(1,4-dibenzyl-piperazin-2-yl)-diphenyl-methanol | 17532-22-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1,4-dibenzyl-piperazin-2-yl)-diphenyl-methanol
• 英文别名: (1,4-dibenzylpiperazin-2-yl)diphenylmethanol；α-<2-(1,4-Dibenzyl-piperazinyl)>-benzhydrol
• CAS: 17532-22-8
• 化学式: C₃₁H₃₂N₂O
• 分子量: 448.608
• InChiKey: HXVUWCMCQNZLDG-UHFFFAOYSA-N

物化性质

• 沸点：
  586.1±45.0 °C(Predicted)
• 密度：
  1.165±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.31
• 重原子数：
  34.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  26.71
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (1,4-dibenzyl-piperazin-2-yl)-diphenyl-methanol 在 盐酸 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 20.0 ℃ 、317.17 kPa 条件下， 反应 31.0h， 生成 1,1-diphenyltetrahydro-1H-oxazolo[3,4-α]pyrazin-3(5H)-one
  参考文献：
  名称：

  Identification of Neuropeptide S Antagonists: Structure–Activity Relationship Studies, X-ray Crystallography, and in Vivo Evaluation

  摘要：

  Modulation of the neuropeptide S (NPS) system has been linked to a variety of CNS disorders such as panic disorder, anxiety, sleeping disorders, asthma, obesity, PTSD, and substance abuse. In this study, a series of diphenyltetrahydro-1H-oxazolo[3,4-α]pyrazin-3(5H)-ones were synthesized and evaluated for antagonist activity at the neuropeptide S receptor. The absolute configuration was determined by chiral resolution of the key synthetic intermediate, followed by analysis of one of the individual enantiomers by X-ray crystallography. The R isomer was then converted to a biologically active compound (34) that had a Ke of 36 nM. The most potent compound displayed enhanced aqueous solubility compared with the prototypical antagonist SHA-68 and demonstrated favorable pharmacokinetic properties for behavioral assessment. In vivo analysis in mice indicated a significant blockade of NPS induced locomotor activity at an ip dose of 50 mg/kg. This suggests that analogs having improved drug-like properties will facilitate more detailed studies of the neuropeptide S receptor system.

  DOI：

  10.1021/cn500113c
• 作为产物：
  描述：

  苯基锂 、 哌嗪2-甲酸二盐酸盐 以 四氢呋喃 为溶剂， 以50%的产率得到(1,4-dibenzyl-piperazin-2-yl)-diphenyl-methanol
  参考文献：
  名称：

  Identifying structural features on 1,1-diphenyl-hexahydro-oxazolo[3,4-a]pyrazin-3-ones critical for Neuropeptide S antagonist activity

  摘要：

  A series of 7-substituted 1,1-diphenyl-hexahydro-oxazolo[3,4-a]pyrazin-3-ones were synthesized and tested for Neuropeptide S (NPS) antagonist activity. A concise synthetic route was developed, which features a DMAP catalyzed carbamate formation. 4-Fluorobenzyl urea (1c) and benzyl urea (1d) were identified as the most potent antagonists among the compounds examined. Structure-activity relationships (SARs) demonstrate that a 7-position urea functionality is required for potent antagonist activity and alkylation of the urea nitrogen (1e) or replacement with carbon or oxygen (5a) results in reduced potency. In addition, compounds with alpha-methyl substitution (1b) or elongated alkyl chains (1h and 1j) had reduced potency, indicating a limited tolerance for 7-position substituents. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.098