Synthesis and antiviral activity of new dimeric inhibitors against HIV-1

  • Bioorg Med Chem. 2008 Jan 1;16(1):511-7. doi: 10.1016/j.bmc.2007.09.015.
Krzysztof Danel  1 ,  Louise M Larsen ,  Erik B Pedersen ,  Giuseppina Sanna ,  Paolo La Colla ,  Roberta Loddo
Affiliations
  • 1. Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
PMID: 17904371 DOI: 10.1016/j.bmc.2007.09.015
Abstract

This paper describes the synthesis and the Antiviral activities of dimeric compounds derived from homo and asymmetric combinations of N-1 propynyloxymethyl analogues 1a,b of MKC-442, an N-1 4-iodobenzyloxymethyl analogue of TNK-651 5, potent contraceptive norgestrel and AZT. They were obtained by Sonogashira reaction, 'click' chemistry or Pd-catalyzed oxidative coupling. The iodo precursor 5 turned out as a potent compound against wild type and mutated HIV-1 virus. All dimeric compounds showed lower activity against HIV-1 than MKC-442, except the asymmetric dimer of AZT and 1a which showed an activity comparable to MKC-442.