5-(2-chloro-1H-pyrrol-1-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid | 1345992-74-6

• 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-chloro-1H-pyrrol-1-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid
• CAS: 1345992-74-6
• 化学式: C₁₅H₁₀Cl₃N₃O₂
• 分子量: 370.622
• InChiKey: HGFMPGKKBNURFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.63
• 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：
  0.07
• 拓扑面积：
  60.05
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  5-(2-chloro-1H-pyrrol-1-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid 、 3,4-二氯苄胺 在 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97%的产率得到5-(2-chloro-1H-pyrrol-1-yl)-N-(3,4-dichlorobenzyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  1-Aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide: An effective scaffold for the design of either CB1 or CB2 receptor ligands

  摘要：

  New 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized as cannabinoid (CB) receptor ligands. Compound 11 (CB1 K-i = 2.3 nM, CB1 SI = 163.6) showed CB1 receptor affinity and selectivity superior to Rimonabant and AM251. Acute administration of 2 mg/kg 11 reduced sucrose, but not regular food, intake in rats. On the other hand, compound 23 (CB2 K-i = 0.51 nM, CB2 SI =30.0) showed significant affinity and selectivity for the CB2 receptor. The results presented here show that the 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide may serve as an effective scaffold for the design of either CB1 or CB2 receptor ligands. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.09.037
• 作为产物：
  描述：

  ethyl 1-(2,4-dichlorophenyl)-4-methyl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxylate 在 N-氯代丁二酰亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.5h， 生成 5-(2-chloro-1H-pyrrol-1-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  1-Aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide: An effective scaffold for the design of either CB1 or CB2 receptor ligands

  摘要：

  New 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized as cannabinoid (CB) receptor ligands. Compound 11 (CB1 K-i = 2.3 nM, CB1 SI = 163.6) showed CB1 receptor affinity and selectivity superior to Rimonabant and AM251. Acute administration of 2 mg/kg 11 reduced sucrose, but not regular food, intake in rats. On the other hand, compound 23 (CB2 K-i = 0.51 nM, CB2 SI =30.0) showed significant affinity and selectivity for the CB2 receptor. The results presented here show that the 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide may serve as an effective scaffold for the design of either CB1 or CB2 receptor ligands. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.09.037

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。