1-(4-氟苯基)-4-(1-哌嗪基)-1-丁酮 | 2560-31-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-(4-氟苯基)-4-(1-哌嗪基)-1-丁酮
• 中文别名: 1-(4-氟-苯基)-4-哌嗪-1-基-丁-1-酮
• 英文名称: 1-(4-fluorophenyl)-4-piperazinylbutanone
• 英文别名: 1-(4-fluoro-phenyl)-4-piperazin-1-yl-butan-1-one；4-(p-fluorophenyl)-4-oxobutylpiperazine；1-3-(4-fluorobenzoyl)propyl piperazine；1-(4-Fluorophenyl)-4-(piperazin-1-yl)butan-1-one；1-(4-fluorophenyl)-4-piperazin-1-ylbutan-1-one
• CAS: 2560-31-8
• 化学式: C₁₄H₁₉FN₂O
• mdl: MFCD00738861
• 分子量: 250.316
• InChiKey: POWKNAVDGFNMSG-UHFFFAOYSA-N

物化性质

• 熔点：
  69-71 °C
• 沸点：
  385.5±32.0 °C(Predicted)
• 密度：
  1.099±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-氟苯基)-4-(1-哌嗪基)-1-丁酮 在 PPA 、 sodium carbonate 、 potassium iodide 作用下， 以 various solvent(s) 为溶剂， 反应 25.0h， 生成 3-[[4-[4-(4-fluorophenyl)-4-oxobutyl]piperazin-1-yl]methyl]-3,4-dihydro-2H-naphthalen-1-one
  参考文献：
  名称：

  Synthesis and antidopaminergic activity of some 3-(aminomethyl)tetralones as analogs of butyrophenone

  摘要：

  Starting from beta-benzoylpropionic acid was synthesized 3-(aminomethyl)tetralones in which the amino substituent was 4-(N-piperazinyl)-p-fluorobutyrophenone (14), 4-benzoylpiperidine (15), 4-hydroxy-4-phenylpiperidine (16) or 4-(o-methoxyphenyl)piperazine (17). The possible dopamine antagonist activity of these compounds was investigated in both ''in vitro'' and ''in vivo'' experiments. These compounds potently inhibited [H-3]spiperone binding to D2 striatal receptors and moderately inhibited [H-3]SCH-23390 binding to D1 striatal receptors (K(i)s in the nanomolar and micromolar ranges, respectively). Apomorphine-induced stereotypies and amphetamine group toxicity were antagonized, to different extents, by the compounds under study, with a potency similar to that of haloperidol. Interestingly, no catalepsy was observed after administration of the new compounds (2-8 mg/kg). The most active compounds ''in vivo'' 14 and 15 possessed two butyrophenone pharmacophores. However, the tetralone moiety appeared not critical for their antidopaminergic activity, since all target compounds were less active than haloperidol. These studies provide a pharmacological basis for future research on these new compounds devoid of cataleptogenic activity.

  DOI：

  10.1021/jm00111a046
• 作为产物：
  描述：

  1-(3-[2-(4-氟苯基)-[1,3]二氧杂烷-2-基]丙基)哌嗪 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 1-(4-氟苯基)-4-(1-哌嗪基)-1-丁酮
  参考文献：
  名称：

  Synthesis and antidopaminergic activity of some 3-(aminomethyl)tetralones as analogs of butyrophenone

  摘要：

  Starting from beta-benzoylpropionic acid was synthesized 3-(aminomethyl)tetralones in which the amino substituent was 4-(N-piperazinyl)-p-fluorobutyrophenone (14), 4-benzoylpiperidine (15), 4-hydroxy-4-phenylpiperidine (16) or 4-(o-methoxyphenyl)piperazine (17). The possible dopamine antagonist activity of these compounds was investigated in both ''in vitro'' and ''in vivo'' experiments. These compounds potently inhibited [H-3]spiperone binding to D2 striatal receptors and moderately inhibited [H-3]SCH-23390 binding to D1 striatal receptors (K(i)s in the nanomolar and micromolar ranges, respectively). Apomorphine-induced stereotypies and amphetamine group toxicity were antagonized, to different extents, by the compounds under study, with a potency similar to that of haloperidol. Interestingly, no catalepsy was observed after administration of the new compounds (2-8 mg/kg). The most active compounds ''in vivo'' 14 and 15 possessed two butyrophenone pharmacophores. However, the tetralone moiety appeared not critical for their antidopaminergic activity, since all target compounds were less active than haloperidol. These studies provide a pharmacological basis for future research on these new compounds devoid of cataleptogenic activity.

