2-(3-fluoro-4-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole | 177660-67-2

• 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-(3-fluoro-4-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole
• 英文别名: 1-[4-(methylsulfonyl)phenyl]-2-(4-methoxy-3-fluorophenyl)-4-trifluoromethyl-1H-imidazole；1h-Imidazole,2-(3-fluoro-4-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-；2-(3-fluoro-4-methoxyphenyl)-1-(4-methylsulfonylphenyl)-4-(trifluoromethyl)imidazole
• CAS: 177660-67-2
• 化学式: C₁₈H₁₄F₄N₂O₃S
• 分子量: 414.38
• InChiKey: UFSJAWLGOHKVBH-UHFFFAOYSA-N

物化性质

• 沸点：
  573.5±60.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  69.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(3-fluoro-4-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole 在 三乙基硼 、 正丁基氯化镁 、 hydroxylamine-O-sulfonic acid 作用下， 生成 4-[2-(3-fluoro-4-methoxyphenyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide
  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：

  3-氟-4-甲氧基苯腈 在 三甲基铝 、 碳酸氢钠 、 对甲苯磺酸 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 112.5h， 生成 2-(3-fluoro-4-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole
  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

• Combination therapy using COX-2 selective inhibitor and thromboxane inhibitor and compositions therefor
  申请人：——

  公开号：US20020016342A1

  公开（公告）日：2002-02-07

  The present invention provides a method for the treatment or prophylaxis of COX-2-mediated conditions in patients who are at risk of developing thromboembolic events which comprises administering to said patient a therapeutically or prophylactically effective amount of a COX-2 selective inhibitor and a cardiovascular protective amount of a thromboxane inhibitor, as well as compositions therefor.

  本发明提供了一种治疗或预防COX-2介导的病症的方法，适用于有发生血栓栓塞事件风险的患者，包括向该患者施用治疗或预防有效量的COX-2选择性抑制剂和心血管保护量的血栓素抑制剂，以及相应的组合物。
• Methods for treating or reducing the risk of pain and inflammatory disorders by administering inhibitors of activated thrombin activatable fibrinolysis inhibitor
  申请人：——

  公开号：US20030035795A1

  公开（公告）日：2003-02-20

  The invention includes methods for treating or reducing the risk of inflammation in a patient which comprises treating the patient with an inhibitor of activated thrombin activatable fibrinolysis inhibitor. Such diseases include but are not limited to nephritis, systemic lupus erythematosus, rheumatoid arthritis, glomerulonephritis, and sacoidosis. The invention includes methods for treating or reducing the risk of pain in a patient which comprises treating the patient with an inhibitor of activated thrombin activatable fibrinolysis inhibitor. In one class of these methods, the inhibitor of activated thrombin activatable fibrinolysis inhibitor is selected from the group consisting of 2-(6-amino-pyridin-3-ylmethyl)-3-butyl-succinic acid, 2-(6-amino-pyridin-3-ylmethyl)-3-phenethyl-succinic acid, 2-(6-amino-pyridin-3-ylmethyl)-3-methyl-succinic acid, 2-(6-amino-5-methyl-pyridin-3-ylmethyl)-3-[(1-benzyloxycarbonylamino-2-methyl-propyl)hydroxy-phosphinoyl]-propionic acid, 2-(6-amino-pyridin-3-ylmethyl)-3-[hydroxy-(3-phenyl-propyl)-phosphinoyl]-propionic acid, 2-(amino-pyridin-3-ylmethyl)-N-hydroxy-succinamic acid, 3-(6-amino-pyridin-3-yl)-2-mercaptomethyl-propionic acid, 2-(2-amino-pyridin-4-ylmethyl)-3-mercapto-propionic acid, 2-(6-amino-pyridin-3-ylmethyl)-2-mercaptomethyl-butyric acid, 3-(6-amino-5-methyl-pyridin-3-yl)-2-mercaptomethyl-2-methyl-propionic acid, 3-(6-amino-5-methyl-pyridin-3-yl)-2-mercaptomethyl-propionic acid, 3-(6-amino-4-methyl-pyridin-3-yl)-2-mercaptomethyl-propionic acid, and 3-(6-amino-pyridin-3-yl)-2-mercaptomethyl-butyric acid or a pharmaceutically acceptable salt thereof. The invention is also a method for treating or reducing the risk of inflammation in a patient, or treating or reducing the risk of pain, which comprises treating the patient with a composition comprising an inhibitor of activated thrombin activatable fibrinolysis inhibitor and an NSAID, e.g., a COX-2 inhibitor. Such diseases include but are not limited to nephritis, systemic lupus, erythematosus, rheumatoid arthritis, glomerulonephritis, and sacoidosis.

