dl-(4S,5S)-1-benzyl-4-methyl-2,5-diphenyl-4,5-dihydro-1H-imidazole-4-carboxylic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: dl-(4S,5S)-1-benzyl-4-methyl-2,5-diphenyl-4,5-dihydro-1H-imidazole-4-carboxylic acid
• 英文别名: 1-benzyl-4-methyl-2,5-diphenyl-4,5-dihydro-1H-imidazole-4-carboxylic acid；DL-(3S,4S)-1-benzyl-4-methyl-2,5-diphenyl-4,5-dihydro-1H-imidazole-4-carboxylic acid；(4S,5S)-3-benzyl-5-methyl-2,4-diphenyl-4H-imidazole-5-carboxylic acid
• 化学式: C₂₄H₂₂N₂O₂
• 分子量: 370.451
• InChiKey: DBWDTHQDQGJSGW-URXFXBBRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  dl-(4S,5S)-1-benzyl-4-methyl-2,5-diphenyl-4,5-dihydro-1H-imidazole-4-carboxylic acid 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以79%的产率得到dl-(4S,5S)-1-benzyl-4-methyl-2,5-diphenyl-4,5-dihydro-1H-imidazole-4-yl-methanol
  参考文献：
  名称：

  硅介导的 1,3-偶极环加成多组分合成高取代咪唑啉

  摘要：

  报道了高度官能化咪唑啉的非对映选择性多组分合成。硅介导的 1,3 偶极环加成原位产生的 munchnone 与亚胺导致形成高度取代的咪唑啉。咪唑啉具有四点多样性和两个立体中心，环加成反应适用于芳基、烷基、酰基和杂环取代。

  DOI：

  10.1055/s-2003-40196
• 作为产物：
  描述：

  苯甲醛 在 三甲基氯硅烷 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 6.0h， 生成 dl-(4S,5S)-1-benzyl-4-methyl-2,5-diphenyl-4,5-dihydro-1H-imidazole-4-carboxylic acid
  参考文献：
  名称：

  Azomethine ylide mediated inversion of configuration of quaternary imidazoline carbon: converting trans- to its cis-imidazolines

  摘要：

  An efficient synthetic methodology of converting trans-4,5-diaryl-2-imidazolines to the corresponding cis-4,5-diaryl-2-imidazolines has been developed. This methodology features mild reaction conditions and a simple one-pot two-step procedure. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2011.07.022

文献信息

• NF-kB inhibitors and uses threreof
  申请人：Board of Trustees of MICHIGAN STATE UNIVERSITY

  公开号：US20030232998A1

  公开（公告）日：2003-12-18

  A new class of imidazolines as 4-position acids or esters with very potent anti-inflammatory as well as antimicrobial activity is described. The synthesis of these imidazolines includes a multicomponent reaction applicable to a combinatorial synthetic approach. The combination of these two key characteristics provides an effective therapeutic drug in the treatment of septic shock as well as many other inflammatory (arthritis and asthma) and infectious disorders. The use of this novel class of non-steroidal agents as anti-inflammatory agents (for the treatment of asthma, etc.), antibacterial agents, and antiseptic agents is described. The compounds are also useful in the treatment of tumors (such as cancers). The imidazolines are potent inhibitors of the transcription factor NF-&kgr;B as well as potent activity against the Gram (+) bacterium. The compositions are also useful for treating autoimmune diseases and for inhibiting rejection of organ and tissue transplants.

  描述了一类新型的咪唑啉化合物，作为4-位置酸或酯具有非常强大的抗炎和抗菌活性。这些咪唑啉的合成包括一种适用于组合合成方法的多组分反应。这两个关键特性的结合提供了一种有效的治疗药物，可用于治疗败血症休克以及许多其他炎症（如关节炎和哮喘）和传染性疾病。描述了这一新型非甾体类抗炎药物（用于治疗哮喘等）、抗菌药物和防腐剂的用途。这些化合物还可用于治疗肿瘤（如癌症）。咪唑啉是转录因子NF-κB的强效抑制剂，对革兰氏阳性细菌也具有强效活性。这些组合物还可用于治疗自身免疫性疾病，并抑制器官和组织移植的排斥。
• Multi-substituted imidazolines and method of use thereof
  申请人：Board of Trustees of MICHIGAN STATE UNIVERSITY

  公开号：US20030232870A1

  公开（公告）日：2003-12-18

  A new class of imidazolines as 4-position acids or esters with very potent anti-inflammatory as well as antimicrobial activity is described. The synthesis of these imidazolines includes a multicomponent reaction applicable to a combinatorial synthetic approach. The combination of these two key characteristics provides an effective therapeutic drug in the treatment of septic shock as well as many other inflammatory (arthritis and asthma) and infectious disorders. The use of this novel class of non-steroidal agents as anti-inflammatory agents (for the treatment of asthma etc.), antibacterial agents and antiseptic agents is described. The compounds are also useful in the treatment of tumors (such as cancers). The imidazolines are potent inhibitors of the transcription factor NF-&kgr;B as well as potent activity against the Gram (+) bacterium B. subtillus and B. cereus with MIC values in the range of 50 &mgr;m/mL.

