCH FOUNDATION

  公开号：EP1984325A2

  公开（公告）日：2008-10-29