ethyl 1,5-bis(4-chlorophenyl)-1H-pyrazole-3-carboxylate | 1082746-75-5

• 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 1,5-bis(4-chlorophenyl)-1H-pyrazole-3-carboxylate
• 英文别名: Ethyl 1,5-bis(4-chlorophenyl)pyrazole-3-carboxylate
• CAS: 1082746-75-5
• 化学式: C₁₈H₁₄Cl₂N₂O₂
• 分子量: 361.227
• InChiKey: PMHPHUDSSKEYKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 1,5-bis(4-chlorophenyl)-1H-pyrazole-3-carboxylate 在 吡啶 、 lithium aluminium tetrahydride 、 甲基磺酰氯 作用下， 以 四氢呋喃 为溶剂， 反应 13.0h， 生成 2-((1,5-bis(4-chlorophenyl)-1H-pyrazol-3-yl)methyl)isoindoline-1,3-dione
  参考文献：
  名称：

  ジフェニルピラゾール誘導体及びその医薬用途

  摘要：

  该发明提供了具有抑制MALTI的蛋白酶活性的作用，并可用作自身免疫性疾病如多发性硬化症和银屑病的治疗药物或预防药物的化合物。该发明提供了代表为下式的二苯基哌唑衍生物或其药理学上可接受的盐。【选择图】无

  公开号：

  JP2017214315A
• 作为产物：
  描述：

  苯乙酮 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 生成 ethyl 1,5-bis(4-chlorophenyl)-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  Structure–activity relationship studies of 3-substituted pyrazoles as novel allosteric inhibitors of MALT1 protease

  摘要：

  DOI：

  10.1016/j.bmcl.2021.127996

文献信息

• Synthesis, anti-inflammatory screening, molecular docking, and COX-1,2/-5-LOX inhibition profile of some novel quinoline derivatives
  作者：Ibrahim Chaaban、Ola H. Rizk、Tamer M. Ibrahim、Shery S. Henen、El-Sayeda M. El-Khawass、Aida E. Bayad、Ibrahim M. El-Ashmawy、Hisham A. Nematalla

  DOI：10.1016/j.bioorg.2018.03.023

  日期：2018.8

  New quinoline compounds comprising pyrazole scaffold through different amide linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory activity. Eight compounds (5c, 11b,c, 12c, 14a,b, 20a and 21a) were found to exhibit promising anti-inflammatory profiles in acute and sub-acute inflammatory models. They were screened for their ulcerogenic activity and none of

  合成了包含通过不同酰胺键的吡唑支架的新喹啉化合物。评价合成的化合物的抗炎活性。发现了八种化合物（5c，11b，c，12c，14a，b，20a和21a）在急性和亚急性炎症模型中显示出有希望的抗炎特性。对它们的致溃疡活性进行了筛选，没有一个与参考药物塞来昔布相比具有显着的致溃疡活性，并且实验动物对它们具有很好的耐受性，并具有较高的安全系数（ALD 50  > 0.3 g / kg）。化合物5c，11b，c，图12c，14a，b，20a和21a显示出显着的体外LOX抑制活性，高于齐留通。体外COX-1 / COX-2抑制研究表明，化合物12c，14a，b和20a对COX-2的选择性高于对COX-1的选择性。在测试的化合物中，具有IC 50的12c，14a和14b表现出对COX-2的最高抑制活性分别为0.1、0.11和0.11μM。对接实验试图推测COX-2酶结合位点中活性最高的化合物的结合模式，
• Antiobesity designed multiple ligands: Synthesis of pyrazole fatty acid amides and evaluation as hypophagic agents
  作者：Mario Alvarado、Pilar Goya、Manuel Macías-González、Francisco Javier Pavón、Antonia Serrano、Nadine Jagerovic、Jose Elguero、Angel Gutiérrez-Rodríguez、Santiago García-Granda、Margarita Suardíaz、Fernando Rodríguez de Fonseca

  DOI：10.1016/j.bmc.2008.10.023

  日期：2008.12

  Searching for new antiobesity agents, a new series of fatty acid amide derivatives of 1,5-diarylpyrazole have been synthesized as dual peroxisome proliferator activated receptor alpha (PPARalpha)/cannabinoid receptor ligands. The compounds have been evaluated in vivo and in vitro as PPARalpha activators and as cannabinoids in two tests of the mouse tetrad. In vivo, food intake studies have been performed

