4-[4-[[1-(4-Chlorophenyl)pyrazol-4-yl]methyl]piperazin-1-yl]phenol | 1430732-11-8

• 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: 4-[4-[[1-(4-Chlorophenyl)pyrazol-4-yl]methyl]piperazin-1-yl]phenol
• 英文别名: 4-[4-[[1-(4-chlorophenyl)pyrazol-4-yl]methyl]piperazin-1-yl]phenol
• CAS: 1430732-11-8
• 化学式: C₂₀H₂₁ClN₄O
• 分子量: 368.866
• InChiKey: HBGSAORKQHKGPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  44.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-[[1-(4-氯苯基)吡唑-4-基]甲基]-4-苯基哌嗪 在 Cunninghamella echinulata ATCC 9244 、 liquid potato dextrose soy medium 作用下， 反应 96.0h， 生成 4-[4-[[1-(4-Chlorophenyl)pyrazol-4-yl]methyl]piperazin-1-yl]phenol
  参考文献：
  名称：

  Biotransformation of LASSBio-579 and pharmacological evaluation of p -hydroxylated metabolite a N -phenylpiperazine antipsychotic lead compound

  摘要：

  Using a combination of docking and molecular dynamics simulations, we predicted that p-hydroxylation by CYP1A2 would be the main metabolic pathway for the 1-[1-(4-chlorophenyl)-1H-4pyrazolylmethyl]phenylhexahydropiperazine, LASSBio-579 (3). As the result of a screening process with strains of filamentous fungi, Cunninghamella echinulata ATCC 9244 was chosen to scale up the preparation of the p-hydroxylated metabolite (4). About 30 min after i.p. administration of (3) to rats was identified as the p-hydroxylated metabolite, confirming our in silico previsions. Chemical synthesis of the metabolite was performed and allowed its pharmacological evaluation in binding assays revealing its high affinity for D2 and D4 receptors, indicating that this metabolite should participate to the antipsychotic effect of (3) in vivo. Furthermore, we report here that both (3) and its p-hydroxylated metabolite (4) have a much lower affinity than clozapine for two receptors involved in adverse reactions. Voltammetric assays were useful to understand the redox profile of (3). (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.08.011

文献信息

• Biotransformation of LASSBio-579 and pharmacological evaluation of p -hydroxylated metabolite a N -phenylpiperazine antipsychotic lead compound
  作者：Tatiana F. Gomes、Thais E.T. Pompeu、Daniel A. Rodrigues、François Noël、Ricardo Menegatti、Carolina H. Andrade、José R. Sabino、Eric S. Gil、Teresa Dalla Costa、Andresa H. Betti、Camila B. Antonio、Stela M.K. Rates、Carlos A.M. Fraga、Eliezer J. Barreiro、Valéria de Oliveira

  DOI：10.1016/j.ejmech.2012.08.011

  日期：2013.4

  Using a combination of docking and molecular dynamics simulations, we predicted that p-hydroxylation by CYP1A2 would be the main metabolic pathway for the 1-[1-(4-chlorophenyl)-1H-4pyrazolylmethyl]phenylhexahydropiperazine, LASSBio-579 (3). As the result of a screening process with strains of filamentous fungi, Cunninghamella echinulata ATCC 9244 was chosen to scale up the preparation of the p-hydroxylated metabolite (4). About 30 min after i.p. administration of (3) to rats was identified as the p-hydroxylated metabolite, confirming our in silico previsions. Chemical synthesis of the metabolite was performed and allowed its pharmacological evaluation in binding assays revealing its high affinity for D2 and D4 receptors, indicating that this metabolite should participate to the antipsychotic effect of (3) in vivo. Furthermore, we report here that both (3) and its p-hydroxylated metabolite (4) have a much lower affinity than clozapine for two receptors involved in adverse reactions. Voltammetric assays were useful to understand the redox profile of (3). (C) 2012 Elsevier Masson SAS. All rights reserved.