5-(4-bromobenzyl)-3-(3,5-dichlorophenyl)-5-methyl-2-thioxoimidazolidin-4-one | 213209-22-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 5-(4-bromobenzyl)-3-(3,5-dichlorophenyl)-5-methyl-2-thioxoimidazolidin-4-one
• 英文别名: 5-[(4-Bromophenyl)methyl]-3-(3,5-dichlorophenyl)-5-methyl-2-sulfanylideneimidazolidin-4-one
• CAS: 213209-22-4
• 化学式: C₁₇H₁₃BrCl₂N₂OS
• 分子量: 444.179
• InChiKey: WACSCAHPGXHMHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(4-bromobenzyl)-3-(3,5-dichlorophenyl)-5-methyl-2-thioxoimidazolidin-4-one 在 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 3-(4-Bromo-benzyl)-1-(3,5-dichloro-phenyl)-3-methyl-1H-imidazo[1,2-a]imidazol-2-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 、 ethyl 2-amino-2-(4-bromobenzyl)-propanoate 以 1,4-二氧六环 为溶剂， 以90%的产率得到5-(4-bromobenzyl)-3-(3,5-dichlorophenyl)-5-methyl-2-thioxoimidazolidin-4-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