Scholarlink

<p>Bioavailability is a critical determinant factor of a drug, especially for its therapeutic efficacy, safety and commercial feasibility. Many active small molecule drugs suffer from poor oral bioavailability. 3-Butylisobenzofuran-1(3H)-one (NBP) is an approved small molecule agent by the CFDA for the treatment of acute cerebral ischemic stroke. NBP inhibits platelet aggregation, reduces brain infarct size, and attenuates ischemic-induced oxidative damage. However, the efficacy of NBP is limited due to its low bioavailability and high hydrophobicity. Sometimes, administration of high doses and increased frequency of NBP causes hepatotoxicity. Here, we designed, synthesized and evaluated a series of novel 6-substituted 3-butylisobenzofuran-1(3H)-one derivatives in vitro and in vivo and compared them with NBP or Br-NBP. Several compounds in the series showed better protective effects by preventing H<sub>2</sub>O<sub>2</sub>-induced LDH release and reduced ROS production in PC12 cells. In the in vivo pharmacokinetic study, compound <b>23</b> and compound <b>24</b> showed improved oral bioavailability and achieved F% = 52% and 44%, respectively. In addition, ADMET profiling and molecular docking simulations of <b>23</b> and <b>24</b> with MAO-A and MAO-B were conducted and the data included.</p> Graphical abstract

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Design, synthesis, and biological evaluation of novel isobenzofuran-1(3H)-one derivatives with antioxidant properties and improved oral bioavailability

  • 期刊论文

  • 发表日期：

    2026年6月30日

查看全文
  • Debasis Das,
  • Kun Zhang,
  • Lingzhi Xie,
  • Yong Li,
  • Yimeng Wu,
  • Dandan Qiao,
  • Yuxi Cao,
  • Jianhe Jia,
  • Jian Hong

摘要

Bioavailability is a critical determinant factor of a drug, especially for its therapeutic efficacy, safety and commercial feasibility. Many active small molecule drugs suffer from poor oral bioavailability. 3-Butylisobenzofuran-1(3H)-one (NBP) is an approved small molecule agent by the CFDA for the treatment of acute cerebral ischemic stroke. NBP inhibits platelet aggregation, reduces brain infarct size, and attenuates ischemic-induced oxidative damage. However, the efficacy of NBP is limited due to its low bioavailability and high hydrophobicity. Sometimes, administration of high doses and increased frequency of NBP causes hepatotoxicity. Here, we designed, synthesized and evaluated a series of novel 6-substituted 3-butylisobenzofuran-1(3H)-one derivatives in vitro and in vivo and compared them with NBP or Br-NBP. Several compounds in the series showed better protective effects by preventing H2O2-induced LDH release and reduced ROS production in PC12 cells. In the in vivo pharmacokinetic study, compound 23 and compound 24 showed improved oral bioavailability and achieved F% = 52% and 44%, respectively. In addition, ADMET profiling and molecular docking simulations of 23 and 24 with MAO-A and MAO-B were conducted and the data included.

Graphical abstract