benzyl 2-(benzyloxy)-4-(N-(4-cyclohexylbenzyl)-2-(N,1-dimethyl-1H-imidazole-4-sulfonamido)acetamido)benzoate | 1334493-36-5

• 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: benzyl 2-(benzyloxy)-4-(N-(4-cyclohexylbenzyl)-2-(N,1-dimethyl-1H-imidazole-4-sulfonamido)acetamido)benzoate
• 英文别名: benzyl 4-[(4-cyclohexylphenyl)methyl-[2-[methyl-(1-methylimidazol-4-yl)sulfonylamino]acetyl]amino]-2-phenylmethoxybenzoate
• CAS: 1334493-36-5
• 化学式: C₄₁H₄₄N₄O₆S
• 分子量: 720.89
• InChiKey: ADPAAIYBJHVXPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  52
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  119
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  benzyl 2-(benzyloxy)-4-(N-(4-cyclohexylbenzyl)-2-(N,1-dimethyl-1H-imidazole-4-sulfonamido)acetamido)benzoate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以98%的产率得到4-(N-(4-cyclohexylbenzyl)-2-(N,1-dimethyl-1H-imidazole-4-sulfonamido)acetamido)-2-hydroxybenzoic acid
  参考文献：
  名称：

  Identification of a non-phosphorylated, cell permeable, small molecule ligand for the Stat3 SH2 domain

  摘要：

  Signal transducer and activator of transcription 3 (Stat3) protein is a cytosolic transcription factor that is aberrantly activated in numerous human cancers. Inhibitors of activated Stat3-Stat3 protein complexes have been shown to hold therapeutic promise for the treatment of human cancers harboring activated Stat3. Herein, we report the design and synthesis of a focused library of salicylic acid containing Stat3 SH2 domain binders. The most potent inhibitor, 17o, effectively disrupted Stat3-phosphopeptide complexes (K(i) = 13 mu M), inhibited Stat3-Stat3 protein interactions (IC(50) = 19 mu M) and silenced intracellular Stat3 phosphorylation and Stat3-target gene expression profiles. Inhibition of Stat3 function in both breast and multiple myeloma (MM) tumor cells correlated with induced cell death (EC(50) = 10 and 16 mu M, respectively). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.056
• 作为产物：
  描述：

  4-氨基水杨酸 在 lithium hydroxide monohydrate 、 potassium tert-butylate 、 sodium cyanoborohydride 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三苯基二氯化膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.42h， 生成 benzyl 2-(benzyloxy)-4-(N-(4-cyclohexylbenzyl)-2-(N,1-dimethyl-1H-imidazole-4-sulfonamido)acetamido)benzoate
  参考文献：
  名称：

  Identification of a non-phosphorylated, cell permeable, small molecule ligand for the Stat3 SH2 domain

  摘要：

  Signal transducer and activator of transcription 3 (Stat3) protein is a cytosolic transcription factor that is aberrantly activated in numerous human cancers. Inhibitors of activated Stat3-Stat3 protein complexes have been shown to hold therapeutic promise for the treatment of human cancers harboring activated Stat3. Herein, we report the design and synthesis of a focused library of salicylic acid containing Stat3 SH2 domain binders. The most potent inhibitor, 17o, effectively disrupted Stat3-phosphopeptide complexes (K(i) = 13 mu M), inhibited Stat3-Stat3 protein interactions (IC(50) = 19 mu M) and silenced intracellular Stat3 phosphorylation and Stat3-target gene expression profiles. Inhibition of Stat3 function in both breast and multiple myeloma (MM) tumor cells correlated with induced cell death (EC(50) = 10 and 16 mu M, respectively). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.056

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
• Identification of a non-phosphorylated, cell permeable, small molecule ligand for the Stat3 SH2 domain
  作者：Brent D.G. Page、Steven Fletcher、Peibin Yue、Zhihua Li、Xiaolei Zhang、Sumaiya Sharmeen、Alessandro Datti、Jeffrey L. Wrana、Suzanne Trudel、Aaron D. Schimmer、James Turkson、Patrick T. Gunning

  DOI：10.1016/j.bmcl.2011.06.056

  日期：2011.9

  Signal transducer and activator of transcription 3 (Stat3) protein is a cytosolic transcription factor that is aberrantly activated in numerous human cancers. Inhibitors of activated Stat3-Stat3 protein complexes have been shown to hold therapeutic promise for the treatment of human cancers harboring activated Stat3. Herein, we report the design and synthesis of a focused library of salicylic acid containing Stat3 SH2 domain binders. The most potent inhibitor, 17o, effectively disrupted Stat3-phosphopeptide complexes (K(i) = 13 mu M), inhibited Stat3-Stat3 protein interactions (IC(50) = 19 mu M) and silenced intracellular Stat3 phosphorylation and Stat3-target gene expression profiles. Inhibition of Stat3 function in both breast and multiple myeloma (MM) tumor cells correlated with induced cell death (EC(50) = 10 and 16 mu M, respectively). (C) 2011 Elsevier Ltd. All rights reserved.