3'-methyl-6-nitroquipazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3'-methyl-6-nitroquipazine
• 英文别名: 2-(3-Methyl-piperazin-1-yl)-6-nitro-quinoline；2-(3-methylpiperazin-1-yl)-6-nitroquinoline
• 化学式: C₁₄H₁₆N₄O₂
• 分子量: 272.307
• InChiKey: WIRIBEHWECMIRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  74
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(4-bromobutyl)glutarimide 、 3'-methyl-6-nitroquipazine 在 18-冠醚-6 、 potassium carbonate 作用下， 以 甲苯 为溶剂， 反应 120.0h， 生成 1-{4-[2-methyl-4-(6-nitroquinolin-2-yl)piperazin-1-yl]butyl}piperidine-2,6-dione
  参考文献：
  名称：

  Synthesis, in vitro binding studies and docking of long-chain arylpiperazine nitroquipazine analogues, as potential serotonin transporter inhibitors

  摘要：

  It is well known that 6-nitroquipazine exhibits about 150-fold higher affinity for the serotonin transporter (SERT) than quipazine and recently we showed quipazine buspirone analogues with high to moderate SERT affinity. Now we have designed and synthesized several 6-nitroquipazine buspirone derivatives. Unexpectedly, their SERT binding affinities were moderate, and much lower than that of the previously studied quipazine buspirone analogues. To explain these findings, docking studies of both groups of compounds into two different homology models of human SERT was performed using a flexible target-ligand docking approach (4D docking). The crystal structures of leucine transporter from Aquilex aeolicus in complex with leucine and with tryptophan were used as templates for the SERT models in closed and outward-facing conformations, respectively. We found that the latter conformation represents the most reliable model for binding of buspirone analogues. Docking into that model showed that the nitrated compounds acquire a rod like shape in the binding pocket with polar groups (nitro- and imido-) at the ends of the rod. 6-Nitro substituents gave steric clashes with amino acids located at the extracellular loop 4, which may explain their lower affinity than corresponding quipazine buspirone analogues. The results from the present study may suggest chemical design strategies to improve the SERT modulators. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.012
• 作为产物：
  描述：

  2-甲基哌嗪 在 硫酸 、 硝酸 作用下， 以 甲苯 为溶剂， 反应 48.25h， 生成 3'-methyl-6-nitroquipazine
  参考文献：
  名称：

  Serotonin transporter inhibitors: synthesis and binding potency of 2′-methyl- and 3′-methyl-6-nitroquipazine

  摘要：

  Racemic 2'-methyl- and 3'-methyl-6-nitroquipazine ligands were selected as targets, synthesized and evaluated at the serotonin transporter employing an in vitro competitive inhibition assay with [H-3]paroxetine and rat cortical membrane. The 2'-methyl-6-nitroquipazine was found to be 50 times more potent than the 3'-methyl-substituted counterpart and of comparable potency to the known high affinity agent 5-iodo-6-nitroquipazine. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00546-1

文献信息

• Quinoline derivatives, their preparation and pharmaceutical compositions comprising the same
  申请人：Chi Dae-Yoon

  公开号：US20050165006A1

  公开（公告）日：2005-07-28

  Novel quinoline derivatives were prepared and evaluated their pharmaceutical activities. The quinoline derivatives according to the present invention effectively bind serotonin transporter (SERT) which is called serotonin reuptake site. Serotonin is one of the neurotransmitter and the lack of its concentration in synapse cause the depression. The quinoline derivatives in this invention can interrupt reuptake of serotonin into presynaptic neuron resulting the increasement of concentration of serotonin in synapse as well as stimulating the signal through the binding with serotonin recepter. Thus, they can be used for the prevention and treatment of mental disorder, especially depression, caused by the deficiency of serotonin concentration in synapse.

