5-amino-1-(2-hydroxypentyl)-1H-pyrazole-4-carboxylic acid ethyl ester | 1123763-28-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-amino-1-(2-hydroxypentyl)-1H-pyrazole-4-carboxylic acid ethyl ester
• 英文别名: Ethyl 5-amino-1-(2-hydroxypentyl)pyrazole-4-carboxylate
• CAS: 1123763-28-9
• 化学式: C₁₁H₁₉N₃O₃
• 分子量: 241.29
• InChiKey: SOHNNFXDZRCYRF-UHFFFAOYSA-N

物化性质

• 熔点：
  84-86 °C(Solvent: Ethanol)
• 沸点：
  405.0±35.0 °C(predicted)
• 密度：
  1.25±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  90.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  苯甲酰基异硫氰酸酯 、 5-amino-1-(2-hydroxypentyl)-1H-pyrazole-4-carboxylic acid ethyl ester 以 四氢呋喃 为溶剂， 以55 %的产率得到ethyl 5-(3-benzoylthioureido)-1-(2-hydroxypentyl)-1H-pyrazole-4-carboxylate
  参考文献：
  名称：

  New Pyrazolyl Thioureas Active against the Staphylococcus Genus

  摘要：

  To meet the urgent need for new antibacterial molecules, a small library of pyrazolyl thioureas (PTUs) was designed, synthesized and tested against difficult-to-treat human pathogens. The prepared derivatives are characterized by a carboxyethyl functionality on C4 and different hydroxyalkyl chains on N1. Compounds 1a–o were first evaluated against a large panel of Gram-positive and Gram-negative pathogens. In particular, the majority of PTUs proved to be active against different species of the Staphylococcus genus, with MIC values ranging from 32 to 128 µg/mL on methicillin-resistant Staphylococcus strains, often responsible for severe pulmonary disease in cystic fibrosis patients. Time-killing experiments were also performed for the most active compounds, evidencing a bacteriostatic mechanism of action. For most active derivatives, cytotoxicity was evaluated in Vero cells, and at the tested concentrations and at the experimental exposure time of 24 h, none of the compounds analysed showed significant toxicity. In addition, favourable drug-like, pharmacokinetic and toxicity properties were predicted for all new synthesized derivatives. Overall, the collected data confirmed the PTU scaffold as a promising chemotype for the development of novel antibacterial agents active against Gram-positive multi-resistant strains frequently isolated from cystic fibrosis patients.

  DOI：

  10.3390/ph17030376
• 作为产物：
  描述：

  丙基环氧乙烷 在 hydrazine hydrate 作用下， 以 乙醇 为溶剂， 反应 8.0h， 生成 5-amino-1-(2-hydroxypentyl)-1H-pyrazole-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  New Pyrazolyl Thioureas Active against the Staphylococcus Genus

  摘要：

  To meet the urgent need for new antibacterial molecules, a small library of pyrazolyl thioureas (PTUs) was designed, synthesized and tested against difficult-to-treat human pathogens. The prepared derivatives are characterized by a carboxyethyl functionality on C4 and different hydroxyalkyl chains on N1. Compounds 1a–o were first evaluated against a large panel of Gram-positive and Gram-negative pathogens. In particular, the majority of PTUs proved to be active against different species of the Staphylococcus genus, with MIC values ranging from 32 to 128 µg/mL on methicillin-resistant Staphylococcus strains, often responsible for severe pulmonary disease in cystic fibrosis patients. Time-killing experiments were also performed for the most active compounds, evidencing a bacteriostatic mechanism of action. For most active derivatives, cytotoxicity was evaluated in Vero cells, and at the tested concentrations and at the experimental exposure time of 24 h, none of the compounds analysed showed significant toxicity. In addition, favourable drug-like, pharmacokinetic and toxicity properties were predicted for all new synthesized derivatives. Overall, the collected data confirmed the PTU scaffold as a promising chemotype for the development of novel antibacterial agents active against Gram-positive multi-resistant strains frequently isolated from cystic fibrosis patients.

  DOI：

  10.3390/ph17030376

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。
• Synthesis, functional proteomics and biological evaluation of new 5-pyrazolyl ureas as potential anti-angiogenic compounds
  作者：Elva Morretta、Adama Sidibè、Andrea Spallarossa、Antonello Petrella、Elda Meta、Olga Bruno、Maria Chiara Monti、Chiara Brullo

  DOI：10.1016/j.ejmech.2021.113872

  日期：2021.12

  Based on biological results of previous synthesized pyrazolyl ureas able to interfere with angiogenesis process, we planned and synthesized the new benzyl-urea derivatives 2–4; some of them showed an interesting anti-proliferative profile and particularly 4e potently inhibited HUVEC proliferation. To shed light on the mechanism of action of 4e, its interactome has been deeply inspected to identify

  基于以往合成的能够干扰血管生成的吡唑脲的生物学结果，我们规划并合成了新的苄基脲衍生物2-4；其中一些显示出有趣的抗增殖特性，特别是4e有效抑制 HUVEC 增殖。为了阐明4e的作用机制，对其相互作用组进行了深入检查，以确定最突出的蛋白质伙伴，主要考虑激酶组和磷酸组，通过药物亲和力响应靶稳定性实验，然后进行靶向有限蛋白水解分析。从这些研究中，PP1γ 成为最可靠的4HUVEC 中的潜在目标。对 PP1γ 进行分子对接模拟以预测4e结合模式。为了评估其潜在的抗血管生成作用，在体外测试了4e以验证对激酶和磷酸盐活性的干扰。总体而言，我们的结果证明4e具有有趣的抗血管生成作用，可能是由于其在细胞内水平对 PP1γ 信号通路的作用。
• Design, synthesis and biological evaluation of new pyrazolyl-ureas and imidazopyrazolecarboxamides able to interfere with MAPK and PI3K upstream signaling involved in the angiogenesis
  作者：Elda Meta、Chiara Brullo、Adama Sidibe、Beat A. Imhof、Olga Bruno

  DOI：10.1016/j.ejmech.2017.03.066

  日期：2017.6

  Taking into account the structure activity relationship information given by our previous studies, we designed and synthesized a small library of pyrazolylureas and imidazopyrazolecarboxamides fluorinated on urea moiety and differently decorated on pyrazole nucleus. All compounds were preliminary screened by Western blotting technique to evaluate their activity on MAPK and PI3K pathways by monitoring ERK1/2, p38MAPK and Akt phosphorylation, and also screened with a wound healing assay to assess their capacity in inhibiting endothelial cell migration, using human umbilical vein endothelial cells stimulated with VEGF. Pyrazoles and imidazopyrazoles did not show the same activity profile. SAR consideration showed that specific substituents and their position in pyrazole nucleus, as well as the type of substituent on the phenylurea moiety play a pivotal role in determining increase or decrease of kinases phosphorylation. On the other hand the loss of flexibility in imidazopyrazole derivatives is responsible for activity potentiation. Screening of the compound library for inhibition of endothelial cell migration, a function required for angiogenesis, showed significant activity for compound 3. This compound might interfere with cell migration by modulating the activity of different upstream target kinases. Therefore, compound 3 represents a potential inhibitor of angiogenesis. Furthermore, it may be used as a tool to identify unknown mediators of endothelial migration and thereby unveiling new therapeutic targets for controlling pathological angiogenesis in diseases such as cancers. (C) 2017 Elsevier Masson SAS. All rights reserved.
• 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.