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

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 (EC(50) = 15.3-18.5 microg/ml). The CC(50) values of 2a-c measured using Vero cells ranged at 37.5-50.0 microg/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.

[1]  J. Lehn,et al.  Structure and Properties of Supramolecular Polymers Generated from Heterocomplementary Monomers Linked through Sextuple Hydrogen-Bonding Arrays , 2006 .

[2]  M. Uyeda,et al.  Anti-herpes virus type 1 activity of oleanane-type triterpenoids. , 2005, Biological & pharmaceutical bulletin.

[3]  M. Uyeda,et al.  Synthesis and antiviral activities of some 4,4'- and 2,2'-dihydroxytriphenylmethanes. , 2003, Chemical & pharmaceutical bulletin.

[4]  M. Uyeda,et al.  Synthesis and antiviral activities of some 4,4'-dihydroxytriphenylmethanes. , 2004, Chemical & pharmaceutical bulletin.

[5]  Ivan Huc,et al.  Protonation-induced transition between two distinct helical conformations of a synthetic oligomer via a linear intermediate. , 2003, Angewandte Chemie.

[6]  Daoben Zhu,et al.  Self-assembly and characterization of supramolecular [60]fullerene-containing 2,6-diacylamidopyridine with uracil derivative by hydrogen-bonding interaction. , 2002, Organic letters.

[7]  K. Hamase,et al.  Reversed-Phase HPLC of Monosaccharides in Glycoproteins Derivatized with Aminopyrazine with Fluorescence Detection , 2000 .

[8]  M. Mazik,et al.  Hydrogen-bonding motifs in the crystals of secondary diamides with 2-amino-6-methyl- and 2,6-diaminopyridine subunits , 1999 .

[9]  S. Skulstad,et al.  The herpes simplex virus type 1 particle: structure and molecular functions , 1994 .

[10]  K. Mitsui,et al.  Synthesis of 2,6-diamidopyridine derivatives and their functions as flavin receptors in chloroform , 1994 .

[11]  D. Toomre,et al.  Biotinylated diaminopyridine: an approach to tagging oligosaccharides and exploring their biology. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[12]  A. Hamilton,et al.  Hydrogen Bonding and Molecular Recognition: Synthetic, Complexation, and Structural Studies on Barbiturate Binding to an Artificial Receptor , 1991 .

[13]  M. Haffey,et al.  Selective activity and cellular pharmacology of (1R-1 alpha,2 beta,3 alpha)-9-[2,3-bis(hydroxymethyl)cyclobutyl]guanine in herpesvirus-infected cells. , 1991, Molecular pharmacology.

[14]  A. Hamilton,et al.  Molecular recognition of biologically interesting substrates: synthesis of an artificial receptor for barbiturates employing six hydrogen bonds , 1988 .

[15]  R. Schinazi,et al.  Effect of combinations of acyclovir with vidarabine or its 5'-monophosphate on herpes simplex viruses in cell culture and in mice , 1982, Antimicrobial Agents and Chemotherapy.