4-[4-(3,3-diphenyl-allyl)-piperazin-1-yl]-benzoic acid ethyl ester | 921195-79-1

• 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: 4-[4-(3,3-diphenyl-allyl)-piperazin-1-yl]-benzoic acid ethyl ester
• 英文别名: ethyl 4-(4-(3,3-diphenylallyl)piperazin-1-yl)benzoate；ethyl 4-[4-(3,3-diphenylprop-2-enyl)piperazin-1-yl]benzoate
• CAS: 921195-79-1
• 化学式: C₂₈H₃₀N₂O₂
• 分子量: 426.558
• InChiKey: RBANAKFPFACLJP-UHFFFAOYSA-N

物化性质

• 沸点：
  593.1±50.0 °C(Predicted)
• 密度：
  1.122±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[4-(3,3-diphenyl-allyl)-piperazin-1-yl]-benzoic acid ethyl ester 在 lithium hydrochloride monohydrate 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 16.0h， 生成 4-[4-(3,3-二苯基丙-2-烯基)哌嗪-1-基]苯甲酸
  参考文献：
  名称：

  APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES

  摘要：

  揭示了一种抑制抗凋亡Bcl-2蛋白活性的化合物，含有这些化合物的组合物以及治疗在其中表达抗凋亡Bcl-2蛋白的疾病的方法。

  公开号：

  US20100184750A1
• 作为产物：
  描述：

  β-苯基肉桂醛 、 4-(1-哌嗪基)苯甲酸乙酯 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 4-[4-(3,3-diphenyl-allyl)-piperazin-1-yl]-benzoic acid ethyl ester
  参考文献：
  名称：

  APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES

  摘要：

  揭示了一种抑制抗凋亡Bcl-2蛋白活性的化合物，含有这些化合物的组合物以及治疗在其中表达抗凋亡Bcl-2蛋白的疾病的方法。

  公开号：

  US20100184750A1

文献信息

• Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
  申请人：Abbott Laboratories

  公开号：US08338466B2

  公开（公告）日：2012-12-25

  Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.

  本发明涉及一些化合物，其抑制抗凋亡Bcl-2蛋白的活性，包含这些化合物的组合物以及治疗在其中表达抗凋亡Bcl-2蛋白的疾病的方法。
• APOPTOSIS-INDUCING AGENT FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES
  申请人：AbbVie Inc.

  公开号：US20160002187A1

  公开（公告）日：2016-01-07

  Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.

  公开了一种抑制抗凋亡Bcl-2蛋白活性的化合物，包含这些化合物的组合物以及用于治疗表达抗凋亡Bcl-2蛋白的疾病的方法。
• Design, Synthesis, and Computational Studies of Inhibitors of Bcl-X_L
  作者：Cheol-Min Park、Tetsuro Oie、Andrew M. Petros、Haichao Zhang、Paul M. Nimmer、Rodger F. Henry、Steven W. Elmore

  DOI：10.1021/ja0650347

  日期：2006.12.1

  One of the primary objectives in the design of protein inhibitors is to shape the three-dimensional structures of small molecules to be complementary to the binding site of a target protein. In the course of our efforts to discover potent inhibitors of Bcl-2 family proteins, we found a unique folded conformation adopted by tethered aromatic groups in the ligand that significantly enhanced binding affinity to Bcl-X-L. This finding led us to design compounds that were biased by nonbonding interactions present in a urea tether to adopt this bioactive, folded motif. To characterize the key interactions that induce the desired conformational bias, a series of substituted N,N'-diarylureas were prepared and analyzed using X-ray crystallography and quantum mechanical calculations. Stabilizing pi-stacking interactions and destabilizing steric interactions were predicted to work in concert in two of the substitution patterns to promote the bioactive conformation as a global energy minimum and result in a high target binding affinity. Conversely, intramolecular hydrogen bonding present in the third substitution motif promotes a less active, extended conformer as the energetically favored geometry. These findings were corroborated when the inhibition constant of binding to Bcl-X-L was determined for fully elaborated analogues bearing these structural motifs. Finally, we obtained the NMR solution structure of the disubstituted N,N'-diarylurea bound to Bcl-X-L demonstrating the folded conformation of the urea motif engaged in extensive pi-interactions with the protein.
• US8338466B2
  申请人：——

  公开号：US8338466B2

  公开（公告）日：2012-12-25
• US8426422B2
  申请人：——

  公开号：US8426422B2

  公开（公告）日：2013-04-23