(S)-2-amino-7-bromoheptanoic acid | 591773-04-5

• 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: (S)-2-amino-7-bromoheptanoic acid
• 英文别名: (2S)-2-amino-7-bromoheptanoic acid
• CAS: 591773-04-5
• 化学式: C₇H₁₄BrNO₂
• 分子量: 224.098
• InChiKey: AVGFIAFJIVVFOT-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  11
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-amino-7-bromoheptanoic acid 在 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 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 thioacetic acid S-{(S)-6-[((S)-4-oxo-azetidine-2-carbonyl)-amino]-6-phenylcarbamoyl-hexyl} ester
  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：

  2-acetamido-7-bromo-2-ethoxycarbonylheptanoic acid 在 sodium hydroxide 、 Aspergillus genus aminoacylase 、 cobalt(II) chloride 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 36.0h， 生成 (S)-2-amino-7-bromoheptanoic acid
  参考文献：
  名称：

  用于侧链修饰的1-α-氨基-ω-溴链烷酸的合成

  摘要：

  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。

  DOI：

  10.1016/j.tetlet.2003.11.007

文献信息

• Histone deacetylase inhibitors and process for producing the same
  申请人：Yoshida Minoru

  公开号：US20050277583A1

  公开（公告）日：2005-12-15

  Compounds represented by formula (1) have strong inhibitory activity that is selective towards HDAC1 and HDAC4. Therefore, the compounds of the present invention are useful as pharmaceutical agents for treating or preventing diseases caused by HDAC1 and HDAC4.

  由式（1）表示的化合物具有强大的抑制活性，且对HDAC1和HDAC4具有选择性。因此，本发明的化合物可用作治疗或预防由HDAC1和HDAC4引起的疾病的药物。
• Design, Synthesis, Structure−Selectivity Relationship, and Effect on Human Cancer Cells of a Novel Series of Histone Deacetylase 6-Selective Inhibitors
  作者：Yukihiro Itoh、Takayoshi Suzuki、Akiyasu Kouketsu、Nobuaki Suzuki、Satoko Maeda、Minoru Yoshida、Hidehiko Nakagawa、Naoki Miyata

  DOI：10.1021/jm7009217

  日期：2007.11.1

  To uncover novel histone deacetylase 6 (HDAC6)-selective inhibitors and to elucidate the structural requirements for their inhibitory activity, we designed and prepared a series of thiolate analogues based on the structure of an HDAC6-selective substrate and evaluated their properties by Western blotting and enzyme assays. Several thiolate analogues were found to be potent and selective HDAC6 inhibitors. Study of the structure -selectivity relationship revealed that the presence of a bulky alkyl group and tert-butylcarbamate group in these compounds is important for HDAC6-selective inhibition. Compounds 16b and 20b, the most selective and active compounds in this series, exerted a synergistic inhibition of cancer cell growth in combination with paclitaxel. They also blocked the growth of estrogen receptor alpha-positive breast cancer MCF-7 cells that had been treated with estrogen. These findings suggested that HDAC6-selective inhibitors have potential as anticancer agents.
• An efficient synthesis of SK-658 and its analogs as potent histone deacetylase inhibitors
  作者：Md. Shahidul Islam、Md. Nurul Islam、Md. Ashraful Hoque、Norikazu Nishino、Tamaki Kato、Hyun-Jung Kim、Akihiro Ito、Minoru Yoshida

  DOI：10.1016/j.bioorg.2015.02.009

  日期：2015.4

  SK-658 is a potent histone deacetylase (HDAC) inhibitor that showed higher activity than SAHA due to the presence of extended hydrophobic group. We designed and synthesized thioester and SS-hybrid bearing SK-658 analogs as HDAC inhibitors. All the compounds were active in nano molar range and showed higher inhibitory activity than SAHA and SK-658. Among these, disulfide compounds showed the highest activity. (C) 2015 Elsevier Inc. All rights reserved.
• Highly Potent and Selective Histone Deacetylase 6 Inhibitors Designed Based on a Small-Molecular Substrate
  作者：Takayoshi Suzuki、Akiyasu Kouketsu、Yukihiro Itoh、Shinya Hisakawa、Satoko Maeda、Minoru Yoshida、Hidehiko Nakagawa、Naoki Miyata

  DOI：10.1021/jm060554y

  日期：2006.8.1

  To find novel histone deacetylase 6 (HDAC6)-selective inhibitors and clarify the structural requirements for HDAC6-selective inhibition, we prepared thiolate analogues designed based on the structure of an HDAC6-selective substrate and evaluated the histone/ alpha-tubulin acetylation selectivity by Western blot analysis. Aliphatic compounds 17b-20b selectively caused alpha-tubulin acetylation over histone H4 acetylation. In enzyme assays using HDAC1, HDAC4, and HDAC6, compounds 17a-19a exhibited HDAC6-selective inhibition over HDAC1 and HDAC4.
• 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.