tert-butyl (2-(4-(chloromethyl)benzamido)-4-(thiophen-2-yl)phenyl)carbamate | 953434-83-8

• 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: tert-butyl (2-(4-(chloromethyl)benzamido)-4-(thiophen-2-yl)phenyl)carbamate
• 英文别名: tert-Butyl 2-(4-(chloromethyl)benzamido)-4-(thiophen-2-yl)phenylcarbamate；tert-butyl N-[2-[[4-(chloromethyl)benzoyl]amino]-4-thiophen-2-ylphenyl]carbamate
• CAS: 953434-83-8
• 化学式: C₂₃H₂₃ClN₂O₃S
• 分子量: 442.966
• InChiKey: QZWOJQXFUVEKOU-UHFFFAOYSA-N

物化性质

• 沸点：
  497.4±45.0 °C(Predicted)
• 密度：
  1.303±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  95.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (2-(4-(chloromethyl)benzamido)-4-(thiophen-2-yl)phenyl)carbamate 在 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 tert-butyl (2-(4-(aminomethyl)benzamido)-4-(thiophen-2-yl)phenyl)carbamate
  参考文献：
  名称：

  新型N-（2-氨基苯基）苯甲酰胺衍生物作为组蛋白脱乙酰基酶抑制剂的设计，合成及其抗肿瘤活性的研究

  摘要：

  组蛋白脱乙酰基酶（HDAC）是有希望的癌症治疗靶标，因为对HDAC的抑制作用会触发肿瘤细胞的生长停滞或凋亡。在本研究中，合成了一系列新的氟化N-（2-氨基苯基）苯甲酰胺衍生物，以研究HDAC的潜在抑制作用和相关的抗癌活性。在合成的衍生物中，与SAHA相比，化合物24a在人癌细胞系（HCT-116，MCF-7和A549）中显示出对HDAC的强抑制活性和更高的抗肿瘤功效。此外，动物研究表明，化合物24a在HCT-116结肠癌异种移植小鼠模型中显示出强大的体内抗肿瘤功效。

  DOI：

  10.1002/bkcs.12254
• 作为产物：
  描述：

  4-羟甲基苯甲酸 在 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 3.0h， 生成 tert-butyl (2-(4-(chloromethyl)benzamido)-4-(thiophen-2-yl)phenyl)carbamate
  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。
• Image-Guided Synthesis Reveals Potent Blood-Brain Barrier Permeable Histone Deacetylase Inhibitors
  作者：Young Jun Seo、Yeona Kang、Lisa Muench、Alicia Reid、Shannon Caesar、Logan Jean、Florence Wagner、Edward Holson、Stephen J. Haggarty、Philipp Weiss、Payton King、Pauline Carter、Nora D. Volkow、Joanna S. Fowler、Jacob M. Hooker、Sung Won Kim

  DOI：10.1021/cn500021p

  日期：2014.7.16

  deacetylase (HDAC) inhibitors, which are used to study/treat brain diseases, show low blood-brain barrier (BBB) penetration. In addition to low HDAC potency and selectivity observed, poor brain penetrance may account for the high doses needed to achieve therapeutic efficacy. Here we report the development and evaluation of highly potent and blood-brain barrier permeable HDAC inhibitors for CNS applications

  最近的研究表明，用于研究/治疗脑部疾病的几种组蛋白去乙酰化酶 (HDAC) 抑制剂显示出低血脑屏障 (BBB) 渗透率。除了观察到的低 HDAC 效力和选择性外，脑外显率差可能是实现治疗效果所需的高剂量的原因。在这里，我们报告了基于图像引导方法的用于 CNS 应用的高效和血脑屏障可渗透 HDAC 抑制剂的开发和评估，该方法涉及基于苯甲酰胺 HDAC 抑制剂 MS-275 的一系列化合物的平行合成和放射性标记，如一个模板。BBB 渗透通过狒狒模型中的快速碳 11 标记和 PET 成像进行优化，并使用来自每种化合物的 BBB 渗透的成像衍生数据反馈到设计过程中。总共评估了 17 种化合物，揭示了具有高结合亲和力和 BBB 渗透性的分子。在该苯甲酰胺系列中赋予 BBB 渗透的关键元素是碱性苄胺。这些衍生物对重组人 HDAC1 和 HDAC2 表现出 1-100 nM 的抑制活性。三种碳 11 标记的氨基甲基苯甲酰胺衍生物显示出高
• 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。
• Inhibitors of Histone Deacetylase
  申请人：Moradei Oscar

  公开号：US20080132503A1

  公开（公告）日：2008-06-05

  The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

  本发明涉及抑制组蛋白去乙酰化酶。本发明提供了抑制组蛋白去乙酰化酶酶活性的化合物和方法。本发明还提供了治疗细胞增殖性疾病和病症的组合物和方法。
• 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。