1-(2,5-二氯苯基)哌嗪 | 1013-27-0

• 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: 1-(2,5-二氯苯基)哌嗪
• 英文名称: 1-(2,5-dichlorophenyl)piperazine
• CAS: 1013-27-0
• 化学式: C₁₀H₁₂Cl₂N₂
• mdl: MFCD02258886
• 分子量: 231.125
• InChiKey: JHICIIDUQBMMRM-UHFFFAOYSA-N

物化性质

• 沸点：
  125-128 °C(Press: 0.5 Torr)
• 密度：
  1.272±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  1-(2,5-二氯苯基)哌嗪 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 21.0h， 生成 4-[4-(2,5-dichlorophenyl)-1-piperazinyl]butylamine
  参考文献：
  名称：

  Synthesis, Screening, and Molecular Modeling of New Potent and Selective Antagonists at the α_1d Adrenergic Receptor

  摘要：

  In the present study, more than 75 compounds structurally related to BMY 7378 have been designed and synthesized. Structural variations of each part of the reference molecule have been introduced, obtaining highly selective ligands for the aid adrenergic receptor. The molecular determinants for selectivity at this receptor are essentially, held by the phenyl substituent in the phenylpiperazine moiety. The integration of an extensive SAR analysis with docking simulations using the rhodopsin-based models of the three alpha(1)-AR subtypes and of the 5-HT1A receptor provides significant insights into the characterization of the receptor binding sites as well as into the molecular determinants of ligand selectivity at the alpha(1d)-AR and the 5-HT1A receptors. The results of multiple copies simultaneous search (MCSS) on the substituted phenylpiperazines together with those of manual docking of compounds BAN 7378 and 69 into the putative binding sites of the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT1A receptors suggest that the phenylpiperazine moiety would dock into a site formed by amino acids in helices 3, 4, 5, 6 and extracellular loop 2, (E2), whereas the spirocyclic ring of the ligand docks into a site formed by amino acids of helices 1, 2, 3, and 7. This docking mode is consistent with the SAR data produced in this work. Furthermore, the binding site of the imide moiety does not allow for the simultaneous involvement of the two carbonyl oxygen atoms in H-bonding, interactions, consistent with the SAR data, in particular with the results obtained with the lactam derivative 128. The results of docking simulations also suggest that the second and third extracellular loops may act as selectivity filters for the substituted phenylpiperazines. The most potent and selective compounds for alpha(1d) adrenergic receptor, i.e., 69 (Rec 26D/038) and 128 (Rec 26D/073), are characterized by the presence of the 2,5-dichlorophenylpiperazine moiety.

  DOI：

  10.1021/jm030944+
• 作为产物：
  描述：

  2,5-二氯苯胺 、 二(2-氯乙基)胺盐酸盐 以62%的产率得到1-(2,5-二氯苯基)哌嗪
  参考文献：
  名称：

  Practical Method for Parallel Synthesis of Diversely Substituted 1- henylpiperazines

  摘要：

  已经开发出一种简单实用的方法，用于制备以替代1-苯基哌嗪构建块为内容的“库”，采用并行格式。

  DOI：

  10.2174/157017811799304386

文献信息

• Novel N-acylated heterocycles
  申请人：Recordati S.A.

  公开号：US20030162777A1

  公开（公告）日：2003-08-28

  Described are compositions comprising a muscarinic receptor antagonist and an N-acylated heterocycle derivative having affinity for serotonergic receptors, and enantiomers, diastereoisomers, N-oxides, polymorphs, solvates and pharmaceutically acceptable salts thereof. The combination of a muscarinic receptor antagonist and an N-acylated heterocycle, or an enantiomer, diastereoisomer, N-oxide, polymorph, solvate or pharmaceutically acceptable salt thereof, is useful in the treatment of patients with neuromuscular dysfunction of the lower urinary tract and diseases related to 5-HT 1A receptors.

  描述了包含一种肌氨酸受体拮抗剂和一种对5-HT 1A 受体具有亲和力的N-酰化杂环衍生物的组合物，以及它们的对映体、二对映体、N-氧化物、多型体、溶剂合物和药用可接受盐。肌氨酸受体拮抗剂和N-酰化杂环，或其对映体、二对映体、N-氧化物、多型体、溶剂合物或药用可接受盐的组合，在治疗患有下尿路神经肌肉功能障碍和与5-HT 1A 受体相关疾病的患者中是有用的。
• [1,8]naphthyridin-2-ones and related compounds for the treatment of schizophrenia
  申请人：Clark D. Jerry

  公开号：US20050043309A1

  公开（公告）日：2005-02-24

  This invention relates to compounds of the formula 1 wherein G, D, A, Z, Q, X, Y, R 1 , and R 4 through R 7 are defined as in the specification, processes for preparing the same and intermediates used in making the same, and pharmaceutical compositions containing such compounds and their use in the treatment of central nervous system disorders and other disorders.

