7-(benzothiazol-2-yl)amino-7-oxoheptylboronic acid | 1150696-90-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 7-(benzothiazol-2-yl)amino-7-oxoheptylboronic acid
• 英文别名: [7-(1,3-Benzothiazol-2-ylamino)-7-oxoheptyl]boronic acid
• CAS: 1150696-90-4
• 化学式: C₁₄H₁₉BN₂O₃S
• 分子量: 306.193
• InChiKey: LYUCPPOOGUHWEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.66
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-(1,3-benzothiazol-2-yl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)heptanamide 在 sodium periodate 、 ammonium acetate 、 水 作用下， 以 丙酮 为溶剂， 反应 48.0h， 以28 mg的产率得到7-(benzothiazol-2-yl)amino-7-oxoheptylboronic 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

文献信息

• Design, Synthesis, and Biological Activity of Boronic Acid-Based Histone Deacetylase Inhibitors
  作者：Nobuaki Suzuki、Takayoshi Suzuki、Yosuke Ota、Tatsuya Nakano、Masaaki Kurihara、Haruhiro Okuda、Takao Yamori、Hiroki Tsumoto、Hidehiko Nakagawa、Naoki Miyata

  DOI：10.1021/jm900125m

  日期：2009.5.14

  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.