[(Tert-butoxycarbonyl)amino][4-({[2-[(tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]acetic acid | 947755-94-4

• 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-butoxycarbonyl)amino][4-({[2-[(tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]acetic acid
• 英文别名: 2-[(2-methylpropan-2-yl)oxycarbonylamino]-2-[4-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-thiophen-2-ylphenyl]carbamoyl]phenyl]acetic acid
• CAS: 947755-94-4
• 化学式: C₂₉H₃₃N₃O₇S
• 分子量: 567.663
• InChiKey: OYSWHUMTGXSOCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  171
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [(Tert-butoxycarbonyl)amino][4-({[2-[(tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]acetic acid 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 amino[4-({[2-amino-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]acetic acid
  参考文献：
  名称：

  Phenylglycine and phenylalanine derivatives as potent and selective HDAC1 inhibitors (SHI-1)

  摘要：

  An HTS screening campaign identified a series of low molecular weight phenols that showed excellent selectivity (> 100-fold) for HDAC1/HDAC2 over other Class I and Class II HDACs. Evolution and optimization of this HTS hit series provided HDAC1-selective (SHI-1) compounds with excellent anti-proliferative activity and improved physical properties. Dose-dependent efficacy in a mouse HCT116 xenograft model was demonstrated with a phenylglycine SHI-1 analog. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.02.012
• 作为产物：
  描述：

  Ethyl [(tert-butoxycarbonyl)amino][4-({[2-[(tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]acetate 在 lithium hydroxide 、 水 、 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 生成 [(Tert-butoxycarbonyl)amino][4-({[2-[(tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]acetic acid
  参考文献：
  名称：

  [EN] SILICON DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS
  [FR] DÉRIVÉS DE SILICIUM SOUS LA FORME D'INHIBITEURS D'HISTONE DÉSACÉTYLASE

  摘要：

  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。

  公开号：

  WO2009020589A1

文献信息

• Inhibitors of Histone Deacetylase
  申请人：Grimm Jonathan B.

  公开号：US20090069250A1

  公开（公告）日：2009-03-12

  The present invention relates to a novel class of 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 sale 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化合物。这些化合物可以抑制组蛋白去乙酰化酶，并适用于在选择性诱导终末分化、阻止肿瘤细胞生长和/或凋亡的过程中使用，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，这些肿瘤由肿瘤细胞增殖引起。本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。本发明还提供包含本发明化合物的药物组合物，以及这些药物组合物的销售用剂量方案，易于遵循，并在体内产生这些化合物的治疗有效量。
• [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。
• Inhibitors of histone deacetylase
  申请人：Merck Sharp & Dohme Corp.

  公开号：US08168658B2

  公开（公告）日：2012-05-01

  The present invention relates to a novel class of 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患有以肿瘤细胞增殖为特征的患者。本发明的化合物也可用于预防和治疗TRX介导的疾病，如自身免疫、过敏和炎症性疾病，并预防和/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本发明化合物的制药组合物和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。
• 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。
• INHIBITORS OF HISTONE DEACETYLASE
  申请人：Merck & Co., Inc.

  公开号：EP1991226A2

  公开（公告）日：2008-11-19