Discovery of 3,3'-Spiro[Azetidine]-2-oxo-indoline Derivatives as Fusion Inhibitors for Treatment of RSV Infection
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.
| Errataetall: |
ErratumIn: ACS Med Chem Lett. 2018 Mar 30;9(4):397. - PMID 29671838 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
ACS medicinal chemistry letters - 9(2018), 2 vom: 08. Feb., Seite 94-97 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shi, Weihua [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 01.10.2020 published: Electronic-eCollection ErratumIn: ACS Med Chem Lett. 2018 Mar 30;9(4):397. - PMID 29671838 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1021/acsmedchemlett.7b00418 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM281153213 |
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| 500 | |a ErratumIn: ACS Med Chem Lett. 2018 Mar 30;9(4):397. - PMID 29671838 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a He, Haiying |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Fubiao |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Fusen |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Ya |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Lijuan |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Lixia |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Minggao |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Kunmin |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Zhengxian |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xinsheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Chun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Shuhui |e verfasserin |4 aut | |
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