4-(4-(2-trifluoromethyl-benzyl)-piperazin-1-yl)-benzoic acid | 916204-12-1

• 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-(2-trifluoromethyl-benzyl)-piperazin-1-yl)-benzoic acid
• 英文别名: 4-[4-[[2-(Trifluoromethyl)phenyl]methyl]piperazin-1-yl]benzoic acid
• CAS: 916204-12-1
• 化学式: C₁₉H₁₉F₃N₂O₂
• 分子量: 364.367
• InChiKey: SZVIEHQEAADGLW-UHFFFAOYSA-N

物化性质

• 沸点：
  475.5±45.0 °C(Predicted)
• 密度：
  1.314±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  7

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-benzyl)-piperazin-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， 反应 16.0h， 生成 N-Benylpiperazine derivative, 23j
  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：

  4-(1-哌嗪基)苯甲酸乙酯 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-(2-trifluoromethyl-benzyl)-piperazin-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 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
• [EN] APOPTOSIS PROMOTERS<br/>[FR] PROMOTEURS D'APOPTOSE
  申请人：ABBOTT LAB

  公开号：WO2006127364A1

  公开（公告）日：2006-11-30

  [EN] Compounds of formula (I), in which B¹ and X¹ 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.
  [FR] L'invention concerne les composés représentés par la formule (I), dans laquelle B¹ et X¹ représentent conjointement alcylène, substituée ou non substituée par =O, et possédant une fraction CH2 non remplacée ou remplacée par CH=CH, O, NH ou N(alkyle), qui inhibe l'activité des membres de la famille de protéines antiapoptotiques Bcl-2, des compositions contenant ces composés et des méthodes permettant de traiter des pathologies au cours desquelles sont exprimés un ou plusieurs membres d'une famille de protéines antiapoptotiques.