2. Academic Validation
  3. 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

  • ACS Med Chem Lett. 2018 Jan 10;9(2):94-97. doi: 10.1021/acsmedchemlett.7b00418.
Weihua Shi 1,  Zhigan Jiang 1,  Haiying He 1,  Fubiao Xiao 1,  Fusen Lin 1,  Ya Sun 1,  Lijuan Hou 1,  Liang Shen 1,  Lixia Han 1,  Minggao Zeng 1,  Kunmin Lai 1,  Zhengxian Gu 1,  Xinsheng Chen 1,  Tao Zhao 2,  Li Guo 2,  Chun Yang 2,  Jian Li 1,  Shuhui Chen 1
Affiliations

Affiliations

  • 1 WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, P. R. China.
  • 2 Buchang Pharmaceutical, 50 Gaoxin Road, Gaoxin District, Xi'an 710075, Shanxi Province, P. R. China.
PMID: 29456794 DOI: 10.1021/acsmedchemlett.7b00418
Abstract

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.

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