(4RS,5RS)-ethyl 1-benzyl-2,4-diphenyl-5-(pyridin-4-yl)-4,5-dihydro-1H-imidazole-4-carboxylate | 635683-09-9

• 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: (4RS,5RS)-ethyl 1-benzyl-2,4-diphenyl-5-(pyridin-4-yl)-4,5-dihydro-1H-imidazole-4-carboxylate
• 英文别名: rel-Ethyl (4R,5R)-4,5-dihydro-2,4-diphenyl-1-(phenylmethyl)-5-(4-pyridinyl)-1H-imidazole-4-carboxylate；ethyl (4S,5S)-3-benzyl-2,5-diphenyl-4-pyridin-4-yl-4H-imidazole-5-carboxylate
• CAS: 635683-09-9
• 化学式: C₃₀H₂₇N₃O₂
• 分子量: 461.563
• InChiKey: XRXVETUVIWTMSY-FIBWVYCGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.54
• 重原子数：
  35.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  54.79
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  2,4-二苯基-5(4H)-噁唑酮 在 4-二甲氨基吡啶 、 三甲基氯硅烷 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 (4RS,5RS)-ethyl 1-benzyl-2,4-diphenyl-5-(pyridin-4-yl)-4,5-dihydro-1H-imidazole-4-carboxylate
  参考文献：
  名称：

  Inhibition of the Human Proteasome by Imidazoline Scaffolds

  摘要：

  The proteasome has emerged as the primary target for the treatment of multiple myeloma. Unfortunately, nearly all patients develop resistance to competitive-type proteasome inhibitors such as bortezomib. Herein, we describe the optimization of noncompetitive proteasome inhibitors to yield derivatives that exhibit nanomolar potency (compound 49, IC50 130 nM) toward proteasome inhibition and overcome bortezomib resistance. These studies illustrate the feasibility of the development of noncompetitive proteasome inhibitors as additives and/or alternatives to competitive proteasome inhibitors.

  DOI：

  10.1021/jm400235r

文献信息

• 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.