1-(4-nitro-2-(trifluoromethyl)phenyl)-4-(3-(trifluoromethyl)phenyl)piperazine | 608531-87-9

• 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: 1-(4-nitro-2-(trifluoromethyl)phenyl)-4-(3-(trifluoromethyl)phenyl)piperazine
• 英文别名: 1-[4-Nitro-2-(trifluoromethyl)phenyl]-4-[3-(trifluoromethyl)phenyl]piperazine
• CAS: 608531-87-9
• 化学式: C₁₈H₁₅F₆N₃O₂
• 分子量: 419.326
• InChiKey: BIMRRHJIGBDAAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-(4-nitro-2-(trifluoromethyl)phenyl)-4-(3-(trifluoromethyl)phenyl)piperazine 在 palladium on activated charcoal 氢气 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 4.0h， 生成 1-[2-[3-(Trifluoromethyl)-4-[4-[3-(trifluoromethyl)phenyl]piperazino]phenylaminomethyl]-3-fluoro-6-nitrophenyl]piperidine-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of piperazine-based derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)

  摘要：

  Compound 2 was identified by high throughput screening as a novel PAI-1 inhibitor. Systematic optimization of the A, B, and C segments of 2 resulted in the identification of a more potent compound 39 with good oral bioavailability. The synthesis and SAR data are presented in this report. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.035
• 作为产物：
  描述：

  2-氟-5-硝基三氟甲苯 、 1-(3-三氟甲基苯基)哌嗪 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 生成 1-(4-nitro-2-(trifluoromethyl)phenyl)-4-(3-(trifluoromethyl)phenyl)piperazine
  参考文献：
  名称：

  Synthesis and biological evaluation of piperazine-based derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)

  摘要：

  Compound 2 was identified by high throughput screening as a novel PAI-1 inhibitor. Systematic optimization of the A, B, and C segments of 2 resulted in the identification of a more potent compound 39 with good oral bioavailability. The synthesis and SAR data are presented in this report. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.035

文献信息

• [EN] SUBSTITUTED PIPERAZINE ANTITHROMBOTIC PAI-1 INHIBITORS<br/>[FR] INHIBITEURS ANTITHROMBOTIQUES DE PAI-1, A BASE DE PIPERAZINE SUBSTITUEE
  申请人：SCHERING AG

  公开号：WO2003080060A1

  公开（公告）日：2003-10-02

  This invention is directed to substituted piperazine compounds of formula (I) and their pharmaceutically acceptable salts which are useful as antithrombotic agents by inhibiting plasminogen activator inhibitor-1 (PAI-1). In addition, the present invention relates to pharmaceutical compositions and their pharmaceutically acceptable salts, containing the substituted piperazine compounds, derivatives of the substituted piperazine compounds, and methods of using the compounds to treat disease-states characterized by thrombotic activity.

  本发明涉及公式（I）的取代哌嗪化合物及其药学上可接受的盐，其通过抑制纤溶酶原激活剂抑制物-1（PAI-1）而用作抗血栓剂。此外，本发明涉及含有取代哌嗪化合物、取代哌嗪化合物衍生物的药物组合物及其药学上可接受的盐，以及使用这些化合物治疗以血栓形成活动为特征的疾病状态的方法。
• Arylpiperazines for Management of Benign Prostatic Hyperplasia: Design, Synthesis, Quantitative Structure−Activity Relationships, and Pharmacokinetic Studies
  作者：Amit Sarswat、Rajeev Kumar、Lalit Kumar、Nand Lal、Smriti Sharma、Yenamandra S. Prabhakar、Shailendra K. Pandey、Jawahar Lal、Vikas Verma、Ashish Jain、Jagdamba P. Maikhuri、Diwakar Dalela、Kirti、Gopal Gupta、Vishnu L. Sharma

  DOI：10.1021/jm101163m

  日期：2011.1.13

  A series of 27 aryl/heteroaryl/aralkyl/aroyl piperazines were synthesized, and most of these compounds reduced prostate weight of mature rats by 15-47% Three compounds, 10, 12, and 18, had better activity profile (reduced prostate weight by 47%, 43%, and 39%, respectively) than the standard drug flutamide (24% reduction) QSAR suggested structures with more cyclic and branched moieties, increased topological separation of 0 and N therein, and reduced solvation connectivity index for better activity Pharmacokinetic study with compound 10 at an oral dose of 10 0 mg/kg indicated good absorption, negligible extrahepatic elimination, and rapid distribution to the target organ (prostate) but restricted entry through the blood brain barrier A 10-fold decrease in PSA and 15-fold increase in ER-beta gene expressions of human prostate cancer cells (LNCaP) by compound 10 in vitro indicated AR and ER-beta mediated actions The findings may stimulate further explorations of identified lead for the management of benign prostatic hyperplasia
• Synthesis and biological evaluation of piperazine-based derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
  作者：Bin Ye、Yuo-Ling Chou、Rushad Karanjawala、Wheeseong Lee、Shou-Fu Lu、Kenneth J. Shaw、Steven Jones、Dao Lentz、Amy Liang、Jih-Lie Tseng、Qingyu Wu、Zuchun Zhao

  DOI：10.1016/j.bmcl.2003.11.035

  日期：2004.2

  Compound 2 was identified by high throughput screening as a novel PAI-1 inhibitor. Systematic optimization of the A, B, and C segments of 2 resulted in the identification of a more potent compound 39 with good oral bioavailability. The synthesis and SAR data are presented in this report. (C) 2003 Elsevier Ltd. All rights reserved.