1-(2,4-Dichloro-phenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carbonyl chloride | 221385-48-4

• 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-Dichloro-phenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carbonyl chloride
• CAS: 221385-48-4
• 化学式: C₁₇H₁₁Cl₃N₂O
• 分子量: 365.646
• InChiKey: FRUFMRRVMAPCQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.53
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  34.89
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-(2,4-Dichloro-phenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carbonyl chloride 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 氯仿 为溶剂， 反应 9.5h， 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：

  ethyl 3-methyl-2,4-dioxo-4-phenylbutanoate lithium salt 在 氯化亚砜 、 硫酸 、 potassium hydroxide 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 22.5h， 生成 1-(2,4-Dichloro-phenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carbonyl chloride
  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

文献信息

• Structure−Activity Relationships of Pyrazole Derivatives as Cannabinoid Receptor Antagonists
  作者：Ruoxi Lan、Qian Liu、Pusheng Fan、Sonyuan Lin、Susanthi R. Fernando、Deirdre McCallion、Roger Pertwee、Alexandros Makriyannis

  DOI：10.1021/jm980363y

  日期：1999.2.1

  and synthesized to aid in the characterization of the cannabinoid receptor binding sites and also to serve as potentially useful pharmacological probes. Therapeutically, such compounds may have the ability to antagonize harmful side effects of cannabinoids and cannabimimetic agents. Structural requirements for potent and selective brain cannabinoid CB1 receptor antagonistic activity included (a) a para-substituted

  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
• 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.