4-(4-氯苯基)-1-哌嗪丁胺 | 92328-97-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 4-(4-氯苯基)-1-哌嗪丁胺
• 英文名称: 4-(4-chlorophenyl)-1-piperazinebutanamine
• 英文别名: 1-(4-Chlorphenyl)-4-(4-aminobutyl)-piperazin；4-[4-(4-chloro-phenyl)-piperazin-1-yl]-butylamine；4-[4-(4-Chlorophenyl)piperazin-1-yl]butan-1-amine
• CAS: 92328-97-7
• 化学式: C₁₄H₂₂ClN₃
• mdl: MFCD11164473
• 分子量: 267.802
• InChiKey: QDSZTKVTBFVIQK-UHFFFAOYSA-N

物化性质

• 沸点：
  407.9±45.0 °C(Predicted)
• 密度：
  1.120±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-氯苯基)-1-哌嗪丁胺 在 盐酸羟胺 、 sodium acetate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 为溶剂， 生成
  参考文献：
  名称：

  Design, synthesis and evaluation of bitopic arylpiperazinephenyl-1,2,4-oxadiazoles as preferential dopamine D3 receptor ligands

  摘要：

  The dopamine D3 receptor (D3R) was proposed as a therapeutic target for drug development to treat drug abuse and addiction and neuropsychiatric disorders. Several D3R-selective modulators over the dopamine D2 receptor (D2R) can avoid extrapyramidal symptoms (EPS) and hyperprolactinemia. However, few biased D3R ligands were identified or showed a narrow range of selectivity at the D3R over D2R because of their high sequence homology. Herein, we designed, synthesized and evaluated the binding affinity of a series of bitopic ligands: arypiperazine-phenyl-1,2,4-oxadiazoles. Compound 9e center dot HCl was the most potent and selective D3R modulator among these bitopic ligands. Molecular modeling revealed that D3R selectivity depends on the divergence of secondary binding pocket (SBP) in D3R and D2R. Specifically, non-conserved Tyr36, EL1 especially non-conserved Thr92 and Gly94, and EL2 Val180, Cys181 and Ser182 of D3R may contribute to D3R specificity over D2R. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.002
• 作为产物：
  描述：

  1-(4-氯苯基)哌嗪 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 4-(4-氯苯基)-1-哌嗪丁胺
  参考文献：
  名称：

  Design, synthesis and evaluation of bitopic arylpiperazinephenyl-1,2,4-oxadiazoles as preferential dopamine D3 receptor ligands

  摘要：

  The dopamine D3 receptor (D3R) was proposed as a therapeutic target for drug development to treat drug abuse and addiction and neuropsychiatric disorders. Several D3R-selective modulators over the dopamine D2 receptor (D2R) can avoid extrapyramidal symptoms (EPS) and hyperprolactinemia. However, few biased D3R ligands were identified or showed a narrow range of selectivity at the D3R over D2R because of their high sequence homology. Herein, we designed, synthesized and evaluated the binding affinity of a series of bitopic ligands: arypiperazine-phenyl-1,2,4-oxadiazoles. Compound 9e center dot HCl was the most potent and selective D3R modulator among these bitopic ligands. Molecular modeling revealed that D3R selectivity depends on the divergence of secondary binding pocket (SBP) in D3R and D2R. Specifically, non-conserved Tyr36, EL1 especially non-conserved Thr92 and Gly94, and EL2 Val180, Cys181 and Ser182 of D3R may contribute to D3R specificity over D2R. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.002

文献信息

• Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D3 receptor ligands
  作者：Peng-Jen Chen、Michelle Taylor、Suzy A. Griffin、Armaghan Amani、Hamed Hayatshahi、Kenneth Korzekwa、Min Ye、Robert H. Mach、Jin Liu、Robert R. Luedtke、John C. Gordon、Benjamin E. Blass

  DOI：10.1016/j.bmcl.2019.07.020

  日期：2019.9

  As part of our on-going effort to explore the role of dopamine receptors in drug addiction and identify potential novel therapies for this condition, we have a identified a series of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide D3 ligands. Members of this class are highly selective for D3 versus D2, and we have identified two compounds (13g and 13r) whose rat in vivo IV pharmacokinetic

  为了探索多巴胺受体在药物成瘾中的作用并确定针对这种情况的潜在新疗法，我们正在进行的工作包括确定一系列N-（4-（4-苯基哌嗪-1-基）丁基）-4-（噻吩-3-基）苯甲酰胺D 3配体。该类别的成员对D 3和D 2具有高度选择性，并且我们鉴定了两种化合物（13g和13r），它们的大鼠体内IV药代动力学特性表明它们适用于评估物质使用失调的体内功效模型。
• An Interactive SAR Approach to Discover Novel Hybrid Thieno Probes as Ligands for D2-Like Receptors with Affinities in the Subnanomolar Range
  作者：Mohamed A. O. Abdel-Fattah、Jochen Lehmann、Ashraf H. Abadi