  通过本发明制备了新型喹啉衍生物，并评估了它们的药物活性。本发明的喹啉衍生物能够有效地结合血清素转运体（SERT），也称为血清素再摄取位点。血清素是一种神经递质，如果突触中缺乏其浓度，则会导致抑郁症。本发明中的喹啉衍生物可以中断血清素重新摄取到突触前神经元中，从而增加突触中血清素的浓度，并通过与血清素受体结合刺激信号。因此，它们可以用于预防和治疗由突触中血清素浓度不足引起的心理障碍，特别是抑郁症。
• Syntheses and binding affinities of 6-nitroquipazine analogues for serotonin transporter. Part 1
  作者：Byoung Se Lee、Soyoung Chu、Byung Chul Lee、Dae Yoon Chi、Yearn Seong Choe、Kyung Ja Jeong、Changbae Jin

  DOI：10.1016/s0960-894x(00)00290-0

  日期：2000.7

  6-Nitroquipazine has been known as one of the most potent and selective inhibitors of serotonin transporter in vitro and in vivo. Nine derivatives of 6-nitroquipazine were synthesized and tested for their potential abilities to displace [H-3]citalopram binding to the rat cortical membranes. (C) 2000 Elsevier Science Ltd. All rights reserved.
• [EN] QUINOLINE DERIVATIVES, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME<br/>[FR] DERIVES DE QUINOLINE, PREPARATIONS DE CES DERIVES ET COMPOSITIONS PHARMACEUTIQUES COMPRENANT CES DERIVES
  申请人：CHEMON INC

  公开号：WO2003082286A1

  公开（公告）日：2003-10-09

  Novel quinoline derivatives were prepared and evaluated their pharmaceutical activities. The quinoline derivatives according to the present invention effectively bind serotonin transporter (SERT) which is called serotonin reuptake site. Serotonin is one of the neurotransmitter and the lack of its concentration in synapse cause the depression. The quinoline derivatives in this invention can interrupt reuptake of serotonin into presynaptic neuron resulting the increasement of concentration of serotonin in synapse as well as stimulating the signal through the binding with serotonin recepter. Thus, they can be used for the prevention and treatment of mental disorder, especially depression, caused by the deficiency of serotonin concentration in synapse.
• Synthesis, in vitro binding studies and docking of long-chain arylpiperazine nitroquipazine analogues, as potential serotonin transporter inhibitors
  作者：Małgorzata Jarończyk、Karol Wołosewicz、Mari Gabrielsen、Gabriel Nowak、Irina Kufareva、Aleksander P. Mazurek、Aina W. Ravna、Ruben Abagyan、Andrzej J. Bojarski、Ingebrigt Sylte、Zdzisław Chilmonczyk

  DOI：10.1016/j.ejmech.2012.01.012

  日期：2012.3

  It is well known that 6-nitroquipazine exhibits about 150-fold higher affinity for the serotonin transporter (SERT) than quipazine and recently we showed quipazine buspirone analogues with high to moderate SERT affinity. Now we have designed and synthesized several 6-nitroquipazine buspirone derivatives. Unexpectedly, their SERT binding affinities were moderate, and much lower than that of the previously studied quipazine buspirone analogues. To explain these findings, docking studies of both groups of compounds into two different homology models of human SERT was performed using a flexible target-ligand docking approach (4D docking). The crystal structures of leucine transporter from Aquilex aeolicus in complex with leucine and with tryptophan were used as templates for the SERT models in closed and outward-facing conformations, respectively. We found that the latter conformation represents the most reliable model for binding of buspirone analogues. Docking into that model showed that the nitrated compounds acquire a rod like shape in the binding pocket with polar groups (nitro- and imido-) at the ends of the rod. 6-Nitro substituents gave steric clashes with amino acids located at the extracellular loop 4, which may explain their lower affinity than corresponding quipazine buspirone analogues. The results from the present study may suggest chemical design strategies to improve the SERT modulators. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Serotonin transporter inhibitors: synthesis and binding potency of 2′-methyl- and 3′-methyl-6-nitroquipazine
  作者：John M Gerdes、Steven C DeFina、Paul A Wilson、Scott E Taylor

  DOI：10.1016/s0960-894x(00)00546-1

  日期：2000.12

  Racemic 2'-methyl- and 3'-methyl-6-nitroquipazine ligands were selected as targets, synthesized and evaluated at the serotonin transporter employing an in vitro competitive inhibition assay with [H-3]paroxetine and rat cortical membrane. The 2'-methyl-6-nitroquipazine was found to be 50 times more potent than the 3'-methyl-substituted counterpart and of comparable potency to the known high affinity agent 5-iodo-6-nitroquipazine. (C) 2000 Elsevier Science Ltd. All rights reserved.