(S)-[6-bromo-1-(2-oxo-4-trifluoromethyl-2H-chromen-7-ylcarbamoyl)hexyl]carbamic acid tert-butyl ester | 908859-95-0

• 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: (S)-[6-bromo-1-(2-oxo-4-trifluoromethyl-2H-chromen-7-ylcarbamoyl)hexyl]carbamic acid tert-butyl ester
• 英文别名: tert-butyl (S)-7-bromo-1-oxo-1-(2-oxo-4-(trifluoromethyl)-2H-chromen-7-ylamino)heptan-2-ylcarbamate；tert-butyl N-[(2S)-7-bromo-1-oxo-1-[[2-oxo-4-(trifluoromethyl)chromen-7-yl]amino]heptan-2-yl]carbamate
• CAS: 908859-95-0
• 化学式: C₂₂H₂₆BrF₃N₂O₅
• 分子量: 535.358
• InChiKey: AQUGDMGIATYQHM-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-[6-bromo-1-(2-oxo-4-trifluoromethyl-2H-chromen-7-ylcarbamoyl)hexyl]carbamic acid tert-butyl ester 、 2-甲基硫代丙i酸 在 三乙胺 作用下， 以 乙醇 为溶剂， 以54%的产率得到(S)-thioisobutyric acid S-[6-tert-butoxycarbonylamino-6-(4-trifluoromethyl-2-oxo-2H-chromen-7-ylcarbamoyl)hexyl] ester
  参考文献：
  名称：

  Highly Potent and Selective Histone Deacetylase 6 Inhibitors Designed Based on a Small-Molecular Substrate

  摘要：

  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.

  DOI：

  10.1021/jm060554y
• 作为产物：
  描述：

  (S)-2-amino-7-bromoheptanoic acid 在 吡啶 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.25h， 生成 (S)-[6-bromo-1-(2-oxo-4-trifluoromethyl-2H-chromen-7-ylcarbamoyl)hexyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Highly Potent and Selective Histone Deacetylase 6 Inhibitors Designed Based on a Small-Molecular Substrate

  摘要：

  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.

  DOI：

  10.1021/jm060554y

文献信息

• 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.
• 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.