2-amino-N-(biphenyl-3-yl)-7-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)heptanamide | 1150698-06-8

• 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: 2-amino-N-(biphenyl-3-yl)-7-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)heptanamide
• 英文别名: 2-amino-N-(3-phenylphenyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)heptanamide
• CAS: 1150698-06-8
• 化学式: C₂₅H₃₅BN₂O₃
• 分子量: 422.375
• InChiKey: ALUNNLHZIASBPE-UHFFFAOYSA-N

物化性质

• 沸点：
  582.6±50.0 °C(predicted)
• 密度：
  1.09±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.27
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  噻唑-5-甲酸 、 2-amino-N-(biphenyl-3-yl)-7-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)heptanamide 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-[1-oxo-1-(3-phenylanilino)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)heptan-2-yl]-1,3-thiazole-5-carboxamide
  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
• 作为产物：
  描述：

  tert-butyl N-[1-oxo-1-(3-phenylanilino)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)heptan-2-yl]carbamate 在 盐酸 作用下， 以 氯仿 、 乙酸乙酯 为溶剂， 反应 2.0h， 以100%的产率得到2-amino-N-(biphenyl-3-yl)-7-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)heptanamide
  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.