Synthesis and antiviral activity of new dimeric inhibitors against HIV-1.
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.
Danel
Krzysztof
K
Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Larsen
Louise M
LM
Pedersen
Erik B
EB
Sanna
Giuseppina
G
La Colla
Paolo
P
Loddo
Roberta
R
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D019281:Dimerization; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009154:Mutation; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D014498:Uracil / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D015215:Zidovudine / Q000737:chemistry / Q000494:pharmacology
D019380:Anti-HIV Agents; D011743:Pyrimidines; C519627:TNK-651; D015215:Zidovudine; D014498:Uracil; C083858:emivirine