4-[4-(3,3-二苯基丙-2-烯基)哌嗪-1-基]苯甲酸 | 916204-11-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-[4-(3,3-二苯基丙-2-烯基)哌嗪-1-基]苯甲酸
• 英文名称: 4-[4-(3,3-diphenyl-allyl)-piperazin-1-yl]-benzoic acid
• 英文别名: 4-[4-(3,3-Diphenylprop-2-en-1-yl)piperazin-1-yl]benzoic acid；4-[4-(3,3-diphenylprop-2-enyl)piperazin-1-yl]benzoic acid
• CAS: 916204-11-0
• 化学式: C₂₆H₂₆N₂O₂
• 分子量: 398.505
• InChiKey: CNHQQFVSXKBISR-UHFFFAOYSA-N

物化性质

• 沸点：
  618.5±55.0 °C(Predicted)
• 密度：
  1.178±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[4-(3,3-二苯基丙-2-烯基)哌嗪-1-基]苯甲酸 、 4-(5-nitro-1,3-dioxo-6-thiomorpholino-1H-benzo[de]isoquinolin-2(3H)-yl)benzenesulfonamide 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 4-(4-(3,3-diphenylallyl)piperazin-1-yl)-N-((4-(5-nitro-1,3-dioxo-6-thiomorpholino-1H-benzo[de]isoquinolin-2(3H)-yl)phenyl)sulfonyl)benzamide
  参考文献：
  名称：

  Novel Naphthalimide-Benzoic Acid Conjugates as Potential Apoptosis-Inducing Agents: Design, Synthesis, and Biological Activity

  摘要：

  A series of novel naphthalimide derivatives with 4‐[4‐(3,3‐diphenylallyl)piperazin‐1‐yl]benzoic acid as side chain were designed and synthesized. Their antitumor activities were evaluated against a variety of cancer cell lines in vitro. Preliminary results showed that most of the derivatives had cytotoxic activity comparable with that of amonafide, with IC50 values of 10−6–10−5 m. Interestingly, compound 12e had the unique antitumor activity against MCF‐7 among the cancer cell lines tested. More importantly, flow cytometric analysis indicated that compared with amonafide, the target compounds could effectively induce G2/M arrest and progress to apoptosis in HL‐60 cells after double staining with annexin V–FITC and propidium iodide. The present work provided a novel class of naphthalimide‐based derivatives with potential apoptosis‐inducing and improved antitumor activity for further optimization.

  DOI：

  10.1111/j.1747-0285.2011.01232.x
• 作为产物：
  描述：

  4-(1-哌嗪基)苯甲酸乙酯 在 lithium hydroxide 、 sodium triacetoxyborohydride 作用下， 以 四氢呋喃 、 甲醇 、 水 、 1,2-二氯乙烷 为溶剂， 反应 2.0h， 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：

  Design, Synthesis, and Computational Studies of Inhibitors of Bcl-X_L

  摘要：

  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.

  DOI：

  10.1021/ja0650347

文献信息

• APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES
  申请人：Kunzer Aaron R.

  公开号：US20100184766A1

  公开（公告）日：2010-07-22

  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治疗表达抗凋亡Bcl-2蛋白疾病的方法。
• Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
  申请人：Hexamer Laura A.

  公开号：US08426422B2

  公开（公告）日：2013-04-23

  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.

  本发明揭示了一种抑制抗凋亡Bcl-2蛋白活性的化合物，包含该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。
• 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。
• Novel naphthalimide derivatives as potential apoptosis-inducing agents: Design, synthesis and biological evaluation
  作者：Aibin Wu、Yufang Xu、Xuhong Qian、Jin Wang、Jianwen Liu

  DOI：10.1016/j.ejmech.2009.07.011

  日期：2009.11

  A series of novel naphthalimide derivatives with flexible alkyl/aryl moieties were designed and synthesized. Their antitumor activities were evaluated against HeLa, A549, P388, HL-60, MCF-7, HCT-8 and A375 cancer cell lines in vitro. The preliminary results showed that most of the derivatives had comparable antitumor activities over Amonafide with the IC50 values of 10(-6) to 10(-5) M. More importantly, flow cytometric analysis indicated that the derivatives could effectively induce G(2)/M arrest and progress to apoptosis in HL-60 cell line after double staining with annexin V-FITC and propidium iodide. The present work provided a novel class of naphthalimide-based derivatives with potent apoptosis-inducing and antitumor activities for further optimization. (C) 2009 Elsevier Masson SAS. All rights reserved.
• APOPTOSIS PROMOTERS
  申请人：ABBOTT LABORATORIES

  公开号：EP1888543B1

  公开（公告）日：2012-08-01