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.