Synthesis and Structure-Activity Relationship of N-(3-Oxo-1-Thia-4-Azaspiro[4.5]Decan-4-Yl)Carboxamide Inhibitors of Influenza Virus Hemagglutinin Mediated Fusion

GRAPHICAL ABSTRACT

Abstract

We report on synthesis and the structure-activity relationship of carboxamide-derived inhibitors of the influenza virus fusion function of the viral hemagglutinin. The newly synthesized carboxamides have a backbone structure similar to reported fusion inhibitors, consisting of an aromatic ring system linked to a non-aromatic cyclic system via an amide bridge. Condensation of 2-hydroxybenzohydrazide, 5-chloro-2-hydroxybenzohydrazide or 3-hydroxynaphthalene-2-carbohydrazide, appropriate carbonyl compounds and sulfanyl acids yielded corresponding N-(3- oxo-1-thia-4-azaspiro[4.5]decan-4-yl)carboxamides, using a one-pot three-component cyclocondensation method. The compounds were characterized by IR, ¹H-NMR,¹³C-NMR, and elemental analysis. All compounds were evaluated for antiviral activity against influenza A (H1N1, H3N2) and influenza B viruses in MDCK cell cultures. The contributions of different substituents on the antiinfluenza effect were discussed.

Keywords:

• Hydrazides
• spirothiazolidinone
• synthesis
• antiinfluenza activity
• hemagglutinin