  描述了一类新型的咪唑啉，作为4位酸或酯，具有非常强大的抗炎和抗微生物活性。这些咪唑啉的合成包括适用于组合合成方法的多组分反应。这两个关键特性的结合提供了一种有效的治疗药物，可用于治疗脓毒性休克以及许多其他炎症（关节炎和哮喘）和传染性疾病。描述了这种新型非甾体类抗炎药物（用于哮喘等的治疗）、抗菌药物和防腐剂的用途。这些化合物还可用于肿瘤的治疗（如癌症）。咪唑啉是转录因子NF-κB的强效抑制剂，并对革兰氏阳性细菌B. subtillus和B. cereus具有强大的活性，MIC值在50 μm/mL的范围内。
• NF-kappaB inhibitors and uses thereof
  申请人：Tepe J. Jetze

  公开号：US20050020586A1

  公开（公告）日：2005-01-27

  A new class of imidazolines as 4-position esters with very potent anti-inflammatory as well as antimicrobial activity is described. The synthesis of these imidazolines includes a multicomponent reaction applicable to a combinatorial synthetic approach. The combination of these two key characteristics provides an effective therapeutic drug in the treatment of septic shock as well as many other inflammatory (arthritis and asthma) and infectious disorders. The use of this novel class of non-steroidal agents as anti-inflammatory agents (for the treatment of asthma, etc.), antibacterial agents, and antiseptic agents is described. The compounds are also useful in the treatment of tumors (such as cancers). The imidazolines are potent inhibitors of the transcription factor NF-kB as well as potent activity against the Gram (+) bacterium. The compositions are also useful for treating autoimmune diseases and for inhibiting rejection of organ and tissue transplants.

  描述了一类新型的4-位置酯基咪唑啉类化合物，具有非常强效的抗炎和抗微生物活性。这些咪唑啉类化合物的合成包括一种适用于组合合成方法的多组分反应。这两种关键特性的结合提供了一种有效的治疗药物，可用于治疗脓毒性休克以及许多其他炎症性（如关节炎和哮喘）和传染性疾病。描述了这种新型的非甾体类药物作为抗炎药物（用于治疗哮喘等）、抗菌药物和防腐剂的用途。这些化合物还可用于治疗肿瘤（如癌症）。这些咪唑啉类化合物是转录因子NF-kB的有效抑制剂，对革兰氏阳性细菌也具有强效活性。这些化合物还可用于治疗自身免疫性疾病以及抑制器官和组织移植的排斥反应。
• Diastereochemical Diversity of Imidazoline Scaffolds via Substrate Controlled TMSCl Mediated Cycloaddition of Azlactones
  作者：Vasudha Sharma、Jetze J. Tepe

  DOI：10.1021/ol052118w

  日期：2005.10.1

  We report herein a trimethylsilyl chloride mediated substrate controlled 1,3-dipolar cycloaddition for the diastereoselective synthesis of either syn- or anti-imidazolines. This method provides scaffolds with four points of diversity and control over two stereocenters.
• Structural–activity relationship study of highly-functionalized imidazolines as potent inhibitors of nuclear transcription factor-κB mediated IL-6 production
  作者：Daljinder K. Kahlon、Theresa A. Lansdell、Jason S. Fisk、Jetze J. Tepe

  DOI：10.1016/j.bmc.2009.03.002

  日期：2009.4

  We herein describe the synthesis and anti-inflammatory properties of a small library of imidazoline-based NF-kappa B inhibitors. The structure-activity relationship of various substituents on an imidazoline core structure was evaluated for the ability to inhibit NF-kappa B mediated IL-6 production. Optimization of the scaffolds was pursued by correlating luciferase-based NF-kappa B reporter assays with inhibition of IL-6 production in IL-1 beta stimulated human blood. Several derivatives were found to inhibit NF-kappa B mediated IL-6 production in the nanomolar range in IL-1 beta stimulated human blood. (C) 2009 Elsevier Ltd. All rights reserved.