2-methyl-3-[1-[4-[[2-(trimethylsilyl)-ethyl]sulfonyl]phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine | 177662-71-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-methyl-3-[1-[4-[[2-(trimethylsilyl)-ethyl]sulfonyl]phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine
• 英文别名: 2-methyl-3-[1-[4-[[2-(trimethylsilyl)ethyl]sulfonyl]phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine；2-methyl-3.-[1-[4-[[2(trimethylsilyl)ethyl]sulfonyl]phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine；trimethyl-[2-[4-[2-(2-methylpyridin-3-yl)-4-(trifluoromethyl)imidazol-1-yl]phenyl]sulfonylethyl]silane
• CAS: 177662-71-4
• 化学式: C₂₁H₂₄F₃N₃O₂SSi
• 分子量: 467.587
• InChiKey: VMHYYHSKVXDXNX-UHFFFAOYSA-N

物化性质

• 沸点：
  585.9±60.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.37
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  73.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-methyl-3-[1-[4-[[2-(trimethylsilyl)-ethyl]sulfonyl]phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine 在 四丁基氟化铵 、 sodium acetate 、 hydroxylamine-O-sulfonic acid 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 4-[2-(2-methyl-pyridin-3-yl)-4-trifluoromethyl-imidazol-1-yl]-benzenesulfonamide
  参考文献：
  名称：

  Selective Cyclooxygenase-2 Inhibitors:  Heteroaryl Modified 1,2-Diarylimidazoles Are Potent, Orally Active Antiinflammatory Agents

  摘要：

  A series of heteroaryl modified 1,2-diarylimidazoles has been synthesized and found to be potent and highly selective (1000-9000-fold) inhibitors of the human COX-2. 3-Pyridyl derived COX-2 selective inhibitor (25) exhibited excellent activity in acute (carrageenan induced paw edema, ED50 = 5.4 mg/kg) and chronic (adjuvant induced arthritis, ED50 = 0.25 mg/kg) models of inflammation. The relatively long half-life of 25 in rat and dog prompted investigation of the pyridyl and other heteroaromatic systems containing potential metabolic functionalities. A number of substituted pyridyl and thiazole containing compounds (e.g., 44, 46, 54, 76, and 78) demonstrated excellent oral activity in every efficacy model evaluated. Several orally active diarylimidazoles exhibited desirable pharmacokinetics profiles and showed no CI toxicity in the rat up to 100 mg/kg in both acute and chronic models. The paper describes facile and practical syntheses of the targeted diarylimidazoles. The structure-activity relationships and antiinflammatory properties of a series of diarylimidazoles are discussed.

  DOI：

  10.1021/jm0000719
• 作为产物：
  描述：

  3-氰基-2-甲基吡啶 在 Oxone 、 sodium hexamethyldisilazane 、 碳酸氢钠 、 对甲苯磺酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 水 、 异丙醇 、 甲苯 为溶剂， 反应 17.5h， 生成 2-methyl-3-[1-[4-[[2-(trimethylsilyl)-ethyl]sulfonyl]phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine
  参考文献：
  名称：

  Selective Cyclooxygenase-2 Inhibitors:  Heteroaryl Modified 1,2-Diarylimidazoles Are Potent, Orally Active Antiinflammatory Agents

  摘要：

  A series of heteroaryl modified 1,2-diarylimidazoles has been synthesized and found to be potent and highly selective (1000-9000-fold) inhibitors of the human COX-2. 3-Pyridyl derived COX-2 selective inhibitor (25) exhibited excellent activity in acute (carrageenan induced paw edema, ED50 = 5.4 mg/kg) and chronic (adjuvant induced arthritis, ED50 = 0.25 mg/kg) models of inflammation. The relatively long half-life of 25 in rat and dog prompted investigation of the pyridyl and other heteroaromatic systems containing potential metabolic functionalities. A number of substituted pyridyl and thiazole containing compounds (e.g., 44, 46, 54, 76, and 78) demonstrated excellent oral activity in every efficacy model evaluated. Several orally active diarylimidazoles exhibited desirable pharmacokinetics profiles and showed no CI toxicity in the rat up to 100 mg/kg in both acute and chronic models. The paper describes facile and practical syntheses of the targeted diarylimidazoles. The structure-activity relationships and antiinflammatory properties of a series of diarylimidazoles are discussed.

  DOI：

  10.1021/jm0000719

文献信息

• 1,2-aryl and heteroaryl substituted imidazolyl compounds for the
  申请人：GD Searle & Co

  公开号：US05616601A1

  公开（公告）日：1997-04-01

  A class of imidazolyl compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula I: ##STR1## wherein R.sup.1 -R.sup.6 are as described in the specification; or a pharmaceutically-acceptable salt thereof.

