2-(2-bromoethoxy)benzonitrile | 59825-56-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(2-bromoethoxy)benzonitrile
• CAS: 59825-56-8
• 化学式: C₉H₈BrNO
• mdl: MFCD09817367
• 分子量: 226.073
• InChiKey: PKMYDQVQJFGGBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  33
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-aminobutyl)tetrahydrocyclopenta[c]pyrrole-1,3(2H,3aH)-dione 、 2-(2-bromoethoxy)benzonitrile 以 乙腈 为溶剂， 反应 15.0h， 以42%的产率得到2-(2-{[4-(1,3-dioxotetrahydro-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)butyl]amino}ethoxy)benzonitrile
  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
• 作为产物：
  描述：

  邻羟基苯甲腈 、 1,2-二溴乙烷 在 potassium carbonate 、 potassium iodide 作用下， 以 丁酮 为溶剂， 反应 48.0h， 以67%的产率得到2-(2-bromoethoxy)benzonitrile
  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

• [EN] DOPAMINE D2 RECEPTOR LIGANDS<br/>[FR] LIGANDS DES RÉCEPTEURS DOPAMINERGIQUES D2
  申请人：BROAD INST INC

  公开号：WO2016100940A1

  公开（公告）日：2016-06-23

  The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity. The present invention relates to novel compounds that modulate dopamine D2 receptors. In particular, compounds of the present invention show functional selectivity at the dopamine D2 receptors and exhibit selectivity downstream of the D2 receptors, on the 0- arrestin pathway and/or on the cAMP pathway.

  本发明涉及新型多巴胺D2受体配体。该发明进一步涉及功能偏向的多巴胺D2受体配体以及利用这些化合物治疗或预防与多巴胺活性失调相关的中枢神经系统和全身性疾病。本发明涉及调节多巴胺D2受体的新型化合物。具体而言，本发明的化合物在多巴胺D2受体上显示功能选择性，并在D2受体下游、0-阿雷斯汀途径和/或cAMP途径上表现出选择性。
• Dopamine D2 receptor ligands
  申请人：The Broad Institute, Inc.

  公开号：US10633336B2

  公开（公告）日：2020-04-28

  The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity. The present invention relates to novel compounds that modulate dopamine D2 receptors. In particular, compounds of the present invention show functional selectivity at the dopamine D2 receptors and exhibit selectivity downstream of the D2 receptors, on the 0-arrestin pathway and/or on the cAMP pathway.

  本发明涉及新型多巴胺D2受体配体。本发明进一步涉及具有功能偏倚的多巴胺 D2 受体配体，以及使用这些化合物治疗或预防与多巴胺能活性失调相关的中枢神经系统和全身性疾病。本发明涉及调节多巴胺 D2 受体的新型化合物。特别是，本发明的化合物在多巴胺 D2 受体上表现出功能选择性，并在 D2 受体下游、0-arrestin 通路和/或 cAMP 通路上表现出选择性。
• DOPAMINE D2 RECEPTOR LIGANDS
  申请人：The Broad Institute Inc.

  公开号：EP3233077A1

  公开（公告）日：2017-10-25
• US4027028A
  申请人：——

  公开号：US4027028A

  公开（公告）日：1977-05-31
• 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.