5-chloro-2-ethyl-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-chloro-2-ethyl-N-(4-(4-(4-(trifluoromethoxy)phenyl)piperidin-1-yl)benzyl)pyrazolo[1,5-a]pyridin-3-carboxamide
• 英文别名: 5-chloro-2-ethyl-N-[[4-[4-[4-(trifluoromethoxy)phenyl]piperidin-1-yl]phenyl]methyl]pyrazolo[1,5-a]pyridine-3-carboxamide
• 化学式: C₂₉H₂₈ClF₃N₄O₂
• 分子量: 557.015
• InChiKey: AKBXPTKBRLBEQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  39
• 可旋转键数：
  7
• 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：
  7

反应信息

• 作为反应物：
  描述：

  5-chloro-2-ethyl-N-(4-(4-(4-(trifluoromethoxy)phenyl)piperidin-1-yl)benzyl)pyrazolo[1,5-a]pyridin-3-carboxamide 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以92.2%的产率得到5-chloro-2-ethyl-N-methyl-N-(4-(4-(4-(trifluoromethoxy)phenyl)piperidin-1-yl)benzyl)pyrazolo[1,5-a]pyridin-3-carboxamide
  参考文献：
  名称：

  吡唑并[1,5-a]吡啶类化合物及其应用

  摘要：

  本发明公开一种具有式(Ⅰ)结构特征的吡唑并[1,5‑a]吡啶类化合物或其药学上可接受的盐或其立体异构体或其前药分子及其应用。该类化合物具有良好的体外抗结核病菌活性，化合物的最小抑菌浓度(MIC)低于0.1μg/mL，部分达到0.01μg/mL，对临床分选的耐多药结核菌(MDR‑TB)菌株具有很强的抑制作用。体内实验中，本发明所述的吡唑并[1,5‑a]吡啶类化合物在20mg/kg/d的剂量下，可有效清除小鼠体内H37Ra的感染量，是一类新型的抗结核化合物。

  公开号：

  CN105524058B
• 作为产物：
  描述：

  4-(4-(4-(trifluoromethoxy)phenyl)piperidin-1-yl)benzonitrile 在 lithium aluminium tetrahydride 、 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 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 5-chloro-2-ethyl-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：US10155756B2

  公开（公告）日：2018-12-18

  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.

  本发明公开了具有式（I）所示结构特征的吡唑并[1,5-a]吡啶化合物或其药学上可接受的盐、立体异构体或原药分子及其用途。此类化合物具有良好的体外抗结核活性，其最小抑菌浓度（MIC）低于 0.1 μg/mL，部分达到 0.01 μg/mL，对临床筛选出的耐多药结核菌株（MDR-TB）具有很强的抑制作用。在体内实验中，本公开的吡唑并[1,5-a]吡啶化合物在20 mg/kg/d的剂量下可以有效清除小鼠体内H37Ra的感染剂量，从而成为一种新型的抗结核化合物。
• 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.
• 吡唑并[1,5-a]吡啶类化合物及其应用
  申请人：广州艾格生物科技有限公司

  公开号：CN105524058B

  公开（公告）日：2018-03-27

  本发明公开一种具有式(Ⅰ)结构特征的吡唑并[1,5‑a]吡啶类化合物或其药学上可接受的盐或其立体异构体或其前药分子及其应用。该类化合物具有良好的体外抗结核病菌活性，化合物的最小抑菌浓度(MIC)低于0.1μg/mL，部分达到0.01μg/mL，对临床分选的耐多药结核菌(MDR‑TB)菌株具有很强的抑制作用。体内实验中，本发明所述的吡唑并[1,5‑a]吡啶类化合物在20mg/kg/d的剂量下，可有效清除小鼠体内H37Ra的感染量，是一类新型的抗结核化合物。