1-(2,4-dichlorophenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carboxylic acid | 221385-47-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2,4-dichlorophenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carboxylic acid
• 英文别名: 1-(2,4-Dichlorophenyl)-4-methyl-5-phenyl-pyrazole-3-carboxylic acid；1-(2,4-dichlorophenyl)-4-methyl-5-phenylpyrazole-3-carboxylic acid
• CAS: 221385-47-3
• 化学式: C₁₇H₁₂Cl₂N₂O₂
• 分子量: 347.2
• InChiKey: NGJTWWWUHPKDKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2,4-dichlorophenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carboxylic acid 在 氯化亚砜 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 氯仿 、 甲苯 为溶剂， 反应 12.0h， 生成 1-(2,4-dichlorophenyl)-N'-[(E)-(4-hydroxy-3-methoxyphenyl)methylidene]-4-methyl-5-phenyl-1H-pyrazole-3-carbohydrazide
  参考文献：
  名称：

  1,5-Diarylpyrazole and vanillin hybrids: Synthesis, biological activity and DFT studies

  摘要：

  Herein, we report the design and synthesis of 13 diarylpyrazole hybrids with vanillin constructed as dual compounds against oxidative stress and diabetes. Compounds were tested in two different antioxidant assays. It was found that all compounds showed an important antioxidant activity in both DPPH and ORAC models and the activity was even more remarkable than vanillin. In addition, the hypoglycemic effect of compounds 1, 2, 4 and 12 was evaluated. Interestingly, compound 1 had the most potent hypoglycemic effect with a glycemia reduction of 71%, which was higher than rimonabant. Finally, a DFT study to propose a reasonable antioxidant mechanism is detailed. Both thermodynamic and kinetic studies indicated that the most feasible mechanism consists in the HAT abstraction of the phenolic hydrogen due to the formation of an stable transition state through the most rapid and exergonic path, while the SPLET mechanism is the most significant at higher pH values. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.06.010
• 作为产物：
  描述：

  2,4-二氯苯肼盐酸盐 在 氢氧化钾 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 47.0h， 生成 1-(2,4-dichlorophenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  吡唑衍生物作为大麻素受体拮抗剂的构效关系。

  摘要：

  作为一种有效的脑大麻素受体（CB1）拮抗剂，联芳吡唑N-（哌啶-1-基）-5-（4-氯苯基）-1-（2，4-二氯苯基）-4-甲基-1H -吡唑-3-甲酰胺（SR141716A; 1）是用于启动研究的主要化合物，旨在研究相关化合物的构效关系，并寻找更具选择性和效用的拟大麻素配体。设计并合成了一系列吡唑衍生物，以帮助表征大麻素受体结合位点，并用作潜在有用的药理探针。在治疗上，此类化合物可能具有拮抗大麻素和拟大麻剂的有害副作用的能力。有效和选择性的脑大麻素CB1受体拮抗活性的结构要求包括（a）在5位的对位取代苯环，（b）在3位的羧酰胺基和（c）2,4-二氯苯基在吡唑环的1-位上的取代基。该系列中最有效的化合物在吡唑环的5-位包含对碘苯基，在3-位包含哌啶基羧酰胺和在吡唑环的1-位包含2,4-二氯苯基。该化合物的碘化性质可作为富伽玛SPECT（单光子发射计算机断层扫描）配体，提供额外的实用性，可用

  DOI：

  10.1021/jm980363y

文献信息

• [EN] PYRAZOLE CARBOXYLIC ACID ANALOGUES AS ANTI-MYCOBACTERIAL DRUG CANDIDATES<br/>[FR] ANALOGUES D'ACIDE PYRAZOLE CARBOXYLIQUE EN TANT QUE CANDIDATS MÉDICAMENTS ANTI-MYCOBACTÉRIENS
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2014174457A1

  公开（公告）日：2014-10-30

  The present invention relates to the pyrazole carboxylic acid analogues of Formula (1) or stereoisomers, or esters or pharmaceutically acceptable salts thereof, as potent anti- mycobacterial agents. Formula Further it discloses the pharmaceutical composition comprising compounds of Formula-I for the treatment of mycobacterial infections.

