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


Goktas F., VANDERLINDEN E., NAESENS L., Cesur Z., Cesur N., Tas P.

PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS, vol.190, no.7, pp.1075-1087, 2015 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 190 Issue: 7
  • Publication Date: 2015
  • Doi Number: 10.1080/10426507.2014.965819
  • Journal Name: PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1075-1087
  • Keywords: Hydrazides, spirothiazolidinone, synthesis, antiinfluenza activity, hemagglutinin, MICROWAVE-ASSISTED SYNTHESIS, DERIVATIVES
  • Istanbul University Affiliated: Yes

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, H-1-NMR,C-13-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.