(S)-thioacetic acid S-(6-tert-butoxycarbonylamino-6-cycloheptylcarbamoylhexyl)ester | 908860-19-5

• 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)-thioacetic acid S-(6-tert-butoxycarbonylamino-6-cycloheptylcarbamoylhexyl)ester
• 英文别名: S-[(6S)-7-(cycloheptylamino)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-7-oxoheptyl] ethanethioate
• CAS: 908860-19-5
• 化学式: C₂₁H₃₈N₂O₄S
• 分子量: 414.61
• InChiKey: CHSNZCMCXQRSEG-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-thioacetic acid S-(6-tert-butoxycarbonylamino-6-cycloheptylcarbamoylhexyl)ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.17h， 生成 ((S)-1-Cycloheptylcarbamoyl-6-mercapto-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
• 作为产物：
  描述：

  (S)-2-tert-butyloxycarbonylamino-7-bromoheptanoic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 1-羟基苯并三唑一水物 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 (S)-thioacetic acid S-(6-tert-butoxycarbonylamino-6-cycloheptylcarbamoylhexyl)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.