7,7-bis-(quinolin-8-ylcarbamoyl)-heptanoic acid ethyl ester | 329967-23-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7,7-bis-(quinolin-8-ylcarbamoyl)-heptanoic acid ethyl ester
• 英文别名: ethyl 8-oxo-8-(quinolin-8-ylamino)-7-(quinolin-8-ylcarbamoyl)octanoate
• CAS: 329967-23-9
• 化学式: C₂₉H₃₀N₄O₄
• 分子量: 498.582
• InChiKey: MCUBNMOHCODAHP-UHFFFAOYSA-N

物化性质

• 沸点：
  780.5±60.0 °C(Predicted)
• 密度：
  1.276±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7,7-bis-(quinolin-8-ylcarbamoyl)-heptanoic acid ethyl ester 在 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 、 O-(叔丁基二苯基硅烷基)羟胺 、 水 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 2-(quinolin-8-ylcarbamoyl)-octanedioic acid 8-hydroxyamide 1-quinolin-8-ylamide
  参考文献：
  名称：

  Derivatives of 1-amino-1-(hetero)arylaminocarbonyl-6-hydroxyaminocarbonylhexane useful in the treatment of tumors

  摘要：

  公开号：

  EP1231919B1
• 作为产物：
  描述：

  2-tert-butoxycarbonyl-octanedioic acid 1-tert-butyl ester 8-ethyl ester 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 7,7-bis-(quinolin-8-ylcarbamoyl)-heptanoic acid ethyl ester
  参考文献：
  名称：

  Derivatives of 1-amino-1-(hetero)arylaminocarbonyl-6-hydroxyaminocarbonylhexane useful in the treatment of tumors

  摘要：

  公开号：

  EP1231919B1

文献信息

• Novel class of cytodifferentiating agents and histone deacetylase inhibitors, and methods of use thereof
  申请人：Sloan Kettering Institute for Cancer Research

  公开号：US20040002506A1

  公开（公告）日：2004-01-01

  The present invention provides the compound having the formula: 1 wherein each of R 1 and R 2 is, substituted or unsubstituted, aryl, cycloalkyl, cycloalkylamino, naphtha, pyridineamino, piperidino, t-butyl, aryloxy, arylalkyloxy, or pyridine group; wherein A is an amido moiety, —O—, —S—, —NH—, or —CH 2 —; and wherein n is an integer from 3 to 8. The present invention also provides a method of selectively inducing growth arrest, terminal differentiation and/or apoptosis of neoplastic cells and thereby inhibiting proliferation of such cells. Moreover, the present invention provides a method of treating a patient having a tumor characterized by proliferation of neoplastic cells. Lastly, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically acceptable amount of the compound above.

  本发明提供了具有以下式子的化合物：1其中R1和R2中的每一个都是取代或未取代的芳基，环烷基，环烷基氨基，萘基，吡啶氨基，哌啶基，叔丁基，芳基氧基，芳基烷氧基或吡啶基；其中A是酰胺基团，-O-，-S-，-NH-或-CH2-；n是从3到8的整数。本发明还提供了一种选择性诱导肿瘤细胞生长停滞、终端分化和/或凋亡的方法，从而抑制这些细胞的增殖。此外，本发明还提供了一种治疗具有肿瘤细胞增殖特征的患者的方法。最后，本发明提供了一种包含药学上可接受的载体和上述化合物的治疗上可接受的量的制药组合物。
• Class of cytodifferentiating agents and histone deacetylase inhibitors, and methods of use thereof
  申请人：Sloan-Kettering Institute for Cancer Research

  公开号：US07126001B2

  公开（公告）日：2006-10-24

  The present invention provides the compound having the formula: wherein each of R1 and R2 is, substituted or unsubstituted, aryl, cycloalkyl, cycloalkylamino, naphtha, pyridineamino, piperidino, t-butyl, aryloxy, arylalkyloxy, or pyridine group; wherein A is an amido moiety, —O—, —S—, —NH—, or —CH2—; and wherein n is an integer from 3 to 8. The present invention also provides a method of selectively inducing growth arrest, terminal differentiation and/or apoptosis of neoplastic cells and thereby inhibiting proliferation of such cells. Moreover, the present invention provides a method of treating a patient having a tumor characterized by proliferation of neoplastic cells. Lastly, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically acceptable amount of the compound above.

