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Arch Pharm (Weinheim). 2019 Sep 18:e1900028. doi: 10.1002/ardp.201900028. [Epub ahead of print]
Novel N-(1-thia-4-azaspiro[4.5]decan-4-yl)carboxamide derivatives as potent and selective influenza virus fusion inhibitors.
G?ktaş F1, ?zbil M2, Cesur N1, Vanderlinden E3, Naesens L3, Cesur Z1.
Author information
1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey. 2 Department of Molecular Biology and Genetics, Istanbul Arel University, Istanbul, Turkey. 3 Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
Abstract
Hemagglutinin is the surface protein of the influenza virus that mediates both binding and penetration of the virus into host cells. We here report on the synthesis and structure-activity relationship of some novel N-(1-thia-4-azaspiro[4.5]decan-4-yl)-carboxamide compounds carrying the 5-chloro-2-methoxybenzamide structure, designed as influenza virus fusion inhibitors. The carboxamides (1a-h, 2a-h) have a similar backbone structure as the fusion inhibitors that we reported on previously. Compounds 2b and 2d displayed inhibitory activity against influenza A/H3N2 virus replication (average antiviral EC50 : 2.1 ?M for 2b and 3.4 ?M for 2d). Data obtained in the hemolysis inhibition assay supported that these compounds act as inhibitors of the influenza virus hemagglutinin-mediated fusion process.
? 2019 Deutsche Pharmazeutische Gesellschaft.
KEYWORDS:
antiviral activity; cycloaddition; influenza virus; structure elucidation; synthesis
PMID: 31531897 DOI: 10.1002/ardp.201900028
Novel N-(1-thia-4-azaspiro[4.5]decan-4-yl)carboxamide derivatives as potent and selective influenza virus fusion inhibitors.
G?ktaş F1, ?zbil M2, Cesur N1, Vanderlinden E3, Naesens L3, Cesur Z1.
Author information
1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey. 2 Department of Molecular Biology and Genetics, Istanbul Arel University, Istanbul, Turkey. 3 Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
Abstract
Hemagglutinin is the surface protein of the influenza virus that mediates both binding and penetration of the virus into host cells. We here report on the synthesis and structure-activity relationship of some novel N-(1-thia-4-azaspiro[4.5]decan-4-yl)-carboxamide compounds carrying the 5-chloro-2-methoxybenzamide structure, designed as influenza virus fusion inhibitors. The carboxamides (1a-h, 2a-h) have a similar backbone structure as the fusion inhibitors that we reported on previously. Compounds 2b and 2d displayed inhibitory activity against influenza A/H3N2 virus replication (average antiviral EC50 : 2.1 ?M for 2b and 3.4 ?M for 2d). Data obtained in the hemolysis inhibition assay supported that these compounds act as inhibitors of the influenza virus hemagglutinin-mediated fusion process.
? 2019 Deutsche Pharmazeutische Gesellschaft.
KEYWORDS:
antiviral activity; cycloaddition; influenza virus; structure elucidation; synthesis
PMID: 31531897 DOI: 10.1002/ardp.201900028