  DOI：10.1002/cbdv.201300204

  日期：2013.12

  ,3-dione derivatives was synthesized to serve as probes for dopaminergic receptors. Among this series, compound 6a showed the highest affinity towards D4 and D3 receptors with Ki values in the low nanomolar range, and D2/D4- and D2/D3-selectivity indices of 72 and 20, respectively. Optimization rounds were adopted and led to the D4-selective ligand thiophene-2-carboxamide 9a with a Ki (D4) value of

  合成了一系列的[（苯基哌嗪基）烷基]-异吲哚-1,3-二酮衍生物，用作多巴胺能受体的探针。在该系列中，化合物6a对D4和D3受体的亲和力最高，Ki值在低纳摩尔范围内，D2 / D4-和D2 / D3-选择性指数分别为72和20。采用最优化回合，得到Ki（D4）值为0.62 nM的D4选择性配体噻吩-2-羧酰胺9a，其丁基类似物10a的Ki（D4）和Ki（D3）值为0.03和0.26 nM。对接实验揭示了独特的D4残基Arg186在操纵配体D4亚型受体选择性中的重要性。
• NOVEL CHROMENE AND THIOCHROMENE CARBOXAMIDE DERIVATIVES, METHODS FOR PREPARING SAME AND THERAPEUTIC APPLICATIONS OF SAME
  申请人：Sokoloff Pierre

  公开号：US20100029682A1

  公开（公告）日：2010-02-04

  The present invention relates to novel chromene or thiochromene carboxamide derivatives, the preparation of same, pharmaceutical compositions of same and the use of same as dopamine D3 ligands as a medicament for central nervous system disorders.

  本发明涉及新型香豆素或硫代香豆素羧酰胺衍生物、其制备方法、相应的药物组成物以及将其用作中枢神经系统疾病的多巴胺D3受体配体的药物。
• Quinoline- and isoquinoline-sulfonamide derivatives of LCAP as potent CNS multi-receptor—5-HT1A/5-HT2A/5-HT7 and D2/D3/D4—agents: The synthesis and pharmacological evaluation
  作者：Paweł Zajdel、Krzysztof Marciniec、Andrzej Maślankiewicz、Grzegorz Satała、Beata Duszyńska、Andrzej J. Bojarski、Anna Partyka、Magdalena Jastrzębska-Więsek、Dagmara Wróbel、Anna Wesołowska、Maciej Pawłowski

  DOI：10.1016/j.bmc.2011.12.039

  日期：2012.2

  Two series of arylpiperazinyl-alkyl quinoline-, isoquinoline-, naphthalene-sulfonamides with flexible (13-26) and semi-rigid (33-36) alkylene spacer were synthesized and evaluated for 5-HT1A, 5-HT2A, 5-HT6, 5-HT7 and selected compounds for D-2, D-3, D-4 receptors. The compounds with a mixed 5-HT and D receptors profile 16 (N-4-[4-(3-chlorophenyl)-piperazin-1-yl]-butyl}-3-quinolinesulfonamide) and 36 (4-(4-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-ethyl}-piperidine-1-sulfonyl)-isoquinoline), displaying antagonistic activity at 5-HT7, 5-HT2A, D2 postsynaptic sites, produced antidepressant-like effects in the forced swim test in mice and showed significant anxiolytic activity in the plus-maze test in rats. The lead compound 36, a multi-receptor 5-HT2A/5-HT7/D-2/D-3/D-4 agent, also displayed significant antipsychotic properties in the MK-801-induced hyperlocomotor activity in mice. (C) 2011 Elsevier Ltd. All rights reserved.
• A Structure−Affinity Relationship Study on Derivatives of <i>N</i>-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide, a High-Affinity and Selective D₄ Receptor Ligand
  作者：Roberto Perrone、Francesco Berardi、Nicola A. Colabufo、Marcello Leopoldo、Vincenzo Tortorella

  DOI：10.1021/jm991138z

  日期：2000.1.1

  N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (1), a high-affinity and selective dopamine D-4 receptor ligand, was chosen as a lead, and structural modifications were done on its amide bond and on its alkyl chain linking the benzamide moiety to the piperazine ring and by preparing some semirigid analogues. The binding profile at dopamine D-4 and dopamine D-2, serotonin 5-HT1A, and adrenergic ar receptors of 16 new compounds was determined. From the results emerged that the modification of the amide bond and the elongation of the intermediate alkyl chain caused a decrease in dopamine D-4 receptor affinity. All prepared semirigid analogues displayed D-4 receptor affinity values in the same range of the opened counterparts.