3-chloro-5-phenylpyridazine-4-carbonitrile | 474381-73-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-chloro-5-phenylpyridazine-4-carbonitrile
• 英文别名: 3-Chloro-5-phenyl-pyridazine-4-carbonitrile
• CAS: 474381-73-2
• 化学式: C₁₁H₆ClN₃
• 分子量: 215.642
• InChiKey: GWKKHJDIEUWFHO-UHFFFAOYSA-N

物化性质

• 熔点：
  105-108 °C
• 沸点：
  483.1±45.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-chloro-5-phenylpyridazine-4-carbonitrile 在 一水合肼 作用下， 以 乙醇 为溶剂， 以88%的产率得到4-phenyl-1H-pyrazolo[3,4-c]pyridazin-3-ylamine
  参考文献：
  名称：

  吡唑并[3,4-c]哒嗪为新型和选择性的细胞周期蛋白依赖性激酶抑制剂。

  摘要：

  在由BASF Bioresearch Corp.（马萨诸塞州伍斯特）进行的高通量筛选中鉴定出吡唑并哒嗪1a为有效的CDK1 / cyclin B抑制剂，并显示出对CDK家族具有选择性。已合成了铅化合物的类似物，并测试了其抗肿瘤活性。使用构象搜索和自动对接技术的组合，已建立了先导化合物和CDK2 ATP结合位点之间的复合物的分子模型。所得复合物的稳定性已通过分子动力学模拟进行了评估，并且在拟议的化合物1a结合方式的基础上，对合成的类似物所获得的实验结果进行了合理化处理。SAR研究的结果，

  DOI：

  10.1021/jm058013g
• 作为产物：
  描述：

  3-oxo-5-phenyl-2,3-dihydropyridazine-4-carbonitrile 在 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以6%的产率得到3-chloro-5-phenylpyridazine-4-carbonitrile
  参考文献：
  名称：

  吡唑并[3,4-c]哒嗪为新型和选择性的细胞周期蛋白依赖性激酶抑制剂。

  摘要：

  在由BASF Bioresearch Corp.（马萨诸塞州伍斯特）进行的高通量筛选中鉴定出吡唑并哒嗪1a为有效的CDK1 / cyclin B抑制剂，并显示出对CDK家族具有选择性。已合成了铅化合物的类似物，并测试了其抗肿瘤活性。使用构象搜索和自动对接技术的组合，已建立了先导化合物和CDK2 ATP结合位点之间的复合物的分子模型。所得复合物的稳定性已通过分子动力学模拟进行了评估，并且在拟议的化合物1a结合方式的基础上，对合成的类似物所获得的实验结果进行了合理化处理。SAR研究的结果，

  DOI：

  10.1021/jm058013g

文献信息

• Inhibitors of GSK-3 and crystal structures of GSK-3 protein and protein complexes
  申请人：——

  公开号：US20030125332A1

  公开（公告）日：2003-07-03

  The present invention relates to inhibitors of GSK-3 and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors and methods of utilizing those compositions in the treatment and prevention of various disorders, such as diabetes and Alzheimer's disease. In addition, the invention relates to molecules or molecular complexes which comprise binding pockets of GSK-3&bgr; or its homologues. The invention relates to a computer comprising a data storage medium encoded with the structure coordinates of such binding pockets. The invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. The invention relates to methods of using the structure coordinates to screen for and design compounds that bind to GSK-3&bgr; protein or homologues thereof. The invention also relates to crystallizable compositions and crystals comprising GSK-3&bgr; protein or GSK-3&bgr; protein complexes.

  本发明涉及GSK-3的抑制剂及制备这些抑制剂的方法。本发明还提供了包含这些抑制剂的药物组合物，并提供了利用这些组合物在治疗和预防各种疾病，如糖尿病和阿尔茨海默病等方面的方法。此外，本发明涉及包含GSK-3β或其同源物的结合口袋的分子或分子复合物。本发明涉及一种计算机，其包括一个数据存储介质，编码有这些结合口袋的结构坐标。本发明还涉及利用这些结构坐标来解决同源蛋白质或蛋白质复合物的结构的方法。本发明涉及利用这些结构坐标来筛选和设计能够结合到GSK-3β蛋白或其同源物的化合物的方法。本发明还涉及包含GSK-3β蛋白或GSK-3β蛋白复合物的可结晶组合物和晶体。
• Inhibitors of GSK-3 and crystal structures of GSK-3beta protein and protein complexes
  申请人：ter Haar Ernst

  公开号：US20080262205A1

  公开（公告）日：2008-10-23

  The present invention relates to inhibitors of GSK-3 and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors and methods of utilizing those compositions in the treatment and prevention of various disorders, such as diabetes and Alzheimer's disease. In addition, the invention relates to molecules or molecular complexes which comprise binding pockets of GSK-3β or its homologues. The invention relates to a computer comprising a data storage medium encoded with the structure coordinates of such binding pockets. The invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. The invention relates to methods of using the structure coordinates to screen for and design compounds that bind to GSK-3β protein or homologues thereof. The invention also relates to crystallizable compositions and crystals comprising GSK-3β protein or GSK-3β protein complexes.

