4-({[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-thienyl)phenyl]amino}carbonyl)benzoic acid | 1003315-21-6

• 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-({[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-thienyl)phenyl]amino}carbonyl)benzoic acid
• 英文别名: 4-({[2-[(tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)benzoic acid；4-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-thiophen-2-ylphenyl]carbamoyl]benzoic acid
• CAS: 1003315-21-6
• 化学式: C₂₃H₂₂N₂O₅S
• 分子量: 438.504
• InChiKey: LSWQGNHAUFZDPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  133
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-({[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-thienyl)phenyl]amino}carbonyl)benzoic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 4-N-(2-amino-5-thiophen-2-ylphenyl)-1-N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]benzene-1,4-dicarboxamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of colchicine derivatives as novel tubulin and histone deacetylase dual inhibitors

  摘要：

  A new class of colchicine derivatives were designed and synthesized as tubulin-HDAC dual inhibitors. Biological evaluations of these hybrids included the inhibitory activity of HDAC, tubulin polymerization analysis, in vitro cell cycle analysis in HCT-116 cells and cytotoxicity against different cancer cell lines. Hybrid 6d behaved as potent HDAC-tubulin dual inhibitor and showed comparable cytotoxicity with colchicine. Compound ha exhibited powerful tubulin inhibitory activity, moderate anti-HDAC activity and the most potent cytotoxicity (IC50 = 2-105 nM). (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.035
• 作为产物：
  描述：

  对苯二甲酸单甲酯 在 氯化亚砜 、 水 、 三乙胺 、 N,N-二甲基甲酰胺 、 lithium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 6.0h， 生成 4-({[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-thienyl)phenyl]amino}carbonyl)benzoic acid
  参考文献：
  名称：

  Design, synthesis and biological evaluation of colchicine derivatives as novel tubulin and histone deacetylase dual inhibitors

  摘要：

  A new class of colchicine derivatives were designed and synthesized as tubulin-HDAC dual inhibitors. Biological evaluations of these hybrids included the inhibitory activity of HDAC, tubulin polymerization analysis, in vitro cell cycle analysis in HCT-116 cells and cytotoxicity against different cancer cell lines. Hybrid 6d behaved as potent HDAC-tubulin dual inhibitor and showed comparable cytotoxicity with colchicine. Compound ha exhibited powerful tubulin inhibitory activity, moderate anti-HDAC activity and the most potent cytotoxicity (IC50 = 2-105 nM). (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.035

文献信息

• [EN] SILICON DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS<br/>[FR] DÉRIVÉS DE SILICIUM SOUS LA FORME D'INHIBITEURS D'HISTONE DÉSACÉTYLASE
  申请人：MERCK & CO INC

  公开号：WO2009020589A1

  公开（公告）日：2009-02-12

  The present invention relates to a novel class of Silicon derivatives. The Silicon compounds can be used to treat cancer. The Silicon compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the Silicon derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the Silicon derivatives in vivo.

  本发明涉及一类新型的硅衍生物。这些硅化合物可用于治疗癌症。这些硅化合物还可以抑制组蛋白去乙酰化酶，并适用于选择性诱导终末分化，阻止肿瘤细胞的生长和/或凋亡，从而抑制这些细胞的增殖。因此，本发明的化合物在治疗具有肿瘤特征的患者方面是有用的。该发明的化合物还可能在预防和治疗TRX介导的疾病方面有用，如自身免疫、过敏和炎症性疾病，以及预防和/或治疗中枢神经系统（CNS）疾病，如神经退行性疾病。本发明还提供了包含这些硅衍生物的药物组合物以及这些药物组合物的安全用量方案，易于遵循，并在体内产生治疗有效量的硅衍生物。
• Parallel medicinal chemistry approaches to selective HDAC1/HDAC2 inhibitor (SHI-1:2) optimization
  作者：Solomon D. Kattar、Laura M. Surdi、Anna Zabierek、Joey L. Methot、Richard E. Middleton、Bethany Hughes、Alexander A. Szewczak、William K. Dahlberg、Astrid M. Kral、Nicole Ozerova、Judith C. Fleming、Hongmei Wang、Paul Secrist、Andreas Harsch、Julie E. Hamill、Jonathan C. Cruz、Candia M. Kenific、Melissa Chenard、Thomas A. Miller、Scott C. Berk、Paul Tempest

