1-(2-hydroxypropyl)-5-[3-(4-benzyl)piperazinylureido]-1H-pyrazole-4-carboxylic acid ethyl ester | 1162655-57-3

• 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: 1-(2-hydroxypropyl)-5-[3-(4-benzyl)piperazinylureido]-1H-pyrazole-4-carboxylic acid ethyl ester
• 英文别名: Ethyl 5-[(4-benzylpiperazine-1-carbonyl)amino]-1-(2-hydroxypropyl)pyrazole-4-carboxylate
• CAS: 1162655-57-3
• 化学式: C₂₁H₂₉N₅O₄
• 分子量: 415.492
• InChiKey: CGHQRCNGEMKHJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  99.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  光气 、 1-苄基哌嗪 、 5-amino-1-(2-hydroxypropyl)-1H-pyrazole-4-carboxylic acid ethyl ester 在 sodium acetate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 以58%的产率得到1-(2-hydroxypropyl)-5-[3-(4-benzyl)piperazinylureido]-1H-pyrazole-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  1-Methyl and 1-(2-hydroxyalkyl)-5-(3-alkyl/cycloalkyl/phenyl/naphthylureido)-1H-pyrazole-4-carboxylic acid ethyl esters as potent human neutrophil chemotaxis inhibitors

  摘要：

  In this paper we report the synthesis and the chemotaxis inhibitory activity of a number of 1H-pyrazole-4-carboxylic acid ethyl esters 2 functionalized in N1 with a methyl group or different hydroxyalkyl chains and in position 5 with a series of 3-substituted urea groups. These compounds were designed as development of previous pyrazole-urea derivatives that resulted potent IL8-induced neutrophil chemotaxis inhibitors in vitro. Most of the new compounds revealed a potent inhibition of both IL8- and fMLP-OMe-stimulated neutrophil chemotaxis. The most active compounds in the fMLP-OMe induced chemotaxis test showed IC(50) in the range 0.19 nM-2 mu M; but we observed a very strong inhibition in the IL8- induced chemotaxis test, having the most active compounds IC(50) at pM concentrations. In vivo compounds 2e and 2f, although to a lesser extent, at 50 mg/kg os decreased granulocyte infiltration in zymosan-induced peritonitis in mice. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.03.035

文献信息

• 1-Methyl and 1-(2-hydroxyalkyl)-5-(3-alkyl/cycloalkyl/phenyl/naphthylureido)-1H-pyrazole-4-carboxylic acid ethyl esters as potent human neutrophil chemotaxis inhibitors
  作者：Olga Bruno、Chiara Brullo、Francesco Bondavalli、Silvia Schenone、Susanna Spisani、Maria Sofia Falzarano、Katia Varani、Elisabetta Barocelli、Vigilio Ballabeni、Carmine Giorgio、Massimiliano Tognolini

  DOI：10.1016/j.bmc.2009.03.035

  日期：2009.5

  In this paper we report the synthesis and the chemotaxis inhibitory activity of a number of 1H-pyrazole-4-carboxylic acid ethyl esters 2 functionalized in N1 with a methyl group or different hydroxyalkyl chains and in position 5 with a series of 3-substituted urea groups. These compounds were designed as development of previous pyrazole-urea derivatives that resulted potent IL8-induced neutrophil chemotaxis inhibitors in vitro. Most of the new compounds revealed a potent inhibition of both IL8- and fMLP-OMe-stimulated neutrophil chemotaxis. The most active compounds in the fMLP-OMe induced chemotaxis test showed IC(50) in the range 0.19 nM-2 mu M; but we observed a very strong inhibition in the IL8- induced chemotaxis test, having the most active compounds IC(50) at pM concentrations. In vivo compounds 2e and 2f, although to a lesser extent, at 50 mg/kg os decreased granulocyte infiltration in zymosan-induced peritonitis in mice. (C) 2009 Elsevier Ltd. All rights reserved.