  这项发明涉及公式1的化合物 其中G、D、A、Z、Q、X、Y、R 1 和R 4 至R 7 的定义如规范中所述，制备这些化合物的方法以及用于制备这些化合物的中间体，以及含有这些化合物的药物组合物及其在治疗中枢神经系统疾病和其他疾病中的用途。
• SULFONYL PYRROLIDINES, METHOD FOR PRODUCING THE SAME AND THEIR USE AS DRUGS
  申请人：Keil Stefanie

  公开号：US20080045540A1

  公开（公告）日：2008-02-21

  The invention relates to substituted sulfonylpyrrolidines of the formula I and to the physiologically tolerated salts thereof, as well as to their use as medicaments.

  该发明涉及公式I的取代磺酰吡咯烷化合物及其生理耐受盐，以及它们作为药物的用途。
• Rational Design, Synthesis, Biological Evaluation, Homology and Docking Studies of Coumarin Derivatives as α1-Adrenoceptor Antagonists
  作者：Xiang Zhou、Ya-Dong Chen、Tao Wang、Xiao-Bing Wang、Ling-Yi Kong

  DOI：10.1002/cbdv.201000135

  日期：2011.6

  -adrenoceptor (AR) antagonists, a novel class of coumarin (=2H-1-benzopyran-2-one) derivatives have been successfully designed and synthesized with high efficacies for α(1) -AR. These synthesized coumarin derivatives exhibited high efficacies towards α(1) -AR in in vitro pharmacological assays. Compared with prazosin (pK(i) value of 8.77), among those coumarins, tolylpiperazine-substituted derivatives, 7 and 8

  根据一些尿液选择性α（1）肾上腺素能受体（AR）拮抗剂的三点药效基团，已经成功设计并合成了新型香豆素（= 2H-1-苯并吡喃-2-酮）衍生物。对于α（1）-AR。这些合成的香豆素衍生物在体外药理试验中显示出对α（1）-AR的高效率。与哌唑嗪相比（pK（i）值为8.77），在这些香豆素中，甲苯​​基哌嗪取代的衍生物7和8的pK（i）值分别为8.81和8.77。这些香豆素衍生物对α（1A）-肾上腺素受体的功效趋势通过密集的分子对接进一步合理化。我们的工作表明，设计的香豆素衍生物可以在体外抑制α（1）-AR。
• Studies on 2(1H)-quinolinone derivatives as neuroleptic agents. I. Synthesis and biological activities of (4-phenyl-1-piperazinyl)-propoxy-2(1H)-quinolinone derivatives.
  作者：KAZUO BANNO、TAKAFUMI FUJIOKA、TETSURO KIKUCHI、YASUO OSHIRO、TAKASHI HIYAMA、KAZUYUKI NAKAGAWA

  DOI：10.1248/cpb.36.4377

  日期：——

  With the aim of developing a novel neuroleptic drug, a series of ω-(4-phenyl-1-piperazinyl)-alkoxy-2 (1H)-quinolinone derivatives have been synthesized and tested for anti-methamphetamine and anti-epinephrine activities. Most of the derivatives were found to possess a potent antimethamphetamine activity in the jumping behavior test on mice treated with 3-(3, 4-dihydroxyphenyl)-L-alanine (L-DOPA) and methamphetamine, or in the lethality test with methamphetamine-treated mice. They also showed relatively high anti-epinephrine potency depending on the nature or number of substituents on the phenyl group in the 4-phenyl-1-piperazinyl moiety; some of these compounds induced only weak catalepsy in mice. Among them, 7-3-[4-(2, 3-dimethylphenyl)-1-piperazinyl]propoxy}-2 (1H)-quinolinone (OPC-4392), which was suggested to be a dopamine autoreceptor agonist, was selected for further investigations. The structure-activity relationships are also discussed.

  为了开发一种新型的神经安定药物，合成了一系列ω-(4-苯基-1-哌嗪基)-烷氧基-2(1H)-喹啉酮衍生物，并测试了它们的抗甲基苯丙胺和抗肾上腺素活性。大多数衍生物在3-(3, 4-二羟基苯基)-L-天冬氨酸（L-DOPA）和甲基苯丙胺处理的小鼠的跳跃行为测试中显示出强效的抗甲基苯丙胺活性，或者在甲基苯丙胺处理的小鼠的致死性测试中表现出显著效果。它们还表现出相对较高的抗肾上腺素效能，这取决于取代基在4-苯基-1-哌嗪基上的性质或数量；其中一些化合物在小鼠中仅引起轻微的强直症。在这些化合物中，7-3-[4-(2, 3-二甲基苯基)-1-哌嗪基]丙氧基}-2(1H)-喹啉酮（OPC-4392），被认为是一种多巴胺自受体激动剂，已被选定用于进一步研究。同时，本文也讨论了结构-活性关系。