2-(4-bromobutyl)hexahydro-3H-pyrrolo[1,2-a]pyrazine-1,4-dione | 328410-04-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(4-bromobutyl)hexahydro-3H-pyrrolo[1,2-a]pyrazine-1,4-dione
• 英文别名: 2-(4-bromobutyl)-1,3-dioxoperhydropyrrolo[1,2-a]pyrazine；2-(4-bromobutyl)-1,4-dioxoperhydropyrrolo[1,2-a]pyrazine；4-Bromobutyl1,4-dioxoperhydropyrrolo[1,2-a]pyrazine；2-(4-bromobutyl)-6,7,8,8a-tetrahydro-3H-pyrrolo[1,2-a]pyrazine-1,4-dione
• CAS: 328410-04-4
• 化学式: C₁₁H₁₇BrN₂O₂
• 分子量: 289.172
• InChiKey: JOFRXMVCYBHFOJ-UHFFFAOYSA-N

物化性质

• 沸点：
  475.0±45.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(3,4-dihydro-2H-1,5-benzodioxepin-6-yl)piperazine 、 2-(4-bromobutyl)hexahydro-3H-pyrrolo[1,2-a]pyrazine-1,4-dione 生成 2-[4-[4-(3,4-dihydro-2H-1,5-benzodioxepin-6-yl)piperazin-1-yl]butyl]-1,4-dioxoperhydropyrrolo[1,2-a]pyrazine
  参考文献：
  名称：

  ARYLPIPERAZINE DERIVATIVE AND USE THEREOF AS 5-HT1A RECEPTOR LIGANDS

  摘要：

  小说替代了具有5-羟色胺1A（5-HT1A）受体亚型配体活性的芳基哌嗪衍生物，包括它们的立体化异构体、制备方法以及它们在治疗帕金森病、血栓栓塞性卒中引起的脑损伤、颅脑外伤、抑郁症、偏头痛、疼痛、精神病、焦虑症、攻击性障碍或泌尿道障碍的药物组成物中的使用。

  公开号：

  US20090036455A1
• 作为产物：
  描述：

  1,4-二溴丁烷 、 六氢吡咯并[1,2-a]吡嗪-1,4-二酮 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 4.0h， 以55%的产率得到2-(4-bromobutyl)hexahydro-3H-pyrrolo[1,2-a]pyrazine-1,4-dione
  参考文献：
  名称：

  New Serotonin 5-HT_1A Receptor Agonists with Neuroprotective Effect against Ischemic Cell Damage

  摘要：

  We report the synthesis of new compounds 4 35 based on structural modifications of different moieties of previously described lead UCM-2550. The new nonpiperazine derivatives, representing second-generation agonists, were assessed for binding affinity, selectivity, and functional activity at the 5-HT1A receptor (5-HT1AR). Computational beta(2)-based homology models of the ligand receptor complexes were used to explain the observed structure affinity relationships. Selected candidates were also evaluated for their potential in vitro and in vivo neuroprotective properties. Interestingly, compound 26 (2-{6-[(3,4:-dihydro-2H-chromen-2-ylmethyl)amino]hexyl}-tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione) has been characterized as a high-affinity and potent 5-HT1AR agonist (K-i, = 5.9 nM, EC50 = 21.8 nM) and exhibits neuroprotective effect in neurotoxicity assays in primary cell cultures from rat hippocampus and in the MCAO model of focal cerebral ischemia in rats.

  DOI：

  10.1021/jm2007886

文献信息

• 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。
• ARYLPIPERAZINE DERIVATIVE AND USE THEREOF AS 5-HT1A RECEPTOR LIGANDS
  申请人：Lopez-Rodriguez Maria Luz

  公开号：US20090036455A1

  公开（公告）日：2009-02-05

  Novel substituted arylpiperazine derivatives with activity as 5-hydroxytryptamine 1A (5-HT 1A ) 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.

  小说替代了具有5-羟色胺1A（5-HT1A）受体亚型配体活性的芳基哌嗪衍生物，包括它们的立体化异构体、制备方法以及它们在治疗帕金森病、血栓栓塞性卒中引起的脑损伤、颅脑外伤、抑郁症、偏头痛、疼痛、精神病、焦虑症、攻击性障碍或泌尿道障碍的药物组成物中的使用。
• Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 5. Study of the Physicochemical Influence of the Pharmacophore on 5-HT_1A/α₁-Adrenergic Receptor Affinity:  Synthesis of a New Derivative with Mixed 5-HT_1A/D₂ Antagonist Properties
  作者：María L. López-Rodríguez、M. José Morcillo、Esther Fernández、Esther Porras、Luis Orensanz、M Eugenia Beneytez、Jorge Manzanares、Jose Angel Fuentes

  DOI：10.1021/jm000929u

  日期：2001.1.1

  In this paper we have designed and synthesized a test series of 32 amide arylpiperazine derivatives VI in order to gain insight into the physicochemical influence of the pharmacophores of 5-HT1A and alpha (1)-adrenergic receptors. The training set was designed applying a fractional factorial design using six physicochemical descriptors. The amide moiety is a bicyclohydantoin or a diketopiperazine (X = -(CH2)(3)-, -(CH2)(4)-; m = 0, 1), the spacer length is 3 or 4 methylene units, which are the optimum values for both receptors, and the aromatic substituent R occupies the ortho- or meta-position and has been selected from a database of 387 substituents using the EDISFAR program. The 5-HT1A and alpha (1)-adrenergic receptor binding affinities of synthesized compounds VI (1-32) have been determined. This data set has been used to derive classical quantitative structure-activity relationships (QSAR) and neural-networks models for both receptors (following paper). A comparison of these models gives information for the design of the new ligand EF-7412 (46) (5-HT1A: K-i = 27 nM; alpha (1): K-i > 1000 nM). This derivative displays affinity for the dopamine D-2 receptor (K-i = 22 nM) and is selective versus all other receptors examined (5-HT2A, 5-HT3, 5-HT4 and Bz; K-i > 1000 nM). EF-7412 (46) acts as an antagonist in vivo in pre- and postsynaptic 5-HT1A receptor sites and; as an antagonist in the dopamine D-2 receptor. Thus, EF-7412 (46) is a derivative with mixed 5-HT1A/D-2 antagonist properties and this derivative could be useful as a pharmacological tool.
• ARYLPIPERAZINE DERIVATIVES AND USE THEREOF AS 5-HT1A RECEPTOR LIGANDS
  申请人：Schwarz Pharma, S.L.

  公开号：EP1830854A1

  公开（公告）日：2007-09-12
• [EN] ARYLPIPERAZINE DERIVATIVES AND USE THEREOF AS 5-HT1A RECEPTOR LIGANDS<br/>[FR] DERIVES D'ARYLPIPERAZINE ET LEUR UTILISATION COMME LIGANDS DU RECEPTEUR AS 5-HT1A
  申请人：CEPA SCHWARZ PHARMA S L

  公开号：WO2006069993A1

  公开（公告）日：2006-07-06

  [EN] 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.
  [FR] La présente invention concerne de nouveaux dérivés substitués d'arylpipérazine présentant une activité en tant que ligands du sous-type de récepteur de la 5-hydroxytryptamine 1A (5-HT1A ), à leurs stéréo-isomères, à des procédés de leur préparation, et à leur utilisation et à des compositions pharmaceutiques les contenant destinées au traitement de la maladie de Parkinson, des lésions cérébrales dues à un accident thrombo-embolique, des traumatismes crânio-encéphaliques, des dépressions, des migraines, des douleurs, des psychoses, des troubles de l'anxiété, des désordres agressifs ou des troubles du système urinaire.