5-(5-(cyclopropylethynyl)thiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide | 1020106-17-5

• 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-(cyclopropylethynyl)thiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
• 英文别名: 5-[5-(2-cyclopropylethynyl)thiophen-2-yl]-1-(2,4-dichlorophenyl)-4-methyl-N-piperidin-1-ylpyrazole-3-carboxamide
• CAS: 1020106-17-5
• 化学式: C₂₅H₂₄Cl₂N₄OS
• 分子量: 499.464
• InChiKey: PZSBYWQVUJSNFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 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-氨基哌啶 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以90 mg的产率得到5-(5-(cyclopropylethynyl)thiophen-2-yl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-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

文献信息

• 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.
• US7834046B2
  申请人：——

  公开号：US7834046B2

  公开（公告）日：2010-11-16
• [EN] THIOPHENE COMPOUNDS<br/>[FR] COMPOSÉS THIOPHÈNE
  申请人：NAT HEALTH RESEARCH INSTITUTES

  公开号：WO2008057681A2

  公开（公告）日：2008-05-15

  [EN] This invention relates to a group of thiophene compounds as shown in the specification. These compounds can be used to treat cannabinoid-receptor mediated disorders.
  [FR] L'invention concerne un groupe de composés thiophène tel que défini dans la description. Ces composés peuvent être utilisés pour traiter des troubles dont la médiation est assurée par les récepteurs aux cannabinoïdes.
• Bioisosteric Replacement of the Pyrazole 5-Aryl Moiety of <i>N</i>-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1<i>H</i>-pyrazole-3-carboxamide (SR141716A). A Novel Series of Alkynylthiophenes as Potent and Selective Cannabinoid-1 Receptor Antagonists
  作者：Shi-Liang Tseng、Ming-Shiu Hung、Chun-Ping Chang、Jen-Shin Song、Chia-Liang Tai、Hua-Hao Chiu、Wan-Ping Hsieh、Yinchiu Lin、Wan-Ling Chung、Chun-Wei Kuo、Chien-Huang Wu、Cheng-Ming Chu、Yen-Shih Tung、Yu-Sheng Chao、Kak-Shan Shia

  DOI：10.1021/jm800066v

  日期：2008.9.11

  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.