  DOI：10.1016/j.bmcl.2008.12.083

  日期：2009.2

  successful application of both solid and solution phase library synthesis, combined with tight integration into the medicinal chemistry effort, resulted in the efficient optimization of a novel structural series of selective HDAC1/HDAC2 inhibitors by the MRL-Boston Parallel Medicinal Chemistry group. An initial lead from a small parallel library was found to be potent and selective in biochemical assays

  固相和溶液相文库合成的成功应用以及紧密整合到药物化学研究中，导致了MRL-波士顿并行药物化学小组对选择性HDAC1 / HDAC2抑制剂的新型结构系列的有效优化。在小型生化分析中，发现一个来自小型平行文库的起始引物有效且具有选择性。先进的化合物是迭代文库设计的高潮，并具有出色的生化和细胞效能，以及在动物模型中可接受的PK和功效。
• PHOSPHORUS DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS
  申请人：Close Joshua

  公开号：US20090270351A1

  公开（公告）日：2009-10-29

  The present invention relates to a novel class of phosphorus derivatives. The phosphorus compounds can be used to treat cancer. The phosphorus compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the phosphorus derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the phosphorus derivatives in vivo.

  本发明涉及一种新型的磷衍生物。这些磷化合物可以用于治疗癌症。这些磷化合物还可以抑制组蛋白去乙酰化酶，适用于选择性诱导终末分化，并阻止肿瘤细胞的生长和/或凋亡，从而抑制这些细胞的增殖。因此，本发明的化合物对于治疗具有肿瘤细胞增殖特征的患者非常有用。本发明的化合物还可以用于预防和治疗TRX介导的疾病，例如自身免疫、过敏和炎症性疾病，以及预防和/或治疗中枢神经系统（CNS）疾病，例如神经退行性疾病。本发明还提供了包含这些磷衍生物的药物组合物和这些药物组合物的安全剂量方案，这些方案易于遵循，并在体内产生治疗有效量的磷衍生物。
• Phosphorus derivatives as histone deacetylase inhibitors
  申请人：Merck Sharp & Dohme Corp.

  公开号：US07981874B2

  公开（公告）日：2011-07-19

  The present invention relates to a novel class of phosphorus derivatives. The phosphorus compounds can be used to treat cancer. The phosphorus compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the phosphorus derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the phosphorus derivatives in vivo.

  本发明涉及一类新型的磷衍生物。这些磷化合物可用于治疗癌症。这些磷化合物还可以抑制组蛋白去乙酰化酶，适用于选择性诱导末端分化，阻止肿瘤细胞的生长和/或凋亡，从而抑制这些细胞的增殖。因此，本发明的化合物可用于治疗具有肿瘤细胞增殖特征的患者。本发明的化合物还可以用于预防和治疗TRX介导的疾病，如自身免疫性、过敏性和炎症性疾病，以及中枢神经系统（CNS）疾病的预防和/或治疗，如神经退行性疾病。本发明还提供了包含这些磷衍生物的药物组合物和这些药物组合物的安全剂量方案，易于遵循，并且在体内产生治疗有效量的磷衍生物。
• SILICON DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS
  申请人：Grimm Jonathan

  公开号：US20110130361A1

  公开（公告）日：2011-06-02

  The present invention relates to a novel class of Silicon derivatives. The Silicon compounds can be used to treat cancer. The Silicon compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the Silicon derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the Silicon derivatives in vivo.

  本发明涉及一种新型的硅衍生物类。这些硅化合物可用于治疗癌症。这些硅化合物还可以抑制组蛋白去乙酰化酶，并适用于选择性诱导终末分化，阻止肿瘤细胞的生长和/或凋亡，从而抑制这些细胞的增殖。因此，本发明的化合物适用于治疗肿瘤细胞增殖的患者。本发明的化合物还可以用于预防和治疗TRX介导的疾病，如自身免疫性、过敏性和炎症性疾病，并用于预防和/或治疗中枢神经系统（CNS）疾病，如神经退行性疾病。本发明还提供了包含这些硅衍生物的药物组合物以及这些药物组合物的安全用量方案，易于遵循，并在体内产生治疗有效量的硅衍生物。