1-<6-fluoro-3-(4-fluorophenyl)indan-1-yl>piperazine | 344551-41-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 1-<6-fluoro-3-(4-fluorophenyl)indan-1-yl>piperazine
• 英文别名: 1-(3-(4'-fluorophenyl)-6-fluoro-1-indanyl)piperazine；1-[6-fluoro-3-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-yl]piperazine
• CAS: 344551-41-3
• 化学式: C₁₉H₂₀F₂N₂
• 分子量: 314.378
• InChiKey: QODVJLDATQKBIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-<6-fluoro-3-(4-fluorophenyl)indan-1-yl>piperazine 在 lithium aluminium tetrahydride 作用下， 以 乙醚 、 甲苯 为溶剂， 反应 0.5h， 生成 1-[(1R,3R)-6-Fluoro-3-(4-fluoro-phenyl)-indan-1-yl]-4-((E)-3-phenyl-allyl)-piperazine
  参考文献：
  名称：

  Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans

  摘要：

  A series of 1-piperazino-3-phenylindans was synthesized and tested for neuroleptic and thymoleptic activity. Neuroleptic activity was found only in trans racemates and was associated with one of the enantiomers only. The potent and long-acting neuroleptic compound trans-4-[3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-yl]-1-piperazineethanol (Lu 18-012, tefludazine) was developed by systematic variation of structural components. Thymoleptic activity was optimized, especially with respect to dopamine-uptake inhibition. No geometrical stereoselectivity was found with regard to dopamine-uptake inhibition, but a high enantioselectivity could be demonstrated for both cis and trans racemates. The most potent compounds were 1-piperazino-3-(3,4-dichlorophenyl)indans with IC50 values of about 2nM for inhibition of dopamine uptake.

  DOI：

  10.1021/jm00361a002
• 作为产物：
  描述：

  2-溴-4-三氟甲基苯甲醛 在 哌啶 、 sodium tetrahydroborate 、 正丁基锂 、 氯化亚砜 、 硫酸 、 magnesium 、 溶剂黄146 作用下， 以 甲醇 、 乙醚 、 正己烷 、 甲苯 、 丁酮 为溶剂， 反应 31.0h， 生成 1-<6-fluoro-3-(4-fluorophenyl)indan-1-yl>piperazine
  参考文献：
  名称：

  Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans

  摘要：

  A series of 1-piperazino-3-phenylindans was synthesized and tested for neuroleptic and thymoleptic activity. Neuroleptic activity was found only in trans racemates and was associated with one of the enantiomers only. The potent and long-acting neuroleptic compound trans-4-[3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-yl]-1-piperazineethanol (Lu 18-012, tefludazine) was developed by systematic variation of structural components. Thymoleptic activity was optimized, especially with respect to dopamine-uptake inhibition. No geometrical stereoselectivity was found with regard to dopamine-uptake inhibition, but a high enantioselectivity could be demonstrated for both cis and trans racemates. The most potent compounds were 1-piperazino-3-(3,4-dichlorophenyl)indans with IC50 values of about 2nM for inhibition of dopamine uptake.

  DOI：

  10.1021/jm00361a002

文献信息

• Antihypertensive activity in a series of 1-piperazino-3-phenylindans with potent 5-HT2-antagonistic activity
  作者：Klaus P. Boegesoe、Joern Arnt、Vita Boeck、A. Vibeke Christensen、John Hyttel、Klaus Gundertofte Jensen

  DOI：10.1021/jm00120a003

  日期：1988.12

  enantiomers with 1R,3S absolute configuration. 1S,3R enantiomers inhibited the uptake of dopamine and norepinephrine in vitro. The compound with the best antihypertensive activity was (+)-(1R,3S)-1-[2-[4-[3-(4-fluorophenyl)-1-indanyl]-1- piperazinyl]ethyl]-2-imidazolidinone (Lu 21-098, irindalone). Its pharmacological profile resembled that of the standard compound ketanserin. There was a close structural

  合成了一系列反式-1-哌嗪子-3-苯基茚满，其目的是用周围的5-羟基色胺（5-HT2）拮抗作用来取代它们建立的抗精神病药。在茚满环中具有未取代或氟取代的6-位并且具有通过乙烯链连接至哌嗪环的五元或六元杂环的化合物，满足了该目的。一些化合物在有意识的，自发性高血压大鼠（SHR）中具有有效的降压活性。在成髓大鼠中，它们拮抗5-HT诱导的升压作用，其剂量比拮抗去氧肾上腺素的升压作用所需的剂量低100-1000倍。该作用是立体选择性的，并且与具有1R，3S绝对构型的对映异构体有关。1S，3R对映体在体外抑制多巴胺和去甲肾上腺素的摄取。降压活性最好的化合物是（+）-（1R，3S）-1- [2- [4- [3-（4-氟苯基）-1-茚满基] -1-哌嗪基]乙基] -2-咪唑啉酮（Lu 21-098，irindalone）。它的药理特性与标准化合物酮色林相似。酮色林和伊立酮之间存在紧密的结构对应关系，这种
• Indane derivatives, pharmaceutical compositions thereof and method of
  申请人：Kefalas A/S

  公开号：US04443448A1

  公开（公告）日：1984-04-17

  The present invention relates to novel 1-piperazino-3-phenyl-indane derivatives which have pronounced psychopharmacological activity such as neuroleptic activity, analgesic activity, antidepressant activity and, at the same time, a low degree of undesired side-effects, methods for the preparation of said indane derivatives, pharmaceutical compositions containing same, and methods for the treatment of psychic disorders, such as psychoses and depressions and pain, by administering a therapeutically active amount of one of said derivatives to a living animal body, including human beings.

  本发明涉及新的1-哌嗪基-3-苯基-茚衍生物，具有明显的精神药理学活性，如神经阻滞活性、镇痛活性、抗抑郁活性，并且同时具有低程度的不良副作用，制备该茚衍生物的方法、含有该茚衍生物的制药组合物，以及通过向生物体，包括人类，施用所述衍生物之一的治疗有效量来治疗精神障碍，如精神病和抑郁症以及疼痛的方法。
• Indane derivatives, methods of their preparation and compositions containing them
  申请人：KEFALAS A/S

  公开号：EP0035363A1

  公开（公告）日：1981-09-09

  1-Piperazino-3-phenylindane derivatives of the formula: wherein R1, R2, R3 and R4 are as defined in Claim 1, and their pharmaceutically acceptable acid addition salts. The compounds are prepared by the usual methods for analogous compounds. They have been found to have psychopharmacological and analgetic activity. Pharmaceutical compositions containing the compounds have been disclosed.

  式中 R1、R2、R3 和 R4 如权利要求 1 所定义的 1-哌嗪基-3-苯基茚满衍生物及其药学上可接受的酸加成盐。 这些化合物是用类似化合物的常规方法制备的。 它们具有精神药理学和镇痛活性。 含有这些化合物的药物组合物已被公开。
• BOGESO, K. P., J. MED. CHEM., 1983, 26, N 7, 935-947
  作者：BOGESO, K. P.

  DOI：——

  日期：——
• US4443448A
  申请人：——

  公开号：US4443448A

  公开（公告）日：1984-04-17