Identification of fused bicyclic derivatives of pyrrolidine and imidazolidinone as dengue virus-2 NS2B-NS3 protease inhibitors

• Verfasst von: Weng, Zhibing [VerfasserIn]
• Verfasst von: Graf, Dominik Korbinian [VerfasserIn]
• Verfasst von: Klein, Christian D. [VerfasserIn]
• Titel: Identification of fused bicyclic derivatives of pyrrolidine and imidazolidinone as dengue virus-2 NS2B-NS3 protease inhibitors
• Verf.angabe: Zhibing Weng, Xiaoxia Shao, Dominik Graf, Chunguang Wang, Christian D. Klein, Jing Wang, Guo-Chun Zhou
• Jahr des Originals: 2016
• Umfang: 9 S.
• Fussnoten: Published online: 21 September 2016 ; Gesehen am 29.08.2018
• Titel Quelle: Enthalten in: European journal of medicinal chemistry
• Jahr Quelle: 2017
• Band/Heft Quelle: 125(2017), S. 751-759
• ISSN Quelle: 1768-3254
• DOI: doi:10.1016/j.ejmech.2016.09.063
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1580494048

Abstract

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.