N-methyl-N-[2-(2'-phenylbenzyloxy)-4-nitrophenyl]-methanesulfonamide

• 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-methyl-N-[2-(2'-phenylbenzyloxy)-4-nitrophenyl]-methanesulfonamide
• 英文别名: N-[2-(biphenyl-2-ylmethoxy)-4-nitro-phenyl]-N-methyl-methanesulfonamide；N-methyl-N-[4-nitro-2-[(2-phenylphenyl)methoxy]phenyl]methanesulfonamide
• 化学式: C₂₁H₂₀N₂O₅S
• 分子量: 412.466
• InChiKey: STFSBIKCKYKMEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基-5-硝基苯酚 在 sodium hydroxide 、 二甲基硫 、 三氟化硼乙醚 、 sodium hydride 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 10.67h， 生成 N-methyl-N-[2-(2'-phenylbenzyloxy)-4-nitrophenyl]-methanesulfonamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Selective Aromatase Expression Regulators in Breast Cancer Cells

  摘要：

  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.

  DOI：

  10.1021/jm061133j

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。
• 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).
• 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
• US7741520B2
  申请人：——

  公开号：US7741520B2

  公开（公告）日：2010-06-22
• [EN] SULFONANILIDE ANALOGS AS SELECTIVE AROMATASE MODULATORS<br/>[FR] ANALOGUES DE SULFONANILIDES COMME MODULATEURS SÉLECTIFS DES AROMATASES
  申请人：UNIV OHIO STATE RES FOUND

  公开号：WO2007120379A2

  公开（公告）日：2007-10-25

  [EN] Compounds and methods suppressing aromatase activity expression in cancer cells. Provided are compounds are those of formula I: wherein R1 may be alkyl, cycloakyl, haloalkyl, aryl, substituted aryl, haloaryl, alkoxy, alkylaryl, and arylalkyl; R2 is H, alkyl, aryl, alkylaryl, arylalkyl, and cycloalkyl; R3, with the base nitrogen, forms an amide or sulfonamide; R4 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.
  [FR] L'invention concerne des composés et des procédés permettant de supprimer l'expression de l'activité d'aromatase dans les cellules cancéreuses. Elle concerne des composés de formule I : dans laquelle R1 peut être un groupe alkyle, cycloalkyle, halogénoalkyle, aryle, aryle substitué, halogénoaryle, alcoxy, alkylaryle et arylalkyle ; R2 est H ou un groupe alkyle, aryle, alkylaryle, arylalkyle et cycloalkyle ; R3 forme avec l'azote de base un groupe amide ou sulfonamide ; R4 est choisi parmi les groupes nitro, amine, amide et benzamide ; ou un de leurs sels pharmaceutiquement acceptables. L'invention concerne également des inhibiteurs d'aromatases sélectifs à petite molécule, de masse moléculaire inférieure à 500 g/mol. Dans certains modes de réalisation, les inhibiteurs d'aromatases sélectifs à petite molécule décrits ici ont une masse moléculaire inférieure à 450 g/mol. L'invention concerne en outre des procédés de suppression de l'expression de l'activité d'aromatase dans des cellules cancéreuses, comprenant l'administration d'une quantité pharmaceutiquement efficace d'un inhibiteur d'aromatase à petite molécule à un sujet nécessitant un tel traitement. Dans un mode de réalisation, les cellules cancéreuses sont des cellules de cancer du sein.