  DOI：

  10.1021/jm00111a046

文献信息

• 1-3-(4-Fluorobenzoyl)propyl-4-substituted phenoxy ethyl piperazine
  申请人：Kali-Chemie Aktiengesellschaft

  公开号：US03966735A1

  公开（公告）日：1976-06-29

  Piperazine derivatives having the following general formula ##EQU1## in which n is 2 or 3, X is an oxy or thio radical, and A and B are each a radical of the group consisting of phenyl radicals containing at most three substituents of the group consisting of nitro, trifluoromethyl, halogen, cyano, and alkyl, alkoxy, alkylthio, acyl, and alkylsulfonyl radicals containing at most 6 carbon atoms, and similar cycloalkyl and cycloalkylalkyl radicals, their acid addition salts, processes for their production, and pharmaceutical compositions containing the same. The compounds have a very favorable action on the central nervous system and are effective agents for the treatment of anxiety states, psychoses, emotional disturbances, aggressive tendencies, and can be used generally for the treatment of psychiatrically disturbed and psychoneurotic patients.

  哌嗪衍生物具有以下一般公式##EQU1##其中n为2或3，X为氧基或硫基，A和B分别为苯基基团，最多含有三个取代基，所述取代基包括硝基、三氟甲基、卤素、氰基、烷基、烷氧基、烷硫基、酰基和最多含有6个碳原子的烷基磺酰基基团，以及类似的环烷基和环烷基烷基基团，它们的酸盐，其生产方法，以及含有它们的药物组合物。这些化合物对中枢神经系统有非常有利的作用，是治疗焦虑状态、精神病、情绪障碍、攻击性倾向的有效药物，并且通常可用于治疗精神紊乱和神经症患者。
• Syntheses of Novel Diphenyl Piperazine Derivatives and Their Activities as Inhibitors of Dopamine Uptake in the Central Nervous System
  作者：Makoto Kimura、Tomoko Masuda、Koji Yamada、Masaki Mitani、Nobuo Kubota、Nobuyuki Kawakatsu、Kenichi Kishii、Masato Inazu、Yuji Kiuchi、Katsuji Oguchi、Takayuki Namiki

  DOI：10.1016/s0968-0896(03)00061-0

  日期：2003.4

  A new series of diphenyl piperazine derivatives containing the phenyl substituted aminopropanol moiety, which were modified at sites between the diphenyl and piperazine moieties, was prepared and evaluated for dopamine transporter binding affinity with [(3)H]GBR12935 in rat striatal membranes. These synthesized compounds showed apparent dopamine transporter binding affinities (IC(50)<30 nM) and some

  制备了一系列新的含有苯基取代的氨基丙醇部分的二苯基哌嗪衍生物，该衍生物在二苯基和哌嗪部分之间的位点进行了修饰，并评估了大鼠纹状体膜中多巴胺转运蛋白与[（3）H] GBR12935的结合亲和力。这些合成的化合物表现出明显的多巴胺转运蛋白结合亲和力（IC（50）<30 nM），其中一些活性与被称为强力多巴胺摄取抑制剂的GBR12909活性相当，显示出具有纳摩尔范围IC（50）值的活性。其中，使用体内脑微透析评估了大鼠纹状体中1- [4,4-双（4-氟苯基）丁基] -4- [2-羟基-3-（苯基氨基）丙基]哌嗪2的细胞外多巴胺水平。腹膜内给药2（0.01、0.03或0。1 mmol / kg）引起大鼠纹状体透析液中多巴胺水平的剂量依赖性增加。2引起的多巴胺水平的最大增加大于GBR12909。这些新颖的二苯基哌嗪衍生物的药理数据表明，该化合物在中枢神经系统中具有有效的多巴胺摄取抑制活性。
• Tricyclic potential neuroleptics: 2-chloro-11-[4-(4-fluoroaralkyl)piperazino]-10,11-dihydrodibenzo[b,f]thiepins and related compounds
  作者：Václav Bártl、Antonín Dlabač、Miroslav Protiva

