Novel N-(1-thia-4-azaspiro[4.5]decan-4-yl)carboxamide derivatives as potent and selective influenza virus fusion inhibitors

Goktas F., Ozbil M., Cesur N., Vanderlinden E., Naesens L., Cesur Z.

ARCHIV DER PHARMAZIE, cilt.352, sa.11, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 352 Sayı: 11
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1002/ardp.201900028
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: antiviral activity, cycloaddition, influenza virus, structure elucidation, synthesis, HEMAGGLUTININ, GROMACS, MODELS, WATER, ACIDS
  • İstanbul Üniversitesi Adresli: Evet

Özet

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 mu M for 2b and 3.4 mu 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.