2-(4-{[(2-aminophenyl)amino]carbonyl}-benzyl)-N,N'-diphenylmalonamide

• 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: 2-(4-{[(2-aminophenyl)amino]carbonyl}-benzyl)-N,N'-diphenylmalonamide
• 英文别名: N-(2-aminophenyl)-4-(3-oxo-3-(phenylamino)-2-(phenylcarbamoyl)propyl)benzamide；2-[[4-[(2-aminophenyl)carbamoyl]phenyl]methyl]-N,N'-diphenylpropanediamide
• 化学式: C₂₉H₂₆N₄O₃
• 分子量: 478.55
• InChiKey: LWSRLDHSRLTUCC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  113
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N,N'-二(苯基)丙二酰胺 在 氢氧化钾 、 sodium hydride 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(4-{[(2-aminophenyl)amino]carbonyl}-benzyl)-N,N'-diphenylmalonamide
  参考文献：
  名称：

  Design of novel histone deacetylase inhibitors

  摘要：

  Histone deacetylase (HDAC) inhibitors that target Class I and Class 11 HDACs are of synthetic and therapeutic interest and ongoing clinical studies indicate that they show great promise for the treatment of cancer. Moreover, Zolinza(R) (vorinostat) was recently approved by the FDA for the treatment of the cutaneous manifestations of cutaneous T-cell lymphoma [Nat. Rev. Drug Disc. 2007, 6 21]. As part of a broader effort to more fully explore the structure-activity relationships (SAR) of HDAC inhibitors, we sought to identify novel HDAC inhibitor structures through iterative design by utilizing low affinity ligands as synthetic starting points for SAR development. Novel and potent HDAC inhibitors have been identified using this approach and herein we report the optimization of the recognition elements of a novel series of malonyl-derived HDAC inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.080

文献信息

• 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。
• MODIFIED MALONATE DERIVATIVES
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1896395B1

  公开（公告）日：2015-07-15
• US8158825B2
  申请人：——

  公开号：US8158825B2

  公开（公告）日：2012-04-17
• Design of novel histone deacetylase inhibitors
  作者：Phieng Siliphaivanh、Paul Harrington、David J. Witter、Karin Otte、Paul Tempest、Sam Kattar、Astrid M. Kral、Judith C. Fleming、Sujal V. Deshmukh、Andreas Harsch、Paul J. Secrist、Thomas A. Miller

  DOI：10.1016/j.bmcl.2007.05.080

  日期：2007.8

  Histone deacetylase (HDAC) inhibitors that target Class I and Class 11 HDACs are of synthetic and therapeutic interest and ongoing clinical studies indicate that they show great promise for the treatment of cancer. Moreover, Zolinza(R) (vorinostat) was recently approved by the FDA for the treatment of the cutaneous manifestations of cutaneous T-cell lymphoma [Nat. Rev. Drug Disc. 2007, 6 21]. As part of a broader effort to more fully explore the structure-activity relationships (SAR) of HDAC inhibitors, we sought to identify novel HDAC inhibitor structures through iterative design by utilizing low affinity ligands as synthetic starting points for SAR development. Novel and potent HDAC inhibitors have been identified using this approach and herein we report the optimization of the recognition elements of a novel series of malonyl-derived HDAC inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.