1-fluoro-2-iodo-3-(trifluoromethoxy)benzene | 866632-57-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-fluoro-2-iodo-3-(trifluoromethoxy)benzene
• 英文别名: 2-fluoro-1-iodo-6-trifluoromethoxybenzene
• CAS: 866632-57-7
• 化学式: C₇H₃F₄IO
• 分子量: 305.998
• InChiKey: ZJUKYJWQBPKNAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-fluoro-2-iodo-3-(trifluoromethoxy)benzene 在 盐酸 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 铁粉 、 sodium carbonate 、 三乙胺 作用下， 以 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 28.0h， 生成 3-[5-(2-fluoro-6-trifluoromethoxyphenyl)-1H-benzimidazol-2-yl]-1-oxa-2-azaspiro[4.5]dec-2-ene
  参考文献：
  名称：

  Design and Optimization of Benzimidazole-Containing Transient Receptor Potential Melastatin 8 (TRPM8) Antagonists

  摘要：

  Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel that is thermo-responsive to cool to cold temperatures (8-28 degrees C) and also may be activated by chemical agonists such as menthol and Antagonism of TRPM8 activation is currently under investigation for the treatment of painful conditions related to cold, such as cold allodynia and cold hyperalgesia The design, synthesis, and optimization of a class of selective TRPM8 antagonists based on a benzimidazole scaffold is described, leading to the identification of compounds that exhibited potent antagonism of TRPM8 in cell-based functional assays for human, rat, and canine TRPM8 channels Numerous compounds in the series demonstrated excellent in vivo activity in the TRPM8-selective "wet-dog shakes" (WDS) pharmacodynamic model and in the rat chronic constriction injury (CCI)-induced model of neuropathic pain Taken together the present results suggest that the in vivo antagonism of TRPM8 constitutes a viable new strategy for treating a variety of disorders associated with cold hypersensitivity, including certain types of neuropathic pain

  DOI：

  10.1021/jm101075v
• 作为产物：
  描述：

  间氟三氟甲氧基苯 在 正丁基锂 、 碘 、 sodium carbonate 、 sodium thiosulfate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.5h， 生成 1-fluoro-2-iodo-3-(trifluoromethoxy)benzene
  参考文献：
  名称：

  [EN] BIARYL SUBSTITUTED PYRAZINONES AS SODIUM CHANNEL BLOCKERS
  [FR] PYRAZINONES SUBSTITUEES PAR BIARYLE UTILISEES COMME BLOQUANTS DES CANAUX SODIQUES

  摘要：

  公式I所代表的取代联苯基吡嗪酮化合物，或其药学上可接受的盐。药物组合物包括有效量的即时化合物，单独或与一个或多个其他治疗活性化合物结合，并含有药学上可接受的载体。治疗与或由钠通道活性相关的病症的方法，例如急性疼痛、慢性疼痛、内脏疼痛、炎症性疼痛、神经痛、尿失禁、瘙痒、过敏性皮炎、癫痫、肠易激综合征、抑郁症、焦虑症、多发性硬化症和躁郁症，包括给予有效量的目前化合物，单独或与一个或多个其他治疗活性化合物结合。一种给予局部麻醉的方法包括给予即时发明的化合物的有效量，单独或与一个或多个其他治疗活性化合物结合，并含有药学上可接受的载体。

  公开号：

  WO2005097136A1

文献信息

• SUBSTITUTED BENZIMDAZOLE DERIVATIVES USEFUL AS TRPM8 RECEPTOR MODULATORS
  申请人：PLAYER Mark R.

  公开号：US20120202856A1

  公开（公告）日：2012-08-09

  The present invention is directed to benzimidazole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by TRP M8, including for example, inflammatory pain, inflammatory hyperalgesia, inflammatory hypersensitivity condition, neuropathic pain, neuropathic cold allodynia, inflammatory somatic hyperalgesia, inflammatory visceral hyperalgesia, cardiovascular disease aggravated by cold and pulmonary disease aggravated by cold.

  本发明涉及苯并咪唑衍生物，包含它们的药物组合物以及它们在治疗由TRP M8调节的疾病和症状中的应用，例如炎症性疼痛、炎症性过敏症、炎症性过敏性疾病、神经病性疼痛、神经性寒冷触痛、炎症性体部过敏症、炎症性内脏过敏症、受冷加重的心血管疾病和受冷加重的肺部疾病。
• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：GLAXO GROUP LTD

  公开号：WO2013029338A1

  公开（公告）日：2013-03-07

  Disclosed are novel retinoid-related orphan receptor gamma (RORy) modulators and their use in the treatment of diseases mediated by RORy.

  揭示了一种新型的视黄醇相关孤儿受体γ（RORγ）调节剂，以及它们在治疗由RORγ介导的疾病中的用途。
• [EN] HETEROCYCLIC BENZIMIDAZOLES AS TRPM8 MODULATORS<br/>[FR] BENZIMIDAZOLES HÉTÉROCYCLIQUES EN TANT QUE MODULATEURS DE TRPM8
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2010045166A1

  公开（公告）日：2010-04-22

  Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein W1, W2, W3, R1, R1a, R2, R2a, R3, V, Q, and X are defined herein.

  揭示了用于治疗各种疾病、综合症、症状和疾病的化合物、组合物和方法，包括疼痛。这些化合物由以下式（I）表示：其中W1、W2、W3、R1、R1a、R2、R2a、R3、V、Q和X在此处定义。
• HETEROCYCLIC BENZIMIDAZOLES AS TRPM8 MODULATORS
  申请人：Player Mark R.

  公开号：US20100093788A1

  公开（公告）日：2010-04-15

  Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula I as follows: wherein W 1 , W 2 , W 3 , R 1 , R 1a , R 2 , R 2a , R 3 , V, Q, and X are defined herein.

  本发明涉及一种用于治疗各种疾病、综合症、病况和疾患，包括疼痛的化合物、组合物和方法。这些化合物由以下公式I表示：其中W1、W2、W3、R1、R1a、R2、R2a、R3、V、Q和X在此被定义。
• Biaryl Substituted Pyrazinones as Sodium Channel Blockers
  申请人：Liang Jun

  公开号：US20080280873A1

  公开（公告）日：2008-11-13

  Biaryl substituted pyrazinone compounds represented by Formula I, or pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprise an effective amount of the instant compounds, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier. Methods of treating conditions associated with, or caused by, sodium channel activity, including, for example, acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain, urinary incontinence, itchiness, allergic dermatitis, epilepsy, irritable bowel syndrome, depression, anxiety, multiple sclerosis, and bipolar disorder, comprise administering an effective amount of the present compounds, either alone, or in combination with one or more other therapeutically active compounds. A method of administering local anesthesia comprises administering an effective amount of a compound of the instant invention, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier.

  公式I所代表的取代联苯基吡唑酮化合物，或其药学上可接受的盐。制药组合物包括有效量的本化合物，单独或与一个或多个其他治疗活性化合物结合，并含有药学上可接受的载体。治疗与钠通道活性相关或由此引起的疾病的方法，包括例如急性疼痛、慢性疼痛、内脏疼痛、炎症性疼痛、神经病理性疼痛、尿失禁、瘙痒、过敏性皮炎、癫痫、肠易激综合征、抑郁症、焦虑症、多发性硬化症和躁郁症，包括单独或与一个或多个其他治疗活性化合物结合的本化合物的有效量的给药。一种局部麻醉的给药方法包括给予本发明化合物的有效量，单独或与一个或多个其他治疗活性化合物结合，并含有药学上可接受的载体。