5-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methyl-1-(2,4,6-trichlorophenyl)-1H-pyrazole-3-carboxylic acid | 1015765-77-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methyl-1-(2,4,6-trichlorophenyl)-1H-pyrazole-3-carboxylic acid
• 英文别名: 5-(2,5-Dimethylpyrrol-1-yl)-4-methyl-1-(2,4,6-trichlorophenyl)pyrazole-3-carboxylic acid
• CAS: 1015765-77-1
• 化学式: C₁₇H₁₄Cl₃N₃O₂
• 分子量: 398.676
• InChiKey: ZFWOCVZQMURRQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 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：

  5-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methyl-1-(2,4,6-trichlorophenyl)-1H-pyrazole-3-carboxylic acid 、 1-氨基哌啶 在 polymer bound p-toluenesulfonic acid 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以70%的产率得到5-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methyl-N-(piperidin-1-yl)-1-(2,4,6-trichlorophenyl)-1H-pyrazole-3-carboxamide
  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
• 作为产物：
  描述：

  ethyl 5-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methyl-1-(2,4,6-trichlorophenyl)-1H-pyrazole-3-carboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 以98%的产率得到5-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methyl-1-(2,4,6-trichlorophenyl)-1H-pyrazole-3-carboxylic acid
  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

• Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii
  作者：Filomena Sannio、Antonella Brizzi、Rosita Del Prete、Marialuce Avigliano、Tiziana Simone、Carlotta Pagli、Teresa Ferraro、Filomena De Luca、Marco Paolino、Federico Corelli、Claudia Mugnaini、Jean-Denis Docquier

  DOI：10.3390/antibiotics11121832

  日期：——

  Furthermore, an evaluation of their activity as potential antibiotic adjuvants allowed for the identification of two highly active compounds on MDR Acinetobacter baumannii, including colistin-resistant isolates. This work confirms the interest in pyrazole amides as a starting point for the optimization of synergistic antibacterial compounds active on antibiotic-resistant, Gram-negative pathogens.

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