1-(4-hydroxyphenyl)-4-{[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl]methyl}piperazine | 1224470-74-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(4-hydroxyphenyl)-4-{[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl]methyl}piperazine
• 英文别名: 4-[4-[[1-(4-chlorophenyl)triazol-4-yl]methyl]piperazin-1-yl]phenol
• CAS: 1224470-74-9
• 化学式: C₁₉H₂₀ClN₅O
• 分子量: 369.854
• InChiKey: QOTVTVRIMDVXGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  57.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-[[1-(4-氯苯基)三唑-4-基]甲基]-4-苯基哌嗪 在 Cunninghamella echinulata ATCC 9244 作用下， 反应 72.0h， 以62.5%的产率得到1-(4-hydroxyphenyl)-4-{[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl]methyl}piperazine
  参考文献：
  名称：

  Design of new dopamine D2 receptor ligands: Biosynthesis and pharmacological evaluation of the hydroxylated metabolite of LASSBio-581

  摘要：

  LASSBio-581 is a N-phenylpiperazine derivative designed for the treatment of schizophrenia. In this study, four strains of filamentous fungi were screened for their capabilities to biotransform LASSBio-581. Cunninghamella echinulata ATCC 9244 was chosen to scale up the biosynthesis of the p-hydroxylated metabolite of LASSBio-581. The chemical structure of the metabolite was confirmed by NMR, LC-MS and X-ray crystallography. Binding studies performed on brain homogenate indicated that the p-hydroxylated metabolite can be considered more selective for dopamine receptors than LASSBio-581, and, therefore, can be used to design new selective dopamine inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.034

文献信息

• Searching for multi-target antipsychotics: Discovery of orally active heterocyclic N-phenylpiperazine ligands of D2-like and 5-HT1A receptors
  作者：Gilda Neves、Ricardo Menegatti、Camila B. Antonio、Luiza R. Grazziottin、Renan O. Vieira、Stela M.K. Rates、François Noël、Eliezer J. Barreiro、Carlos A.M. Fraga

  DOI：10.1016/j.bmc.2010.01.040

  日期：2010.3

  We described herein the design, synthesis, and pharmacological evaluation of N-phenylpiperazine heterocyclic derivatives as multi-target compounds potentially useful for the treatment of schizophrenia. The isosteric replacement of the heterocyclic ring at the biaryl motif generating pyrazole, 1,2,3-triazole, and 2-methylimidazole[1,2-a]pyridine derivatives resulted in 21 analogues with different substitutions at the para-biaryl and para-phenylpiperazine positions. Among the compounds prepared, 4 (LASSBio-579) and 10 (LASSBio-664) exhibited an adequate binding profile and a potential for schizophrenia positive symptoms treatment without cataleptogenic effects. Structural features of this molecular scaffold are discussed regarding binding affinity and selectivity for D-2-like, 5-HT1A, and 5-HT2A receptors. (C) 2010 Elsevier Ltd. All rights reserved.
• Design of new dopamine D2 receptor ligands: Biosynthesis and pharmacological evaluation of the hydroxylated metabolite of LASSBio-581
  作者：Francine Pazini、Ricardo Menegatti、José R. Sabino、Carolina H. Andrade、Gilda Neves、Stela M.K. Rates、François Noël、Carlos A.M. Fraga、Eliezer J. Barreiro、Valéria de Oliveira

  DOI：10.1016/j.bmcl.2010.03.034

  日期：2010.5

  LASSBio-581 is a N-phenylpiperazine derivative designed for the treatment of schizophrenia. In this study, four strains of filamentous fungi were screened for their capabilities to biotransform LASSBio-581. Cunninghamella echinulata ATCC 9244 was chosen to scale up the biosynthesis of the p-hydroxylated metabolite of LASSBio-581. The chemical structure of the metabolite was confirmed by NMR, LC-MS and X-ray crystallography. Binding studies performed on brain homogenate indicated that the p-hydroxylated metabolite can be considered more selective for dopamine receptors than LASSBio-581, and, therefore, can be used to design new selective dopamine inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.