(3-(4-chlorophenyl)-1H-pyrazol-5-yl)(4-(2-(3-fluorobenzyloxy)phenyl)piperazin-1-yl)methanone | 1277167-72-2

• 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: (3-(4-chlorophenyl)-1H-pyrazol-5-yl)(4-(2-(3-fluorobenzyloxy)phenyl)piperazin-1-yl)methanone
• 英文别名: [3-(4-chlorophenyl)-1H-pyrazol-5-yl]-[4-[2-[(3-fluorophenyl)methoxy]phenyl]piperazin-1-yl]methanone
• CAS: 1277167-72-2
• 化学式: C₂₇H₂₄ClFN₄O₂
• 分子量: 490.965
• InChiKey: LUMGDOAZBANGEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  61.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氟溴苄 在 N-甲基吗啉 、 盐酸 、 18-冠醚-6 、 HATU 、 水 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 45.0h， 生成 (3-(4-chlorophenyl)-1H-pyrazol-5-yl)(4-(2-(3-fluorobenzyloxy)phenyl)piperazin-1-yl)methanone
  参考文献：
  名称：

  Discovery of 3-aryl-5-acylpiperazinyl-pyrazoles as antagonists to the NK3 receptor

  摘要：

  A series of 3-aryl-5-acylpiperazinyl-pyrazoles (e.g., 3a-b) initially identified through a high-throughput screening campaign using the aequorin Ca2+ bioluminescence assay as novel, potent small molecule antagonists of the G protein-coupled human tachykinin NK3 receptor (hNK3-R) is described. Preliminary profiling revealed poor plasma and metabolic stability for these structures in rodents. Further optimization efforts resulted in analogs with improved potency, stability, and pharmacokinetic properties as well as good brain permeability, for example, compounds 26 and 42. Unexpected cytotoxicity was observed in such N-Me pyrazole structures as compounds 41-42. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.033

文献信息

• Discovery of 3-aryl-5-acylpiperazinyl-pyrazoles as antagonists to the NK3 receptor
  作者：Hamid R. Hoveyda、Marie-Odile Roy、Sebastien Blanc、Sophie Noël、Joseph M. Salvino、Mark A. Ator、Graeme Fraser

  DOI：10.1016/j.bmcl.2011.02.033

  日期：2011.4

  A series of 3-aryl-5-acylpiperazinyl-pyrazoles (e.g., 3a-b) initially identified through a high-throughput screening campaign using the aequorin Ca2+ bioluminescence assay as novel, potent small molecule antagonists of the G protein-coupled human tachykinin NK3 receptor (hNK3-R) is described. Preliminary profiling revealed poor plasma and metabolic stability for these structures in rodents. Further optimization efforts resulted in analogs with improved potency, stability, and pharmacokinetic properties as well as good brain permeability, for example, compounds 26 and 42. Unexpected cytotoxicity was observed in such N-Me pyrazole structures as compounds 41-42. (C) 2011 Elsevier Ltd. All rights reserved.