2,2-dimethyl-5-[(4-nitro-phenyl)hydrazono]-tetrahydro-pyran-4-one

• 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: 2,2-dimethyl-5-[(4-nitro-phenyl)hydrazono]-tetrahydro-pyran-4-one
• 英文别名: (5E)-2,2-dimethyl-5-[(4-nitrophenyl)hydrazinylidene]oxan-4-one
• 化学式: C₁₃H₁₅N₃O₄
• 分子量: 277.28
• InChiKey: BJNYPMAYLLZSJA-RVDMUPIBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  96.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  丙二腈 、 2,2-dimethyl-5-[(4-nitro-phenyl)hydrazono]-tetrahydro-pyran-4-one 在 哌啶 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以53%的产率得到3-Amino-6,6-dimethyl-2-[4-nitrophenyl]-2,8-dihydro-6H-pyrano[3,4-c]pyridazine-4-carbonitrile
  参考文献：
  名称：

  Synthesis and biological activity of a novel class of pyridazine analogues as non-competitive reversible inhibitors of protein tyrosine phosphatase 1B (PTP1B)

  摘要：

  A series of novel pyridazine analogues were prepared and the structure activity relationship of their behavior as inhibitors of PTP1B was evaluated. Most of the analogues had potencies in the low micromolar range. The in vitro kinetics of this compound series demonstrated that they were reversible non-competitive binders. This indicates that there may exist another site in the enzyme through which enzyme activity can be inhibited, which is not a recognized interaction domain. Some of the analogues exhibited high selectivity for other PTPases, for example, compound 12mp showed 20-fold selectivity for PTP1B (IC50 = 5.6 muM) versus both TCPTP and LAR (>100 muM, respectively). In contrast to many tyrosine phosphatase mimetic inhibitors, this compound class lacks negative charge and thus showed high permeability across cell membranes. Selective analogues in the series were analyzed in an in vitro cellular assay, which showed increased insulin-stimulated insulin receptor phosphorylation. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00176-1
• 作为产物：
  描述：

  5-甲基-1,4-己二烯-3-酮 在 硫酸 、 sodium hydride 、 mercury(II) sulfate 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 生成 2,2-dimethyl-5-[(4-nitro-phenyl)hydrazono]-tetrahydro-pyran-4-one
  参考文献：
  名称：

  Synthesis and biological activity of a novel class of pyridazine analogues as non-competitive reversible inhibitors of protein tyrosine phosphatase 1B (PTP1B)

  摘要：

  A series of novel pyridazine analogues were prepared and the structure activity relationship of their behavior as inhibitors of PTP1B was evaluated. Most of the analogues had potencies in the low micromolar range. The in vitro kinetics of this compound series demonstrated that they were reversible non-competitive binders. This indicates that there may exist another site in the enzyme through which enzyme activity can be inhibited, which is not a recognized interaction domain. Some of the analogues exhibited high selectivity for other PTPases, for example, compound 12mp showed 20-fold selectivity for PTP1B (IC50 = 5.6 muM) versus both TCPTP and LAR (>100 muM, respectively). In contrast to many tyrosine phosphatase mimetic inhibitors, this compound class lacks negative charge and thus showed high permeability across cell membranes. Selective analogues in the series were analyzed in an in vitro cellular assay, which showed increased insulin-stimulated insulin receptor phosphorylation. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00176-1

文献信息

• Synthesis and biological activity of a novel class of pyridazine analogues as non-competitive reversible inhibitors of protein tyrosine phosphatase 1B (PTP1B)
  作者：C Liljebris

  DOI：10.1016/s0968-0896(02)00176-1

  日期：2002.10

  A series of novel pyridazine analogues were prepared and the structure activity relationship of their behavior as inhibitors of PTP1B was evaluated. Most of the analogues had potencies in the low micromolar range. The in vitro kinetics of this compound series demonstrated that they were reversible non-competitive binders. This indicates that there may exist another site in the enzyme through which enzyme activity can be inhibited, which is not a recognized interaction domain. Some of the analogues exhibited high selectivity for other PTPases, for example, compound 12mp showed 20-fold selectivity for PTP1B (IC50 = 5.6 muM) versus both TCPTP and LAR (>100 muM, respectively). In contrast to many tyrosine phosphatase mimetic inhibitors, this compound class lacks negative charge and thus showed high permeability across cell membranes. Selective analogues in the series were analyzed in an in vitro cellular assay, which showed increased insulin-stimulated insulin receptor phosphorylation. (C) 2002 Elsevier Science Ltd. All rights reserved.