  该发明涉及治疗或减少患者炎症风险的方法，包括使用活化凝血酶活化的纤溶抑制剂治疗患者。这些疾病包括但不限于肾炎、系统性红斑狼疮、类风湿关节炎、肾小球肾炎和结节病。该发明还涉及治疗或减少患者疼痛风险的方法，包括使用活化凝血酶活化的纤溶抑制剂治疗患者。在这些方法的一类中，活化凝血酶活化的纤溶抑制剂选择自2-(6-氨基吡啶-3-基甲基)-3-丁基琥珀酸、2-(6-氨基吡啶-3-基甲基)-3-苯乙基琥珀酸、2-(6-氨基吡啶-3-基甲基)-3-甲基琥珀酸、2-(6-氨基-5-甲基吡啶-3-基甲基)-3-[(1-苄氧羰基氨基-2-甲基-丙基)羟基磷酰基]-丙酸、2-(6-氨基吡啶-3-基甲基)-3-[羟基-(3-苯基-丙基)-磷酰基]-丙酸、2-(氨基吡啶-3-基甲基)-N-羟基琥酰胺酸、3-(6-氨基吡啶-3-基)-2-巯基甲基丙酸、2-(2-氨基吡啶-4-基甲基)-3-巯基丙酸、2-(6-氨基吡啶-3-基甲基)-2-巯基甲基丁酸、3-(6-氨基-5-甲基吡啶-3-基)-2-巯基甲基-2-甲基丙酸、3-(6-氨基-5-甲基吡啶-3-基)-2-巯基甲基丙酸、3-(6-氨基-4-甲基吡啶-3-基)-2-巯基甲基丙酸和3-(6-氨基吡啶-3-基)-2-巯基甲基丁酸或其药学上可接受的盐。该发明还是一种治疗或减少患者炎症风险，或治疗或减少疼痛风险的方法，包括使用含有活化凝血酶活化的纤溶抑制剂和NSAID（例如COX-2抑制剂）的组合物治疗患者。这些疾病包括但不限于肾炎、系统性红斑狼疮、类风湿关节炎、肾小球肾炎和结节病。
• Use of a COX-2 inhibitor and a NK-1 receptor antagonist for treating inflammation
  申请人：——

  公开号：US20040097573A1

  公开（公告）日：2004-05-20

  The present invention provides the use of a COX-2 inhibitior and an NK-1 receptor antagonist for the treatment or prevention of inflammatory disorders.

  本发明提供了利用COX-2抑制剂和NK-1受体拮抗剂用于治疗或预防炎症性疾病的方法。
• Combination therapy for treating neurodegenerative disease
  申请人：——

  公开号：US20020115689A1

  公开（公告）日：2002-08-22

  The instant invention provides a novel drug combination comprised of an HMG-CoA reductase inhibitor and a selective COX-2 inhibitor, which is useful for treating, preventing, delaying the onset of and/or reducing the risk of developing Alzheimer's disease. One object of the instant invention is to administer the above-described combination therapy to people who do not yet show clinical signs of Alzheimer's disease, but who are at risk of developing Alzheimer's disease. These individuals may already show signs of mild cognitive impairment. Toward this end, the instant invention provides methods for preventing or reducing the risk of developing Alzheimer's by administering the above-described combination therapy to said at risk persons. Such treatment may halt or reduce the rate of further cognitive decline or, in fact, reverse cognitive decline. The present invention also provides for a method of preventing cognitive impairment or dementia, reducing the risk of cognitive decline or impairment or reducing cognitive decline or impairment resulting from stroke, stroke, cerebral ischemia or de-myelinating disorders.

  本发明提供了一种新颖的药物组合，包括HMG-CoA还原酶抑制剂和选择性COX-2抑制剂，用于治疗、预防、延缓阿尔茨海默病的发作和/或减少发展阿尔茨海默病的风险。本发明的一个目的是将上述所述的组合疗法用于尚未表现出阿尔茨海默病临床症状，但处于患阿尔茨海默病风险的人群。这些个体可能已经表现出轻度认知障碍的迹象。为此，本发明提供了通过向上述风险人群施用上述组合疗法来预防或减少发展阿尔茨海默病的方法。这种治疗可能会阻止或减少进一步的认知下降速度，或者实际上逆转认知下降。本发明还提供了一种预防认知障碍或痴呆、减少认知下降或障碍风险或减少由中风、脑卒中、脑缺血或脱髓鞘性疾病导致的认知下降或障碍的方法。
• 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。