3-amino-2-phenyl-2,8-dihydro-6H-pyrano[3,4-c]pyridazine-4-carbonitrile | 406698-15-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃并[3，4-c]哒嗪
• 英文名称: 3-amino-2-phenyl-2,8-dihydro-6H-pyrano[3,4-c]pyridazine-4-carbonitrile
• 英文别名: 3-Amino-2-phenyl-6,8-dihydropyrano[3,4-c]pyridazine-4-carbonitrile
• CAS: 406698-15-5
• 化学式: C₁₄H₁₂N₄O
• 分子量: 252.275
• InChiKey: LPOXYZFZFMIAMW-UHFFFAOYSA-N

物化性质

• 沸点：
  473.6±55.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  74.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-amino-2-phenyl-2,8-dihydro-6H-pyrano[3,4-c]pyridazine-4-carbonitrile 在 硫酸 作用下， 反应 1.0h， 以80%的产率得到3-amino-2-phenyl-2,8-dihydro-6H-pyrano[3,4-c]pyridazine-4-carboxylic acid amide
  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：

  丙二腈 、 3-(phenylhydrazono)-tetrahydro-pyran-4-one 在 吗啉 作用下， 以 二甲基亚砜 为溶剂， 反应 0.25h， 以91%的产率得到3-amino-2-phenyl-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

文献信息

• Novel compounds
  申请人：——

  公开号：US20020115663A1

  公开（公告）日：2002-08-22

  The present invention is directed to novel pyridazine compounds of the formula I 1 as well as pharmaceutically and pharmacologically acceptable salts, and hydrates thereof; to a process for their preparation, their use and pharmaceutical compositions comprising said novel compounds. These novel compounds are useful in therapy, particularly for the treatment of type 2 diabetes mellitus.

  本发明涉及一种新型吡啶并嗪化合物，其化学式为I1，以及其药学和药理学上可接受的盐和水合物；以及它们的制备方法，用途和包含这些新型化合物的药物组合物。这些新型化合物在治疗中具有用途，特别是用于治疗2型糖尿病。
• [EN] NOVEL PYRIDAZINE COMPOUNDS FOR THE TREATMENT OF DIABETES<br/>[FR] NOUVEAUX COMPOSES DE PYRIDAZINE POUR LE TRAITEMENT DE DIABETES
  申请人：BIOVITRUM AB

  公开号：WO2002026743A1

  公开（公告）日：2002-04-04

  The present invention is directed to novel pyridazine compounds of the formula (I) as well as pharmaceutically and pharmaceutically acceptable salts, and hydrates thereof; to a process for their preparation, their use and pharmaceutical compositions comprising said novel compounds. These novel compounds are useful in therapy, particularly for the treatment of type 2 diabetes mellitus.
• 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.