(S)-6-(benzenecarbonylamino)-7-(biphenyl-3-ylamino)-7-oxo-heptylboronic acid | 1150698-01-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-6-(benzenecarbonylamino)-7-(biphenyl-3-ylamino)-7-oxo-heptylboronic acid
• 英文别名: (S)-6-(Benzenecarbonylamino)-7-(biphenyl-3-ylamino)-7-oxoheptylboronic acid；[(6S)-6-benzamido-7-oxo-7-(3-phenylanilino)heptyl]boronic acid
• CAS: 1150698-01-3
• 化学式: C₂₆H₂₉BN₂O₄
• 分子量: 444.338
• InChiKey: QCMOMEOGDAWUFS-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.12
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  98.7
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (S)-1-(biphenyl-3-ylaminocarbonyl)-6-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)hexylbenzamide 在 sodium periodate 、 ammonium acetate 、 水 作用下， 以 丙酮 为溶剂， 反应 48.0h， 以647 mg的产率得到(S)-6-(benzenecarbonylamino)-7-(biphenyl-3-ylamino)-7-oxo-heptylboronic acid
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Boronic Acid-Based Histone Deacetylase Inhibitors

  摘要：

  Guided by the proposed catalytic mechanism of histone deacetylases (HDACs), we designed and synthesized a series of boronic acid-based HDAC inhibitors bearing an alpha-amino acid moiety. In this series, compounds (S)-18, 20, and 21 showed potent HDAC-inhibitory activity, highlighting the significance of the (S)-amino acid moiety. In cancer cell growth inhibition assays, compounds (S)-18. 20, and 21 exerted strong activity, and the values of the ratio of the concentration causing 50% growth inhibition (GI(50)) to the concentration causing 50% enzyme inhibition (IC50), i.e., GI(50)/IC50, were low. The potency of these compounds was similar to that of clinically used suberoylanilide hydroxamic acid (SAHA) (2). The results of Western blot analysis indicated that the-cancer cell growth-inhibitory activity of compounds (S)-18, 20, and 21 is the result of HDAC inhibition. A molecular modeling study suggested that the hydrated boronic acid interacts with zinc ion, Tyr residue, and His residue in the active site of HDACs. Our findings indicate that these boronic acid derivatives represent an entry into a new class of HDAC inhibitors.

  DOI：

  10.1021/jm900125m