5-trifluoromethyl-2-methyl-N-(4-(4-(4-(trifluoromethoxy)phenyl)piperidin-1-yl)benzyl)pyrazolo[1,5-a]pyridin-3-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 5-trifluoromethyl-2-methyl-N-(4-(4-(4-(trifluoromethoxy)phenyl)piperidin-1-yl)benzyl)pyrazolo[1,5-a]pyridin-3-carboxamide
• 英文别名: 2-methyl-N-[[4-[4-[4-(trifluoromethoxy)phenyl]piperidin-1-yl]phenyl]methyl]-5-(trifluoromethyl)pyrazolo[1,5-a]pyridine-3-carboxamide
• 化学式: C₂₉H₂₆F₆N₄O₂
• 分子量: 576.541
• InChiKey: QBHCXRYDYKLKKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  58.9
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-三氟甲基吡啶 在 2,4,6-三甲基苯磺酰羟胺 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 5-trifluoromethyl-2-methyl-N-(4-(4-(4-(trifluoromethoxy)phenyl)piperidin-1-yl)benzyl)pyrazolo[1,5-a]pyridin-3-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Pyrazolo[1,5-a]pyridine-3-carboxamides as Novel Antitubercular Agents

  摘要：

  A series of pyrazolo[1,5-a]pyridine-3-carboxamide derivatives were designed and synthesized as new anti-Mycobacterium tuberculosis (Mtb) agents. The compounds exhibit promising in vitro potency with nanomolar MIC values against the drug susceptive H37Rv strain and a panel of clinically isolated multidrug-resistant Mtb (MDR-TB) strains. One of the representative compounds (5k) significantly reduces the bacterial burden in an autoluminescent H37Ra infected mouse model, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.

  DOI：

  10.1021/acsmedchemlett.5b00176

文献信息

• PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AND USE THEREOF
  申请人：GUANGZHOU INSTITUTES OF BIOMEDICINE AND HEALTH CHINESE ACADEMY OF SCIENCES

  公开号：US20170313697A1

  公开（公告）日：2017-11-02

  Disclosed in the disclosure are a pyrazolo[1,5-a]pyrideine compound with structural features as shown in formula (I) or a pharmaceutically acceptable salt, stereoisomer or prodrug molecule thereof and a use thereof. Such compounds have a good in vitro antituberculosis activity, and the minimal inhibitory concentration (MIC) of the compounds is lower than 0.1 μg/mL and partially achieves 0.01 μg/mL, and have a very strong inhibiting effect on clinically selected multi-drug resistant tuberculosis (MDR-TB) strains. In an in vivo experiment, the pyrazolo[1,5-a]pyrideine compounds of the present disclosure can effectively scavenge the infectious dose of H37Ra in a mouse body at 20 mg/kg/d does, thereby being a new type of antituberculosis compound.
• Design, Synthesis, and Biological Evaluation of Pyrazolo[1,5-<i>a</i>]pyridine-3-carboxamides as Novel Antitubercular Agents
  作者：Jian Tang、Bangxing Wang、Tian Wu、Junting Wan、Zhengchao Tu、Moses Njire、Baojie Wan、Scott G. Franzblauc、Tianyu Zhang、Xiaoyun Lu、Ke Ding

  DOI：10.1021/acsmedchemlett.5b00176

  日期：2015.7.9

  A series of pyrazolo[1,5-a]pyridine-3-carboxamide derivatives were designed and synthesized as new anti-Mycobacterium tuberculosis (Mtb) agents. The compounds exhibit promising in vitro potency with nanomolar MIC values against the drug susceptive H37Rv strain and a panel of clinically isolated multidrug-resistant Mtb (MDR-TB) strains. One of the representative compounds (5k) significantly reduces the bacterial burden in an autoluminescent H37Ra infected mouse model, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.