tert-butyl (2-(4-aminobenzamido)-4-(thiophen-2-yl)phenyl)carbamate | 956427-79-5

• 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: tert-butyl (2-(4-aminobenzamido)-4-(thiophen-2-yl)phenyl)carbamate
• 英文别名: Tert-butyl [2-[(4-aminobenzoyl)amino]-4-(2-thienyl)phenyl]carbamate；tert-butyl N-[2-[(4-aminobenzoyl)amino]-4-thiophen-2-ylphenyl]carbamate
• CAS: 956427-79-5
• 化学式: C₂₂H₂₃N₃O₃S
• 分子量: 409.509
• InChiKey: HODSICIXTPTMMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (2-(4-aminobenzamido)-4-(thiophen-2-yl)phenyl)carbamate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 tert-butyl [2-{[4-({3-[acetyl(methyl)amino]propanoyl}amino)benzoyl]amino}-4-(2-thienyl)phenyl]carbamate
  参考文献：
  名称：

  [EN] DISUBSTITUTED ANILINE COMPOUNDS
  [FR] COMPOSÉS DE L'ANILINE DISUBSTITUÉS

  摘要：

  公开号：

  WO2007127137A3
• 作为产物：
  描述：

  4-(2,2,2-trifluoro-acetylamino)-benzoyl chloride 在 吡啶 、 水 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 tert-butyl (2-(4-aminobenzamido)-4-(thiophen-2-yl)phenyl)carbamate
  参考文献：
  名称：

  具有针对白血病和结肠直肠癌的有效口服活性的选择性HDAC抑制剂：设计，构效关系和抗肿瘤活性研究。

  摘要：

  以前，我们报道了一系列基于N-羟基肉桂酰胺的HDAC抑制剂的发现，其中化合物11y具有高HDAC1 / 3选择性。在本研究中，11y的结构衍生化导致了一系列新的基于苯甲酰胺的HDAC抑制剂。大多数化合物显示出高的HDAC抑制能力。化合物11a（在帽中具有4-甲氧基苯甲酰基作为N-取代基，而4-（氨基甲基）苯甲酰基作为连接基团）在一定程度上显示出对HDAC1的选择性，并且显示出对几种肿瘤细胞系的有效抗增殖活性。体内研究表明，化合物11a在血液肿瘤细胞U937异种移植模型和实体肿瘤细胞HCT116异种移植模型中均显示出有效的口服抗肿瘤活性，且无明显毒性。进一步改性苯甲酰胺3，

  DOI：

  10.1016/j.ejmech.2017.03.069

文献信息

• Optimization of Class I Histone Deacetylase PROTACs Reveals that HDAC1/2 Degradation is Critical to Induce Apoptosis and Cell Arrest in Cancer Cells
  作者：Joshua P. Smalley、India M. Baker、Wiktoria A. Pytel、Li-Ying Lin、Karen J. Bowman、John W. R. Schwabe、Shaun M. Cowley、James T. Hodgkinson

  DOI：10.1021/acs.jmedchem.1c02179

  日期：2022.4.14

  Class I histone deacetylase (HDAC) enzymes 1, 2, and 3 organize chromatin as the catalytic subunits within seven distinct multiprotein corepressor complexes and are established drug targets. We report optimization studies of benzamide-based Von Hippel–Lindau (VHL) E3-ligase proteolysis targeting chimeras (PROTACs) and for the first time describe transcriptome perturbations resulting from these degraders

  I 类组蛋白脱乙酰酶 (HDAC) 酶 1、2 和 3 将染色质组织为七种不同的多蛋白辅阻遏物复合物中的催化亚基，并且是既定的药物靶标。我们报告了基于苯甲酰胺的 Von Hippel–Lindau (VHL) E3 连接酶蛋白水解靶向嵌合体 (PROTAC) 的优化研究，并首次描述了由这些降解剂引起的转录组扰动。通过修饰接头和 VHL 配体，我们鉴定了具有亚微摩尔 DC 50的 PROTAC 7、9和22HCT116 细胞中 HDAC1 和/或 HDAC3 的值。观察到 HDAC3 的钩状效应，可以通过修改 VHL 配体与接头的连接位置来消除这种效应。更有效的 HDAC1/2 降解剂与更大的总差异表达基因和增强的 HCT116 细胞凋亡相关。我们证明 PROTAC 对 HDAC1/2 的降解与增强的全局基因表达和细胞凋亡相关，这对于开发更有效且副作用更少的 HDAC 疗法非常重要。
• Disubstituted Aniline Compounds
  申请人：Heidebrecht Richard

  公开号：US20090221669A1

  公开（公告）日：2009-09-03

  The present invention relates to a novel class of disubstituted aniline compounds. These compounds can inhibit hi-stone 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 compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

  本发明涉及一类新型的二取代苯胺化合物。这些化合物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，以及中枢神经系统（CNS）疾病的预防和/或治疗，例如神经退行性疾病。本发明还提供了包含本发明的化合物的制药组合物和这些制药组合物的安全用量方案，这些方案易于遵循，并在体内产生治疗有效量的这些化合物。
• 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。
• Disubstituted aniline compounds
  申请人：Merck Sharp & Dohme Corp.

  公开号：US08119685B2

  公开（公告）日：2012-02-21

  The present invention relates to a novel class of disubstituted aniline compounds. These compounds can 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 compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

  本发明涉及一种新型的二取代苯胺化合物。这些化合物可以抑制组蛋白去乙酰化酶，并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本发明化合物的制药组合物以及这些制药组合物的安全剂量方案，易于遵循，并在体内产生治疗有效量的这些化合物。