N-long-chain monoacylated derivatives of 2,6-diaminopyridine with antiviral activity

Abstract

N-Monoacyl-2,6-diaminopyridines (2a-c) and N,N′-diacyl-2,6- diaminopyridines (3a-c) were synthesized from 2,6-diaminopyridine by acylation with the corresponding acyl halide or by dehydration with the corresponding carboxylic acid using 1,3-dicyclohexylcarbodiimide (DCC). The antiviral activities of N-monoacyl- and N,N′-diacyl-2,6-diaminopyridines (2a-c and 3a-c) were estimated using plaque reduction assay with HSV-1. All N-monoacyl derivatives (2a-c) showed significant anti-herpes simplex virus (HSV)-1 activity (EC50=15.3-18.5 μg/ml). The CC50 values of 2a-c measured using Vero cells ranged at 37.5-50.0 μg/ml. These compounds showed no significant antibacterial activities with Escherichia coli or Staphylococcus aureus even at a concentration of 1 mg/ml. The N,N′-diacyl derivatives (3a-c) showed no significant anti-HSV-1 activity. © 2007 Pharmaceutical Society of Japan.