New spirothiazolidinone derivatives: Synthesis and antiviral evaluation

Abstract

A new series ofN-(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,H-1 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 EC(50)values of 0.5 and 0.2 mu M 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 EC(50)values of 9.8 and 8.6 mu M, and a favorable selectivity index for4f. This indicates the versatility of the spirothiazolidinone scaffold to achieve new classes of antiviral molecules.