N-[[4-[(4-bromophenyl)methyl]-1-(3,5-dichlorophenyl)-4-methyl-5-oxoimidazol-2-yl]amino]formamide | 796872-04-3

• 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: N-[[4-[(4-bromophenyl)methyl]-1-(3,5-dichlorophenyl)-4-methyl-5-oxoimidazol-2-yl]amino]formamide
• CAS: 796872-04-3
• 化学式: C₁₈H₁₅BrCl₂N₄O₂
• 分子量: 470.153
• InChiKey: HTASBOSJWBANBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  73.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[[4-[(4-bromophenyl)methyl]-1-(3,5-dichlorophenyl)-4-methyl-5-oxoimidazol-2-yl]amino]formamide 在 4 A molecular sieve 、 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 6.0h， 以82%的产率得到5-(4-Bromo-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-7H-imidazo[2,1-c][1,2,4]triazol-6-one
  参考文献：
  名称：

  Second-Generation Lymphocyte Function-Associated Antigen-1 Inhibitors:  1H-Imidazo[1,2-α]imidazol-2-one Derivatives

  摘要：

  A novel class of lymphocyte function-associated antigen-1 (LFA-1) inhibitors is described. Discovered during the process to improve the physicochemical and metabolic properties of BIRT377 (1, Figure 1), a previously reported hydantoin-based LFA-1 inhibitor, these compounds are characterized by an imidazole-based 5,5-bicyclic scaffold, the 1,3,3-trisubstituted 1H-imidazo [1,2-alpha]imidazol-2-one (i.e. structure 3). The structure-activity relationship (SAR) shows that electron-withdrawing groups at C-5 on the imidazole ring benefit potency and that oxygen-containing functional groups attached to a C-5-sulfonyl or sulfonamide group further improve potency. This latter gain in potency is attributed to the interaction(s) of the functionalized sulfonyl/sulfonamide groups with the protein, likely polar-polar in nature, as suggested by SAR data. X-ray studies revealed that these bicyclic inhibitors bind to the I-domain of LFA-1 in a pattern similar to that of compound 1.

  DOI：

  10.1021/jm049657b
• 作为产物：
  描述：

  3,5-二氯异硫氰酸苯酯 在 Oxone 、 sodium hydroxide 、 乙二胺四乙酸 、 碳酸氢钠 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 丙酮 为溶剂， 反应 18.67h， 生成 N-[[4-[(4-bromophenyl)methyl]-1-(3,5-dichlorophenyl)-4-methyl-5-oxoimidazol-2-yl]amino]formamide
  参考文献：
  名称：

  Second-Generation Lymphocyte Function-Associated Antigen-1 Inhibitors:  1H-Imidazo[1,2-α]imidazol-2-one Derivatives

  摘要：

  A novel class of lymphocyte function-associated antigen-1 (LFA-1) inhibitors is described. Discovered during the process to improve the physicochemical and metabolic properties of BIRT377 (1, Figure 1), a previously reported hydantoin-based LFA-1 inhibitor, these compounds are characterized by an imidazole-based 5,5-bicyclic scaffold, the 1,3,3-trisubstituted 1H-imidazo [1,2-alpha]imidazol-2-one (i.e. structure 3). The structure-activity relationship (SAR) shows that electron-withdrawing groups at C-5 on the imidazole ring benefit potency and that oxygen-containing functional groups attached to a C-5-sulfonyl or sulfonamide group further improve potency. This latter gain in potency is attributed to the interaction(s) of the functionalized sulfonyl/sulfonamide groups with the protein, likely polar-polar in nature, as suggested by SAR data. X-ray studies revealed that these bicyclic inhibitors bind to the I-domain of LFA-1 in a pattern similar to that of compound 1.

  DOI：

  10.1021/jm049657b