Ethyl 2-acetamido-7-bromoheptanoate | 669091-23-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Ethyl 2-acetamido-7-bromoheptanoate
• CAS: 669091-23-0
• 化学式: C₁₁H₂₀BrNO₃
• 分子量: 294.189
• InChiKey: UAKMGGQQRUZJEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Ethyl 2-acetamido-7-bromoheptanoate 在 aminoacylase 、 cobalt(II) chloride hexahydrate 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 、 sodium thiomethoxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.5h， 生成 (2R)-1-methyl-5-oxo-N-[(1S)-1-(phenylcarbamoyl)-6-sulfanylhexyl]pyrrolidine-2-carboxamide
  参考文献：
  名称：

  ST7612AA1, a Thioacetate-ω(γ-lactam carboxamide) Derivative Selected from a Novel Generation of Oral HDAC Inhibitors

  摘要：

  A systematic study of medicinal chemistry aimed at identifying a new generation of HDAC inhibitors, through the introduction of a thiol zinc-binding group (ZBG) and of an amide-lactam in the ?-position of the polyethylene chain of the vorinostat scaffold, allowed the selection of a new class of potent pan-HDAC inhibitors (pan-HDACis). Simple, highly versatile, and efficient synthetic approaches were used to synthesize a library of these new derivatives, which were then submitted to a screening for HDAC inhibition as well as to a preliminary in vitro assessment of their antiproliferative activity. Molecular docking into HDAC crystal structures suggested a binding mode for these thiol derivatives consistent with the stereoselectivity observed upon insertion of amide-lactam substituents in the ?-position. ST7612AA1 (117), selected as a drug candidate for further development, showed an in vitro activity in the nanomolar range associated with a remarkable in vivo antitumor activity, highly competitive with the most potent HDAC inhibitors, currently under clinical trials. A preliminary study of PK and metabolism is also illustrated.

  DOI：

  10.1021/jm5008209
• 作为产物：
  描述：

  1,5-二溴戊烷 在 sodium ethanolate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 12.5h， 生成 Ethyl 2-acetamido-7-bromoheptanoate
  参考文献：
  名称：

  ST7612AA1, a Thioacetate-ω(γ-lactam carboxamide) Derivative Selected from a Novel Generation of Oral HDAC Inhibitors

  摘要：

  A systematic study of medicinal chemistry aimed at identifying a new generation of HDAC inhibitors, through the introduction of a thiol zinc-binding group (ZBG) and of an amide-lactam in the ?-position of the polyethylene chain of the vorinostat scaffold, allowed the selection of a new class of potent pan-HDAC inhibitors (pan-HDACis). Simple, highly versatile, and efficient synthetic approaches were used to synthesize a library of these new derivatives, which were then submitted to a screening for HDAC inhibition as well as to a preliminary in vitro assessment of their antiproliferative activity. Molecular docking into HDAC crystal structures suggested a binding mode for these thiol derivatives consistent with the stereoselectivity observed upon insertion of amide-lactam substituents in the ?-position. ST7612AA1 (117), selected as a drug candidate for further development, showed an in vitro activity in the nanomolar range associated with a remarkable in vivo antitumor activity, highly competitive with the most potent HDAC inhibitors, currently under clinical trials. A preliminary study of PK and metabolism is also illustrated.

  DOI：

  10.1021/jm5008209

文献信息

• Synthesis of l-α-amino-ω-bromoalkanoic acid for side chain modification
  作者：Louis A. Watanabe、Binoy Jose、Tamaki Kato、Norikazu Nishino、Minoru Yoshida

  DOI：10.1016/j.tetlet.2003.11.007

  日期：2004.1

  l-α-Amino-ω-bromoalkanoic acids with side chain lengths varying from 4 to 10 methylene units have been conveniently synthesized as useful intermediates for the synthesis of functionalized non-natural amino acids.

  侧链长度在4至10个亚甲基单元之间变化的1-α-氨基-ω-溴链烷酸已经方便地合成为有用的中间体，用于合成官能化的非天然氨基酸。
• Inhibitors selective for HDAC6 in enzymes and cells
  作者：Praveer K. Gupta、Robert C. Reid、Ligong Liu、Andrew J. Lucke、Steve A. Broomfield、Melanie R. Andrews、Matthew J. Sweet、David P. Fairlie

  DOI：10.1016/j.bmcl.2010.09.100

  日期：2010.12

  Histone deacetylase inhibitors with anticancer or anti-inflammatory activity bind to Class I or Class I and II HDAC enzymes. Here we compare selectivity of inhibitors of a Class II HDAC enzyme (HDAC6) and find one that retains high selectivity in macrophages. (C) 2010 Elsevier Ltd. All rights reserved.