(E)-2-(4-methoxyphenyl)-3-(4-methylsulfonylphenyl)prop-2-enoic acid | 914800-39-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (E)-2-(4-methoxyphenyl)-3-(4-methylsulfonylphenyl)prop-2-enoic acid
• CAS: 914800-39-8
• 化学式: C₁₇H₁₆O₅S
• 分子量: 332.377
• InChiKey: BDTOGQQVLQOSBE-LFIBNONCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  89
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  O2-acetoxymethyl-1-[N-(2-methylsulfonyloxyethyl)-N-methylamino]diazen-1-ium-1,2-diolate 、 (E)-2-(4-methoxyphenyl)-3-(4-methylsulfonylphenyl)prop-2-enoic acid 在 sodium carbonate 作用下， 以 六甲基磷酰三胺 为溶剂， 反应 91.0h， 以32%的产率得到O²-acetoxymethyl-1-(N-ethyl-N-methylamino)diazen-1-ium-1,2-diolate (E)-3-(4-methanesulfonylphenyl)-2-(4-methoxyphenyl)acrylate
  参考文献：
  名称：

  Diazen-1-ium-1,2-diolated and nitrooxyethyl nitric oxide donor ester prodrugs of anti-inflammatory (E)-2-(aryl)-3-(4-methanesulfonylphenyl)acrylic acids: Synthesis, cyclooxygenase inhibition, and nitric oxide release studies

  摘要：

  A new group of hybrid nitric oxide-releasing anti-inflammatory drugs wherein an O-2-acetoxyrnethyl-1-(N-ethyl-N-methylamino)diazen-1-ium-1,2-diolate (11a-d), or 2-nitrooxyethyl (12a-d), (NO)-N-center dot-donor moiety is attached directly to the carboxylic acid group of (E)-3-(4-methanesulfonylphenyl)-2-(phenyl)acrylic acids were synthesized. The 2-nitrooxyethyl ester prodrugs (12a-d) all exhibited in vitro inhibitory activity against the cyclooxygenase-2 (COX-2) isozyme (IC50 = 0.07-2.8 mu M range). All compounds released a low amount of (NO)-N-center dot upon incubation with phosphate buffer (PBS) at pH 7.4 (1.0-4.8% range). In comparison, the percentage (NO)-N-center dot released was significantly higher (76.2-83.0% range) when the diazen-1-ium-1,2-diolate ester prodrugs were incubated in the presence of rat serum, or moderately higher (7.6-10.1% range) when the nitrooxyethyl ester prodrugs were incubated in the presence Of L-cysteine. These incubation studies suggest that both WO and the parent anti-inflammatory (E)-3-(4-methanesulfonylphenyl)-2-(phenyl)acrylic acid would be released upon in vivo cleavage by non-specific serum esterases in the case of the diazen-1-ium-1,2-diolate esters (11a-d), or interaction with systemic thiols in the case of the nitrate esters (12a-d). O-2-Acetoxymethyl-1-(N-ethyl-N-methylamino)diazen-1-ium-1,2-diolate (E)-3-(4-methanesulfonylphenyl)-2-phenylacrylate (11a) released 83% of the theoretical maximal release of 2 molecules of (NO)-N-center dot/molecule of the parent hybrid ester prodrug upon incubation with rat serum. Hybrid ester anti-inflammatory/(NO)-N-center dot donor prodrugs offer a potential drug design concept targeted toward the development of anti-inflammatory drugs that are devoid of adverse ulcerogenic and/or cardiovascular effects. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.12.006
• 作为产物：
  描述：

  对甲氧基苯乙酸 、 对甲砜基苯甲醛 在 乙酸酐 、 三乙胺 作用下， 反应 16.0h， 以41%的产率得到(E)-2-(4-methoxyphenyl)-3-(4-methylsulfonylphenyl)prop-2-enoic acid
  参考文献：
  名称：

  设计，合成和生物评价（E）-3-（4-甲磺酰基苯基）-2-（芳基）丙烯酸作为环氧合酶和脂氧合酶的双重抑制剂。

  摘要：

  具有取代的苯环（4-H，4-Br，3-Br，4-F，4-OH，4-OMe，4-OAc的一组（E）-3-（4-甲磺酰基苯基）丙烯酸使用立体有择的珀金缩合反应制备附接至丙烯酸C-2位的4-NHAc，和4-NHAc）。一组相关的化合物，其具有连接到丙烯酸C上的4-和3-（4-异丙氧基苯基）苯基，4-和3-（2,4-二氟苯基）苯基和4-和3-（4-甲磺酰基苯基）苯基取代基还使用钯催化的Suzuki交叉偶联反应合成了-2位，以作为双环氧合酶-2（COX-2）和5-脂氧合酶（5-LOX）抑制剂进行评估。（E）-2-（3-溴苯基）-3-（4-甲磺酰基苯基）丙烯酸（9h），以及具有4-（4-异丙氧基苯基，2,4-二氟苯基或4-甲基磺酰基苯基）苯基的化合物在丙烯酸​​C-2位置（11a，b，d），与参考药物rofecoxib（COX-2 IC50 = 0.5 microM，SI> 200）相似，它们是具有高COX-2选择性指数（COX-2

