1-[4-fluoro-2-(2,2,2-trifluoroethoxy)-phenyl]-piperazine | 186387-05-3

• 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-fluoro-2-(2,2,2-trifluoroethoxy)-phenyl]-piperazine
• 英文别名: 1-[4-fluoro-2-(2,2,2-trifluoroethoxy)-phenyl]piperazine；1-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]-piperazine；1-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]piperazine
• CAS: 186387-05-3
• 化学式: C₁₂H₁₄F₄N₂O
• 分子量: 278.25
• InChiKey: ZADZZEZAWMZYEC-UHFFFAOYSA-N

物化性质

• 沸点：
  332.0±42.0 °C(Predicted)
• 密度：
  1.271±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[4-fluoro-2-(2,2,2-trifluoroethoxy)-phenyl]-piperazine 在 四丁基氟化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 3-[3-[4-[2-(2,2,2-Trifluoroethoxy)-4-fluorophenyl]piperazino]propyl]hexahydropyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis, pharmacology and pharmacokinetics of 3-(4-Aryl-piperazin-1-ylalkyl)-uracils as uroselective α1A-antagonists

  摘要：

  Predominance in the urethra and prostate of the alpha(1A)-adrenoceptor subtype, which is believed to be the receptor mediating noradrenaline induced smooth muscle contraction in these tissues, led to the preparation of alpha(1A)-selective antagonists to be tested as uroselective compounds for the treatment of benign prostatic hyperplasia. Thus, a number of selective alpha(1A)-adrenoceptor antagonists were synthesized and assayed in vitro for potency and selectivity. Dog pharmacokinetic parameters of 12 (RO700004) and its metabolite 40 (RO1104253) were established. The relative selectivity of intravenously administered 12, 40 and standard prazosin to inhibit hypogastric nerve stimulation-induced increases in intraurethral prostatic pressure versus phenylephrine-induced increases in diastolic blood pressure in anesthetized dogs was 76, 71 and 0.6, respectively. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00305-6
• 作为产物：
  描述：

  5-氟-2-硝基苯酚 在 N-甲基吡咯烷酮 、 盐酸 、 nickel boride 、 potassium carbonate 、 caesium carbonate 作用下， 以 甲醇 、 二乙二醇二甲醚 为溶剂， 生成 1-[4-fluoro-2-(2,2,2-trifluoroethoxy)-phenyl]-piperazine
  参考文献：
  名称：

  Synthesis, pharmacology and pharmacokinetics of 3-(4-Aryl-piperazin-1-ylalkyl)-uracils as uroselective α1A-antagonists

  摘要：

  Predominance in the urethra and prostate of the alpha(1A)-adrenoceptor subtype, which is believed to be the receptor mediating noradrenaline induced smooth muscle contraction in these tissues, led to the preparation of alpha(1A)-selective antagonists to be tested as uroselective compounds for the treatment of benign prostatic hyperplasia. Thus, a number of selective alpha(1A)-adrenoceptor antagonists were synthesized and assayed in vitro for potency and selectivity. Dog pharmacokinetic parameters of 12 (RO700004) and its metabolite 40 (RO1104253) were established. The relative selectivity of intravenously administered 12, 40 and standard prazosin to inhibit hypogastric nerve stimulation-induced increases in intraurethral prostatic pressure versus phenylephrine-induced increases in diastolic blood pressure in anesthetized dogs was 76, 71 and 0.6, respectively. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00305-6

文献信息

• Isoxazolecarboxamide derivatives
  申请人：Recordati, S.A., Chemical and Pharmacueticals Company

  公开号：US06365591B1

  公开（公告）日：2002-04-02

  The invention relates to novel N-(substituted phenyl)-N′-[&ohgr;-(3-substituted phenyl-4-isoxazolecarbonylamino)alkyl]piperazines, their N-oxides, and pharmaceutically acceptable salts thereof. The compounds are endowed with enhanced selectivity for alpha1-adrenergic receptors and a low activity in lowering blood pressure. The compounds are useful in the treatment of obstructive syndromes of the lower urinary tract, including benign prostatic hyperplasia (BPH), and in the treatment of lower urinary tract symptoms (LUTS) and neurogenic lower urinary tract dysfunction (NLUTD), and other conditions.

  该发明涉及新型N-(取代苯基)-N′-[ω-(3-取代苯基-4-异噁唑甲酰胺)烷基]哌嗪，它们的N-氧化物以及其药用可接受的盐。这些化合物具有增强的α1-肾上腺素受体选择性和降低血压活性较低。这些化合物在治疗下尿路梗阻综合征，包括良性前列腺增生（BPH），以及治疗下尿路症状（LUTS）和神经源性下尿路功能障碍（NLUTD）等疾病方面具有用途。
• 1-(N-phenylalkylaminoalkyl)piperazine derivatives substituted at position 2 of the phenyl ring
  申请人：Recordati S.A., Chemical and Pharmaceutical Comoany

  公开号：US20020193383A1

  公开（公告）日：2002-12-19

  The present invention is directed to novel 1-(N-phenylaminoalkyl)piperazine derivatives substituted at the position 2 of the phenyl ring. Pharmaceutical compositions comprising the compounds of the invention also are contemplated. The compounds of the present invention also are contemplated for use in treating neuromuscular dysfunction of the lower urinary tract in a mammal.

