methyl (2Z)-2-hydroxy-4-(4-(methylsulfonyl)phenyl)-4-oxo-but-2-enoate | 640727-90-8

• 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: methyl (2Z)-2-hydroxy-4-(4-(methylsulfonyl)phenyl)-4-oxo-but-2-enoate
• 英文别名: (Z)-methyl 2-hydroxy-4-(4-(methylsulfonyl)phenyl)-4-oxobut-2-enoate
• CAS: 640727-90-8
• 化学式: C₁₂H₁₂O₆S
• 分子量: 284.29
• InChiKey: ADVGHFRWSKIGLL-XFFZJAGNSA-N

物化性质

• 沸点：
  501.4±50.0 °C(Predicted)
• 密度：
  1.375±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.89
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  97.74
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl (2Z)-2-hydroxy-4-(4-(methylsulfonyl)phenyl)-4-oxo-but-2-enoate 在 四丁基氟化铵 、 三甲基铝 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 8.42h， 生成 1-[1-Cyclohexyl-5-(4-methylsulfonylphenyl)pyrazol-3-yl]-4-hydroxybutan-1-one
  参考文献：
  名称：

  一系列新型的，含一氧化氮供体的吡唑类化合物的合成和选择性的环氧合酶-2抑制活性。

  摘要：

  据报道一系列含有硝酸盐（ONO（2））作为一氧化氮（NO）-供体官能团的新型吡唑的合成。分析了它们在人全血中对COX-1和COX-2的抑制活性。我们的数据表明，吡唑环取代基在COX-2选择性抑制中起重要作用，因此发现环烷基吡唑（6b）是一种有效且选择性的COX-2抑制剂。在中心吡唑环（17b，23b，26b-1）的3位上的其他修饰增强了COX-2抑制能力。在合成的吡唑中，肟（23b）被确定为最有效的COX-2选择性抑制剂。因此，口服给药后在大鼠中进行了药理学分析，结果表明23b在角叉菜胶诱导的气袋模型中具有有效的抗炎活性，并且与背景阿司匹林一起给药时，胃毒性比标准COX-2抑制剂低。我们建议，NO供体COX-2选择性抑制剂的胃耐受性增强，有可能增加该药物类别的临床表现。

  DOI：

  10.1021/jm030276s
• 作为产物：
  描述：

  4-甲硫基苯乙酮 在 Oxone 、 sodium methylate 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 3.0h， 生成 methyl (2Z)-2-hydroxy-4-(4-(methylsulfonyl)phenyl)-4-oxo-but-2-enoate
  参考文献：
  名称：

  一系列新型的，含一氧化氮供体的吡唑类化合物的合成和选择性的环氧合酶-2抑制活性。

  摘要：

  据报道一系列含有硝酸盐（ONO（2））作为一氧化氮（NO）-供体官能团的新型吡唑的合成。分析了它们在人全血中对COX-1和COX-2的抑制活性。我们的数据表明，吡唑环取代基在COX-2选择性抑制中起重要作用，因此发现环烷基吡唑（6b）是一种有效且选择性的COX-2抑制剂。在中心吡唑环（17b，23b，26b-1）的3位上的其他修饰增强了COX-2抑制能力。在合成的吡唑中，肟（23b）被确定为最有效的COX-2选择性抑制剂。因此，口服给药后在大鼠中进行了药理学分析，结果表明23b在角叉菜胶诱导的气袋模型中具有有效的抗炎活性，并且与背景阿司匹林一起给药时，胃毒性比标准COX-2抑制剂低。我们建议，NO供体COX-2选择性抑制剂的胃耐受性增强，有可能增加该药物类别的临床表现。

  DOI：

  10.1021/jm030276s

文献信息

• Oxime and/or hydrozone containing nitrosated and/or nitrosylated cyclooxygenase-2 selective inhibitors, compositions and methods of use
  申请人：NitroMed, Inc.

  公开号：US20040006133A1

  公开（公告）日：2004-01-08

  The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors having at least one oxime group or hydrazone group and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor having at least one oxime group or hydrazone group, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor having at least one oxime group or hydrazone group, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention having at least one oxime group or hydrazone group can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

  该发明描述了具有至少一个肟基团或缩醛基团的新型环氧合酶2（COX-2）选择性抑制剂，以及包含至少一个具有至少一个肟基团或缩醛基团的环氧合酶2（COX-2）选择性抑制剂的新型组合物，以及可选地至少一个供体、转移或释放一氧化氮、刺激内源性一氧化氮合成、提高内源性内皮源性舒张因子水平或是一氧化氮合酶底物的化合物，和/或至少一个治疗剂。该发明还提供了包含至少一个具有至少一个肟基团或缩醛基团的COX-2选择性抑制剂的新型试剂盒，可选地硝化和/或亚硝化，以及可选地至少一个一氧化氮供体，和/或，可选地至少一个治疗剂的试剂盒。该发明的新型环氧合酶2选择性抑制剂具有至少一个肟基团或缩醛基团，可选地硝化和/或亚硝化。该发明还提供了治疗炎症、疼痛和发热的方法；用于治疗和/或改善COX-2选择性抑制剂的胃肠特性；促进伤口愈合；用于治疗和/或预防肾脏和/或呼吸道毒性；用于治疗和/或预防由于环氧合酶-2水平升高而导致的其他疾病；以及用于改善COX-2选择性抑制剂的心血管特性的方法。
• Cyclooxygenase-2 selective inhibitors, compositions and methods of use
  申请人：Bandarage K. Ipul

