2',6'-difluoro-3-nitro-[1,1'-biphenyl]-4-amine | 1259026-54-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2',6'-difluoro-3-nitro-[1,1'-biphenyl]-4-amine
• 英文别名: 2',6'-difluoro-3-nitro-biphenyl-4-ylamine；4-(2,6-difluorophenyl)-2-nitroaniline
• CAS: 1259026-54-4
• 化学式: C₁₂H₈F₂N₂O₂
• 分子量: 250.205
• InChiKey: VJJALHQCAXDDDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2',6'-difluoro-3-nitro-[1,1'-biphenyl]-4-amine 在 盐酸 、 铁粉 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 10.0h， 生成 3-[5-(2,6-difluorophenyl)-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：

  1-溴-2,6-二氟苯 、 4-氨基-3-硝基苯硼酸 在 四(三苯基膦)钯 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 生成 2',6'-difluoro-3-nitro-[1,1'-biphenyl]-4-amine
  参考文献：
  名称：

  SUBSTITUTED BENZIMDAZOLE DERIVATIVES USEFUL AS TRPM8 RECEPTOR MODULATORS

  摘要：

  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。

  公开号：

  US20120202856A1

文献信息

• [EN] SUBSTITUTED BENZIMDAZOLE DERIVATIVES USEFUL AS TRPM8 RECEPTOR MODULATORS<br/>[FR] DÉRIVÉS DE BENZIMIDAZOLE SUBSTITUÉ UTILES COMME MODULATEURS DU RÉCEPTEUR TRPM8
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2012109100A1

  公开（公告）日：2012-08-16

  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.