4-(4-(1,1'-biphenyl-2-ylmethyl)-1-piperazinyl)benzoic acid | 923564-91-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(4-(1,1'-biphenyl-2-ylmethyl)-1-piperazinyl)benzoic acid
• 英文别名: 4-(4-(biphenyl-2-ylmethyl)-piperazin-1-yl)-benzoic acid；4-[4-[(2-Phenylphenyl)methyl]piperazin-1-yl]benzoic acid
• CAS: 923564-91-4
• 化学式: C₂₄H₂₄N₂O₂
• 分子量: 372.467
• InChiKey: FKZZWMHFFBVLAH-UHFFFAOYSA-N

物化性质

• 沸点：
  585.7±50.0 °C(Predicted)
• 密度：
  1.205±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 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-(2-methyl-1-(phenylthio)propan-2-ylamino)-3-nitrobenzenesulfonamide 、 4-(4-(1,1'-biphenyl-2-ylmethyl)-1-piperazinyl)benzoic acid 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 二氯甲烷 为溶剂， 反应 16.0h， 生成 4-(4-(biphenyl-2-ylmethyl)piperazin-1-yl)-N-(4-(2-methyl-1-(phenylthio)propan-2-ylamino)-3-nitrophenylsulfonyl)benzamide
  参考文献：
  名称：

  Studies Leading to Potent, Dual Inhibitors of Bcl-2 and Bcl-xL

  摘要：

  Overexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide.

  DOI：

  10.1021/jm061152t
• 作为产物：
  描述：

  2-苯基溴化甲基苯 在 lithium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 16.25h， 生成 4-(4-(1,1'-biphenyl-2-ylmethyl)-1-piperazinyl)benzoic acid
  参考文献：
  名称：

  Studies Leading to Potent, Dual Inhibitors of Bcl-2 and Bcl-xL

  摘要：

  Overexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide.

  DOI：

  10.1021/jm061152t

文献信息

• Apoptosis promoters
  申请人：Bruncko Milan

  公开号：US20070027135A1

  公开（公告）日：2007-02-01

  Compounds which inhibit the activity of anti-apoptotic family protein members, compositions containing the compounds and methods of treating diseases during which occur expression one or more than one of an anti-apoptotic family protein member are disclosed.

  本文披露了一种抑制抗凋亡家族蛋白成员活性的化合物、含有该化合物的组合物以及治疗在其中发生一个或多个抗凋亡家族蛋白成员表达的疾病的方法。
• Combination Therapy for Treating Cancer and Diagnostic Assays for Use Therein
  申请人：Shah Omar Jameel

  公开号：US20100227838A1

  公开（公告）日：2010-09-09

  The present disclosure relates to a combination of therapeutic agents for use in treating a patient a subject suffering from cancer. In addition, the present disclosure also relates to diagnostic assays useful in classification of patients for treatment with one or more therapeutic agents.

  本公开涉及一种治疗癌症患者的治疗剂组合。此外，本公开还涉及用于分类患者以接受一种或多种治疗剂治疗的诊断检测方法。
• APOPTOSIS PROMOTERS
  申请人：ABBOTT LABORATORIES

  公开号：EP1888543B1

  公开（公告）日：2012-08-01
• COMBINATION THERAPY FOR TREATING CANCER AND DIAGNOSTIC ASSAYS FOR USE THEREIN
  申请人：Abbott Laboratories

  公开号：EP2506853A1

  公开（公告）日：2012-10-10
• US7390799B2
  申请人：——

  公开号：US7390799B2

  公开（公告）日：2008-06-24