  公开号：US20060194861A1

  公开（公告）日：2006-08-31

  The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

  该发明描述了新颖的环氧合酶2（COX-2）选择性抑制剂以及至少包含一种环氧合酶2（COX-2）选择性抑制剂的新型组合物，以及可选地至少包含一种捐赠、转移或释放一氧化氮的化合物，刺激内源性一氧化氮的合成，提高内源性的内皮衍生性松弛因子的水平或是一氧化氮合酶的底物，和/或至少一种治疗剂。该发明还提供了新型工具包，其中包括至少一种COX-2选择性抑制剂，可选地硝化和/或硝酰化，以及可选地至少一种一氧化氮供体和/或可选地至少一种治疗剂。该发明的新型环氧合酶2选择性抑制剂可以可选地硝化和/或硝酰化。该发明还提供了治疗炎症、疼痛和发热的方法；用于治疗和/或改善COX-2选择性抑制剂的胃肠道特性；促进伤口愈合的方法；用于治疗和/或预防肾脏和/或呼吸系统毒性的方法；用于治疗和/或预防由于环氧合酶2水平升高而导致的其他疾病的方法；以及用于改善COX-2选择性抑制剂的心血管特性的方法。
• CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE
  申请人：Bandarage Upul K.

  公开号：US20090005350A1

  公开（公告）日：2009-01-01

  The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

  本发明描述了新型环氧合酶2（COX-2）选择性抑制剂和包含至少一种环氧合酶2（COX-2）选择性抑制剂的新型组合物，以及可选择地至少包含一种捐赠、转移或释放一氧化氮、刺激内源性一氧化氮合成、提高内源性内皮源性舒张因子水平或是一氧化氮合酶底物的化合物和/或至少一种治疗剂的组合物。本发明还提供了包含至少一种COX-2选择性抑制剂，可选择性地硝化和/或硝酰化，以及可选择性地至少一种一氧化氮供体和/或至少一种治疗剂的新型试剂盒。本发明中的新型环氧合酶2选择性抑制剂可以选择性地硝化和/或硝酰化。本发明还提供了治疗炎症、疼痛和发热的方法；用于治疗和/或改善COX-2选择性抑制剂的胃肠道性质；用于促进伤口愈合；用于治疗和/或预防肾脏和/或呼吸系统毒性；用于治疗和/或预防由于环氧合酶-2水平升高而导致的其他疾病；以及用于改善COX-2选择性抑制剂的心血管特征的方法。
• Oxime and/or hydrazone containing nitrosated and/or nitrosylated cyclooxygenase-2 selective inhibitors, compositions and methods of use
  申请人：Ranatunge R. Ramani

  公开号：US20070155734A1

  公开（公告）日：2007-07-05

  The invention provides novel cyclooxygenase 2 (COX-2) selective inhibitors having at least one oxime group or hydrazone group and novel compositions and kits comprising at least one COX-2 selective inhibitor having at least one oxime group or hydrazone group, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention having at least one oxime group or hydrazone group can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

  本发明提供了一种新型环氧合酶2（COX-2）选择性抑制剂，其具有至少一个肟基团或肼基团，以及包含至少一个具有至少一个肟基团或肼基团的COX-2选择性抑制剂的新型组合物和试剂盒，可选地硝化和/或亚硝化，以及可选地至少一种一氧化氮供体和/或至少一种治疗剂。本发明的新型环氧合酶2选择性抑制剂具有至少一个肟基团或肼基团，可选地硝化和/或亚硝化。本发明还提供了治疗炎症、疼痛和发热的方法；用于治疗和/或改善COX-2选择性抑制剂的胃肠性能的方法；用于促进伤口愈合的方法；用于治疗和/或预防肾脏和/或呼吸毒性的方法；用于治疗和/或预防由于环氧合酶2水平升高而导致的其他疾病的方法；以及用于改善COX-2选择性抑制剂的心血管概况的方法。
• Inhibitors of Mycobacterium Tuberculosis Malate Synthase, Methods of Making and Uses Thereof
  申请人：Freundlich Joel S.

  公开号：US20140171444A1

  公开（公告）日：2014-06-19

  The present invention provides aryl- or heteroaryl-diketo acid compounds effective to inhibit an activity of a Mycobacterial malate synthase enzyme or to inhibit a malate synthase activity in other bacteria having the enzyme. The compounds may be phenyl- naphthyl-, or thienyl-substituted diketo acids and carboxylate derivatives thereof. Also provided are methods of treating tuberculosis or other pathophysiological conditions associated with a malate synthase enzyme with the inhibitory compounds and methods of in silico design of the inhibitory compounds. In addition, the present invention provides the inhibitory compounds designed by this method. Furthermore, three-dimensional X-ray crystal structures of the Mycobacterial malate synthase complexed with the inhibitory compounds are provided. Further still a method for stabilizing an aromatic or heteroaromatic diketo acid or its prodrug or close analog in solution by derivatizing at least the ortho position on the aromatic ring is provided.

  本发明提供了芳基或杂环芳基二酮酸化合物，其能够有效抑制结核分枝杆菌苹果酸合酶酶活性或抑制其他具有该酶的细菌的苹果酸合酶活性。这些化合物可以是苯基、萘基或噻吩基取代的二酮酸和其羧酸衍生物。还提供了使用这些抑制剂治疗结核病或其他与苹果酸合酶酶相关的病理生理状况的方法以及通过计算机模拟设计这些抑制剂的方法。此外，本发明还提供了通过这种方法设计的抑制剂。此外，还提供了与抑制剂形成复合物的结核分枝杆菌苹果酸合酶的三维X射线晶体结构。还提供了一种通过在芳香环上至少衍生化邻位位置来稳定溶液中的芳香或杂环芳香二酮酸或其前药或类似物的方法。