N-(2-((2,5-dimethylbenzyl)oxy)-4-nitrophenyl)-N-(methylsulfonyl)methanesulfonamide | 1021926-24-8

• 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-((2,5-dimethylbenzyl)oxy)-4-nitrophenyl)-N-(methylsulfonyl)methanesulfonamide
• CAS: 1021926-24-8
• 化学式: C₁₇H₂₀N₂O₇S₂
• 分子量: 428.487
• InChiKey: ZALVSBCKHISCAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.52
• 重原子数：
  28.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  123.89
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  N-(2-((2,5-dimethylbenzyl)oxy)-4-nitrophenyl)-N-(methylsulfonyl)methanesulfonamide 在 iron(III) chloride 、 水 、 sodium hydride 、 potassium carbonate 、 sodium hydroxide 、 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-[3-(2,5-dimethylbenzyloxy)-4-(N-methanesulfonyl-N-methylamino)phenyl]propionamide
  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， 反应 3.5h， 生成 N-(2-((2,5-dimethylbenzyl)oxy)-4-nitrophenyl)-N-(methylsulfonyl)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