2-(3-bromopropyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione | 790187-26-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 2-(3-bromopropyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione
• 英文别名: 3-Bromopropyl-1,3-dioxoperhydropyrrolo[1,2-c]imidazole；2-(3-bromopropyl)-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazole-1,3-dione
• CAS: 790187-26-7
• 化学式: C₉H₁₃BrN₂O₂
• 分子量: 261.118
• InChiKey: YBKANXYVKYBWGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 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-(4-氟苯基)哌嗪 、 2-(3-bromopropyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione 在 sodium carbonate 作用下， 以 乙腈 为溶剂， 以35%的产率得到2-[3-[4-(4-Fluorophenyl)piperazin-1-yl]propyl]-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazole-1,3-dione
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 1. 2-[[4-(o-Methoxyphenyl)piperazin-1-yl]methyl]-1,3- dioxoperhydroimidazo[1,5-a]pyridine:  A Selective 5-HT_1A Receptor Agonist

  摘要：

  A series of new bicyclohydantoin-arylpiperazines was prepared and evaluated for affinity at 5-HT1A, alpha(1), and D-2 receptors. Most of the compounds showed very low affinity for D-2 receptors, and most of them demonstrated moderate to high affinity for 5-HT1A and alpha(1) receptor binding sites. SAR observations indicated that the length of the alkyl chain between the arylpiperazine and the hydantoin moiety is of great importance for 5-HT1A/alpha(1) affinity and selectivity, n = 1 being the optimal value. Compound 1h, 2-[[4-(o-methoxyphenyl)piperazin-1-yl]methyl]-1,3-dioxoperhydroimidazo[1,5-a]pyridine, bound at 5-HT1A sites with nanomolar affinity (K-i = 31.7 nM) and high selectivity over alpha(1), D-2, and 5-HT2A receptors (K-i > 1000, > 10 000, and > 1000 nM, respectively). Preliminary studies showed that this agent is probably functioning as a partial to full 5-HT1A agonist, and it displayed anxiolytic activity on the social interaction test in mice.

  DOI：

  10.1021/jm960416g
• 作为产物：
  描述：

  四氢-1H-吡咯并[1,2-c]咪唑-1,3(2H)-二酮 、 1,3-二溴丙烷 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67%的产率得到2-(3-bromopropyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-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 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。
• 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.