N-[5-(苯基氨基甲酰基)戊基]氨基甲酸苄酯 | 115012-32-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-[5-(苯基氨基甲酰基)戊基]氨基甲酸苄酯
• 英文名称: N-[5-(phenylcarbamoyl)pentyl]carbamic acid benzyl ester
• 英文别名: (6-phenylcarbamoylpentyl)carbamic acid benzyl ester；6-(benzyloxycarbonylamino)hexaneanilide；Z-ε-Aca-NH-Phenyl；benzyl N-(6-anilino-6-oxohexyl)carbamate
• CAS: 115012-32-3
• 化学式: C₂₀H₂₄N₂O₃
• 分子量: 340.422
• InChiKey: IHNDZZHCHWBCCV-UHFFFAOYSA-N

物化性质

• 沸点：
  578.5±43.0 °C(Predicted)
• 密度：
  1.155±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[5-(苯基氨基甲酰基)戊基]氨基甲酸苄酯 在 钯 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 以93%的产率得到6-amino-N-phenyl-hexanamide hydrochloric acid salt
  参考文献：
  名称：

  Ishibashi, Norio; Kouge, Katsushige; Shinoda,Ichizo, Agricultural and Biological Chemistry, 1988, vol. 52, # 3, p. 819 - 828

  摘要：

  DOI：
• 作为产物：
  描述：

  庚二酸 在 二苯基膦叠氮化物 、 三乙胺 作用下， 以 苯 为溶剂， 反应 26.0h， 生成 N-[5-(苯基氨基甲酰基)戊基]氨基甲酸苄酯
  参考文献：
  名称：

  人组蛋白脱乙酰基酶的新型抑制剂：基于SAHA的非异羟肟酸酯的设计，合成，酶抑制和癌细胞生长抑制。

  摘要：

  为了找到新型的非异羟肟酸酯组蛋白脱乙酰基酶（HDAC）抑制剂，设计并合成了以亚磺酰苯胺异羟肟酸（SAHA）为模型的一系列化合物。在该系列中，发现化合物7（其中SAHA的异羟肟酸被硫醇替代）与SAHA一样有效，该系列的优化导致鉴定出比SAHA更有效的HDAC抑制剂。在癌细胞生长抑制测定中，S-异丁酰基衍生物51显示出强活性，并且其效力与SAHA相当。通过Western印迹分析证实癌细胞生长抑制活性是组蛋白过度乙酰化和随后诱导p21（WAF1 / CIP1）的结果。

  DOI：

  10.1021/jm049207j

文献信息

• Novel class of cytodifferentiating agents and histone deacetylase inhibitors, and methods of use thereof
  申请人：Breslow Ronald

  公开号：US20070010536A1

  公开（公告）日：2007-01-11

  The present invention provides the compound having the formula: 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：其中R1和R2分别为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、芳氧基、芳基烷氧基或吡啶基；其中A为酰胺基、-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括药学上可接受的载体和上述化合物的治疗上可接受的剂量的药物组合物。
• Novel histone deacetylase inhibitors: design, synthesis, enzyme inhibition, and binding mode study of SAHA-Based non-hydroxamates
  作者：Takayoshi Suzuki、Yuki Nagano、Azusa Matsuura、Arihiro Kohara、Shin-ichi Ninomiya、Kohfuku Kohda、Naoki Miyata

  DOI：10.1016/j.bmcl.2003.09.048

  日期：2003.12

  In order to find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) were designed and synthesized as (i) substrate (acetyl lysine) analogues (compounds 3-7), (ii) analogues bearing various functional groups expected to chelate zinc ion (compounds 8-15), and (iii) analogues bearing nucleophilic functional groups which could bind covalently to HDACs (compounds 16-18). In this series, semicarbazide 8b and bromoacetamides 18b,c were found to be potent HDAC inhibitors for non-hydroxamates. (C) 2003 Elsevier Ltd. All rights reserved.
• Design and synthesis of non-hydroxamate histone deacetylase inhibitors: identification of a selective histone acetylating agent
  作者：Takayoshi Suzuki、Azusa Matsuura、Akiyasu Kouketsu、Shinya Hisakawa、Hidehiko Nakagawa、Naoki Miyata

  DOI：10.1016/j.bmc.2005.04.002

  日期：2005.7

  A series of suberoylanilide hydroxamic acid (SAHA)-based non-hydroxamates was designed, synthesized, and evaluated for their histone deacetylase (HDAC) inhibitory activity. Among these, methyl sulfoxide 15 inhibited HDACs in enzyme assays and caused hyperacetylation of histone H4 while not inducing the accumulation of acetylated alpha-tubulin in HCT116 cells. (c) 2005 Elsevier Ltd. All rights reserved.
• Identification of a potent non-hydroxamate histone deacetylase inhibitor by mechanism-based drug design
  作者：Takayoshi Suzuki、Azusa Matsuura、Akiyasu Kouketsu、Hidehiko Nakagawa、Naoki Miyata

  DOI：10.1016/j.bmcl.2004.10.074

  日期：2005.1

  In order to find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, we synthesized several suberoylanilide hydroxamic acid (SAHA)-based compounds designed on the basis of the catalytic mechanism of HDACs. Among these compounds, 5b was found to be as potent as SAHA. Kinetic enzyme assays and molecular modeling suggested that the mercaptoacetamide moiety of 5b interacts with the zinc in the active site of HDACs and removes a water molecule from the reactive site of the deacetylation. (C) 2004 Elsevier Ltd. All rights reserved.
• Phosphorus-Based SAHA Analogues as Histone Deacetylase Inhibitors
  作者：Galina V. Kapustin、György Fejér、Jennifer L. Gronlund、Dewey G. McCafferty、Edward Seto、Felicia A. Etzkorn

  DOI：10.1021/ol035056n

  日期：2003.8.1

  graphicThree analogues of suberoyl anilide hydroxamic acid (SAHA) with phosphorus metal-chelating functionalities were synthesized as inhibitors of histone deacetylases (HDACs). The compounds showed weak activity for HeLa nuclear extracts (IC50 = 0.57-6.1 mM), HDAC8 (IC50 = 0.28-0.41 mM), and histone-deacetylase-like protein (HDLP, IC50 = 0.33-1.9 mM), suggesting that the transition state of HDAC is not analogous to zinc proteases. Anti proliferative activity against A2780 cancer cells (IC50 = 0.11-0.12 mM), comparable to SAHA (0.15 mM), was observed.