N-(azepan-1-yl)-1-(2,4-dichlorophenyl)-5-(5-(hex-1-ynyl)thiophen-2-yl)-4-methyl-1H-pyrazole-3-carboxamide | 1058164-55-8

• 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-(azepan-1-yl)-1-(2,4-dichlorophenyl)-5-(5-(hex-1-ynyl)thiophen-2-yl)-4-methyl-1H-pyrazole-3-carboxamide
• 英文别名: N-(azepan-1-yl)-1-(2,4-dichlorophenyl)-5-(5-hex-1-ynylthiophen-2-yl)-4-methylpyrazole-3-carboxamide
• CAS: 1058164-55-8
• 化学式: C₂₇H₃₀Cl₂N₄OS
• 分子量: 529.533
• InChiKey: JBHSRXZIGNHKIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  、 1-氨基高哌啶 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以87 mg的产率得到N-(azepan-1-yl)-1-(2,4-dichlorophenyl)-5-(5-(hex-1-ynyl)thiophen-2-yl)-4-methyl-1H-pyrazole-3-carboxamide
  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