Identification of fused bicyclic derivatives of pyrrolidine and imidazolidinone as dengue virus-2 NS2B-NS3 protease inhibitors
A series of fused ring derivatives of pyrrolidine and imidazolidinone were designed, synthesized, characterized and assayed against the DENV-2 NS2B-NS3 protease and wild-type DENV-2 virus. The linear dipeptide compound 1 and the non-peptidic fused ring compound 2 show comparable activities against D...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2017
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| In: |
European journal of medicinal chemistry
Year: 2016, Volume: 125, Pages: 751-759 |
| ISSN: | 1768-3254 |
| DOI: | 10.1016/j.ejmech.2016.09.063 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.ejmech.2016.09.063 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0223523416308005 
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| Author Notes: | Zhibing Weng, Xiaoxia Shao, Dominik Graf, Chunguang Wang, Christian D. Klein, Jing Wang, Guo-Chun Zhou |
| Summary: | A series of fused ring derivatives of pyrrolidine and imidazolidinone were designed, synthesized, characterized and assayed against the DENV-2 NS2B-NS3 protease and wild-type DENV-2 virus. The linear dipeptide compound 1 and the non-peptidic fused ring compound 2 show comparable activities against DENV-2 NS2B-NS3 protease and wild-type DENV-2 virus in a viral replication assay. The preliminary SAR reveals that a substituent and its stereochemistry at C-3 position, substitution (X) at N-2 arene and a linker (Y) between C-3 position and its attached arene are important for the fused-ring scaffold of pyrrolidino [1,2-c]imidazolidinone to block the active site of NS2B-NS3 protease. This promising structural core will facilitate the discovery of non-peptidic, potent NS2B-NS3 protease inhibitors to stop dengue virus infections. |
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| Item Description: | Published online: 21 September 2016 Gesehen am 29.08.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1768-3254 |
| DOI: | 10.1016/j.ejmech.2016.09.063 |