5-Chloro-1-(5-Methanesulfonyl-Pyridin-2-yl)-3-Trifluoromethyl-1H-Pyrazole-4-Carbaldehyde | 358742-73-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-Chloro-1-(5-Methanesulfonyl-Pyridin-2-yl)-3-Trifluoromethyl-1H-Pyrazole-4-Carbaldehyde
• 英文别名: 1-[5-(Methylsulfonyl)-2-pyridinyl]-3-(trifluoromethyl)-5-chloro-1H-pyrazole-4-carbaldehyde；5-chloro-1-(5-methylsulfonylpyridin-2-yl)-3-(trifluoromethyl)pyrazole-4-carbaldehyde
• CAS: 358742-73-1
• 化学式: C₁₁H₇ClF₃N₃O₃S
• 分子量: 353.709
• InChiKey: ADUAMHLMMYICEF-UHFFFAOYSA-N

物化性质

• 沸点：
  508.2±50.0 °C(Predicted)
• 密度：
  1.66±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  90.3
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-Chloro-1-(5-Methanesulfonyl-Pyridin-2-yl)-3-Trifluoromethyl-1H-Pyrazole-4-Carbaldehyde 在 potassium permanganate 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 5-Chloro-1-(5-methanesulfonyl-pyridin-2-yl)-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid methyl ester
  参考文献：
  名称：

  有效合成5-烷基氨基和硫醚取代的吡唑

  摘要：

  1-（4-甲基磺酰基-2-吡啶基）-5-氯吡唑在4位上与胺亲核试剂和硫醇的亲核取代反应在温和条件下发生，以高收率提供5-烷基氨基和硫醚吡唑。

  DOI：

  10.1016/j.tetlet.2003.08.054
• 作为产物：
  描述：

  N,N-二甲基甲酰胺 、 2-(5-methanesulfonyl-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-ol 在 三氯氧磷 作用下， 反应 4.0h， 以80%的产率得到5-Chloro-1-(5-Methanesulfonyl-Pyridin-2-yl)-3-Trifluoromethyl-1H-Pyrazole-4-Carbaldehyde
  参考文献：
  名称：

  有效合成5-烷基氨基和硫醚取代的吡唑

  摘要：

  1-（4-甲基磺酰基-2-吡啶基）-5-氯吡唑在4位上与胺亲核试剂和硫醇的亲核取代反应在温和条件下发生，以高收率提供5-烷基氨基和硫醚吡唑。

  DOI：

  10.1016/j.tetlet.2003.08.054

文献信息

• Efficient fluoride-mediated synthesis of 5-alkyl amino- and ether-substituted pyrazoles
  作者：Andrei Shavnya、Subas M. Sakya、Martha L. Minich、Bryson Rast、Kristin Lundy DeMello、Burton H. Jaynes

  DOI：10.1016/j.tetlet.2005.08.022

  日期：2005.10

  Fluoride-mediated nucleophilic substitution reactions of 1-(4-methylsulfonyl (or sulfonamido)-2-pyridyl)-5-chloro-4-cyano pyrazoles with various amines and alcohols occur under mild conditions to provide the 5-alkyl amino and ether pyrazoles in moderate to high yields.

  1-（4-甲基磺酰基（或磺酰胺基）-2-吡啶基）-5-氯-4-氰基吡唑与各种胺和醇的氟化物介导的亲核取代反应在温和条件下发生，以提供5-烷基氨基和醚吡唑中等至高产。
• 5-Heteroatom substituted pyrazoles as canine COX-2 inhibitors. Part III: Molecular modeling studies on binding contribution of 1-(5-methylsulfonyl)pyrid-2-yl and 4-nitrile
  作者：Subas M. Sakya、Xinjun Hou、Martha L. Minich、Bryson Rast、Andrei Shavnya、Kristin M.L. DeMello、Hengmiao Cheng、Jin Li、Burton H. Jaynes、Donald W. Mann、Carol F. Petras、Scott B. Seibel、Michelle L. Haven

