(2E)-3-(dimethylamino)-1-[6-(methoxy)pyrazolo[1,5-b]pyridazin-3-yl]-2-propen-1-one | 551920-19-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2E)-3-(dimethylamino)-1-[6-(methoxy)pyrazolo[1,5-b]pyridazin-3-yl]-2-propen-1-one
• 英文别名: (2E)-3-(dimethylamino)-1-(6-methoxypyrazolo[1,5-b]pyridazin-3-yl)-2-propen-1-one；(E)-3-(dimethylamino)-1-(6-methoxypyrazolo[1,5-b]pyridazin-3-yl)prop-2-en-1-one
• CAS: 551920-19-5
• 化学式: C₁₂H₁₄N₄O₂
• 分子量: 246.269
• InChiKey: SJWAIUCYYFOCSM-VOTSOKGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  59.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2E)-3-(dimethylamino)-1-[6-(methoxy)pyrazolo[1,5-b]pyridazin-3-yl]-2-propen-1-one 在 吗啉 、 potassium carbonate 作用下， 以 乙二醇甲醚 为溶剂， 反应 14.0h， 生成 3-[2-(3-Trifluoromethyl-phenylamino)-pyrimidin-4-yl]-pyrazolo[1,5-b]pyridazin-6-ol
  参考文献：
  名称：

  N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as Potent and Selective Inhibitors of Glycogen Synthase Kinase 3 with Good Cellular Efficacy

  摘要：

  Glycogen synthase kinase 3 regulates glycogen synthase, the rate-determining enzyme for glycogen synthesis. Liver and muscle glycogen synthesis is defective in type 2 diabetics, resulting in elevated plasma glucose levels. Inhibition of GSK-3 could potentially be an effective method to control plasma glucose levels in type 2 diabetics. Structure-activity studies on a N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine series have led to the identification of potent and selective compounds with good cellular efficacy. Molecular modeling studies have given insights into the mode of binding of these inhibitors. Since the initial leads were also potent inhibitors of CDK-2/CDK-4, an extensive SAR was performed at various positions of the pyrazolo[1,5-b]pyridazin core to afford potent GSK-3 inhibitors that were highly selective over CDK-2. In addition, these inhibitors also exhibited very good cell efficacy and functional response. A representative example was shown to have good oral exposure levels, extending their utility in an in vivo setting. These inhibitors provide a viable lead series in the discovery of new therapies for the treatment of type 2 diabetes.

  DOI：

  10.1021/jm040063i
• 作为产物：
  描述：

  3-甲氧基嘧啶 在 potassium hydrogencarbonate 、 hydroxylamine-O-sulfonic acid 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (2E)-3-(dimethylamino)-1-[6-(methoxy)pyrazolo[1,5-b]pyridazin-3-yl]-2-propen-1-one
  参考文献：
  名称：

  N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as Potent and Selective Inhibitors of Glycogen Synthase Kinase 3 with Good Cellular Efficacy

  摘要：

  Glycogen synthase kinase 3 regulates glycogen synthase, the rate-determining enzyme for glycogen synthesis. Liver and muscle glycogen synthesis is defective in type 2 diabetics, resulting in elevated plasma glucose levels. Inhibition of GSK-3 could potentially be an effective method to control plasma glucose levels in type 2 diabetics. Structure-activity studies on a N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine series have led to the identification of potent and selective compounds with good cellular efficacy. Molecular modeling studies have given insights into the mode of binding of these inhibitors. Since the initial leads were also potent inhibitors of CDK-2/CDK-4, an extensive SAR was performed at various positions of the pyrazolo[1,5-b]pyridazin core to afford potent GSK-3 inhibitors that were highly selective over CDK-2. In addition, these inhibitors also exhibited very good cell efficacy and functional response. A representative example was shown to have good oral exposure levels, extending their utility in an in vivo setting. These inhibitors provide a viable lead series in the discovery of new therapies for the treatment of type 2 diabetes.

  DOI：

  10.1021/jm040063i

文献信息

• [EN] PYRADAZINE COMPOUNDS AS GSK-3 INHIBITORS<br/>[FR] COMPOSES DE PYRADAZINE UTILES COMME INHIBITEURS DE GSK-3
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004035588A1

  公开（公告）日：2004-04-29

  The present invention relates generally to inhibitors of the kinases, such as GSK3, and more particularly to fused pyradazine compounds according to formula (I) and methods of their use.

  本发明通常涉及激酶抑制剂，如GSK3，更具体地涉及根据式(I)的融合吡啶并嘧啶化合物及其使用方法。
• Pyradazine compounds as gsk-3 inhibitors
  申请人：Dickerson Howard Scott

  公开号：US20060069097A1

  公开（公告）日：2006-03-30

  The present invention relates generally to inhibitors of the kinases, such as GSK3, and more particularly to fused pyradazine compounds and methods of their use.

  本发明通常涉及抑制激酶的抑制剂，例如GSK3，更具体地涉及融合嘧啶二氮杂环化合物及其使用方法。
• Pyradazine compounds as GSK-3 inhibitors
  申请人：SmithKline Beecham Corporation

  公开号：US07582630B2

  公开（公告）日：2009-09-01

  The present invention relates to pyrazaolpyradazine derivatives that inhibit GSK3 (glycogen synthase kinase), pharmaceutical compositions containing these derivatives, and methods for their use in the treatment of disorder characterized by misregulation of GSK3.

  本发明涉及抑制GSK3（糖原合成酶激酶）的吡唑吡嗪衍生物，含有这些衍生物的制药组合物，以及将其用于治疗GSK3调节失调性疾病的方法。
• Pyrazolopyridazine derivatves
  申请人：Badiang G Jennifer

  公开号：US20050090507A1

  公开（公告）日：2005-04-28

  Fused pyradazine derivatives, which are useful as CDK inhibitors are described herein. The described invention also includes methods of making such fused pyradazines derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.

  本文描述了可用作 CDK 抑制剂的融合哒嗪衍生物。所描述的发明还包括制造这种融合哒嗪衍生物的方法，以及将其用于治疗过度增殖性疾病的方法。
• PYRAZOLOPYRIDAZINE DERIVATIVES
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1463730B1

  公开（公告）日：2006-04-19