  本发明涉及在苯环的位置2被取代的新型1-(N-苯基氨基烷基)哌嗪衍生物。还考虑包括本发明化合物的药物组合物。本发明化合物还被考虑用于治疗哺乳动物下尿路神经肌肉功能障碍。
• Benzopyran derivatives
  申请人：Recordati, S.A. Chemical and Pharmaceutical Company

  公开号：US06403594B1

  公开（公告）日：2002-06-11

  The invention relates to novel benzopyran derivatives of formula I, their N-oxides and pharmaceutically acceptable salts thereof. The compounds are endowed with enhanced selectivity for alpha1-adrenergic receptors and a low activity in lowering blood pressure. The compounds are useful in the treatment of obstructive syndromes of the lower urinary tract, including benign prostatic hyperplasia (BPH), and in the treatment of lower urinary tract symptoms (LUTS), neurogenic lower urinary tract dysfunction (NLUTD), and other conditions.

  该发明涉及公式I的新型苯并吡喃衍生物，它们的N-氧化物及其药用可接受的盐。这些化合物具有增强的α1-肾上腺素受体选择性和降低血压活性较低。这些化合物在治疗下尿路梗阻综合症，包括良性前列腺增生（BPH），以及治疗下尿路症状（LUTS），神经源性下尿路功能障碍（NLUTD）和其他疾病方面是有用的。
• Process for manufacturing alpha1L-adrenoceptor antagonists
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0949250A1

  公开（公告）日：1999-10-13

  The process is useful for making compounds of the formula I: wherein R is hydrogen, methyl, or fluoro. Valuable intermediates in this process include: wherein R is hydrogen, methyl, or fluoro, and L is a leaving group.

  该过程适用于制备化合物I的公式：其中R为氢，甲基或氟。该过程中有价值的中间体包括：其中R为氢，甲基或氟，而L为一个离去基团。
• Thienopyranecarboxamide derivatives
  申请人：Recordati S.A. Chemical and Pharmaceutical Company

  公开号：US20020193381A1

  公开（公告）日：2002-12-19

  The invention is directed to compounds of Formula I: 1 wherein R is an aryl, cycloalkyl or polyhaloalkyl group, R 1 is chosen from the group consisting of alkyl, alkoxy, polyfluoroalkoxy, hydroxy and trifluoromethanesulfonyloxy; each of R 2 and R 3 independently is chosen from the group consisting of a hydrogen, halogen, alkoxy and polyfluoroalkoxy group, and n is 0, 1 or 2. The invention further provides pharmaceutical compositions comprising a compound of Formula I or a N-oxide or pharmaceutically acceptable salt of such a compound in admixture with a pharmaceutically acceptable diluent or carrier. In another aspect, the present invention is directed to methods for selectively preventing contractions of the urethra and lower urinary tract, without substantially affecting blood pressure, by administering one or more selected compounds of Formula I to a mammal (including a human) in need of such treatment in an amount or amounts effective for the particular use. In yet another aspect, the invention is directed to methods for blocking &agr; 1 receptors, by delivering to the environment of said receptors, e.g., to the extracellular medium, (or by administering to a mammal possessing said receptors) an effective amount of a compound of the invention, in this way relieving diseases associated to overactivity of said receptors. It is also an object of the present invention to provide a method of treating BPH which avoids any undue side effects due to acute hypotension (i.e., limited effects on blood pressure). It is another object of the present invention to provide pharmaceutical compositions comprising 7-oxo-7H-thieno[3,2-b] pyran compounds which are selective &agr; 1 adrenoceptor antagonists, which compositions are effective for the treatment of BPH optionally including a carrier or diluent. It is another object of the present invention to provide a method of treating BPH using 7-oxo-7H-thieno[3,2-b] pyran compounds which are selective &agr; 1 adrenoceptor antagonists. Other aspects of the invention are the use of new compounds for lowering intraocular pressure, the treatment of cardiac arrhythmia and erectile dysfunction, treatment of sympathetically mediated pain, treatment of NLUTD, and treatment of LUTS in males and females. In another aspect of the invention, compounds of the invention are administered in combination with anticholinergic compounds.

  本发明涉及式I的化合物：1其中R是芳基，环烷基或多卤代烷基，R1选择自烷基，烷氧基，多氟烷氧基，羟基和三氟甲烷磺酰氧基的群，R2和R3各自独立地选择自氢，卤素，烷氧基和多氟烷氧基的群，n为0、1或2。本发明还提供了含有式I化合物或该化合物的N-氧化物或药学上可接受的盐与药学上可接受的稀释剂或载体混合的制药组合物。在另一个方面，本发明是通过向需要此类治疗的哺乳动物（包括人类）中投与一种或多种选择的式I化合物的数量有效地选择性地预防尿道和下泌尿道收缩，而不会对血压产生实质性影响的方法。在另一个方面，本发明是通过向&agr;1受体的环境中传递有效量的本发明化合物（例如，向细胞外介质中传递或向具有该受体的哺乳动物中给药），从而缓解与该受体过度活跃相关的疾病的方法。本发明的另一个目的是提供一种治疗BPH的方法，该方法避免了由于急性低血压而产生的任何不适当的副作用（即，对血压的影响有限）。本发明的另一个目的是提供包括7-氧代-7H-噻吩[3,2-b]吡喃化合物的制药组合物，该组合物是选择性&agr;1肾上腺素受体拮抗剂，可用于治疗BPH，可选地包括载体或稀释剂。本发明的另一个目的是提供使用7-氧代-7H-噻吩[3,2-b]吡喃化合物的方法，该化合物是选择性&agr;1肾上腺素受体拮抗剂，用于治疗BPH。本发明的其他方面是使用新化合物降低眼压，治疗心律失常和勃起功能障碍，治疗交感神经介导的疼痛，治疗NLUTD以及治疗男性和女性的LUTS。在本发明的另一个方面，本发明化合物与抗胆碱药物复合使用。