3-(4-Bromo-benzyl)-1-(3,5-dichloro-phenyl)-5-iodo-3-methyl-1H-imidazo[1,2-a]imidazol-2-one | 321724-14-5

• 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: 3-(4-Bromo-benzyl)-1-(3,5-dichloro-phenyl)-5-iodo-3-methyl-1H-imidazo[1,2-a]imidazol-2-one
• 英文别名: 5-[(4-bromophenyl)methyl]-7-(3,5-dichlorophenyl)-3-iodo-5-methylimidazo[1,2-a]imidazol-6-one
• CAS: 321724-14-5
• 化学式: C₁₉H₁₃BrCl₂IN₃O
• 分子量: 577.046
• InChiKey: IVETWPTYQWRCOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  38.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  氯甲酸甲酯 、 3-(4-Bromo-benzyl)-1-(3,5-dichloro-phenyl)-5-iodo-3-methyl-1H-imidazo[1,2-a]imidazol-2-one 在 环戊基溴化镁 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 2.5h， 以38%的产率得到5-(4-bromobenzyl)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-α]imidazole-3-carboxylic acid methyl 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
• 作为产物：
  描述：

  3-(4-Bromo-benzyl)-1-(3,5-dichloro-phenyl)-3-methyl-1H-imidazo[1,2-a]imidazol-2-one 在 N-碘代丁二酰亚胺 、 4-甲基苯磺酸吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以80%的产率得到3-(4-Bromo-benzyl)-1-(3,5-dichloro-phenyl)-5-iodo-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

• [EN] DERIVATIVES OF [6,7-DIHYDRO-5H-IMIDAZO[1,2-alpha]IMIDAZOLE-3-SULFONYL]-PYRROLIDINE-2-CARBOXYLIC ACID AMIDE AS ANTI-INFLAMMATORY AGENTS<br/>[FR] DERIVES DE [6,7-DIHYDRO-5H-IMIDAZO[1,2-A]IMIDAZOLE-3-SULFONYL]-PYRROLIDINE-2 D'AMIDE D'ACIDE CARBOXYLIQUE EN TANT QU'AGENTS ANTI-INFLAMMATOIRES
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2004041273A1

  公开（公告）日：2004-05-21

  Derivatives of 6,7-dihydro-5H-imidazo[1,2-α]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid amide which exhibit good inhibitory effect upon the interaction of CAMs and Leukointegrins and are thus useful in the treatment of inflammatory disease.

  6,7-二氢-5H-咪唑[1,2-α]咪唑-3-磺酰基]-吡咯烷-2-羧酸酰胺的衍生物表现出良好的抑制作用，可用于治疗炎症性疾病。
• Alkylation of Magnesium Sulfinates:  A Direct Transformation of Functionalized Aromatic/Heteroaromatic Halides into Sulfones
  作者：Jiang-Ping Wu、Jonathan Emeigh、Xi-Ping Su

  DOI：10.1021/ol0474554

  日期：2005.3.1

  [reaction: see text] Sulfinate alkylation is one of the conventional methods for sulfone synthesis. The alkylation of magnesium sulfinates, which are easily accessible via reactions of organomagnesium intermediates with sulfur dioxide, provides a convenient route for sulfone preparation. In this communication, we report a preliminary study of the alkylation of arylmagnesium sulfinates. An application

  [反应：见正文]亚磺酸盐烷基化是砜合成的常规方法之一。亚磺酸镁的烷基化很容易通过有机镁中间体与二氧化硫的反应获得，为砜的制备提供了便利的途径。在此通讯中，我们报告了对芳基亚磺酸镁烷基化的初步研究。还描述了该反应在将官能化的芳族/杂芳族卤化物直接转化为砜中的应用。
• Derivatives of [6,7-dihydro-5H- Imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid amide
  申请人：Kelly Alfred Terence

  公开号：US20050054704A1

  公开（公告）日：2005-03-10

  Derivatives of 6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid amide which exhibit good inhibitory effect upon the interaction of CAMs and Leukointegrins and are thus useful in the treatment of inflammatory disease.

  6,7-二氢-5H-咪唑[1,2-a]咪唑-3-磺酰基-吡咯烷-2-羧酸酰胺的衍生物表现出良好的抑制作用，可以用于治疗炎症性疾病，因其可以抑制细胞粘附分子和白细胞整合素之间的相互作用。
• Synthesis of 6,7-Dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonic acid amides
  申请人：WANG Xiao-jun

  公开号：US20090088571A1

  公开（公告）日：2009-04-02

  Disclosed is a multi-step process for preparing a compound of Formula I: wherein R 1 to R 3 are as defined herein. The compounds of formula I inhibit the binding of human intercellular adhesion molecules to the Leukointegrins. As a result, these compounds are useful in the treatment of inflammatory and immune cell-mediated diseases.

  本发明揭示了一种制备式I化合物的多步骤过程：其中R1到R3如本文所定义。式I化合物抑制人类细胞间粘附分子与白细胞整合素的结合。因此，这些化合物在治疗炎症和免疫细胞介导的疾病方面是有用的。
• DERIVATIVES OF 6,7-DIHYDRO-5H-IMIDAZO[1,2-alpha]IMIDAZOLE-3-CARBOXYLIC ACID AMIDES
  申请人：Barbosa Antonio Jose del Moral

  公开号：US20110224188A1

  公开（公告）日：2011-09-15

  Derivatives of 6,7-dihydro-5H-imidazo[1,2-α]imidazole-3-carboxylic acid amide exhibit good inhibitory effect upon the interaction of CAMs and Leukointegrins and are thus useful in the treatment of inflammatory disease.

  6,7-二氢-5H-咪唑[1,2-α]咪唑-3-羧酸酰胺的衍生物表现出良好的抑制CAMs和白细胞整合素相互作用的效果，因此在治疗炎症性疾病方面具有用处。