Acetic acid 4-[(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]-butyl ester | 321723-77-7

• 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: Acetic acid 4-[(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]-butyl ester
• 英文别名: 4-[(5R)-5-[(4-bromophenyl)methyl]-7-(3,5-dichlorophenyl)-5-methyl-6-oxoimidazo[1,2-a]imidazol-3-yl]sulfonylbutyl acetate
• CAS: 321723-77-7
• 化学式: C₂₅H₂₄BrCl₂N₃O₅S
• 分子量: 629.359
• InChiKey: IJHCQZSIRPACKX-RUZDIDTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Acetic acid 4-[(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]-butyl ester 在 氢溴酸 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 以84%的产率得到(R)-3-(4-Bromo-benzyl)-1-(3,5-dichloro-phenyl)-5-(4-hydroxy-butane-1-sulfonyl)-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：

  (R)-3-(4-bromobenzyl)-1-(3,5-dichlorophenyl)-3-methyl-imidazo[1,2-a]-imidazol-2-one 在 N-碘代丁二酰亚胺 、 4-甲基苯磺酸吡啶 、 环戊基溴化镁 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.92h， 生成 Acetic acid 4-[(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]-butyl ester
  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
• Second-Generation Lymphocyte Function-Associated Antigen-1 Inhibitors:  1<i>H</i>-Imidazo[1,2-α]imidazol-2-one Derivatives
  作者：Jiang-Ping Wu、Jonathan Emeigh、Donghong A. Gao、Daniel R. Goldberg、Daniel Kuzmich、Clara Miao、Ian Potocki、Kevin C. Qian、Ronald J. Sorcek、Deborah D. Jeanfavre、Kei Kishimoto、Elizabeth A. Mainolfi、Gerald Nabozny、Charline Peng、Patricia Reilly、Robert Rothlein、Rosemarie H. Sellati、Joseph R. Woska、Shirlynn Chen、Jocelyn A. Gunn、Drane O'Brien、Stephen H. Norris、Terence A. Kelly

  DOI：10.1021/jm049657b

  日期：2004.10.1

  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.