Design, synthesis and structure relationships of new N,N',N",N"'-tetrakis (omega-amino alkyl) tetraazamacrocycles.

Journal Article (Journal Article)

A number of N,N',N",N"'-tetrakis (omega-aminoalkyl) tetraazamacrocycles and related compounds were synthesized and evaluated for their inhibitory effects on human immunodeficiency virus type 1 (HIV-1) and duck hepatitis B virus (DHBV) replication. The activity of these compounds was found to be highly dependent upon structural features: (i) the length of the alkyl linker connecting the nitrogen atoms of the macrocyclic ring to the exocyclic nitrogen atoms of the terminal amino groups (five methylenes favoured antiviral activity); (ii) substitution of the terminal amino groups of the linker reduced antiviral activity; and (iii) the size of the tetraazamacrocyclic ring (14 or 15 atoms) did not markedly affect the antiviral activity. Some analogues were potent inhibitors of HIV-1 replication, with anti-HIV activity similar to that of biscyclam (JM 2763). In contrast, other analogues were found to be highly toxic in duck hepatocyte primary culture, the 2.2.15 cell line and to a lesser extent in MT-4 cells. Structural parameters, macrocyclic ring size and metal-chelating ability have been used to develop a structure-activity relationship model in order to aid the design of antiviral molecules derived from N,N',N",N"'-tetrakis (omega-aminoalkyl) tetraazamacrocycles.

Full Text

Duke Authors

Cited Authors

  • Trabaud, C; Dessolin, J; Camplo, M; Hantz, O; Zoulim, F; Borel, C; Meyer, M; Pepe, G; Chermann, JC; Kraus, JL

Published Date

  • January 1998

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 73 - 84

PubMed ID

  • 9875379

International Standard Serial Number (ISSN)

  • 0956-3202


  • eng

Conference Location

  • England