(R)-5-(3-Amino-propane-1-sulfonyl)-3-(4-bromo-benzyl)-1-(3,5-dichloro-phenyl)-3-methyl-1H-imidazo[1,2-a]imidazol-2-one | 321721-24-8

• 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: (R)-5-(3-Amino-propane-1-sulfonyl)-3-(4-bromo-benzyl)-1-(3,5-dichloro-phenyl)-3-methyl-1H-imidazo[1,2-a]imidazol-2-one
• 英文别名: (5R)-3-(3-aminopropylsulfonyl)-5-[(4-bromophenyl)methyl]-7-(3,5-dichlorophenyl)-5-methylimidazo[1,2-a]imidazol-6-one
• CAS: 321721-24-8
• 化学式: C₂₂H₂₁BrCl₂N₄O₃S
• 分子量: 572.31
• InChiKey: APECBVUSSLUJRS-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  乙酰氯 、 (R)-5-(3-Amino-propane-1-sulfonyl)-3-(4-bromo-benzyl)-1-(3,5-dichloro-phenyl)-3-methyl-1H-imidazo[1,2-a]imidazol-2-one 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以73%的产率得到N-{3-[(R)-5-(4-Bromo-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-propyl}-acetamide
  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：

  (R)-methanesulfonic acid 3-[5-(4-bromobenzyl)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-α]imidazolyl-3-sulfonyl]propyl ester 在 氨 作用下， 以 乙醇 为溶剂， 以66.5%的产率得到(R)-5-(3-Amino-propane-1-sulfonyl)-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

文献信息

• US7550494B2
  申请人：——

  公开号：US7550494B2

  公开（公告）日：2009-06-23