(4R,5s)-2-(4-(叔丁基)-2-乙氧基苯基)-4,5-双(4-氯苯基)-4,5-二甲基-4,5-二氢-1H-咪唑 | 939981-35-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: (4R,5s)-2-(4-(叔丁基)-2-乙氧基苯基)-4,5-双(4-氯苯基)-4,5-二甲基-4,5-二氢-1H-咪唑
• 英文名称: (4S*,5R*)-4,5-bis(4-chlorophenyl)-2-(4-(tert-butyl)-2-ethoxy-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazole
• 英文别名: (4s,5r)-2-(4-Tert-Butyl-2-Ethoxyphenyl)-4,5-Bis(4-Chlorophenyl)-4,5-Dimethyl-4,5-Dihydro-1h-Imidazole；(4S,5R)-2-(4-tert-butyl-2-ethoxyphenyl)-4,5-bis(4-chlorophenyl)-4,5-dimethyl-1H-imidazole
• CAS: 939981-35-8
• 化学式: C₂₉H₃₂Cl₂N₂O
• 分子量: 495.492
• InChiKey: OOVOROVEJRZNDO-ISILISOKSA-N

物化性质

• 密度：
  1.15

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  33.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4R,5s)-2-(4-(叔丁基)-2-乙氧基苯基)-4,5-双(4-氯苯基)-4,5-二甲基-4,5-二氢-1H-咪唑 在 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 7.0h， 生成 1-{4-[(4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazin-1-yl}-ethanone
  参考文献：
  名称：

  Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development

  摘要：

  The p53 tumor suppressor is a potent transcription factor that plays a key role in the regulation of cellular responses to stress. It is controlled by its negative regulator MDM2, which binds directly to p53 and inhibits its transcriptional activity. MDM2 also targets p53 for degradation by the proteasome. Many tumors produce high levels of MDM2, thereby impairing p53 function. Restoration of p53 activity by inhibiting the p53-MDM2 interaction may represent a novel approach to cancer treatment. RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2. In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts.

  DOI：

  10.1021/ml4000657
• 作为产物：
  描述：

  4-叔丁基-2-乙氧基苯甲酸甲酯 在 三甲基铝 、 rochelle salt 作用下， 以 甲苯 、 水 为溶剂， 反应 3.0h， 生成 (4R,5s)-2-(4-(叔丁基)-2-乙氧基苯基)-4,5-双(4-氯苯基)-4,5-二甲基-4,5-二氢-1H-咪唑
  参考文献：
  名称：

  4,4,5,5, Tetrasubstituted imidazolines

  摘要：

  提供了一种公式I的化合物以及其药用可接受的盐和酯，其中X1，X2，R1，R2，R3，R4，R5和R6如本文所述。这些化合物作为抗癌药物表现活性。

  公开号：

  US20070129416A1

文献信息

• 4,4,5,5, tetrasubstituted imidazolines
  申请人：Hoffmann-La Roche Inc.

  公开号：US07851626B2

  公开（公告）日：2010-12-14

  There is provided a compound of formula I and the pharmaceutically acceptable salts and esters thereof wherein X1, X2, R1, R2, R3, R4, R5 and R6 are herein described. The compounds exhibit activity as anticancer agents.

  提供了一个公式I的化合物及其药学上可接受的盐和酯，其中X1、X2、R1、R2、R3、R4、R5和R6在此描述。这些化合物表现出抗癌剂的活性。
• 2,4,5-triphenyl imidazoline derivatives as inhibitors of the interaction between p53 and mdm2 proteins for use as anticancer agents
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2130822A1

  公开（公告）日：2009-12-09

  The present invention relates to compounds of formula I and the pharmaceutically acceptable salts and esters thereof wherein X1, X2, R1, R2, R3, R4, R5 and R6 are defined as in claim. The compounds exhibit activity as anticancer agents.

  本发明涉及式 I 的化合物 及其药学上可接受的盐和酯，其中 X1、X2、R1、R2、R3、R4、R5 和 R6 的定义如权利要求所述。这些化合物具有抗癌活性。
• 2,4,5-triphenyl imidazoline derivatives as inhibitors of the interaction between P53 and MDM2 proteins for use as anticancer agents
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2311814A1

  公开（公告）日：2011-04-20

  There is provided a compound of formula I and the pharmaceutically acceptable salts and esters thereof wherein X1, X2, R1, R2, R3, R4, R5 and R6 are herein described. The compounds exhibit activity as anticancer agents.

  提供了一种式 I 的化合物 及其药学上可接受的盐和酯，其中 X1、X2、R1、R2、R3、R4、R5 和 R6 如本文所述。这些化合物具有抗癌活性。
• Deconstruction of a Nutlin: Dissecting the Binding Determinants of a Potent Protein–Protein Interaction Inhibitor
  作者：David C. Fry、Charles Wartchow、Bradford Graves、Cheryl Janson、Christine Lukacs、Ursula Kammlott、Charles Belunis、Stefan Palme、Christian Klein、Binh Vu

  DOI：10.1021/ml400062c

  日期：2013.7.11

  Protein-protein interaction (PPI) systems represent a rich potential source of targets for drug discovery, but historically have proven to be difficult, particularly in the lead. identification stage. Application of the fragment-based approach may help toward success with this target class. To provide an example toward understanding the potential issues associated with such an application, we have deconstructed one of the best established protein-protein inhibitors, the Nutlin series that inhibits the interaction between MDM2 and p53, into fragments, and surveyed the resulting binding properties using heteronuclear single quantum coherence nuclear magnetic resonance (HSQC NMR), surface plasmon resonance (SPR), and X-ray crystallography. We report the relative contributions toward binding affinity for each key substituents of the Nutlin molecule and show that this series could hypothetically have been discovered via fragment approach. We find that the smallest fragment of Nutlin that retains binding accesses two subpockets of MDM2 and has a molecular weight at the high end of the range that normally defines fragments.
• 2,4,5-TRIPHENYL IMIDAZOLINE DERIVATIVES AS INHIBITORS OF THE INTERACTION BETWEEN P53 AND MDM2 PROTEINS FOR USE AS ANTICANCER AGENTS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP1960368B1

  公开（公告）日：2015-05-06