2-(4-{[2-(5,6,7,8-tetrahydronaphthalen-1-yloxy)ethyl]-amino}butyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione

• 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-(4-{[2-(5,6,7,8-tetrahydronaphthalen-1-yloxy)ethyl]-amino}butyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione
• 英文别名: 2-[4-[2-(5,6,7,8-tetrahydronaphth-1-yloxy)ethylamino]butyl]-1,3-dioxoperhydorpyrrolo[1,2-c]imidazole；2-[4-[2-(5,6,7,8-tetrahydronaphth-1-yloxy)ethylamino]butyl]-1,3-dioxoperhydropyrrolo[1,2-c]imidazole；2-[4-[2-(5,6,7,8-Tetrahydronaphthalen-1-yloxy)ethylamino]butyl]-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazole-1,3-dione
• 化学式: C₂₂H₃₁N₃O₃
• 分子量: 385.506
• InChiKey: HAWLNWMPWCIBNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  四氢萘酚 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 、 丁酮 为溶剂， 反应 63.0h， 生成 2-(4-{[2-(5,6,7,8-tetrahydronaphthalen-1-yloxy)ethyl]-amino}butyl)tetrahydro-1H-pyrrolo[1,2-c]imidazole-1,3(2H)-dione
  参考文献：
  名称：

  New Serotonin 5-HT_1A Receptor Agonists Endowed with Antinociceptive Activity in Vivo

  摘要：

  We report the synthesis of new compounds 4-35 based on two different openings (A and B) of the chromane ring present in the previously identified 5-HT1A receptor (5-HT1AR) ligand 3. The synthesized compounds were assessed for binding affinity, selectivity, and functional activity at the 5-HT1AR Selected candidates resulting from B opening were also evaluated for their potential antinociceptive effect in vivo and pharmacokinetic properties in vitro. Analogue 19 [2-(4-{[2-(2-ethoxyphenoxy)ethyl]amino}butyl)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 = 2.3 nM; EC50 = 19 nM). Pharmacokinetic studies indicated that compound 19 displays a good metabolic stability in human liver microsomes (t(1/2) similar to 3 h and CLint = 3.5 mL/min/kg, at 5 mu M), and a low level of protein binding (25%, at 5 mu M). Interestingly, 19 (3 mg/kg, ip, and 30 mg/kg, po) caused significant attenuation of formalin-induced behavior in early and late phases of the mouse intradermal formalin test of pain, and this in vivo effect was reversed by the selective 5-HT1AR antagonist WAY-100635. Thus, the new 5-HT1AR agonist identified in this work, 19, exhibits oral analgesic activity, and the results herein represent a step toward identifying new therapeutics for the control of pain.

  DOI：

  10.1021/jm400766k

文献信息

• Diaza- or Thiazadione Derivatives With Neuroprotective Activity
  申请人：Lopez-Rodriguez Maria Luz

  公开号：US20080200470A1

  公开（公告）日：2008-08-21

  The present invention relates to certain derivatives of cycloalkanediones invariably substituted with a chroman-2-yl, 2-quinolyl or —O-phenyl residue which are serotonin (5-hydroxytryptamine, 5-HT) 5-HT 1A receptor subtype agonists modulators, to their stereochemical isomers and to their use in the preparation of a medicament for the treatment of pathological states for which an agonist a modulator of these receptors is indicated.

  本发明涉及某些环戊二酮衍生物，该衍生物不变地取代为一种色甘酸-2-基，2-喹啉基或-O-苯基残基，它们是血清素（5-羟色胺，5-HT）5-HT1A受体亚型激动剂调节剂，其立体化学异构体以及它们在制备治疗需要这些受体的激动剂调节剂的病理状态的药物中的使用。
• DIAZA- OR THIAZADIONE DERIVATIVES WITH NEUROPROTECTIVE ACTIVITY
  申请人：Schwarz Pharma, s.l.

  公开号：EP1711500A1

  公开（公告）日：2006-10-18
• [EN] DIAZA- OR THIAZADIONE DERIVATIVES WITH NEUROPROTECTIVE ACTIVITY<br/>[FR] DERIVES DE DIAZA- OU THIAZADIONE PRESENTANT UNE ACTIVITE NEUROPROTECTRICE
  申请人：CEPA SCHWARZ PHARMA S L

  公开号：WO2005075480A1

  公开（公告）日：2005-08-18

  The present invention relates to certain derivatives of cycloalkanediones invariably substituted with a chroman-2-yl, 2-quinolyl or -O-phenyl residue which are serotonin (5-hydroxytryptamine, 5-HT) 5-HT1A receptor subtype agonists modulators, to their stereochemical isomers and to their use in the preparation of a medicament for the treatment of pathological states for which an agonist a modulator of these receptors is indicated.
• [EN] METHODS FOR PREVENTING AND/OR TREATING PAIN AND/OR MIGRAINE<br/>[FR] PROCÉDÉS POUR PRÉVENIR ET/OU TRAITER LA DOULEUR ET/OU LA MIGRAINE
  申请人：SCHWARZ PHARMA S L

  公开号：WO2008015538A2

  公开（公告）日：2008-02-07

  [EN] The present invention relates to methods for preventing and/or treating pain and/or migraine in a subject in need of such prevention and/or treatment. These methods comprise administering to the subject a diaza- and thiaza- cycloalkanedione compound, an isomer of the compound, or a hydrate, solvate, or salt of the compound or isomer.
  [FR] La présente invention concerne des procédés pour prévenir et/ou traiter la douleur et/ou la migraine chez un sujet ayant besoin d'une telle prévention et/ou d'un tel traitement. Ces procédés consistent à administrer au sujet un composé de diaza- et thiaza- cycloalcanedione, un isomère du composé, ou un hydrate, un solvate ou un sel du composé ou de l'isomère.
• New Serotonin 5-HT_1A Receptor Agonists Endowed with Antinociceptive Activity <i>in Vivo</i>
  作者：Margarita Valhondo、Isabel Marco、Mar Martín-Fontecha、Henar Vázquez-Villa、José A. Ramos、Reinhard Berkels、Thomas Lauterbach、Bellinda Benhamú、María L. López-Rodríguez

  DOI：10.1021/jm400766k

  日期：2013.10.24

  We report the synthesis of new compounds 4-35 based on two different openings (A and B) of the chromane ring present in the previously identified 5-HT1A receptor (5-HT1AR) ligand 3. The synthesized compounds were assessed for binding affinity, selectivity, and functional activity at the 5-HT1AR Selected candidates resulting from B opening were also evaluated for their potential antinociceptive effect in vivo and pharmacokinetic properties in vitro. Analogue 19 [2-(4-[2-(2-ethoxyphenoxy)ethyl]amino}butyl)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 = 2.3 nM; EC50 = 19 nM). Pharmacokinetic studies indicated that compound 19 displays a good metabolic stability in human liver microsomes (t(1/2) similar to 3 h and CLint = 3.5 mL/min/kg, at 5 mu M), and a low level of protein binding (25%, at 5 mu M). Interestingly, 19 (3 mg/kg, ip, and 30 mg/kg, po) caused significant attenuation of formalin-induced behavior in early and late phases of the mouse intradermal formalin test of pain, and this in vivo effect was reversed by the selective 5-HT1AR antagonist WAY-100635. Thus, the new 5-HT1AR agonist identified in this work, 19, exhibits oral analgesic activity, and the results herein represent a step toward identifying new therapeutics for the control of pain.