  DOI：10.1016/j.bmcl.2006.11.026

  日期：2007.2

  structure-activity relationship toward canine COX-1 and COX-2 in vitro whole blood activity of 4-hydrogen versus 4-cyano substituted 5-aryl or 5-heteroatom substituted N-phenyl versus N-2-pyridyl sulfone pyrazoles is discussed. The differences between the pairs of compounds with the 4-nitrile pyrazole derivatives having substantially improved in vitro activity are highlighted for both COX-2 and COX-1. This difference

  讨论了4-氢与4-氰基取代的5-芳基或5-杂原子取代的N-苯基与N-2-吡啶基砜吡唑对犬COX-1和COX-2体外全血活性的结构-活性关系。对于COX-2和COX-1都突出显示了化合物对与具有显着改善的体外活性的4-腈吡唑衍生物之间的差异。如我们的分子模型研究所示，活性的这种差异可能是由于4-氰​​基的氢键与Ser 530的作用所致。此外，我们的模型表明，吡啶基氮与Tyr 355的氢键键合可能对苯砜类似物的活性增加有潜在的贡献。
• Pyrazole ether derivatives as anti-inflammatory/analgesic agents
  申请人：——

  公开号：US20020058681A1

  公开（公告）日：2002-05-16

  The present invention relates to compounds of the formula 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , A, X and Y are defined as in the specification, to pharmaceutical compositions containing them and to their medicinal use. The compounds of the invention are useful in the treatment or alleviation of inflammation and other inflammation associated disorders, such as arthritis, colon cancer, and Alzheimer's disease in mammals, preferably humans, dogs, cats and livestock animals.

  本发明涉及公式1中的化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、A、X和Y的定义如规范中所述，以及含有它们的药物组合物和它们的药用。本发明的化合物在治疗或缓解炎症和其他与炎症相关的疾病方面具有用处，如关节炎、结肠癌和阿尔茨海默病等哺乳动物，最好是人类、狗、猫和家畜动物。
• 5-Heteroatom-substituted pyrazoles as canine COX-2 inhibitors: Part 2. Structure–activity relationship studies of 5-alkylethers and 5-thioethers
  作者：Subas M. Sakya、Hengmiao Cheng、Kristin M. Lundy DeMello、Andrei Shavnya、Martha L. Minich、Bryson Rast、Jason Dutra、Chao Li、Robert J. Rafka、David A. Koss、Jin Li、Burton H. Jaynes、Carl B. Ziegler、Donald W. Mann、Carol F. Petras、Scott B. Seibel、Annette M. Silvia、David M. George、Anne Hickman、Michelle L. Haven、Michael P. Lynch

  DOI：10.1016/j.bmcl.2005.11.110

  日期：2006.3

  Structure-activity relationship (SAR) studies of novel 2-[3-trifluoromethyl-5-alky](thio)ether pyrazo-1-yl]-5-methanesulfonyl pyridine derivatives for canine COX enzymes are described. The 4-cyano-5-alkyl ethers were found to have excellent potency and selectivity, whereas the 5-thioethers were potent but less selective than the ether analogs in a canine whole blood, (CWB) COX-2 assay. (C) 2006 Elsevier Ltd. All rights reserved.
• 5-Heteroatom substituted pyrazoles as canine COX-2 inhibitors. Part 1: Structure–activity relationship studies of 5-alkylamino pyrazoles and discovery of a potent, selective, and orally active analog
  作者：Subas M. Sakya、Kristin M. Lundy DeMello、Martha L. Minich、Bryson Rast、Andrei Shavnya、Robert J. Rafka、David A. Koss、Hengmiao Cheng、Jin Li、Burton H. Jaynes、Carl B. Ziegler、Donald W. Mann、Carol F. Petras、Scott B. Seibel、Annette M. Silvia、David M. George、Lisa A. Lund、Suzanne St. Denis、Anne Hickman、Michelle L. Haven、Michael P. Lynch

  DOI：10.1016/j.bmcl.2005.10.006

  日期：2006.1

  Structure-activity relationship (SAR) studies of the novel 2-[3-di and trifluoromethyl-5-alkylamino pyrazo-1-yl]-5-methanesulfonyl (SO2Me)/sulfamoyl (SO2NH2)-pyridine derivatives for canine COX enzymes are described. The studies led to the identification of 2e as lead with potent in vitro activity, selectivity, and in vivo activity in dogs and cats. (c) 2005 Elsevier Ltd. All rights reserved.