  描述了一类咪唑基化合物，用于治疗炎症和与炎症相关的疾病。特别感兴趣的化合物由以下式I定义：##STR1##其中R.sup.1 -R.sup.6如规范中所述；或其药用盐。
• Heterocyclo-substituted imidazoles for the treatment of inflammation
  申请人：Khanna K. Ish

  公开号：US20050096368A1

  公开（公告）日：2005-05-05

  A class of imidazolyl compounds is described for use in treating inflammation. Compounds of particular interest are defined by formula (V), wherein R 3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, heteroaralkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocyclocarbonyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy. aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl; wherein R 4 is a radical selected from hydrido, alkyl and halo; and wherein R 13 and R 14 are independently selected from aryl and heterocyclo, wherein R 13 and R 14 are optionally substituted at a substitutable position with one or more radicals independently selected from alkylsulfonyl, aminosulfonyl, halo, alkylthio, alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino and nitro; provided at least one of R 13 and R 14 is aryl substituted with alkylsulfonyl or aminosulfonyl; or a pharmaceutically-acceptable salt thereof.

  描述了一类咪唑基化合物用于治疗炎症。特别感兴趣的化合物由公式（V）定义，其中R3是从氢基，烷基，卤代烷基，芳基烷基，杂环烷基，杂环芳基烷基，酰基，氰基，烷氧基，烷硫基，烷硫基烷基，烷基磺酰基，环烷硫基，环烷硫基烷基，环烷磺酰基，环烷磺酰基烷基，卤代烷基磺酰基，芳基磺酰基，卤代基，羟基烷基，烷氧基烷基，烷基羧酰基，芳基羧酰基，芳基烷基羧酰基，杂环羧酰基，氰基烷基，氨基烷基，烷基氨基烷基，N-芳基氨基烷基，N-烷基-N-芳基氨基烷基，羧基烷基，烷氧基羧酰基烷基，烷氧基羧酰基，卤代烷基羧酰基，羧基，氨基羧酰基，烷基氨基羧酰基，杂环芳基烷氧基烷基，杂环芳基氧基烷基，杂环芳基硫基烷基，芳基硫醇基烷基，芳基氧基烷基，芳基硫醇基，芳基氧基。芳基烷硫基烷基，芳基烷氧基烷基，芳基和杂环芳基;其中R4是从氢基，烷基和卤代基中选择的基团;并且R13和R14分别从芳基和杂环芳基中选择，其中R13和R14在可取代位置上可以选择一个或多个基团独立地选择，包括烷基磺酰基，氨基磺酰基，卤代基，烷硫基，烷基，氰基，羧基，烷氧基羧酰基，卤代烷基，羟基，烷氧基，羟基烷基，烷氧基烷基，卤代烷氧基，氨基，烷基氨基，芳基氨基和硝基; 提供至少一个R13和R14被烷基磺酰基或氨基磺酰基取代的芳基，或其药学上可接受的盐。
• A process for the preparation of 4-¬2-(aryl or heterocyclo)-1H-imidazol-1-yl|benzenesulfonamides
  申请人：G.D. Searle LLC

  公开号：EP1193265B1

  公开（公告）日：2006-11-29
• Selective Cyclooxygenase-2 Inhibitors:  Heteroaryl Modified 1,2-Diarylimidazoles Are Potent, Orally Active Antiinflammatory Agents
  作者：Ish K. Khanna、Yi Yu、Renee M. Huff、Richard M. Weier、Xiangdong Xu、Francis J. Koszyk、Paul W. Collins、J. Nita Cogburn、Peter C. Isakson、Carol M. Koboldt、Jaime L. Masferrer、William E. Perkins、Karen Seibert、Amy W. Veenhuizen、Jinhua Yuan、Dai-Chang Yang、Yan Y. Zhang

  DOI：10.1021/jm0000719

  日期：2000.8.1

  A series of heteroaryl modified 1,2-diarylimidazoles has been synthesized and found to be potent and highly selective (1000-9000-fold) inhibitors of the human COX-2. 3-Pyridyl derived COX-2 selective inhibitor (25) exhibited excellent activity in acute (carrageenan induced paw edema, ED50 = 5.4 mg/kg) and chronic (adjuvant induced arthritis, ED50 = 0.25 mg/kg) models of inflammation. The relatively long half-life of 25 in rat and dog prompted investigation of the pyridyl and other heteroaromatic systems containing potential metabolic functionalities. A number of substituted pyridyl and thiazole containing compounds (e.g., 44, 46, 54, 76, and 78) demonstrated excellent oral activity in every efficacy model evaluated. Several orally active diarylimidazoles exhibited desirable pharmacokinetics profiles and showed no CI toxicity in the rat up to 100 mg/kg in both acute and chronic models. The paper describes facile and practical syntheses of the targeted diarylimidazoles. The structure-activity relationships and antiinflammatory properties of a series of diarylimidazoles are discussed.