5-(5-(but-1-ynyl)-thiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid ethyl ester | 1058164-69-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(5-(but-1-ynyl)-thiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid ethyl ester
• CAS: 1058164-69-4
• 化学式: C₂₁H₁₈Cl₂N₂O₂S
• 分子量: 433.358
• InChiKey: NJLMHAOZTUDYEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.15
• 重原子数：
  28.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  44.12
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  5-(5-(but-1-ynyl)-thiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid ethyl ester 在 甲醇 、 氢氧化钾 作用下， 以94%的产率得到5-(5-(but-1-ynyl)-thiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  Bioisosteric Replacement of the Pyrazole 5-Aryl Moiety of N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A). A Novel Series of Alkynylthiophenes as Potent and Selective Cannabinoid-1 Receptor Antagonists

  摘要：

  Replacing the conventional pyrazole 5-aryl substituent of 1 (SR141716A) with the 2-thienyl rnoiety appended with ail appropriate alkynyl unit, a novel class of 5-(5-alkynyl-2-thienyl)pyrazole derivatives, behaving as highly potent CB1 receptor antagonists with good CB1/2 selectivity, was discovered, many of which, its typified by compound 18, showed significant weight reduction in diet-indUced obese Mouse model, thus pharmacologically validating that the bioisosteric replacement described above is viable. Also encouraging was the finding that a subtle structural modification of the newly developed series could result in a distinct difference in the intrinsic property, as demonstrated by compounds 12 (NA) and its methylated structural isomers 15 (PA) and 18 (IA). Moreover, current structure-activity relationship Studies revealed that around the pyrazole 5-position of 1, a deep and flat crevice surrounded by a sequence of hydrophobic/aromatic residues as indicated by the CB I-receptor homology model might exist in the binding site.

  DOI：

  10.1021/jm800066v
• 作为产物：
  描述：

  1-丁炔 、 5-(5-bromothiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid ethyl ester 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 C.I.酸性橙108 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 6.0h， 以92%的产率得到5-(5-(but-1-ynyl)-thiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Bioisosteric Replacement of the Pyrazole 5-Aryl Moiety of N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A). A Novel Series of Alkynylthiophenes as Potent and Selective Cannabinoid-1 Receptor Antagonists

  摘要：

  Replacing the conventional pyrazole 5-aryl substituent of 1 (SR141716A) with the 2-thienyl rnoiety appended with ail appropriate alkynyl unit, a novel class of 5-(5-alkynyl-2-thienyl)pyrazole derivatives, behaving as highly potent CB1 receptor antagonists with good CB1/2 selectivity, was discovered, many of which, its typified by compound 18, showed significant weight reduction in diet-indUced obese Mouse model, thus pharmacologically validating that the bioisosteric replacement described above is viable. Also encouraging was the finding that a subtle structural modification of the newly developed series could result in a distinct difference in the intrinsic property, as demonstrated by compounds 12 (NA) and its methylated structural isomers 15 (PA) and 18 (IA). Moreover, current structure-activity relationship Studies revealed that around the pyrazole 5-position of 1, a deep and flat crevice surrounded by a sequence of hydrophobic/aromatic residues as indicated by the CB I-receptor homology model might exist in the binding site.

  DOI：

  10.1021/jm800066v