  本发明涉及GSK-3抑制剂及其制备方法。本发明还提供了包含该抑制剂的药物组合物以及将这些组合物用于治疗和预防各种疾病，如糖尿病和阿尔茨海默病的方法。此外，本发明涉及包含GSK-3β或其同源物的结合口袋的分子或分子复合物。本发明涉及一台计算机，该计算机包括编码有这些结合口袋的结构坐标的数据存储介质。本发明还涉及使用结构坐标来解决同源蛋白质或蛋白质复合物的结构的方法。本发明涉及使用结构坐标来筛选和设计与GSK-3β蛋白质或其同源物结合的化合物的方法。本发明还涉及包含GSK-3β蛋白质或GSK-3β蛋白质复合物的可结晶化组合物和晶体。
• Inhibitors of GSK-3 and crystal structures of GSK-3β protein and protein complexes
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US07390808B2

  公开（公告）日：2008-06-24

  The present invention relates to inhibitors of GSK-3 and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors and methods of utilizing those compositions in the treatment and prevention of various disorders, such as diabetes and Alzheimer's disease. In addition, the invention relates to molecules or molecular complexes which comprise binding pockets of GSK-3β or its homologues. The invention relates to a computer comprising a data storage medium encoded with the structure coordinates of such binding pockets. The invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. The invention relates to methods of using the structure coordinates to screen for and design compounds that bind to GSK-3β protein or homologues thereof. The invention also relates to crystallizable compositions and crystals comprising GSK-3β protein or GSK-3β protein complexes.

  本发明涉及GSK-3抑制剂及其生产方法。本发明还提供了包含这些抑制剂的药物组合物，并利用这些组合物治疗和预防各种疾病，如糖尿病和阿尔茨海默病。此外，本发明涉及包含GSK-3β或其同源物的结合口袋的分子或分子复合物。本发明涉及一台计算机，其包含一个数据存储介质，编码有这种结合口袋的结构坐标。本发明还涉及使用结构坐标解决同源蛋白质或蛋白质复合物的结构的方法。本发明涉及使用结构坐标筛选和设计结合于GSK-3β蛋白或其同源物的化合物的方法。本发明还涉及包含GSK-3β蛋白或GSK-3β蛋白复合物的晶体化组合物和晶体。
• INHIBITORS OF GSK-3 AND CRYSTAL STRUCTURES OF GSK-3BETA PROTEIN AND PROTEIN COMPLEXES
  申请人：ter Haar Ernst

  公开号：US20100227814A1

  公开（公告）日：2010-09-09

  The present invention relates to inhibitors of GSK-3 and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors and methods of utilizing those compositions in the treatment and prevention of various disorders, such as diabetes and Alzheimer's disease. In addition, the invention relates to molecules or molecular complexes which comprise binding pockets of GSK-3β or its homologues. The invention relates to a computer comprising a data storage medium encoded with the structure coordinates of such binding pockets. The invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. The invention relates to methods of using the structure coordinates to screen for and design compounds that bind to GSK-3β protein or homologues thereof. The invention also relates to crystallizable compositions and crystals comprising GSK-3β protein or GSK-3β protein complexes.

  本发明涉及GSK-3抑制剂及其制备方法。本发明还提供了包含该抑制剂的制药组合物，并提供了利用该组合物治疗和预防各种疾病，例如糖尿病和阿尔茨海默病的方法。此外，本发明还涉及包含GSK-3β或其同源物的结合口袋的分子或分子复合物。本发明涉及一种计算机，该计算机包括一个数据存储介质，该介质编码有这些结合口袋的结构坐标。本发明还涉及使用结构坐标来解决同源蛋白质或蛋白质复合物的结构的方法。本发明涉及使用结构坐标来筛选和设计与GSK-3β蛋白或其同源物结合的化合物的方法。本发明还涉及包含GSK-3β蛋白或GSK-3β蛋白复合物的可结晶组合物和晶体。
• INHIBITORS OF GSK-3 AND CRYSTAL STRUCTURES OF GSK-3Beta PROTEIN AND PROTEIN COMPLEXES
  申请人：ter Haar Ernst

  公开号：US20110129896A1

  公开（公告）日：2011-06-02

  The present invention relates to inhibitors of GSK-3 and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors and methods of utilizing those compositions in the treatment and prevention of various disorders, such as diabetes and Alzheimer's disease. In addition, the invention relates to molecules or molecular complexes which comprise binding pockets of GSK-3β or its homologues. The invention relates to a computer comprising a data storage medium encoded with the structure coordinates of such binding pockets. The invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. The invention relates to methods of using the structure coordinates to screen for and design compounds that bind to GSK-3β protein or homologues thereof. The invention also relates to crystallizable compositions and crystals comprising GSK-3β protein or GSK-3β protein complexes.

  本发明涉及GSK-3抑制剂及其制备方法。本发明还提供了包含这些抑制剂的制药组合物，并提供了利用这些组合物治疗和预防各种疾病（如糖尿病和阿尔茨海默病）的方法。此外，本发明涉及包含GSK-3β或其同源物的结合口袋的分子或分子复合物。本发明涉及包括编码此类结合口袋的结构坐标的数据存储介质的计算机。本发明还涉及使用结构坐标来解决同源蛋白质或蛋白质复合物的结构的方法。本发明涉及使用结构坐标筛选和设计结合到GSK-3β蛋白质或其同源物的化合物的方法。本发明还涉及包含GSK-3β蛋白质或GSK-3β蛋白质复合物的可结晶组合物和晶体。