  DOI：10.1135/cccc19803182

  日期：——

  Alkylation of 1-ethoxycarbonylpiperazine with 4-fluorobenzyl bromide, 2-(4-fluorophenyl)ethyl bromide and 4,4-bis(4-fluorophenyl)butyl bromide gave the carbamates IIa, IIb and IIf. Two further similar compounds (IIc, IId) were obtained by reactions of 1-(2-chloroethyl)-4-ethoxycarbonylpiperazine with 4-fluorophenol, and with 4-fluorothiophenol, respectively. Hydrolysis of carbamates IIa-f resulted in piperazine derivatives IIIa-f affording the title compounds by substitution reactions with 2,11-dichloro-10,11-dihydrodibenzo[b,f]thiepin. Out of the compounds prepared only the fluorophenethyl derivative Ib and the fluorobenzoylpropyl derivative Ie maintain the neuroleptic character, i.e. clear central depressant and cataleptic activity.

  用4-氟苄基溴、2-(4-氟苯基)乙基溴和4,4-双(4-氟苯基)丁基溴对1-乙氧羰基哌嗪进行烷基化反应，得到了羰酸酯IIa、IIb和IIf。通过1-(2-氯乙基)-4-乙氧羰基哌嗪与4-氟苯酚和4-氟硫酚反应，还得到了两种类似的化合物(IIc、IId)。羰酸酯IIa-f的水解产生哌嗪衍生物IIIa-f，通过与2,11-二氯-10,11-二氢二苯并[b,f]噻吩的取代反应得到了目标化合物。制备的化合物中，只有氟苯乙基衍生物Ib和氟苯甲酰丙基衍生物Ie保持了神经类药物的特性，即具有明显的中枢抑制和僵直活性。
• Novel 1-piperazinecarboxamide derivatives
  申请人：——

  公开号：US04935419A1

  公开（公告）日：1990-06-19

  A series of 1-piperazinecarboxamide derivatives of the following formula: ##STR1## The compounds of the present invention are neuropharmacological agents intended for the treatment of mental disorders, such as psychoses and depression.

  以下是一系列1-哌嗪基甲酰胺衍生物的化学式：##STR1## 本发明的化合物是神经药理学药物，旨在治疗精神障碍，如精神病和抑郁症。
• 2-Chloro-7-fluoro- and 2-chloro-3,7-difluoro-11-[4-(4-fluoroaralkyl)piperazino]-10,11-dihydrodibenzo-[b,f]thiepins and related compounds; Long acting tranquillizers
  作者：Václav Bártl、Jiřina Metyšová、Miroslav Protiva

  DOI：10.1135/cccc19810141

  日期：——

  Substitution reactions of 2,11-dichloro-7-fluoro-(seriesa) and 2,11-dichloro-3,7-difluoro-10,11-dihydrodibenzo[b,f]thiepin (seriesb) with 1-(4-fluorobenzyl)piperazine, 1-[2-(4-fluorophenyl)-ethyl]piperazine, 1-[2-(4-fluorophenoxy)ethyl]piperazine, 1-[2-(4-fluorophenylthio)ethyl]piperazine, 1-[3-(4-fluorobenzoyl)propyl]piperazine and 1-[4,4-bis-(4-fluorophenyl)butyl]piperazine gave the title compounds Ia,b-VIa,b. Compounds of the series a are little toxic, have low cataleptic activity and display a relatively high central depressant activity, being fully developed only after 4 h and persisting until the 3rd-7th day after the oral administration. Compounds of series b are less active and the protracted depressant effects are shown only by substances IIIb and Vb.

  2,11-二氯-7-氟-(系列a)和2,11-二氯-3,7-二氟-10,11-二氢二苯并[b,f]噻吩（系列b）与1-(4-氟苯基)哌嗪、1-[2-(4-氟苯基)乙基]哌嗪、1-[2-(4-氟苯氧基)乙基]哌嗪、1-[2-(4-氟苯基硫基)乙基]哌嗪、1-[3-(4-氟苯甲酰基)丙基]哌嗪和1-[4,4-双(4-氟苯基)丁基]哌嗪发生取代反应，得到标题化合物Ia,b-VIa,b。系列a化合物毒性较小，具有低的瘫痪活性，并表现出相对较高的中枢抑制活性，仅在口服后4小时后完全发展，并持续到第3-7天。系列b化合物活性较低，仅IIIb和Vb物质显示出持久的抑制效果。