N-[4-amino-2-[(2,5-dimethylphenyl)methoxy]phenyl]-N-methylmethanesulfonamide | 1021926-19-1

• 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-[4-amino-2-[(2,5-dimethylphenyl)methoxy]phenyl]-N-methylmethanesulfonamide
• CAS: 1021926-19-1
• 化学式: C₁₇H₂₂N₂O₃S
• 分子量: 334.439
• InChiKey: MNQBRJDAGQAUKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 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：
  81
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[4-amino-2-[(2,5-dimethylphenyl)methoxy]phenyl]-N-methylmethanesulfonamide 、 (3,4-二甲氧基苯基)乙酰氯 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 以95%的产率得到N-[3-(2,5-dimethylbenzyloxy)-4-(N-methanesulfonyl-N-methylamino)phenyl]-(3,4-dimethoxyphenyl)acetamide
  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：

  2,5-二甲基苄氯 在 iron(III) chloride 、 水 、 sodium hydride 、 potassium carbonate 、 锌 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 N-[4-amino-2-[(2,5-dimethylphenyl)methoxy]phenyl]-N-methylmethanesulfonamide
  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

• Synthesis and biological evaluation of selective tubulin inhibitors as anti-trypanosomal agents
  作者：Viharika Bobba、Vishal Nanavaty、Nethrie D. Idippily、Anran Zhao、Bibo Li、Bin Su

  DOI：10.1016/j.bmc.2017.04.009

  日期：2017.6

  African trypanosomiasis is still a threat to human health due to the severe side-effects of current drugs. We identified selective tubulin inhibitors that showed the promise to the treatment of this disease, which was based on the tubulin protein structural difference between mammalian and trypanosome cells. Further lead optimization was performed in the current study to improve the efficiency of the drug candidates. We used Trypanosoma brucei brucei cells as the parasite model, and human normal kidney cells and mouse macrophage cells as the host model to evaluate the compounds. One new analog showed great potency with an IC50 of 70 nM to inhibit the growth of trypanosome cells and did not affect the viability of mammalian cells. Western blot analyses reveal that the compound decreased tubulin polymerization in T. brucei cells. A detailed structure activity relationship (SAR) was summarized that will be used to guide future lead optimization. Published by Elsevier Ltd.
• 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.
• US8802895B2
  申请人：——

  公开号：US8802895B2

  公开（公告）日：2014-08-12
• [EN] AMIDE DERIVATIVES OF BENZENE-SULFONANILIDE, PHARMACEUTICAL COMPOSITION THEREOF AND METHOD FOR CANCER TREATMENT USING THE SAME<br/>[FR] DÉRIVÉS AMIDE DE BENZÈNE-SULFONANILIDE, COMPOSITION PHARMACEUTIQUE LES CONTENANT ET MÉTHODE DE TRAITEMENT DU CANCER LES UTILISANT
  申请人：UNIV STATE CLEVELAND

  公开号：WO2012054417A1

  公开（公告）日：2012-04-26

  The invention provides a compound of formula (I), a pharmaceutical composition thereof, a method of preparing a medicament for the treatment of a cancer, and a method of treating cancers. The invention exhibits merits against cancers such as significantly higher potency and effectiveness over a broader range of cancers. In formula (I), Ra is a benzyl group with alkyl and/or alkoxy; Rb is selected from H and alkyl groups; Rf is an alkyl; and R3 is selected from a (Formula) substituted phenyl, a heterocyclic group, and, Formula, wherein Rc is selected from a fused ring, fused rings, and any bivalent cyclic group. Formula (I)
• 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.