1-苯基-4-[(1-苯基三唑-4-基)甲基]哌嗪 | 668602-03-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 1-苯基-4-[(1-苯基三唑-4-基)甲基]哌嗪
• 英文名称: LASSBio 580
• 英文别名: 1-phenyl-4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methyl]piperazine；1-phenyl-4-[(1-phenyltriazol-4-yl)methyl]piperazine
• CAS: 668602-03-7
• 化学式: C₁₉H₂₁N₅
• 分子量: 319.409
• InChiKey: QLOFPPKCJSHBIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 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：
  37.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-苯基哌嗪 、 1-苯基-1H-1,2,3-噻唑-4-甲醛 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 以72%的产率得到1-苯基-4-[(1-苯基三唑-4-基)甲基]哌嗪
  参考文献：
  名称：

  Design, synthesis and pharmacological profile of novel dopamine D2 receptor ligands

  摘要：

  The present study describes the synthesis and pharmacological profile of three novel heterocyclic compounds originally designed, on the basis of bioisosterism, as dopamine D2 receptor ligands: 1-[1-(4-chlorophenyl)-1H-pyrazol-4-ylmethyl]-4-phenyl-piperazine (LASSBio-579), 1-phenyl-4-(1-phenyl-1H-[1,2,3]triazol-4-ylmethyl)-piperazine (LASSBio-580) and]-[1-(4-chloro-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-4-phenyl-piperazine (LASSBio-581). Binding studies performed on brain homogenate indicated that all three compounds bind selectively to D2 receptors. In addition, electrophysiological studies carried out in cultured hippocampal neurons suggested that LASSBio-579 and 581 act as D2 agonists, whereas LASSBio-580 acts as a D2 antagonist. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00487-5

文献信息

• Synthesis and biological investigations of dopaminergic partial agonists preferentially recognizing the D4 receptor subtype
  作者：Stefan Löber、Harald Hübner、Peter Gmeiner

  DOI：10.1016/j.bmcl.2006.02.075

  日期：2006.6

  Aminomethyl-substituted biaryls bearing a pyrazole or triazole moiety were synthesized and investigated for dopamine and serotonin receptor binding. The N-arylpyrazoles 3b,f,g and 4 revealed K-i values in the subnanomolar range (0.28-0.70 nM) for the dopamine D4 receptor subtype. Employing both mitogenesis and GTP gamma S assays, ligand efficacy was evaluated indicating partial agonist properties. Interestingly, the tetrahydropyrimidine 4 (FAUC 2020) displayed significant intrinsic selectivity for D2(long) over D2(short). (c) 2006 Elsevier Ltd. All rights reserved.
• Design, synthesis and pharmacological profile of novel dopamine D2 receptor ligands
  作者：Ricardo Menegatti、Anna C Cunha、Vı́tor F Ferreira、Edna F.R Perreira、Ahmed El-Nabawi、Amira T Eldefrawi、Edson X Albuquerque、Gilda Neves、Stela M.K Rates、Carlos A.M Fraga、Eliezer J Barreiro

  DOI：10.1016/s0968-0896(03)00487-5

  日期：2003.11

  The present study describes the synthesis and pharmacological profile of three novel heterocyclic compounds originally designed, on the basis of bioisosterism, as dopamine D2 receptor ligands: 1-[1-(4-chlorophenyl)-1H-pyrazol-4-ylmethyl]-4-phenyl-piperazine (LASSBio-579), 1-phenyl-4-(1-phenyl-1H-[1,2,3]triazol-4-ylmethyl)-piperazine (LASSBio-580) and]-[1-(4-chloro-phenyl)-1H-[1,2,3]triazol-4-ylmethyl]-4-phenyl-piperazine (LASSBio-581). Binding studies performed on brain homogenate indicated that all three compounds bind selectively to D2 receptors. In addition, electrophysiological studies carried out in cultured hippocampal neurons suggested that LASSBio-579 and 581 act as D2 agonists, whereas LASSBio-580 acts as a D2 antagonist. (C) 2003 Elsevier Ltd. All rights reserved.
• 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.