(S)-S-6-(tert-butoxycarbonyl)-7-(2-hydroxyethylamino)-7-oxoheptyl 2-methylpropanethioate

• 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)-S-6-(tert-butoxycarbonyl)-7-(2-hydroxyethylamino)-7-oxoheptyl 2-methylpropanethioate
• 英文别名: S-[(6S)-7-(2-hydroxyethylamino)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-7-oxoheptyl] 2-methylpropanethioate
• 化学式: C₁₈H₃₄N₂O₅S
• 分子量: 390.544
• InChiKey: BPXYRTWTFKPALM-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  tert-butyl N-[(2S)-7-bromo-1-(2-hydroxyethylamino)-1-oxoheptan-2-yl]carbamate 、 2-甲基硫代丙i酸 在 三乙胺 作用下， 以 乙醇 为溶剂， 生成 (S)-S-6-(tert-butoxycarbonyl)-7-(2-hydroxyethylamino)-7-oxoheptyl 2-methylpropanethioate
  参考文献：
  名称：

  Design, Synthesis, Structure−Selectivity Relationship, and Effect on Human Cancer Cells of a Novel Series of Histone Deacetylase 6-Selective Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm7009217

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.