LASSBio-1762 | 1449038-82-7

• 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: LASSBio-1762
• 英文别名: 1-[5-[1-(4-Chlorophenyl)pyrazol-4-yl]pentyl]-4-phenylpiperazine；1-[5-[1-(4-chlorophenyl)pyrazol-4-yl]pentyl]-4-phenylpiperazine
• CAS: 1449038-82-7
• 化学式: C₂₄H₂₉ClN₄
• 分子量: 408.974
• InChiKey: MKRMGDJUMMLQKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  24.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-(4-chlorophenyl)-4-iodo-1H-pyrazole 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 palladium 10% on activated carbon 、 氢气 、 lithium carbonate 、 三乙胺 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 乙腈 为溶剂， 80.0 ℃ 、275.8 kPa 条件下， 反应 35.41h， 生成 LASSBio-1762
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of new N-phenylpiperazine derivatives designed as homologues of the antipsychotic lead compound LASSBio-579

  摘要：

  In an attempt to increase the affinity of our antipsychotic lead compound LASSBio-579 (1-((1-(4-chlorophenyl)-1H-pyrazol-4-yl)methyl)-4-phenylpiperazine; (2)) for the 5-HT2A receptor, we synthesized five new N-phenylpiperazine derivatives using a linear synthetic route and the homologation strategy. The binding profile of these compounds was evaluated for a series of dopaminergic, serotonergic and alpha-adrenergic receptors relevant for schizophrenia, using classical competition assays. Increasing the length of the spacer between the functional groups of (2) proved to be appropriated since the affinity of these compounds increased 3-10-fold for the 5-HT2A receptor, with no relevant change in the affinity for the D-2-like and 5-HT1A receptors. A GTP-shift assay also indicated that the most promising derivative (1-(4-(1-(4-chlorophenyl)-1H-pyrazol-4-yl) butyl)-4-phenylpiperazine) (LASSBio-1635) (6) has the expected efficacy at the 5-HT2A receptors, acting as an antagonist. Intraperitoneal administration of (6) prevented apomorphine-induced climbing behavior and ketamine-induced hyperlocomotion in mice, in a dose dependent manner. Together, these results show that (6) could be considered as a new antipsychotic lead compound. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.05.027

文献信息

• Synthesis and pharmacological evaluation of new N-phenylpiperazine derivatives designed as homologues of the antipsychotic lead compound LASSBio-579
  作者：Thais E.T. Pompeu、Fernando R.S. Alves、Carolina D.M. Figueiredo、Camila B. Antonio、Vivian Herzfeldt、Bruna C. Moura、Stela M.K. Rates、Eliezer J. Barreiro、Carlos A.M. Fraga、François Noël

  DOI：10.1016/j.ejmech.2013.05.027

  日期：2013.8

  In an attempt to increase the affinity of our antipsychotic lead compound LASSBio-579 (1-((1-(4-chlorophenyl)-1H-pyrazol-4-yl)methyl)-4-phenylpiperazine; (2)) for the 5-HT2A receptor, we synthesized five new N-phenylpiperazine derivatives using a linear synthetic route and the homologation strategy. The binding profile of these compounds was evaluated for a series of dopaminergic, serotonergic and alpha-adrenergic receptors relevant for schizophrenia, using classical competition assays. Increasing the length of the spacer between the functional groups of (2) proved to be appropriated since the affinity of these compounds increased 3-10-fold for the 5-HT2A receptor, with no relevant change in the affinity for the D-2-like and 5-HT1A receptors. A GTP-shift assay also indicated that the most promising derivative (1-(4-(1-(4-chlorophenyl)-1H-pyrazol-4-yl) butyl)-4-phenylpiperazine) (LASSBio-1635) (6) has the expected efficacy at the 5-HT2A receptors, acting as an antagonist. Intraperitoneal administration of (6) prevented apomorphine-induced climbing behavior and ketamine-induced hyperlocomotion in mice, in a dose dependent manner. Together, these results show that (6) could be considered as a new antipsychotic lead compound. (C) 2013 Elsevier Masson SAS. All rights reserved.