4-[4-(2-trifluoromethyl-benzylidene)-piperidin-1-yl]-benzoic acid | 916204-06-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-[4-(2-trifluoromethyl-benzylidene)-piperidin-1-yl]-benzoic acid
• 英文别名: 4-[4-[[2-(Trifluoromethyl)phenyl]methylene]-1-piperidinyl]benzoic acid；4-[4-[[2-(trifluoromethyl)phenyl]methylidene]piperidin-1-yl]benzoic acid
• CAS: 916204-06-3
• 化学式: C₂₀H₁₈F₃NO₂
• 分子量: 361.364
• InChiKey: AVKJJAVBZHUZOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-[[(R)-3-二甲基氨基-1-[(苯基硫基)甲基]丙基]氨基]-3-硝基苯磺酰胺 、 4-[4-(2-trifluoromethyl-benzylidene)-piperidin-1-yl]-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， 生成 4-Piperidinebenzylidene derivative, 10e
  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-(三氟甲基)苄溴 在 sodium hydroxide 、 dimsyl sodium 作用下， 以 1,4-二氧六环 、 二甲基亚砜 、 甲苯 为溶剂， 反应 8.17h， 生成 4-[4-(2-trifluoromethyl-benzylidene)-piperidin-1-yl]-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-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 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。
• APOPTOSIS PROMOTERS
  申请人：ABBOTT LABORATORIES

  公开号：EP1888543B1

  公开（公告）日：2012-08-01
• Apoptosis Promoters
  申请人：Elmore Steven W.

  公开号：US20080194691A1

  公开（公告）日：2008-08-14

  Compounds of formula (I), in which B 1 and X 1 are together alkylene which is unsubstituted or substituted with ═O and having one CH2 moiety unreplaced or replaced with CH═CH, O, NH or N(alkyl), which inhibit the activity of antiapoptotic Bcl-2 family protein members, compositions containing the compounds and methods of treating diseases during which are expressed one or more than one of an anti-apoptotic family protein member are disclosed.
• US7777076B2
  申请人：——

  公开号：US7777076B2

  公开（公告）日：2010-08-17