N-methyl-N-[2-(3',6'-dimethyl-benzyloxy)-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-(3',6'-dimethyl-benzyloxy)-4-nitrophenyl]-methanesulfonamide
• 英文别名: N-[2-[(2,5-dimethylphenyl)methoxy]-4-nitrophenyl]-N-methylmethanesulfonamide
• 化学式: C₁₇H₂₀N₂O₅S
• 分子量: 364.422
• InChiKey: JRGCCNDYXTYYLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-methyl-N-[2-(3',6'-dimethyl-benzyloxy)-4-nitrophenyl]-methanesulfonamide 在 iron(III) chloride 、 水 、 potassium carbonate 、 锌 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 n-hexadecanoic acid [3-(2,5-dimethylbenzyloxy)-4-(N-methanesulfonyl-N-methylamino)phenyl]amide
  参考文献：
  名称：

  From COX-2 inhibitor nimesulide to potent anti-cancer agent: Synthesis, in vitro, in vivo and pharmacokinetic evaluation

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2011.11.012
• 作为产物：
  描述：

  2-氨基-5-硝基苯酚 在 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-methyl-N-[2-(3',6'-dimethyl-benzyloxy)-4-nitrophenyl]-methanesulfonamide
  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。
• 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.
• Lead optimization of COX-2 inhibitor nimesulide analogs to overcome aromatase inhibitor resistance in breast cancer cells
  作者：Bin Su、Shiuan Chen

  DOI：10.1016/j.bmcl.2009.09.109

  日期：2009.12

  A series of COX-2 selective inhibitor nimesulide derivatives were synthesized. Their anti-cell proliferation activities were evaluated with a long-term estrogen deprived MCF-7aro (LTEDaro) breast cancer cell line, which is the biological model of aromatase inhibitor resistance for hormone-dependent breast cancer. Compared to nimesulide which inhibited LTEDaro cell proliferation with an IC50 at 170.30 mu M, several new compounds showed IC50 close to 1.0 mu M. (C) 2009 Elsevier Ltd. All rights reserved.
• 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