  本发明涉及Formula（1）的吡唑羧酸类似物或其立体异构体，或其酯或药用可接受的盐，作为有效的抗分枝杆菌药物。此外，还披露了包含Formula-I化合物的药物组合物，用于治疗分枝杆菌感染。
• “One-Pot” Synthesis of 4-Substituted 1,5-Diaryl-1H-pyrazole-3-carboxylic Acids via a MeONa/LiCl-Mediated Sterically Hindered Claisen Condensation–Knorr Reaction–Hydrolysis Sequence
  作者：Ya-Fei Ji、Jian-An Jiang、Cai-Yan Du、Chun-Hui Gu

  DOI：10.1055/s-0032-1317668

  日期：——

  A "one-pot" synthesis of 4-substituted 1,5-diaryl-1H-pyrazole-3-carboxylic acids was first reported in moderate to good yields. This concise procedure, featuring efficiency and green chemistry, was composed of MeONa/LiCl-mediated sterically hindered Claisen condensation, Knorr reaction and hydrolysis.
• Discovery of Rimonabant and its potential analogues as anti-TB drug candidates
  作者：J. M. Gajbhiye、N. A. More、Manoj D. Patil、R. Ummanni、S. S. Kotapalli、P. Yogeeswari、D. Sriram、V. H. Masand

  DOI：10.1007/s00044-015-1346-4

  日期：2015.7

  Rimonabant and its analogues have been synthesized in moderate to good yields using a simple synthetic route. All the newly synthesized compounds were subjected to in vitro screening against M. tuberculosis and M. smegmatis. The most potent analogue JMG-14 exhibits MIC value of 3.13 compared to 3.25 and 50 A mu g/ml for ethambutol and pyrazinamide, respectively. The molecular docking reveals that pyrazole ring, number and position of halogen atoms play a crucial role in deciding interactions with MTCYP-121. These findings open up a new avenue in the search of potent anti-TB drugs with rimonabant and its novel analogue JMG-14 as lead molecules.
• Synthesis, hypoglycemic activity and molecular modeling studies of pyrazole-3-carbohydrazides designed by a CoMFA model
  作者：Eduardo Hernández-Vázquez、Rodrigo Aguayo-Ortiz、Juan José Ramírez-Espinosa、Samuel Estrada-Soto、Francisco Hernández-Luis

  DOI：10.1016/j.ejmech.2013.07.054

  日期：2013.11

  Diabetes and obesity are two universal health problems that constitute a research objective of several groups due to the lack of efficient and safe drug treatment. In this sense, cannabinoid receptor 1 (CBI) has attracted interest because of its role in food intake and metabolic balance, two targets in the control of metabolic syndrome. In this work, novel 1,5-diaryl pyrazole derivatives were synthesized in accordance with the pKi prediction of a previously reported CoMFA model by our group. To further investigate the biological activity of these compounds in metabolic disorders, their hypoglycemic activity in an in vivo model was tested. Interestingly, a high degree of correlation was observed between the predicted pK(i) and hypoglycemic effect 7 h after administration. Compounds 4, 9 and 13 showed the most significant plasma glucose reduction with decreases of 60%, 64% and 60% respectively. This result not only surpasses the activity of the lead rimonabant, but also that of the reference drug glibenclamide. Moreover, PASS prediction and molecular docking in an excellent validated homology model of CBI suggest that these compounds would probably act as CBI antagonists/inverse agonists and therefore, antiobesity agents. The ligand receptor complexes demonstrate that 1,5-diaryl pyrazole derivatives bind to the proposed binding site where a hydrophobic moiety interacts with the phenyl rings in the pyrazole nucleus and Lys192 forms a hydrogen bond with the oxygen of the carbonyl group. Dynamics simulations were also carried out to study the stability of the ligand receptor complexes where the most active compounds showed smaller Delta G values and more hydrogen bonds throughout the simulation. These compounds are considered useful leads for further optimization in the treatment of such metabolic illnesses. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Development of Yin-Yang ligand for cannabinoid receptors
  作者：Yanli Qiu、Yitian Zhao、Tao Hu、Meifang Yang、Fei Li、Cuixia Li、Weiliang Gu、Xiaodi Yang、Suwen Zhao、Houchao Tao

  DOI：10.1016/j.bioorg.2023.106377

  日期：2023.4