1-(4-氯苯基)-5-(1H-吡咯-1-基)-1H-吡唑-3-羧酸 | 1015765-67-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-(4-氯苯基)-5-(1H-吡咯-1-基)-1H-吡唑-3-羧酸
• 英文名称: 1-(4-chlorophenyl)-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxylic acid
• 英文别名: 1-(4-chlorophenyl)-5-(1H-pyrrol-1yl)-1H-pyrazole-3-carboxylic acid；1-(4-Chlorophenyl)-5-pyrrol-1-ylpyrazole-3-carboxylic acid
• CAS: 1015765-67-9
• 化学式: C₁₄H₁₀ClN₃O₂
• 分子量: 287.705
• InChiKey: AAGYNVOBDABZSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  60
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-氯苯基)-5-(1H-吡咯-1-基)-1H-吡唑-3-羧酸 以 四氢呋喃 为溶剂， 反应 26.0h， 生成 1-(4-chlorophenyl)-N-phenyl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  New 1-phenyl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides inhibit hepatitis C virus replication via suppression of cyclooxygenase-2

  摘要：

  We report here the synthesis and mechanism of inhibition of pyrazolecarboxamide derivatives as a new class of HCV inhibitors. Compounds 6, 7, 8 and 16 inhibited the subgenomic HCV replicon lb genotype at EC50 values between 5 and 8 mu M and displayed an even higher potency against the infectious Jc1 HCV 2a genotype. Compound 6 exhibited an EC50 of 6.7 mu M and selectivity index of 23 against HCV 1b, and reduced the RNA copies of the infectious Jc1 chimeric 2a clone by 82% at 7 mu M. Evaluation of the mode of anti-HCV activity of 6 revealed that it suppressed HCV-induced COX-2 mRNA and protein expression, displaying an IC50 of 3.2 mu M in COX-2 promoter-linked luciferase reporter assay. Conversely, the anti-HCV activity of 6 was abrogated upon over-expression of COX-2. These findings suggest that 6 as a representative of these pyrazolecarboxamides function as anti-HCV agents via targeting COX-2 at both the transcription and translation levels. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.11.042
• 作为产物：
  描述：

  ethyl 1-(4-chlorophenyl)-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 以94%的产率得到1-(4-氯苯基)-5-(1H-吡咯-1-基)-1H-吡唑-3-羧酸
  参考文献：
  名称：

  Synthesis, Cannabinoid Receptor Affinity, and Molecular Modeling Studies of Substituted 1-Aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides

  摘要：

  The new 1-phenyl-5-(1H-pyrrol-1-yl)pyrazole-3-carboxamides were compared with the reference compounds AM251 and SR144528 for cannabinoid hCB(1) and hCB(2) receptor affinity. Compounds bearing 2,4-dichlorophenyl or 2,4-difluorophenyl groups at position 1 and 2,5-dimethylpyrrole moiety at position 5 of the pyrazole nucleus were generally more selective for hCB(1). On the other hand, the N-cyclohexyl group at the 3-carboxamide was the determinant for the hCB2 selectivity, in particular when a 3,4-dichlorophenyl group was also present at position 1. Compound 26 was the most selective ligand for the hCB(1) receptor (K-i (CB2)/K-i (CB1) = 140.7). Derivative 30, the most potent hCB(1) ligand (Ki = 5.6 nM), was equipotent to AM251 and behaved as an inverse agonist in the cAMP assay (EC50 similar to 1 nM). The carbonyl oxygen of both 26 and 30 formed a H-bond with K3.28(192), while the substituents at the nitrogen fitted in a pocket formed by lipophilic residues. This H-bonding interaction was proposed to account for the high affinity for receptors' inactive state and the inverse agonist activity.

  DOI：

  10.1021/jm070566z

文献信息

• Rimonabant-Based Compounds Bearing Hydrophobic Amino Acid Derivatives as Cannabinoid Receptor Subtype 1 Ligands
  作者：Szabolcs Dvorácskó、Marilisa Pia Dimmito、Jessica Sebastiani、Giuseppe La Regina、Romano Silvestri、Stefano Pieretti、Azzurra Stefanucci、Csaba Tömböly、Adriano Mollica

  DOI：10.1021/acsmedchemlett.3c00024

  日期：——

  acids related to the cannabinoid type 1 (CB1) receptor antagonist rimonabant were amidated with valine or tert-leucine, and the resulting acids were further diversified as methyl esters, amides, and N-methyl amides. In vitro receptor binding and functional assays demonstrated a wide series of activities related to the CB1 receptors (CB1Rs). Compound 34 showed a high CB1R binding affinity (Ki = 6.9

