1-(3,4-dihydro-2H-1,5-benzodioxepin-6-yl)piperazine | 98224-28-3

• 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-(3,4-dihydro-2H-1,5-benzodioxepin-6-yl)piperazine
• 英文别名: 1-(1,5-benzodioxepin-6-yl)piperazine；1-(3,4-dihydro-2H-benzo[b][1,4]dioxepin-6-yl)-piperazine；1-(3,4-dihydro-2H-benzo[b][1,4]dioxepin-6-yl)piperazine；Piperazine, 1-(3,4-dihydro-2H-1,5-benzodioxepin-6-yl)-
• CAS: 98224-28-3
• 化学式: C₁₃H₁₈N₂O₂
• 分子量: 234.298
• InChiKey: RKUNMQZMSRXTAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  33.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3,4-dihydro-2H-1,5-benzodioxepin-6-yl)piperazine 在 sodium tetrahydroborate 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 73.0h， 生成 3-(4-(3,4-dihydro-2H-benzo[b][1,4]dioxepin-6-yl)piperazin-1-yl)-1-(5-fluorobenzo[b]thiophen-3-yl)propan-1-ol
  参考文献：
  名称：

  合成和分子建模的新的1-芳基-3- [4-芳基哌嗪-1-基] -1-丙烷衍生物在5-羟色胺转运蛋白和5-HT（1A）受体上具有高亲和力。

  摘要：

  有人提出5-HT（1A）受体拮抗剂可增强选择性5-羟色胺（5-HT）再摄取抑制剂的抗抑郁功效。为了寻求新型有效的抗抑郁药，设计，合成了1-（芳基）-3- [4-芳基哌嗪-1-基] -1-丙烷分子杂化物，并对其5-HT再摄取抑制和5-HT（ 1A）受体亲和力。该设计基于偶联与抑制5-羟色胺再摄取有关的结构部分，例如苯并[b]噻吩衍生物与典型的5-HT（1A）受体配体芳基哌嗪。在结合研究中，几种化合物对5-HT转运蛋白和5-HT（1A）受体表现出亲和力。分子模型研究预测了高亲和力结合所需的药效基团元素，以及能够区分激动剂，部分激动剂，或对5-HT（1A）受体的拮抗作用和对5-HT转运蛋白的抑制。在结合步骤之前，去溶剂化过程中的溶剂相互作用以及焓和人类补偿可能是解释激动剂，部分激动剂和拮抗剂特性的原因。氢键键合能力似乎很重要，可以打破氢螺旋间的氢键或在配体结合后形成其他键。部分激动剂和拮抗剂不能

  DOI：

  10.1021/jm0111200
• 作为产物：
  描述：

  二(2-氯乙基)胺盐酸盐 、 6-amino-3,4-dihydro-2H-1,5-benzodioxepine 在 potassium carbonate 作用下， 以 氯苯 为溶剂， 反应 24.0h， 生成 1-(3,4-dihydro-2H-1,5-benzodioxepin-6-yl)piperazine
  参考文献：
  名称：

  Characterization of Potent and Selective Antagonists at Postsynaptic 5-HT1A Receptors in a Series of N4-Substituted Arylpiperazines

  摘要：

  Benzocycloalkyl and benzocycloalkenyl moities linked, directly or via an alkyl chain, to oxygen-bearing heteroarylpiperazines were synthesized, in an attempt to obtain potent and selective antagonists at postsynaptic 5-HT1A receptors. From the numerous arylpiperazines described in the literature, 1-(2,3-dihydro-1,4-benzodioxin-5-yl)pipe (3a) was chosen as a model of an arylpiperazine in view of its selectivity for 5-HT1A receptors versus alpha(1)-, alpha(2)-, and beta-adrenergic receptors, as well as dopamine D-1 and D-2 receptors. Two other closely-related arylpiperazines, 1-(1,5-benzodioxepin-6-yl)piperazine (3b) and 1-(benzofuran-7-yl)piperazine (3c), were also examined in this study. Al compounds showed high affinity at 5-HT1A sites (8.10 less than or equal to pK(i)s less than or equal to 9.35), and the majority behaved as antagonists in vivo in blocking the hypothermia induced by the 5-HT1A agonist 8-OH-DPAT in the absence of a marked effect alone at equivalent doses. An in vivo evaluation of dopamine D-2 receptor antagonist properties revealed that the majority of compounds was devoid of activity at this site, in marked contrast to BMY 7378 which displayed virtually no selectivity for 5-HT1A versus dopamine D-2 receptors. Moreover, six compounds of the present series, 8, 10, 11, 14, 25, and, 37, showed > 10-fold selectivity in vitro for 5-HT1A versus alpha(1)-adrenergic receptors. Compound 14 displayed an optimal compromise between potency (pK(i) = 8.75), marked antagonist activity, and selectivity toward alpha(1)-adrenergic (81-fold) and dopamine D-2 (195-fold) receptors. These characteristics clearly distinguish 14 from previously-reported ligands such as the postsynaptic 5-HT1A antagonist BMY 7378 and the weak partial agonist NAN 190 which, in contrast to the compounds of this series, belong to the well-exemplified class of imido derivatives of (o-methoxyphenyl)piperazines. The availability of 14 (S 15535) should facilitate the further elucidation of the functional role and potential therapeutic significance of 5-HT1A receptors.

  DOI：

  10.1021/jm00020a020

文献信息

• Arylpiperazine Derivatives and their Use as Selective Dopamine D3 Receptor Ligands
  申请人：Capet Marc

  公开号：US20080214542A1

  公开（公告）日：2008-09-04

  The invention concerns compounds of general formula (I), a method for preparing same, as well as their use as therapeutic agent.

  这项发明涉及一般式（I）的化合物，以及制备这些化合物的方法，以及它们作为治疗剂的用途。
• 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。
• Benzothiophene derivative compounds process of preparation and use thereof
  申请人：——

  公开号：US20040034219A1

  公开（公告）日：2004-02-19

  This invention provides new benzothiophene derivatives of general formula (I) and a process for preparing them, the corresponding compositions and their use for manufacturing a medicine for the treatment of neurological disorders. These new compounds behave as serotonin reuptake inhibitors and show high affinity towards the 5-HT 1A receptor.

  本发明提供了一种新的苯并噻吩衍生物通式（I）及其制备方法、相应的组合物以及它们用于制造治疗神经系统疾病的药物。这些新化合物具有作为5-HT1A受体的血清素再摄取抑制剂的行为，并表现出高亲和力。
• Arylpiperazine derivatives and use thereof as 5-HT1A receptor ligands
  申请人：Cepa Schwarz Pharma s.l.

  公开号：EP1674103A1

  公开（公告）日：2006-06-28

  Novel substituted arylpiperazine derivatives with activity as 5-hydroxytryptamine 1A (5-HT1A) receptor subtype ligands, to their stereochemical isomers, methods of their preparation, and to their use and to pharmaceutical compositions containing them for the treatment of Parkinson disease, cerebral damage by thromboembolic ictus, craneoencephalic traumatisms, depression, migraine, pain, psychosis, anxiety disorders, aggressive disorders or urinary tract disorders.

  这篇文章介绍了一种替代芳基哌嗪衍生物的小说，它具有作为5-羟色胺1A（5-HT1A）受体亚型配体的活性，以及它们的立体化异构体、制备方法、以及它们的用途和包含它们的制药组合物，用于治疗帕金森病、血栓栓塞性卒中引起的脑损伤、颅脑创伤、抑郁症、偏头痛、疼痛、精神病、焦虑症、攻击性疾病或泌尿道疾病。