1-(3-溴苯基)-3-[5-氯-2-(2H-四唑-5-基)苯基]脲 | 674301-11-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-(3-溴苯基)-3-[5-氯-2-(2H-四唑-5-基)苯基]脲
• 英文名称: N-(3-bromo-phenyl)-N'-[3-chloro-6-(1H-tetrazol-5-yl)-phenyl]urea
• 英文别名: 1-(3-bromophenyl)-3-[5-chloro-2-(1H-tetrazol-5-yl-phenyl]urea；1-(3-bromophenyl)-3-[5-chloro-2-(2H-tetrazol-5-yl)phenyl]urea
• CAS: 674301-11-2
• 化学式: C₁₄H₁₀BrClN₆O
• 分子量: 393.63
• InChiKey: KPIUSQVXLDOKOG-UHFFFAOYSA-N

物化性质

• 熔点：
  197-199 °C
• 密度：
  1.778±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  95.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-4-氯苯腈 在 sodium azide 、 三乙胺盐酸盐 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 1-(3-溴苯基)-3-[5-氯-2-(2H-四唑-5-基)苯基]脲
  参考文献：
  名称：

  Bioisosteric Modifications of 2-Arylureidobenzoic Acids:  Selective Noncompetitive Antagonists for the Homomeric Kainate Receptor Subtype GluR5

  摘要：

  2-Arylureidobenzoic acids (AUBAs) have recently been presented as the first series of selective noncompetitive GluR5 antagonists. In this paper we have modified the acidic moiety of the AUBAs by introducing different acidic and neutral groups, and similarly, we have replaced the urea linker of the AUBAs with other structurally related linkers. Replacing the acid with neutral substituents led to inactive compounds in all instances, showing that an acidic moiety is necessary for activity. Replacing the carboxylic moiety in 2a with a sulfonic acid (5c) or a tetrazole ring (5d) improved the potency at GluR5 receptors (compounds 5c and 5d showed IC50 values of 1.5 and 2.0 muM, respectively, compared to compound 2a with IC50 = 4.8 muM). Compound 5c did not show improved in vivo activity in the ATPA rigidity test compared to 2a, whereas compound 5d was 4 times more potent than 2a. All compounds wherein the urea linker had been replaced showed lower or no activity. The results described extend the knowledge of structure-activity relationships for the AUBAs, and compound 5d may prove to be a good candidate for studying GluR5 receptors in vitro and in vivo.

  DOI：

  10.1021/jm030638w

文献信息

• Diarylurea derivatives and their use as chloride channel blockers
  申请人：Dahl H Bjarne

  公开号：US20060160856A1

  公开（公告）日：2006-07-20

  The present invention relates to novel diarylurea derivatives useful as chloride channel blockers. In other aspects the invention relates to the use of these compounds in a method for therapy, such as for the treatment of bone metabolic diseases, diseases responsive to modulation of the mast cell or basophil activity, diseases responsive to inhibition of angiogenesis, or sickle cell anaemia, and to pharmaceutical compositions comprising the compounds of the invention.

  本发明涉及新型二芳基脲衍生物，其作为氯离子通道阻滞剂有用。在其他方面，本发明涉及这些化合物在治疗方法中的使用，例如用于骨代谢性疾病、对肥大细胞或嗜碱性粒细胞活性调节敏感的疾病、对血管生成抑制敏感的疾病或镰刀细胞贫血的治疗，以及包含本发明化合物的制药组合物。
• Bioisosteric Modifications of 2-Arylureidobenzoic Acids:  Selective Noncompetitive Antagonists for the Homomeric Kainate Receptor Subtype GluR5
  作者：Jon Valgeirsson、Elsebet Ø. Nielsen、Dan Peters、Claus Mathiesen、Anders S. Kristensen、Ulf Madsen

  DOI：10.1021/jm030638w

  日期：2004.12.1

  2-Arylureidobenzoic acids (AUBAs) have recently been presented as the first series of selective noncompetitive GluR5 antagonists. In this paper we have modified the acidic moiety of the AUBAs by introducing different acidic and neutral groups, and similarly, we have replaced the urea linker of the AUBAs with other structurally related linkers. Replacing the acid with neutral substituents led to inactive compounds in all instances, showing that an acidic moiety is necessary for activity. Replacing the carboxylic moiety in 2a with a sulfonic acid (5c) or a tetrazole ring (5d) improved the potency at GluR5 receptors (compounds 5c and 5d showed IC50 values of 1.5 and 2.0 muM, respectively, compared to compound 2a with IC50 = 4.8 muM). Compound 5c did not show improved in vivo activity in the ATPA rigidity test compared to 2a, whereas compound 5d was 4 times more potent than 2a. All compounds wherein the urea linker had been replaced showed lower or no activity. The results described extend the knowledge of structure-activity relationships for the AUBAs, and compound 5d may prove to be a good candidate for studying GluR5 receptors in vitro and in vivo.