pyridin-3-ylmethyl [(4-{[(4-aminobiphenyl-3-yl)amino]carbonyl}phenyl)methyl]carbamate | 1013330-56-7

• 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: pyridin-3-ylmethyl [(4-{[(4-aminobiphenyl-3-yl)amino]carbonyl}phenyl)methyl]carbamate
• 英文别名: [4-(4-Amino-biphenyl-3-ylcarbamoyl)-benzyl]-carbamic acid pyridin-3-ylmethyl ester；pyridin-3-ylmethyl N-[[4-[(2-amino-5-phenylphenyl)carbamoyl]phenyl]methyl]carbamate
• CAS: 1013330-56-7
• 化学式: C₂₇H₂₄N₄O₃
• 分子量: 452.513
• InChiKey: AXVLWKBVIHOIQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  34
• 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：
  106
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-吡啶甲醇 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 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.59h， 生成 pyridin-3-ylmethyl [(4-{[(4-aminobiphenyl-3-yl)amino]carbonyl}phenyl)methyl]carbamate
  参考文献：
  名称：

  WO2009/2495

  摘要：

  公开号：

文献信息

• 4-CARBOXYBENZYLAMINO DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS
  申请人：Harrington Paul

  公开号：US20130137690A1

  公开（公告）日：2013-05-30

  The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino 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 4-carboxybenzylamino derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the 4-carboxybenzylamino derivatives in vivo.

  本发明涉及一种新型的4-羧基苯甲基氨基衍生物。这些4-羧基苯甲基氨基化合物可用于治疗癌症。这些4-羧基苯甲基氨基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末端分化，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中非常有用。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，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4-羧基苯甲基氨基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，并且在体内产生治疗有效量的4-羧基苯甲基氨基衍生物。
• 4-carboxybenzylamino derivatives as histone deacetylase inhibitors
  申请人：Harrington Paul

  公开号：US08389553B2

  公开（公告）日：2013-03-05

  The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino 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 4-carboxybenzylamino derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the 4-carboxybenzylamino derivatives in vivo.

  本发明涉及一种新型的4-羧基苯甲酰胺衍生物。这些4-羧基苯甲酰胺化合物可用于治疗癌症。这些4-羧基苯甲酰胺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末端分化，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是有用的。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4-羧基苯甲酰胺衍生物的药物组合物以及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4-羧基苯甲酰胺衍生物。
• Optimization of biaryl Selective HDAC1&2 Inhibitors (SHI-1:2)
  作者：David J. Witter、Paul Harrington、Kevin J. Wilson、Melissa Chenard、Judith C. Fleming、Brian Haines、Astrid M. Kral、J. Paul Secrist、Thomas A. Miller

  DOI：10.1016/j.bmcl.2007.11.047

  日期：2008.1

  A class of biaryl benzamides was identified and optimized as selective HDAC1&2 inhibitors (SHI-1:2). These agents exhibit selectivity over class II HDACs 4-7, as well as class I HDACs 3 and 8; providing examples of selective HDAC inhibitors for the HDAC isoforms most closely associated with cancer. The hypothesis for the increased selectivity is the binding of a pendant aromatic group in the internal cavity of the HDAC1&2 enzymes. SAR development based on an initial lead led to a series of potent and selective inhibitors with reduced off-target activity and tumor growth inhibition activity in a HCT-116 xenograft model. (c) 2007 Elsevier Ltd. All rights reserved.
• US8389553B2
  申请人：——

  公开号：US8389553B2

  公开（公告）日：2013-03-05
• US9096559B2
  申请人：——

  公开号：US9096559B2

  公开（公告）日：2015-08-04