  为了寻找新的减肥药，已经合成了一系列新的1,5-二芳基吡唑脂肪酸酰胺衍生物，作为双重过氧化物酶体增殖物激活受体α（PPARalpha）/大麻素受体配体。在小鼠四联体的两次测试中，已将这些化合物作为PPARalpha激活剂和大麻素在体内和体外进行了评估。在体内，已经对所有化合物进行了食物摄入研究。没有发现明显的大麻素活性，但是一些化合物具有有效的PPARalpha活化剂的作用。几种化合物显示出厌食特性，从而减少了大鼠的食物摄入。
• Discovery of a Novel ASM Direct Inhibitor with a 1,5-Diphenyl-pyrazole Scaffold and Its Antidepressant Mechanism of Action
  作者：Shaochun Shi、Dingchen Ma、Ximing Guo、Yu Chen、Jinying Yu、Xiao Hu、Xuan Wang、Ting Li、Ke Wang、Yunbao Zhi、Guoqing Yang、Lizhi Lin、Qingjing Hao、Yuqiao Yang、Kan Yang、Jinxin Wang

  DOI：10.1021/acs.jmedchem.4c00831

  日期：2024.6.27

  confirmed that acid sphingomyelinase (ASM) activity is associated with depression. The discovery of direct inhibitors against ASM is of great significance for exploring antidepressants and their mechanisms of action. Herein, a series of novel phenylpyrazole analogues were rationally designed and synthesized. Among them, compound 46 exhibited potent inhibitory activity (IC50 = 0.87 μM) and good drug-like properties

  多项研究已证实酸性鞘磷脂酶 (ASM) 活性与抑郁症相关。 ASM直接抑制剂的发现对于探索抗抑郁药物及其作用机制具有重要意义。本文合理设计并合成了一系列新型苯基吡唑类似物。其中，化合物46表现出有效的抑制活性（IC 50 = 0.87 μM）和良好的药物样特性。体内研究表明，化合物46参与多种抗抑郁作用机制，这些机制与神经酰胺的下降有关，包括增加 Bcl-2/Bax 比率和 BDNF 表达，下调 caspase-3 和 caspase-9，改善氧化应激，降低小鼠大脑中促炎细胞因子（如 TNF-α、IL-1β 和 IL-6）的水平，以及升高 5-HT 水平。这些有意义的结果首次揭示了直接抑制剂通过多种抗抑郁作用机制在 CUMS 诱导的小鼠模型中表现出显着的抗抑郁作用。
• Structural study of diarylazoles related to Rimonabant
  作者：Ibon Alkorta、Mario Alvarado、José Elguero、Santiago García-Granda、Pilar Goya、Laura Torre-Fernández、Laura Menéndez-Taboada

  DOI：10.1016/j.molstruc.2008.10.020

  日期：2009.2

  The structures of three diarylazoles (two pyrazoles and one 1,2,4-triazole) related to Rimonabant have been determined by X-ray crystallography. The conformation of both aryl groups in the new structures is discussed with regard to other related compounds reported in the Cambridge Structural Database. The secondary structure of the three compounds is very different. Compound 2 forms a helix, compound 3 forms a structure with the hydrocarbon layers parallel and compound 4 crystallizes forming a double chain. In the solid state, the conformation of both aryl groups, the N-aryl and the C-aryl, was compared with similar compounds reported in the literature. GIAO calculations afford absolute shieldings that were compared with experimental chemical shifts. (C) 2008 Elsevier B.V. All rights reserved.
• Repurposing of a drug scaffold: Identification of novel sila analogues of rimonabant as potent antitubercular agents
  作者：Remya Ramesh、Rahul D. Shingare、Vinod Kumar、Amitesh Anand、Swetha B、Sridhar Veeraraghavan、Srikant Viswanadha、Ramesh Ummanni、Rajesh Gokhale、D. Srinivasa Reddy

  DOI：10.1016/j.ejmech.2016.07.009

  日期：2016.10

  The structural similarity between an MmpL3 inhibitor BM212, and a cannabinoid receptor modulator rimonabant, prompted us to investigate the anti-tubercular activity of rimonabant and its analogues. Further optimization, particularly through incorporation of silicon into the scaffold, resulted in new compounds with significant improvement in anti-tubercular activity against Mycobacterium tuberculosis (H37Rv). The sila analogue 18a was found to be the most potent antimycobacterial compound (MIC, 31 ng/mL) from this series with an excellent selectivity index. (C) 2016 Elsevier Masson SAS. All rights reserved.