  在这项研究中，与大麻素 1 型 (CB1) 受体拮抗剂利莫那班相关的1 H-吡唑-3-羧酸用缬氨酸或叔亮氨酸酰胺化，生成的酸进一步多样化为甲酯、酰胺和N-甲基酰胺。体外受体结合和功能测定证明了与 CB1 受体 (CB1Rs) 相关的一系列广泛活动。化合物34显示出高 CB1R 结合亲和力 ( K i = 6.9 nM) 和激动剂活性 (EC 50 = 46 nM；E max = 135%)。放射性配体结合和 [ 35S]GTPγS 结合测定也证明了其对 CB1Rs 的选择性和特异性。此外，体内实验表明，在福尔马林试验的早期，34比CB1激动剂WIN55,212-2的作用略强，镇痛作用持续时间较短。有趣的是，在酵母聚糖诱导的后肢水肿小鼠模型中，34能够在皮下注射后 24 小时内将足爪体积百分比保持在 75% 以下。腹膜内给药后，34增加了小鼠的食物摄入量，表明对 CB1Rs 具有潜在活性。
• Synthesis, Cannabinoid Receptor Affinity, and Molecular Modeling Studies of Substituted 1-Aryl-5-(1<i>H</i>-pyrrol-1-yl)-1<i>H</i>-pyrazole-3-carboxamides
  作者：Romano Silvestri、Maria Grazia Cascio、Giuseppe La Regina、Francesco Piscitelli、Antonio Lavecchia、Antonella Brizzi、Serena Pasquini、Maurizio Botta、Ettore Novellino、Vincenzo Di Marzo、Federico Corelli

  DOI：10.1021/jm070566z

  日期：2008.3.1

  The new 1-phenyl-5-(1H-pyrrol-1-yl)pyrazole-3-carboxamides were compared with the reference compounds AM251 and SR144528 for cannabinoid hCB(1) and hCB(2) receptor affinity. Compounds bearing 2,4-dichlorophenyl or 2,4-difluorophenyl groups at position 1 and 2,5-dimethylpyrrole moiety at position 5 of the pyrazole nucleus were generally more selective for hCB(1). On the other hand, the N-cyclohexyl group at the 3-carboxamide was the determinant for the hCB2 selectivity, in particular when a 3,4-dichlorophenyl group was also present at position 1. Compound 26 was the most selective ligand for the hCB(1) receptor (K-i (CB2)/K-i (CB1) = 140.7). Derivative 30, the most potent hCB(1) ligand (Ki = 5.6 nM), was equipotent to AM251 and behaved as an inverse agonist in the cAMP assay (EC50 similar to 1 nM). The carbonyl oxygen of both 26 and 30 formed a H-bond with K3.28(192), while the substituents at the nitrogen fitted in a pocket formed by lipophilic residues. This H-bonding interaction was proposed to account for the high affinity for receptors' inactive state and the inverse agonist activity.
• New 1-phenyl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides inhibit hepatitis C virus replication via suppression of cyclooxygenase-2
  作者：Dinesh Manvar、Sveva Pelliccia、Giuseppe La Regina、Valeria Famiglini、Antonio Coluccia、Anna Ruggieri、Simona Anticoli、Jin-Ching Lee、Amartya Basu、Ozge Cevik、Lucia Nencioni、Anna Teresa Palamara、Claudio Zamperini、Maurizio Botta、Johan Neyts、Pieter Leyssen、Neerja Kaushik-Basu、Romano Silvestri

  DOI：10.1016/j.ejmech.2014.11.042

  日期：2015.1

  We report here the synthesis and mechanism of inhibition of pyrazolecarboxamide derivatives as a new class of HCV inhibitors. Compounds 6, 7, 8 and 16 inhibited the subgenomic HCV replicon lb genotype at EC50 values between 5 and 8 mu M and displayed an even higher potency against the infectious Jc1 HCV 2a genotype. Compound 6 exhibited an EC50 of 6.7 mu M and selectivity index of 23 against HCV 1b, and reduced the RNA copies of the infectious Jc1 chimeric 2a clone by 82% at 7 mu M. Evaluation of the mode of anti-HCV activity of 6 revealed that it suppressed HCV-induced COX-2 mRNA and protein expression, displaying an IC50 of 3.2 mu M in COX-2 promoter-linked luciferase reporter assay. Conversely, the anti-HCV activity of 6 was abrogated upon over-expression of COX-2. These findings suggest that 6 as a representative of these pyrazolecarboxamides function as anti-HCV agents via targeting COX-2 at both the transcription and translation levels. (C) 2014 Elsevier Masson SAS. All rights reserved.