New spirothiazolidinone derivatives: Synthesis and antiviral evaluation

Apaydın Ç. B., Loy B. V., Stevaert A., Naesens L.

Phosphorus, Sulfur and Silicon and the Related Elements, vol.196, no.3, pp.294-299, 2020 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 196 Issue: 3
  • Publication Date: 2020
  • Doi Number: 10.1080/10426507.2020.1828886
  • Journal Name: Phosphorus, Sulfur and Silicon and the Related Elements
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED)
  • Page Numbers: pp.294-299
  • Keywords: Human coronavirus, influenza, spirothiazolidinones, antiviral activity, cyclocondensation, HUMAN CORONAVIRUSES 229E, INHIBITORS, OUTBREAK, SARS
  • Istanbul University Affiliated: Yes

Abstract

© 2020 Taylor & Francis Group, LLC.A new series of N-(3-oxo-1-thia-4-azaspiro[4.5]decan-4-yl)carboxamide derivatives were designed, synthesized, and evaluated for their antiviral activity. These new spirothiazolidinone compounds (3a–f, 4a–f) were prepared by a cyclocondensation reaction of hydrazides (1, 2) and appropriate ketones with 2-sulfanylpropionic acid. All compounds were characterized by IR, 1H NMR, and elemental analysis. N-(8-Ethyl-2-methyl-3-oxo-1-thia-4-azaspiro[4.5]decan-4-yl)-4-methylbenzamide (3c) and 4-methyl-N-(2-methyl-3-oxo-8-propyl-1-thia-4-azaspiro[4.5]decan-4-yl)benzamide (3d) exhibited strong activity against influenza A/H3N2 virus, at EC50 values of 0.5 and 0.2 µM and a selectivity index of about 50. Besides, 4-methyl-N-(2-methyl-3-oxo-8-phenyl-1-thia-4-azaspiro[4.5]decan-4-yl)benzamide (3e) and 2-(4-chlorophenoxy)-N-(3-oxo-8-tert-butyl-1-thia-4-azaspiro[4.5]dec-4-yl)acetamide (4f) inhibited human coronavirus 229E, at EC50 values of 9.8 and 8.6 µM, and a favorable selectivity index for 4f. This indicates the versatility of the spirothiazolidinone scaffold to achieve new classes of antiviral molecules.