1-[4-(methylsulfonyl)phenyl]-2-(4-methylphenyl)-4-trifluoromethyl-1H-imidazole | 177660-73-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-[4-(methylsulfonyl)phenyl]-2-(4-methylphenyl)-4-trifluoromethyl-1H-imidazole
• 英文别名: 2-(4-methylphenyl)-1-(4(methylsulfonyl)phenyl)4-trifluoromethyl-1H-imidazole；1-(4-Methanesulfonyl-phenyl)-2-p-tolyl-4-trifluoromethyl-1H-imidazole；2-(4-methylphenyl)-1-(4-methylsulfonylphenyl)-4-(trifluoromethyl)imidazole
• CAS: 177660-73-0
• 化学式: C₁₈H₁₅F₃N₂O₂S
• 分子量: 380.391
• InChiKey: PEUVGLHBVHFKPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  60.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[4-(methylsulfonyl)phenyl]-2-(4-methylphenyl)-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-(4-methylphenyl)-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：

  4-氨基茴香硫醚 在 Oxone 、 sodium hexamethyldisilazane 、 碳酸氢钠 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 水 、 异丙醇 、 甲苯 为溶剂， 反应 16.5h， 生成 1-[4-(methylsulfonyl)phenyl]-2-(4-methylphenyl)-4-trifluoromethyl-1H-imidazole
  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。
• Compositions of a cyclooxygenase-2 selective inhibitor and a sodium ion channel blocker for the treatment of pain, inflammation or inflammation mediated disorders
  申请人：Pharmacia Corporation

  公开号：US20040220187A1

  公开（公告）日：2004-11-04

  The present invention provides compositions and methods for the treatment of pain, inflammation or inflammation-mediated disorders in a subject. More particularly, the invention provides a combination therapy for the treatment of pain, inflammation or inflammation mediated disorders comprising the administration to a subject of a sodium ion channel blocker in combination with a cyclooxygenase-2 selective inhibitor.

  本发明提供了用于治疗疼痛、炎症或炎症介导性疾病的组合物和方法。更具体地，本发明提供了一种联合疗法，用于治疗疼痛、炎症或炎症介导性疾病，包括向受试者施用钠离子通道阻滞剂与环氧合酶-2选择性抑制剂的组合。
• Combination of a Cox-2 inhibitor and a DNA topoisomerase I inhibitor for treatment of neoplasia
  申请人：Masferrer L. Jaime

  公开号：US20050187172A1

  公开（公告）日：2005-08-25

  The present invention provides combinations of a Cox-2 inhibitor and a DNA topoisomerase inhibitor and methods of use thereof for preventing and/or treating neoplasia or or a neoplasia-related disorder in a subject.

  本发明提供了一种COX-2抑制剂和DNA拓扑异构酶抑制剂的组合物，以及它们的使用方法，用于预防和/或治疗受试者中的肿瘤或与肿瘤相关的疾病。
• SPIROPIPERIDINE GLYCINAMIDE DERIVATIVES
  申请人：Bissantz Caterina

  公开号：US20080171759A1

  公开（公告）日：2008-07-17

  In particular, the present invention is concerned with compounds of the general formula (I) wherein X, Y and R 1 to R 10 are as described herein. The compounds are V1a receptor antagonists. The invention also relates to the manufacture of compounds of formula I, pharmaceutical compositions containing them and their use for the treatment of anxiety and depressive disorders and other diseases.

  具体而言，本发明涉及一般式（I）中的化合物，其中X、Y和R1至R10如本文所述。这些化合物是V1a受体拮抗剂。该发明还涉及制备一般式I的化合物、含有它们的药物组合物以及它们用于治疗焦虑和抑郁症等疾病的用途。
• Method for the treatment or prevention of dermatological disorders with a cyclooxygenase-2 inhibitor alone and in combination with a dermatological treatment agent and compositions therewith
  申请人：Pulaski P. Steven

  公开号：US20050014729A1

  公开（公告）日：2005-01-20

  A method for preventing or treating dermatological disorders and dermatological disorder-related complications in a subject involves a monotherapy with a Cox-2 inhibitor or a combination therapy with a Cox-2 inhibitor and a dermatological treatment agent. Also described are therapeutic compositions comprising a Cox-2 inhibitor and a dermatological treatment agent. Pharmaceutical compositions and kits for implementing the present method are also described.

  一种预防或治疗受试者的皮肤病和与皮肤病相关并发症的方法涉及使用Cox-2抑制剂进行单独治疗或与Cox-2抑制剂和皮肤治疗剂的联合治疗。还描述了包含Cox-2抑制剂和皮肤治疗剂的治疗组合物。还描述了用于实施本方法的药物组合物和工具包。