N-[(8-anilino-8-oxooctanoyl)oxy]-N'-phenyloctanediamide

• 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: N-[(8-anilino-8-oxooctanoyl)oxy]-N'-phenyloctanediamide
• 英文别名: octanedioic acid phenylamide (7-phenylcarbamoyl-heptanoyloxy)-amide；Octanedioic acid phenylamide(7-phenylcarbamoyl-heptanoyloxy)-amide；[(8-anilino-8-oxooctanoyl)amino] 8-anilino-8-oxooctanoate
• 化学式: C₂₈H₃₇N₃O₅
• 分子量: 495.619
• InChiKey: VNJJOKIXYAKANS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  36
• 可旋转键数：
  18
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  伏立诺他 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 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 24.08h， 以77%的产率得到N-[(8-anilino-8-oxooctanoyl)oxy]-N'-phenyloctanediamide
  参考文献：
  名称：

  [EN] HISTONE DEACETYLASE INHIBITOR PRODRUGS
  [FR] PROMEDICAMENTS SOUS FORME D'INHIBITEURS D'HISTONES DESACETYLASES

  摘要：

  本发明涉及羟胺酸基组的组蛋白去乙酰化酶（HDAC）抑制剂的前药，例如柳酰苯基羟胺酸（SAHA）。这些前药是酰化衍生物，与游离的羟胺酸相比具有增加的水溶性和细胞渗透性，并且可用于抑制HDACs，并且可用于选择性诱导肿瘤细胞的终末分化、细胞生长停滞和/或凋亡，从而抑制这些细胞的增殖。因此，本发明的前药对于治疗具有肿瘤特征的患者是有用的，这些肿瘤由肿瘤细胞增殖引起。本发明的前药还可用于预防和治疗硫代脱氧核糖核蛋白（TRX）介导的疾病，例如自身免疫、过敏和炎症性疾病，并且用于预防和/或治疗中枢神经系统（CNS）疾病，例如神经退行性疾病。

  公开号：

  WO2005097747A1

文献信息

• Histone Deacetylase Inhibitor Prodrugs
  申请人：Miller Thomas A.

  公开号：US20090023786A1

  公开（公告）日：2009-01-22

  The present invention is directed to prodrugs of hydroxamic acid based histone deacetylase (HDAC) inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The prodrugs are acylated derivatives having increased aqueous solubility and cellular permeability as compared with the free hydroxamic acid, and are useful for inhibiting HDACs, and for selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the prodrugs of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The prodrugs of the invention are also useful in the prevention and treatment of thioredoxin (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.

  本发明涉及基于羟胺酸类组蛋白去乙酰化酶（HDAC）抑制剂的前药，例如亚苄基羟胺酸（SAHA）。这些前药是酰化衍生物，与自由羟胺酸相比具有增加的水溶性和细胞渗透性，并且可用于抑制HDAC，以及选择性地诱导肿瘤细胞的终末分化、细胞生长停滞和/或凋亡，从而抑制这些细胞的增殖。因此，本发明的前药对于治疗具有肿瘤细胞增殖特征的患者是有用的。该发明的前药还可用于预防和治疗硫氧还蛋白（TRX）介导的疾病，例如自身免疫、过敏和炎症性疾病，并用于预防和/或治疗中枢神经系统（CNS）疾病，例如神经退行性疾病。
• Histone deacetylase inhibitor prodrugs
  申请人：Merck HDAC Research, LLC

  公开号：US08227636B2

  公开（公告）日：2012-07-24

  The present invention is directed to prodrugs of hydroxamic acid based histone deacetylase (HDAC) inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The prodrugs are acylated derivatives having increased aqueous solubility and cellular permeability as compared with the free hydroxamic acid, and are useful for inhibiting HDACs, and for selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the prodrugs of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The prodrugs of the invention are also useful in the prevention and treatment of thioredoxin (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.

  本发明涉及羟基酰胺基的组蛋白去乙酰化酶（HDAC）抑制剂的前药，例如亚麻酰苯胺羟基酸（SAHA）。这些前药是酰化衍生物，与自由羟基酸相比具有增加的水溶性和细胞渗透性，并且可用于抑制HDAC，有选择地诱导肿瘤细胞的终末分化、细胞生长停滞和/或凋亡，从而抑制这些细胞的增殖。因此，本发明的前药可用于治疗具有肿瘤细胞增殖特征的患者。本发明的前药也可用于预防和治疗硫氧还蛋白（TRX）介导的疾病，例如自身免疫性、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，例如神经退行性疾病。
• HISTONE DEACETYLASE INHIBITOR PRODRUGS
  申请人：Aton Pharma, Inc.

  公开号：EP1745022B1

  公开（公告）日：2014-08-13
• US8227636B2
  申请人：——

  公开号：US8227636B2

  公开（公告）日：2012-07-24
• [EN] HISTONE DEACETYLASE INHIBITOR PRODRUGS<br/>[FR] PROMEDICAMENTS SOUS FORME D'INHIBITEURS D'HISTONES DESACETYLASES
  申请人：ATON PHARMA INC

  公开号：WO2005097747A1

  公开（公告）日：2005-10-20

  The present invention is directed to prodrugs of hydroxamic acid based histone deacetylase (HDAC) inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The prodrugs are acylated derivatives having increased aqueous solubility and cellular permeability as compared with the free hydroxamic acid, and are useful for inhibiting HDACs, and for selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the prodrugs of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The prodrugs of the invention are also useful in the prevention and treatment of thioredoxin (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.

  本发明涉及羟胺酸基组的组蛋白去乙酰化酶（HDAC）抑制剂的前药，例如柳酰苯基羟胺酸（SAHA）。这些前药是酰化衍生物，与游离的羟胺酸相比具有增加的水溶性和细胞渗透性，并且可用于抑制HDACs，并且可用于选择性诱导肿瘤细胞的终末分化、细胞生长停滞和/或凋亡，从而抑制这些细胞的增殖。因此，本发明的前药对于治疗具有肿瘤特征的患者是有用的，这些肿瘤由肿瘤细胞增殖引起。本发明的前药还可用于预防和治疗硫代脱氧核糖核蛋白（TRX）介导的疾病，例如自身免疫、过敏和炎症性疾病，并且用于预防和/或治疗中枢神经系统（CNS）疾病，例如神经退行性疾病。