N-[(3,4-dichlorophenyl)methyl]-4-methyl-5-(1H-pyrrol-1-yl)-1-(2,4,6-trichlorophenyl)-1H-pyrazole-3-carboxamide | 1015765-40-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-[(3,4-dichlorophenyl)methyl]-4-methyl-5-(1H-pyrrol-1-yl)-1-(2,4,6-trichlorophenyl)-1H-pyrazole-3-carboxamide
• 英文别名: N-[(3,4-dichlorophenyl)methyl]-4-methyl-5-pyrrol-1-yl-1-(2,4,6-trichlorophenyl)pyrazole-3-carboxamide
• CAS: 1015765-40-8
• 化学式: C₂₂H₁₅Cl₅N₄O
• 分子量: 528.652
• InChiKey: DZZPFYHXNFYVEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-methyl-5-(1H-pyrrol-1-yl)-1-(2,4,6-trichlorophenyl)-1H-pyrazole-3-carboxylic acid 、 3,4-二氯苄胺 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68%的产率得到N-[(3,4-dichlorophenyl)methyl]-4-methyl-5-(1H-pyrrol-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