ethyl 3-(3-nitrophenyl)-1H-pyrazole-5-carboxylate | 1025724-57-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 3-(3-nitrophenyl)-1H-pyrazole-5-carboxylate
• 英文别名: ethyl 5-(3-nitrophenyl)-1H-pyrazole-3-carboxylate
• CAS: 1025724-57-5；1316754-31-0
• 化学式: C₁₂H₁₁N₃O₄
• 分子量: 261.237
• InChiKey: VIKHZBXGLAOVFS-UHFFFAOYSA-N

物化性质

• 熔点：
  146 °C
• 沸点：
  502.6±45.0 °C(Predicted)
• 密度：
  1.357±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2933199090

反应信息

• 作为反应物：
  描述：

  ethyl 3-(3-nitrophenyl)-1H-pyrazole-5-carboxylate 在 甲醇 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 生成 N-((S)-2-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)-1-methylethyl)-5-(3-nitrophenyl)-1H-pyrazole-3-formamide
  参考文献：
  名称：

  基于darolutamide结构的新型雄激素受体拮抗剂的开发

  摘要：

  雄激素信号通路在前列腺癌（PCa）的发生发展中发挥着重要作用，而抗雄激素药物是治疗前列腺癌最有效的疗法之一。Darolutamide 4 (ODM-201) 是一种很有前途的第二代抗雄激素药物，因为它具有独特的化学结构和对雄激素受体 (AR) 的良好活性。本文研究了ODM-201的构效关系，合成了37个类似物。与 ODM-201 相比，其中一半表现出相似或更好的抗 AR 转录活性。此外，化合物28t的抑制活性对两种抗性突变体（AR-F876L 和 AR-T877A）的抗性优于 ODM-201。该研究为进一步优化ODM-201和开发抗CRPC药物提供了新线索。

  DOI：

  10.1016/j.bioorg.2022.105829
• 作为产物：
  描述：

  间硝基苯乙酮 在 sodium methylate 、 溶剂黄146 、 肼 作用下， 以 乙醚 为溶剂， 反应 27.0h， 生成 ethyl 3-(3-nitrophenyl)-1H-pyrazole-5-carboxylate
  参考文献：
  名称：

  某些新型3-苯基-N- [3-（4-苯基哌嗪-1基）丙基] -1 H-吡唑-5-羧酰胺衍生物的合成及抗炎活性

  摘要：

  合成了一系列新的3-苯基-N- [3-（4-苯基哌嗪-1基）丙基] -1H-吡唑-5-羧酰胺衍生物，并用角叉菜胶诱导的大鼠爪水肿模型研究了它们的抗炎活性。体内。发现所有合成的化合物都是有效的抗炎药。

  DOI：

  10.1016/j.bmcl.2011.05.105

文献信息

• “On water” synthesis of N-unsubstituted pyrazoles: semicarbazide hydrochloride as an alternative to hydrazine for preparation of pyrazole-3-carboxylate derivatives and 3,5-disubstituted pyrazoles
  作者：Violeta Marković、Milan D. Joksović

  DOI：10.1039/c4gc02028f

  日期：——

  A green, simple and highly efficient method for the synthesis of pyrazole-3-carboxylates and 3,5-disubstituted pyrazoles by cyclization of 4-aryl(hetaryl, alkyl)-2,4-diketoesters and 1,3-diketones with semicarbazide hydrochloride under “on water” conditions has been developed. This method also does not require toxic hydrazine and product purification, eliminating the use of toxic liquid chemicals.

  一种绿色，简单且高效的方法，通过用氨基脲盐酸盐将4-芳基（杂芳基，烷基）-2,4-二酮酸酯和1,3-二酮环化，合成吡唑-3-羧酸酯和3,5-二取代的吡唑在“水上”条件下已经开发出来。该方法也不需要毒性肼和产物纯化，从而消除了对有毒液体化学物质的使用。
• Synthesis and cytotoxicity evaluation of 1-[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl]-3-aryl-1H-pyrazole-5-carboxylic acid derivatives
  作者：Lingaiah Nagarapu、Hanmant K. Gaikwad、Kartheeka Sarikonda、Jhansi Mateti、Rajashaker Bantu、P.S. Raghu、Krishna Madhuri Manda、Shasi Vardhan Kalvendi

