3 years ago

Discovery of 3,3′-Spiro[Azetidine]-2-oxo-indoline Derivatives as Fusion Inhibitors for Treatment of RSV Infection

Discovery of 3,3′-Spiro[Azetidine]-2-oxo-indoline
Derivatives as Fusion Inhibitors for Treatment of RSV Infection
Li Guo, Lixia Han, Liang Shen, Minggao Zeng, Xinsheng Chen, Haiying He, Lijuan Hou, Fusen Lin, Chun Yang, Jian Li, Kunmin Lai, Fubiao Xiao, Tao Zhao, Zhengxian Gu, Zhigan Jiang, Shuhui Chen, Weihua Shi, Ya Sun
A new series of 3,3′-spirocyclic-2-oxo-indoline derivatives was synthesized and evaluated against respiratory syncytial virus (RSV) in a cell-based assay and animal model. Extensive structure–activity relationship study led to a lead compound 14h, which exhibited excellent in vitro potency with an EC50 value of 0.8 nM and demonstrated 71% oral bioavailability in mice. In a mouse challenge model of RVS infection, 14h demonstrated superior efficacy with a 3.9log RSV virus load reduction in the lung following an oral dose of 50 mg/kg.

Publisher URL: http://dx.doi.org/10.1021/acsmedchemlett.7b00418

DOI: 10.1021/acsmedchemlett.7b00418

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.