1-(2,4-二氯苯基)-5-(2,5-二甲基-1H-吡咯-1-基)-4-甲基-1H-吡唑-3-羧酸 | 1015765-71-5

• 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-(2,4-二氯苯基)-5-(2,5-二甲基-1H-吡咯-1-基)-4-甲基-1H-吡唑-3-羧酸
• 英文名称: 1-(2,4-dichlorophenyl)-5-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methyl-1H-pyrazole-3-carboxylic acid
• 英文别名: 1-(2,4-Dichlorophenyl)-5-(2,5-dimethylpyrrol-1-yl)-4-methylpyrazole-3-carboxylic acid
• CAS: 1015765-71-5
• 化学式: C₁₇H₁₅Cl₂N₃O₂
• 分子量: 364.231
• InChiKey: FWUUYEJKYFMNDH-UHFFFAOYSA-N

物化性质

• 熔点：
  205-208 °C(Solvent: Ethanol)
• 沸点：
  558.8±50.0 °C(predicted)
• 密度：
  1.41±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  24
• 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：

  1-(2,4-二氯苯基)-5-(2,5-二甲基-1H-吡咯-1-基)-4-甲基-1H-吡唑-3-羧酸 、 1-氨基戊烷 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， 反应 25.0h， 以71%的产率得到1-(2,4-dichlorophenyl)-5-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methyl-N-pentyl-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Synthesis and biological evaluation of new N-alkyl 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides as cannabinoid receptor ligands

  摘要：

  A series of N-alkyl 1-ary1-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized as new ligands of the human recombinant receptor hCB(1). n-Alkyl carboxamides brought out different SARs from the branched subgroup. Unsubstituted pyrrole derivatives bearing a tert-alkyl chain at the 3-carboxamide nitrogen showed greater hCB1 receptor affinity than the corresponding unbranched compounds. In particular, the tert-butyl group as a chain terminal moiety strongly improved hCB(1) receptor affinity (compound 24: K-i; = 45.6 nM; 29: K-i = 37.5 nM). Acute administration of either compound 12 or 29 resulted in a specific, dose-dependent reduction in food intake in rats. Such results provide an useful basis for the design of new CB1 ligands. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.09.053
• 作为产物：
  描述：

  ethyl 1-(2,4-dichlorophenyl)-5-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methyl-1H-pyrazole-3-carboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 以90%的产率得到1-(2,4-二氯苯基)-5-(2,5-二甲基-1H-吡咯-1-基)-4-甲基-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

• Synthesis, cannabinoid receptor affinity, molecular modeling studies and in vivo pharmacological evaluation of new substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides. 2. Effect of the 3-carboxamide substituent on the affinity and selectivity profile
  作者：Romano Silvestri、Alessia Ligresti、Giuseppe La Regina、Francesco Piscitelli、Valerio Gatti、Antonella Brizzi、Serena Pasquini、Antonio Lavecchia、Marco Allarà、Noemi Fantini、Mauro Antonio Maria Carai、Ettore Novellino、Giancarlo Colombo、Vincenzo Di Marzo、Federico Corelli

  DOI：10.1016/j.bmc.2009.06.027

  日期：2009.8

  New substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized by replacing the 2,4-dichlorobenzyl and cyclohexyl moieties at the 3-carboxamide nitrogen of the previously reported CB1 receptor antagonists/inverse agonists 4 and 5. Several ligands showed potent affinity for the hCB1 receptor, with Ki concentrations comparable to the reference compounds 1, 4 and 5, and exhibited

  通过取代先前报道的3-羧酰胺氮上的2,4-二氯苄基和环己基部分，合成了新的取代的1-芳基-5-（1 H-吡咯-1-基）-1 H-吡唑-3-羧酰胺CB 1受体拮抗剂/反向激动剂4和5。几个配体显示了强的亲合性为HCB 1受体，具有ķ我浓度下媲美的参考化合物1，4和5，并显示出CB 1选择性比得上1和2。对接实验和分子动力学（MD）模拟解释了化合物31和37与hCB 1的强结合亲和力。根据我们以前的研究，31和37与K3.28（192）形成H键，这说明对受体无活性状态和反向激动剂活性具有高亲和力。在对大鼠急性给药后发现食物摄入受到抑制，这支持了CB 1选择性化合物4和52充当拮抗剂/反向激动剂的概念。