  DOI：10.1016/j.ejmech.2010.07.004

  日期：2010.11

  Several novel molecules, 1-(3'-(9H-carbazol-4-yloxy)-2'-hydroxypropyl)-3-aryl-1H-pyrazole-5-carboxylic acid derivatives 3a-g were synthesized and screened to evaluate their cytotoxicity against cancer cells in vitro. The compounds 3a-g has been prepared by the reaction of ethyl 3-aryl-1H-pyrazole-5-carboxylate with 4-oxiranylmethoxy-9H-carbazole in moderate to excellent yields. The cytotoxicity of synthesized compounds was evaluated by a SRB (sulforhodamine B) assay against cancer cell such as SK-N-SH human neuroblastoma (NB), human A549 lung carcinoma, human breast cancer MCF-7 cell lines. The results showed that seven compounds can suppress SK-N-SH tumor cancer cell growth. Among them, compound 3d was the most effective small molecule in inhibiting SK-N-SH cell growth. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Synthesis and acrosin inhibitory activities of 5-phenyl-1H-pyrazole-3-carboxylic acid amide derivatives
  作者：Wei Tian、Guangqian Han、Ju Zhu、Jingjing Qi、Qianqian Chen、Juntao Zhao、Canhui Zheng、Ling Zhang、Youjun Zhou、Jiaguo Lv

  DOI：10.1016/j.bmcl.2013.05.031

  日期：2013.7

  A series of novel 5-phenyl-1H-pyrazole-3-carboxylic acid amide derivatives were designed, synthesized, and their acrosin inhibitory activities in vitro were evaluated. The results of the acrosin inhibitory activity showed that all target compounds were more potent than control TLCK. CompoundsAQ-A1, AQ-D3, AQ-D4, AQ-E4 and AQ-E5 exhibited stronger acrosin inhibitory activities than control ISO-1. Especially, compound AQ-E5 displayed the most potent acrosin inhibitory activity in all the compounds, with an IC50 of 0.01 mu mol/mL. This study provided a new structural class for the development of novel acrosin inhibitory agents. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.
• Synthesis, Structure-Activity Relationship, and Pharmacophore Modeling Studies of Pyrazole-3-Carbohydrazone Derivatives as Dipeptidyl Peptidase IV Inhibitors
  作者：Deyan Wu、Fangfang Jin、Weiqiang Lu、Jin Zhu、Cui Li、Wei Wang、Yun Tang、Hualiang Jiang、Jin Huang、Guixia Liu、Jian Li

  DOI：10.1111/j.1747-0285.2012.01365.x

  日期：2012.6

  Type 2 diabetes mellitus (T2DM) is a metabolic disease and a major challenge to healthcare systems around the world. Dipeptidyl peptidase IV (DPP‐4), a serine protease, has been rapidly emerging as an effective therapeutic target for the treatment for T2DM. In this study, a series of novel DPP‐4 inhibitors, featuring the pyrazole‐3‐carbohydrazone scaffold, have been discovered using an integrated approach of structure‐based virtual screening, chemical synthesis, and bioassay. Virtual screening of SPECS Database, followed by enzymatic activity assay, resulted in five micromolar or low‐to‐mid‐micromolar inhibitory level compounds (1–5) with different scaffold. Compound 1 was selected for the further structure modifications in considering inhibitory activity, structural variability, and synthetic accessibility. Seventeen new compounds were synthesized and tested with biological assays. Nine compounds (6e, 6g, 6k–l, and 7a–e) were found to show inhibitory effects against DPP‐4. Molecular docking models give rational explanation about structure–activity relationships. Based on eight DPP‐4 inhibitors (1–5, 6e, 6k, and 7d), the best pharmacophore model hypo1 was obtained, consisting of one hydrogen bond donor (HBD), one hydrogen bond acceptor (HBA), and two hydrophobic (HY) features. Both docking models and pharmacophore mapping results are in agreement with pharmacological results. The present studies give some guiding information for further structural optimization and are helpful for future DPP‐4 inhibitors design.