1-(2-hydroxybutyl)-5-[3-(4-fluorophenyl)ureido]-1H-pyrazole-4-carboxylic acid ethyl ester | 1123763-25-6

• 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-(2-hydroxybutyl)-5-[3-(4-fluorophenyl)ureido]-1H-pyrazole-4-carboxylic acid ethyl ester
• 英文别名: Ethyl 5-[(4-fluorophenyl)carbamoylamino]-1-(2-hydroxybutyl)pyrazole-4-carboxylate
• CAS: 1123763-25-6
• 化学式: C₁₇H₂₁FN₄O₄
• 分子量: 364.377
• InChiKey: DWFFQVGJGIUTLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-amino-1-(2-hydroxybutyl)-1H-pyrazole-4-carboxylic acid ethyl ester 、 异氰酸对氟苯基酯 以 甲苯 为溶剂， 反应 6.0h， 以50%的产率得到1-(2-hydroxybutyl)-5-[3-(4-fluorophenyl)ureido]-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

• Urea derivatives of 1H-pyrazol-4-carboxylic acid with neutrophil chemotaxis inhibiting activity
  申请人：Universita' Degli Studi Di Genova

  公开号：EP2033955A1

  公开（公告）日：2009-03-11

  Compounds of formula (I), wherein R1 = H, optionally substituted C1-C8 alkyl, -CH2-CH(R3)OR2, where R2 = H or C1-C3 alkyl and R3 = optionally substituted C1-C8 alkyl; Q = NHR4 or a saturated heterocyclic 3-7 membered ring containing nitrogen, where R4 = optionally substituted C3-C8 alkyl, optionally substituted aralkyl, optionally substituted aryl; and enantiomers, diastereoisomers and pharmaceutically acceptable salts thereof; it is also described a process for preparing such compounds, the use of such compounds as a medicament, in particular in the treatment of inflammatory diseases of autoimmune origin, as well as pharmaceutical compositions that comprise such compounds.

  公式(I)的化合物，其中R1 = H，可选地取代的C1-C8烷基，-CH2-CH(R3)OR2，其中R2 = H或C1-C3烷基和R3 = 可选地取代的C1-C8烷基；Q = NHR4或含有氮的饱和杂环3-7元环，其中R4 = 可选地取代的C3-C8烷基，可选地取代的芳烷基，可选地取代的芳基；以及它们的对映异构体、非对映异构体和药用可接受的盐；还描述了制备这些化合物的方法，将这些化合物用作药物，特别是在治疗自身免疫性炎症疾病中的应用，以及包含这些化合物的药物组合物。
• 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.