  本发明提供了具有以下公式的化合物：其中R1和R2中的每一个均为取代或未取代的芳基，环烷基，环烷氨基，萘基，吡啶氨基，哌啶基，叔丁基，芳氧基，芳基烷氧基或吡啶基；其中A是酰胺基，-O-，-S-，-NH-或-CH2-；n为3到8的整数。本发明还提供了一种选择性诱导肿瘤细胞生长停滞、终末分化和/或凋亡，从而抑制这些细胞增殖的方法。此外，本发明还提供了一种治疗患有以肿瘤细胞增殖为特征的肿瘤的患者的方法。最后，本发明提供了一种包含药学上可接受载体和上述化合物的治疗上可接受剂量的药物组合物。
• Cytodifferentiating agents and histone deacetylase inhibitors, and methods of use thereof
  申请人：Sloan-Kettering Institute for Cancer Research

  公开号：US07345174B2

  公开（公告）日：2008-03-18

  The present invention provides the compound having the formula: wherein each of R1 and R2 is, substituted or unsubstituted, aryl, cycloalkyl, cycloalkylamino, naphtha, pyridineamino, piperidino, t-butyl, aryloxy, arylalkyloxy, or pyridine group; wherein A is an amido moiety, —O—, —S—, —NH—, or —CH2—; and wherein n is an integer from 3 to 8. The present invention also provides a method of selectively inducing growth arrest, terminal differentiation and/or apoptosis of neoplastic cells and thereby inhibiting proliferation of such cells. Moreover, the present invention provides a method of treating a patient having a tumor characterized by proliferation of neoplastic cells. Lastly, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically acceptable amount of the compound above.

  本发明提供了具有以下式子的化合物：其中R1和R2分别是取代或未取代的芳基、环烷基、环烷基氨基、萘基、吡啶氨基、哌啶基、叔丁基、芳基氧基、芳基烷氧基或吡啶基团；其中A是酰胺基、-O-、-S-、-NH-或-CH2-；n是3至8的整数。本发明还提供了一种选择性诱导肿瘤细胞生长停止、终端分化和/或凋亡，从而抑制这些细胞的增殖的方法。此外，本发明还提供了一种治疗具有肿瘤细胞增殖特征的患者的方法。最后，本发明提供了一种含有上述化合物的药物组合物，该药物组合物包括药用载体和治疗上可接受的化合物的适量。
• Modified malonate derivatives
  申请人：Merck Sharp & Dohme Corp.

  公开号：US08158825B2

  公开（公告）日：2012-04-17

  The present invention relates to a novel class of modified malonate derivatives. The modified malonate compounds can be used to treat cancer. The modified malonate 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 modified malonate derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the modified malonate derivatives in vivo.

  本发明涉及一类新型的改性丙二酸酯衍生物。这些改性丙二酸酯化合物可用于治疗癌症。这些改性丙二酸酯化合物也可以抑制组蛋白去乙酰化酶，并适用于选择性诱导细胞末端分化、阻止肿瘤细胞生长和/或细胞凋亡，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改性丙二酸酯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，并在体内产生治疗有效量的改性丙二酸酯衍生物。
• Modified Malonate Derivatives
  申请人：Grimm Jonathan

  公开号：US20100160327A1

  公开（公告）日：2010-06-24

  The present invention relates to a novel class of modified malonate derivatives. The modified malonate compounds can be used to treat cancer. The modified malonate 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 modified malonate derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the modified malonate derivatives in vivo.

  本发明涉及一种新的改性丙二酸酯衍生物类，这些改性丙二酸酯化合物可用于治疗癌症。这些改性丙二酸酯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细胞增殖特征的患者方面非常有用。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，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。本发明还提供了包括改性丙二酸酯衍生物的药物组合物和这些药物组合物的安全用药方案，这些方案易于遵循，并在体内产生治疗有效量的改性丙二酸酯衍生物。