ethyl 5-amino-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylate | 1015765-46-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 5-amino-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylate
• 英文别名: Ethyl 5-amino-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxylate
• CAS: 1015765-46-4
• 化学式: C₁₃H₁₃Cl₂N₃O₂
• 分子量: 314.171
• InChiKey: NNIVJFPADONPEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 5-amino-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylate 在 草酰氯 、 lithium hydroxide monohydrate 、 水 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 73.0h， 生成
  参考文献：
  名称：

  “Photo-Rimonabant”: Synthesis and Biological Evaluation of Novel Photoswitchable Molecules Derived from Rimonabant Lead to a Highly Selective and Nanomolar “Cis-On” CB₁R Antagonist

  摘要：

  DOI：

  10.1021/acschemneuro.1c00086
• 作为产物：
  描述：

  potassium (2Z)-3-cyano-1-ethoxy-1-oxobut-2-en-2-olate 、 2,4-二氯苯肼盐酸盐 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以47%的产率得到ethyl 5-amino-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylate
  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

• 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.
• 1-Aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide: An effective scaffold for the design of either CB1 or CB2 receptor ligands
  作者：Francesco Piscitelli、Alessia Ligresti、Giuseppe La Regina、Valerio Gatti、Antonella Brizzi、Serena Pasquini、Marco Allarà、Mauro Antonio Maria Carai、Ettore Novellino、Giancarlo Colombo、Vincenzo Di Marzo、Federico Corelli、Romano Silvestri

  DOI：10.1016/j.ejmech.2011.09.037

  日期：2011.11

  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.
• “Photo-Rimonabant”: Synthesis and Biological Evaluation of Novel Photoswitchable Molecules Derived from Rimonabant Lead to a Highly Selective and Nanomolar “<i>Cis</i>-On” CB₁R Antagonist
  作者：Diego A. Rodríguez-Soacha、Julia Fender、Yesid A. Ramírez、Juan Antonio Collado、Eduardo Muñoz、Rangan Maitra、Christoph Sotriffer、Kristina Lorenz、Michael Decker

  DOI：10.1021/acschemneuro.1c00086

  日期：2021.5.5