4-(N-(4-cyclohexylbenzyl)-2-(2,3,4,5,6-pentafluoro-N-(2,3,4,6-tetrafluorobenzyl)phenylsulfonamido)acetamido)-2-hydroxybenzoic acid | 1455006-66-2

• 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-(4-cyclohexylbenzyl)-2-(2,3,4,5,6-pentafluoro-N-(2,3,4,6-tetrafluorobenzyl)phenylsulfonamido)acetamido)-2-hydroxybenzoic acid
• 英文别名: 4-[(4-Cyclohexylphenyl)methyl-[2-[(2,3,4,5,6-pentafluorophenyl)sulfonyl-[(2,3,4,6-tetrafluorophenyl)methyl]amino]acetyl]amino]-2-hydroxybenzoic acid；4-[(4-cyclohexylphenyl)methyl-[2-[(2,3,4,5,6-pentafluorophenyl)sulfonyl-[(2,3,4,6-tetrafluorophenyl)methyl]amino]acetyl]amino]-2-hydroxybenzoic acid
• CAS: 1455006-66-2
• 化学式: C₃₅H₂₇F₉N₂O₆S
• 分子量: 774.661
• InChiKey: XPZUFPMOYSUSOL-UHFFFAOYSA-N

物化性质

• 沸点：
  810.4±75.0 °C(predicted)
• 密度：
  1.541±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.3
• 重原子数：
  53
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  benzyl 4-amino-2-(benzyloxy)benzoate 在 哌啶 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 caesium carbonate 、 溶剂黄146 、 三苯基二氯化膦 作用下， 以 四氢呋喃 、 甲醇 、 氘代氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 9.75h， 生成 4-(N-(4-cyclohexylbenzyl)-2-(2,3,4,5,6-pentafluoro-N-(2,3,4,6-tetrafluorobenzyl)phenylsulfonamido)acetamido)-2-hydroxybenzoic acid
  参考文献：
  名称：

  Inhibiting Aberrant Signal Transducer and Activator of Transcription Protein Activation with Tetrapodal, Small Molecule Src Homology 2 Domain Binders: Promising Agents against Multiple Myeloma

  摘要：

  The signal transducer and activator of transcription (STAT) proteins represent a family of cytoplasmic transcription factors that regulate a pleiotropic range of biological processes. In particular, Stat3 protein has attracted attention as it regulates the expression of genes involved in a variety of malignant processes, including proliferation, survival, migration, and drug resistance. Multiple myeloma (MM) is an incurable hematologic malignancy that often exhibits abnormally high levels of Stat3 activity. Although current treatment strategies can improve the clinical management of MM, it remains uniformly incurable with a dismal median survival time post-treatment of 3-4 years. Thus, novel targeted therapeutics are critically needed to improve MM patient outcomes. We herein report the development of a series of small molecule Stat3 inhibitors with potent anti-MM activity in vitro. These compounds showed high-affinity binding to Stat3's SH2 domain, inhibited intracellular Stat3 phosphorylation, and induced apoptosis in MM cell lines at low micromolar concentrations.

  DOI：

  10.1021/jm3017255

文献信息

• Substituted 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs as inhibitors of STAT protein
  申请人：University of Central Florida Research Foundation, Inc.

  公开号：US10196373B2

  公开（公告）日：2019-02-05

  In one aspect, the invention relates to substituted 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs, derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，该发明涉及替代的2-羟基-4-(2-(苯磺酰胺基)乙酰胺基)苯甲酸类似物，其衍生物和相关化合物，这些化合物可用作STAT蛋白活性的抑制剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与STAT蛋白活性功能障碍相关的细胞不受控制增殖疾病的方法。本摘要旨在作为在特定领域进行搜索的扫描工具，并不打算限制本发明。
• SUBSTITUTED 2-HYDROXY-4-(2-(PHENYLSULFONAMIDO)ACETAMIDO)BENZOIC ACID ANALOGS AS INHIBITORS OF STAT PROTEIN
  申请人：University of Central Florida Research Foundation, Inc.

  公开号：US20150038708A1

  公开（公告）日：2015-02-05

  In one aspect, the invention relates to substituted 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs, derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本发明涉及替代的2-羟基-4-(2-(苯磺酰胺)乙酰胺)苯甲酸类似物、其衍生物和相关化合物，它们可以作为STAT蛋白活性的抑制剂；制备这些化合物的合成方法；包含这些化合物的制药组合物；以及使用这些化合物和组合物治疗与STAT蛋白活性功能障碍相关的细胞增殖失控症状的方法。本摘要旨在作为特定领域搜索的扫描工具，不意味着对本发明的限制。
• US8846707B2
  申请人：——

  公开号：US8846707B2

  公开（公告）日：2014-09-30
• [EN] SUBSTITUTED 2-HYDROXY-4-(2-(PHENYLSULFONAMIDO)ACETAMIDO)BENZOIC ACID ANALOGS AS INHIBITORS OF STAT PROTEINS<br/>[FR] ANALOGUES DE L'ACIDE 2-HYDROXY-4-(2-(PHÉNYLSULFONAMIDO)ACÉTAMIDO) BENZOÏQUE SUBSTITUÉ UTILISABLES EN TANT QU'INHIBITEURS DES PROTÉINES STAT
  申请人：UNIV CENTRAL FLORIDA RES FOUND

  公开号：WO2012018868A1

  公开（公告）日：2012-02-09

  In one aspect, the invention relates to substituted substituted 2-hydroxy-4-(2- (phenylsulfonamido)acetamido)benzoic acid analogs, derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• Inhibiting Aberrant Signal Transducer and Activator of Transcription Protein Activation with Tetrapodal, Small Molecule Src Homology 2 Domain Binders: Promising Agents against Multiple Myeloma
  作者：Brent D. G. Page、Danielle C. Croucher、Zhi Hua Li、Sina Haftchenary、Victor H. Jimenez-Zepeda、Jennifer Atkinson、Paul A. Spagnuolo、Yoong Lim Wong、Robert Colaguori、Andrew M. Lewis、Aaron D. Schimmer、Suzanne Trudel、Patrick T. Gunning

  DOI：10.1021/jm3017255

  日期：2013.9.26

  The signal transducer and activator of transcription (STAT) proteins represent a family of cytoplasmic transcription factors that regulate a pleiotropic range of biological processes. In particular, Stat3 protein has attracted attention as it regulates the expression of genes involved in a variety of malignant processes, including proliferation, survival, migration, and drug resistance. Multiple myeloma (MM) is an incurable hematologic malignancy that often exhibits abnormally high levels of Stat3 activity. Although current treatment strategies can improve the clinical management of MM, it remains uniformly incurable with a dismal median survival time post-treatment of 3-4 years. Thus, novel targeted therapeutics are critically needed to improve MM patient outcomes. We herein report the development of a series of small molecule Stat3 inhibitors with potent anti-MM activity in vitro. These compounds showed high-affinity binding to Stat3's SH2 domain, inhibited intracellular Stat3 phosphorylation, and induced apoptosis in MM cell lines at low micromolar concentrations.