1-(2,4-dichlorophenyl)-5-(5-(hex-1-ynyl)thiophen-2-yl)-4-methyl-1H-pyrazole-3-carboxylic acid ethyl ester | 1020106-78-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2,4-dichlorophenyl)-5-(5-(hex-1-ynyl)thiophen-2-yl)-4-methyl-1H-pyrazole-3-carboxylic acid ethyl ester
• 英文别名: Ethyl 1-(2,4-dichlorophenyl)-5-(5-hex-1-ynylthiophen-2-yl)-4-methylpyrazole-3-carboxylate
• CAS: 1020106-78-8
• 化学式: C₂₃H₂₂Cl₂N₂O₂S
• 分子量: 461.412
• InChiKey: DBINOHJVZZXAEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2,4-dichlorophenyl)-5-(5-(hex-1-ynyl)thiophen-2-yl)-4-methyl-1H-pyrazole-3-carboxylic acid ethyl ester 在 甲醇 、 氢氧化钾 作用下， 以 甲醇 为溶剂， 以95%的产率得到1-(2,4-dichlorophenyl)-5-(5-(hex-1-ynyl)thiophen-2-yl)-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：

  5-(5-bromothiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid ethyl ester 、 1-己炔 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96%的产率得到1-(2,4-dichlorophenyl)-5-(5-(hex-1-ynyl)thiophen-2-yl)-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

文献信息

• Oxadiazole Compounds
  申请人：Shia Kak-Shan

  公开号：US20080255211A1

  公开（公告）日：2008-10-16

  A compound of formula (I): in which A, R 1 , R 2 , and R 3 are as defined herein. Also disclosed are (1) a pharmaceutical composition containing such a compound, and (2) a method for treating a cannabinoid receptor-mediated disorder using such a compound.

  一种具有以下化学式（I）的化合物：其中A、R1、R2和R3如本文所定义。还公开了（1）含有这种化合物的药物组合物，以及（2）使用这种化合物治疗大麻素受体介导的疾病的方法。
• THIOPHENE COMPOUNDS
  申请人：Shia Kak-Shan

  公开号：US20080090810A1

  公开（公告）日：2008-04-17

  This invention relates to thiophene compounds of formula (I) shown below: Each variable in formula (I) is defined in the specification. These compounds can be used to treat cannabinoid-receptor mediated disorders.

  本发明涉及如下所示的公式（I）的噻吩化合物：公式（I）中的每个变量在规范中有定义。这些化合物可用于治疗大麻素受体介导的疾病。
• Thiophene Compounds
  申请人：Shia Kak-shan

  公开号：US20090029969A2

  公开（公告）日：2009-01-29

  This invention relates to thiophene compounds of formula (I) shown below: Each variable in formula (I) is defined in the specification. These compounds can be used to treat cannabinoid-receptor mediated disorders.
• US7705024B2
  申请人：——

  公开号：US7705024B2

  公开（公告）日：2010-04-27
• US7834046B2
  申请人：——

  公开号：US7834046B2

  公开（公告）日：2010-11-16