  DOI：

  10.1016/j.bmc.2006.08.008

文献信息

• Design, synthesis, and biological evaluation of (E)-3-(4-methanesulfonylphenyl)-2-(aryl)acrylic acids as dual inhibitors of cyclooxygenases and lipoxygenases
  作者：Anne Moreau、Qiao-Hong Chen、P.N. Praveen Rao、Edward E. Knaus

  DOI：10.1016/j.bmc.2006.08.008

  日期：2006.12

  acrylic acid C-2 position were also synthesized, using a palladium-catalyzed Suzuki cross-coupling reaction, for evaluation as dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors. (E)-2-(3-Bromophenyl)-3-(4-methanesulfonylphenyl)acrylic acid (9h), and compounds having 4-(4-isopropyloxyphenyl-, 2,4-difluorophenyl-, or 4-methylsulfonylphenyl)phenyl moieties at the acrylic acid C-2 position

  具有取代的苯环（4-H，4-Br，3-Br，4-F，4-OH，4-OMe，4-OAc的一组（E）-3-（4-甲磺酰基苯基）丙烯酸使用立体有择的珀金缩合反应制备附接至丙烯酸C-2位的4-NHAc，和4-NHAc）。一组相关的化合物，其具有连接到丙烯酸C上的4-和3-（4-异丙氧基苯基）苯基，4-和3-（2,4-二氟苯基）苯基和4-和3-（4-甲磺酰基苯基）苯基取代基还使用钯催化的Suzuki交叉偶联反应合成了-2位，以作为双环氧合酶-2（COX-2）和5-脂氧合酶（5-LOX）抑制剂进行评估。（E）-2-（3-溴苯基）-3-（4-甲磺酰基苯基）丙烯酸（9h），以及具有4-（4-异丙氧基苯基，2,4-二氟苯基或4-甲基磺酰基苯基）苯基的化合物在丙烯酸​​C-2位置（11a，b，d），与参考药物rofecoxib（COX-2 IC50 = 0.5 microM，SI> 200）相似，它们是具有高COX-2选择性指数（COX-2
• Diazen-1-ium-1,2-diolated and nitrooxyethyl nitric oxide donor ester prodrugs of anti-inflammatory (E)-2-(aryl)-3-(4-methanesulfonylphenyl)acrylic acids: Synthesis, cyclooxygenase inhibition, and nitric oxide release studies
  作者：Khaled R.A. Abdellatif、Morshed Alam Chowdhury、Ying Dong、Qiao-Hong Chen、Edward E. Knaus

  DOI：10.1016/j.bmc.2007.12.006

  日期：2008.3.15

  A new group of hybrid nitric oxide-releasing anti-inflammatory drugs wherein an O-2-acetoxyrnethyl-1-(N-ethyl-N-methylamino)diazen-1-ium-1,2-diolate (11a-d), or 2-nitrooxyethyl (12a-d), (NO)-N-center dot-donor moiety is attached directly to the carboxylic acid group of (E)-3-(4-methanesulfonylphenyl)-2-(phenyl)acrylic acids were synthesized. The 2-nitrooxyethyl ester prodrugs (12a-d) all exhibited in vitro inhibitory activity against the cyclooxygenase-2 (COX-2) isozyme (IC50 = 0.07-2.8 mu M range). All compounds released a low amount of (NO)-N-center dot upon incubation with phosphate buffer (PBS) at pH 7.4 (1.0-4.8% range). In comparison, the percentage (NO)-N-center dot released was significantly higher (76.2-83.0% range) when the diazen-1-ium-1,2-diolate ester prodrugs were incubated in the presence of rat serum, or moderately higher (7.6-10.1% range) when the nitrooxyethyl ester prodrugs were incubated in the presence Of L-cysteine. These incubation studies suggest that both WO and the parent anti-inflammatory (E)-3-(4-methanesulfonylphenyl)-2-(phenyl)acrylic acid would be released upon in vivo cleavage by non-specific serum esterases in the case of the diazen-1-ium-1,2-diolate esters (11a-d), or interaction with systemic thiols in the case of the nitrate esters (12a-d). O-2-Acetoxymethyl-1-(N-ethyl-N-methylamino)diazen-1-ium-1,2-diolate (E)-3-(4-methanesulfonylphenyl)-2-phenylacrylate (11a) released 83% of the theoretical maximal release of 2 molecules of (NO)-N-center dot/molecule of the parent hybrid ester prodrug upon incubation with rat serum. Hybrid ester anti-inflammatory/(NO)-N-center dot donor prodrugs offer a potential drug design concept targeted toward the development of anti-inflammatory drugs that are devoid of adverse ulcerogenic and/or cardiovascular effects. (C) 2007 Elsevier Ltd. All rights reserved.