1H-咪唑-4-羧酸,2-(4-氯苯基)-4,5-二氢-4-羟基-1-[4-(甲磺酰)苯基]-,乙基酯 | 177661-69-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 1H-咪唑-4-羧酸,2-(4-氯苯基)-4,5-二氢-4-羟基-1-[4-(甲磺酰)苯基]-,乙基酯
• 英文名称: Ethyl [2-(4-chlorophenyl)-4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4,5-dihydro-1H-imidazol-4-yl]carboxylate
• 英文别名: ethyl 2-(4-chlorophenyl)-5-hydroxy-3-(4-methylsulfonylphenyl)-4H-imidazole-5-carboxylate
• CAS: 177661-69-7
• 化学式: C₁₉H₁₉ClN₂O₅S
• 分子量: 422.889
• InChiKey: RZYSZBAASWFUBM-UHFFFAOYSA-N

物化性质

• 沸点：
  597.5±60.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1H-咪唑-4-羧酸,2-(4-氯苯基)-4,5-二氢-4-羟基-1-[4-(甲磺酰)苯基]-,乙基酯 在 氯化亚砜 、 二异丁基氢化铝 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 94.0h， 生成 2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole-4-acetonitrile
  参考文献：
  名称：

  1,2-Diarylimidazoles as Potent, Cyclooxygenase-2 Selective, and Orally Active Antiinflammatory Agents

  摘要：

  Series of 1,2-diarylimidazoles has been synthesized and found to contain highly potent and selective inhibitors of the human COX-2 enzyme. The paper describes a short synthesis of the target 1,2-diarylimidazoles starting with aryl nitriles. Different portions of the diarylimidazole (I) were modified to establish SAR. Systematic variations of the substituents in the aryl ring B have yielded very potent (IC50 = 10-100 nm) and selective (1000-12500) inhibitors of the COX-2 enzyme. The study on the influence of substituents in the imidazole ring established that a CF3 group at position 4 gives the optimum oral activity. A number of the diarylimidazoles showed excellent inhibition in the adjuvant induced arthritis model (e.g., ED50 = 0.02 mph for 22 and 34). The diarylimidazoles are also potent inhibitors of carrageenan-induced edema (ED50 = 9-30 mph) sind hyperalgesia (ED50 = 11-40 mpk). Several orally active diarylimidazoles show no GI toxicity in the rat and mouse up to 200 mpk.

  DOI：

  10.1021/jm9700225
• 作为产物：
  描述：

  4-甲磺酰基苯胺 在 三甲基铝 、 碳酸氢钠 作用下， 以 异丙醇 为溶剂， 反应 40.5h， 生成 1H-咪唑-4-羧酸,2-(4-氯苯基)-4,5-二氢-4-羟基-1-[4-(甲磺酰)苯基]-,乙基酯
  参考文献：
  名称：

  1,2-Diarylimidazoles as Potent, Cyclooxygenase-2 Selective, and Orally Active Antiinflammatory Agents

  摘要：

  Series of 1,2-diarylimidazoles has been synthesized and found to contain highly potent and selective inhibitors of the human COX-2 enzyme. The paper describes a short synthesis of the target 1,2-diarylimidazoles starting with aryl nitriles. Different portions of the diarylimidazole (I) were modified to establish SAR. Systematic variations of the substituents in the aryl ring B have yielded very potent (IC50 = 10-100 nm) and selective (1000-12500) inhibitors of the COX-2 enzyme. The study on the influence of substituents in the imidazole ring established that a CF3 group at position 4 gives the optimum oral activity. A number of the diarylimidazoles showed excellent inhibition in the adjuvant induced arthritis model (e.g., ED50 = 0.02 mph for 22 and 34). The diarylimidazoles are also potent inhibitors of carrageenan-induced edema (ED50 = 9-30 mph) sind hyperalgesia (ED50 = 11-40 mpk). Several orally active diarylimidazoles show no GI toxicity in the rat and mouse up to 200 mpk.

  DOI：

  10.1021/jm9700225

文献信息

• 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。
• US7220770B2
  申请人：——

  公开号：US7220770B2

  公开（公告）日：2007-05-22
• 1,2-Diarylimidazoles as Potent, Cyclooxygenase-2 Selective, and Orally Active Antiinflammatory Agents
  作者：Ish K. Khanna、Richard M. Weier、Yi Yu、Xiang D. Xu、Francis J. Koszyk、Paul W. Collins、Carol M. Koboldt、Amy W. Veenhuizen、William E. Perkins、Jacquelen J. Casler、Jaime L. Masferrer、Yan Y. Zhang、Susan A. Gregory、Karen Seibert、Peter C. Isakson

  DOI：10.1021/jm9700225

  日期：1997.5.1

  Series of 1,2-diarylimidazoles has been synthesized and found to contain highly potent and selective inhibitors of the human COX-2 enzyme. The paper describes a short synthesis of the target 1,2-diarylimidazoles starting with aryl nitriles. Different portions of the diarylimidazole (I) were modified to establish SAR. Systematic variations of the substituents in the aryl ring B have yielded very potent (IC50 = 10-100 nm) and selective (1000-12500) inhibitors of the COX-2 enzyme. The study on the influence of substituents in the imidazole ring established that a CF3 group at position 4 gives the optimum oral activity. A number of the diarylimidazoles showed excellent inhibition in the adjuvant induced arthritis model (e.g., ED50 = 0.02 mph for 22 and 34). The diarylimidazoles are also potent inhibitors of carrageenan-induced edema (ED50 = 9-30 mph) sind hyperalgesia (ED50 = 11-40 mpk). Several orally active diarylimidazoles show no GI toxicity in the rat and mouse up to 200 mpk.