methyl N-(5-(4-hydroxy-3-methoxybenzoyl)-1H-imidazo(4,5-b)pyridin-2-yl)carbamate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl N-(5-(4-hydroxy-3-methoxybenzoyl)-1H-imidazo(4,5-b)pyridin-2-yl)carbamate
• 英文别名: NTI-007；methyl N-[5-(4-hydroxy-3-methoxy-benzoyl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate；methyl N-[5-(4-hydroxy-3-methoxybenzoyl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate
• 化学式: C₁₆H₁₄N₄O₅
• 分子量: 342.311
• InChiKey: AXHSCFLEHMEYIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5,6-dinitropicolinic acid 在 盐酸 、 aluminum (III) chloride 、 氯化亚砜 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 methyl N-(5-(4-hydroxy-3-methoxybenzoyl)-1H-imidazo(4,5-b)pyridin-2-yl)carbamate
  参考文献：
  名称：

  Design and synthesis of a novel candidate compound NTI-007 targeting sodium taurocholate cotransporting polypeptide [NTCP]–APOA1–HBx–Beclin1-mediated autophagic pathway in HBV therapy

  摘要：

  Sodium taurocholate cotransporting polypeptide (NTCP) is a multiple transmembrane transporter predominantly expressed in the liver, functioning as a functional receptor for HBV. Through our continuous efforts to identify NTCP as a novel HBV target, we designed and synthesized a series of new compounds based on the structure of our previous compound NT-5. Molecular docking and MD simulation validated that a new compound named NTI-007 can tightly bind to NTCP, whose efficacy was also measured in vitro virological examination and cytotoxicity studies. Furthermore, autophagy was observed in NTI-007 incubated HepG2.2.15 cells, and results of q-PCR and Western blotting revealed that NTI-007 induced autophagy through NTCP-APOA1-HBx-Beclin1-mediated pathway. Taken together, considering crucial role of NTCP in HBV infection, NTCP-mediated autophagic pathway may provide a promising strategy of HBV therapy and given efficacy of NTI-007 triggering autophagy. Our study suggests pre-clinical potential of this compound as a novel anti-HBV drug candidate. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.020

文献信息

• Design and synthesis of a novel candidate compound NTI-007 targeting sodium taurocholate cotransporting polypeptide [NTCP]–APOA1–HBx–Beclin1-mediated autophagic pathway in HBV therapy
  作者：Jin Zhang、Lei-lei Fu、Mao Tian、Hao-qiu Liu、Jing-jing Li、Yan Li、Jun He、Jian Huang、Liang Ouyang、Hui-yuan Gao、Jin-hui Wang

  DOI：10.1016/j.bmc.2015.01.020

  日期：2015.3

  Sodium taurocholate cotransporting polypeptide (NTCP) is a multiple transmembrane transporter predominantly expressed in the liver, functioning as a functional receptor for HBV. Through our continuous efforts to identify NTCP as a novel HBV target, we designed and synthesized a series of new compounds based on the structure of our previous compound NT-5. Molecular docking and MD simulation validated that a new compound named NTI-007 can tightly bind to NTCP, whose efficacy was also measured in vitro virological examination and cytotoxicity studies. Furthermore, autophagy was observed in NTI-007 incubated HepG2.2.15 cells, and results of q-PCR and Western blotting revealed that NTI-007 induced autophagy through NTCP-APOA1-HBx-Beclin1-mediated pathway. Taken together, considering crucial role of NTCP in HBV infection, NTCP-mediated autophagic pathway may provide a promising strategy of HBV therapy and given efficacy of NTI-007 triggering autophagy. Our study suggests pre-clinical potential of this compound as a novel anti-HBV drug candidate. (C) 2015 Elsevier Ltd. All rights reserved.