4-(N-(3,5-di-tert-butylbenzyl)-2-((2,3,4,5,6-pentafluoro-N-methylphenyl)sulfonamide)acetamido)-2-hydroxybenzoic acid

• 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: 4-(N-(3,5-di-tert-butylbenzyl)-2-((2,3,4,5,6-pentafluoro-N-methylphenyl)sulfonamide)acetamido)-2-hydroxybenzoic acid
• 英文别名: 4-[(3,5-Ditert-butylphenyl)methyl-[2-[methyl-(2,3,4,5,6-pentafluorophenyl)sulfonylamino]acetyl]amino]-2-hydroxybenzoic acid；4-[(3,5-ditert-butylphenyl)methyl-[2-[methyl-(2,3,4,5,6-pentafluorophenyl)sulfonylamino]acetyl]amino]-2-hydroxybenzoic acid
• 化学式: C₃₁H₃₃F₅N₂O₆S
• 分子量: 656.671
• InChiKey: XPHWHQZYZAEFDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  4-氨基水杨酸 在 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 、 sodium cyanoborohydride 、 溶剂黄146 、 三苯基二氯化膦 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.58h， 生成 4-(N-(3,5-di-tert-butylbenzyl)-2-((2,3,4,5,6-pentafluoro-N-methylphenyl)sulfonamide)acetamido)-2-hydroxybenzoic acid
  参考文献：
  名称：

  Nanomolar-Potency Small Molecule Inhibitor of STAT5 Protein

  摘要：

  We herein report the design and synthesis of the first nanomolar binding inhibitor of STAT5 protein. Lead compound 13a, possessing a phosphotyrosyl-mimicking salicylic acid group, potently and selectively binds to STAT5 over STAT3, inhibits STAT5SH2 domain complexation events in vitro, silences activated STAT5 in leukemic cells, as well as STAT5's downstream transcriptional targets, including MYC and MCL1, and, as a result, leads to apoptosis. We believe 13a represents a useful probe for interrogating STAT5 function in cells as well as being a potential candidate for advanced preclinical trials.

  DOI：

  10.1021/ml500165r

文献信息

• [EN] SULFONAMIDE COMPOUNDS AND THEIR USE AS STAT5 INHIBITORS<br/>[FR] COMPOSÉS DE SULFONAMIDE ET LEUR UTILISATION COMME INHIBITEURS DE STAT5
  申请人：UNIV TORONTO

  公开号：WO2015179956A1

  公开（公告）日：2015-12-03

  The present disclosure relates to compounds having the Formula (Formula (I)) which are inhibitors of STAT5.

  本公开涉及具有化学式（化学式（I））的化合物，这些化合物是STAT5的抑制剂。
• SULFONAMIDE COMPOUNDS AND THEIR USE AS STAT5 INHIBITORS
  申请人：The Governing Council of the University of Toronto

  公开号：EP3148967B1

  公开（公告）日：2019-10-02
• Nanomolar-Potency Small Molecule Inhibitor of STAT5 Protein
  作者：Abbarna A. Cumaraswamy、Andrew M. Lewis、Mulu Geletu、Aleksandra Todic、Diego B. Diaz、Xin Ran Cheng、Carla E. Brown、Rob C. Laister、David Muench、Kagan Kerman、H. Leighton Grimes、Mark D. Minden、Patrick T. Gunning

  DOI：10.1021/ml500165r

  日期：2014.11.13

  We herein report the design and synthesis of the first nanomolar binding inhibitor of STAT5 protein. Lead compound 13a, possessing a phosphotyrosyl-mimicking salicylic acid group, potently and selectively binds to STAT5 over STAT3, inhibits STAT5SH2 domain complexation events in vitro, silences activated STAT5 in leukemic cells, as well as STAT5's downstream transcriptional targets, including MYC and MCL1, and, as a result, leads to apoptosis. We believe 13a represents a useful probe for interrogating STAT5 function in cells as well as being a potential candidate for advanced preclinical trials.