RESUMO
A series of new anti-HIV derivatives containing a novel alpha-thiophenoxyhydroxyethylamide core have been synthesized, using S-phenylbenzenethiosulfonate as the thiosulfenylating reagent. Some of the new synthesized compounds (1a, 1c, 1g, 1i, 1j and 1l) inhibited HIV replication in cell culture assays (syncytia formation) with effective concentrations (EC(50)) ranging from 0.1-1 microM. Incorporation of thiophenoxy substitution within various pseudomimetic peptide backbones provided a series of highly potent HIV inhibitors.
Assuntos
Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , Alcanos/síntese química , Alcanos/farmacologia , Amidas/síntese química , Amidas/farmacologia , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Inibidores da Protease de HIV/síntese química , Inibidores da Protease de HIV/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Replicação Viral/efeitos dos fármacosRESUMO
The syntheses consisting of replacement of proline amino acid by a 3-pyrrolidinone ring in Phe-Pro analogues are described. Preliminary anti-HIV studies demonstrated the potential activity of this new class of compounds.
Assuntos
Fármacos Anti-HIV/síntese química , Dipeptídeos/síntese química , Prolina/química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Dipeptídeos/química , Dipeptídeos/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
We report the synthesis and the anti-HIV activities of new C2-symmetrical and achiral N1,N3-dibenzyl-2-hydroxy-propane isosteres. Some of them showed significant inhibitory activity with respect to HIV-infected MT4 cells (compound 6a and 7a, IC50 = 0.1 microM). These new structurally simple compounds represent new synthons which can be suitable for combinatorial chemistry purposes.
Assuntos
Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , Benzilaminas/síntese química , Benzilaminas/farmacologia , Propanolaminas/síntese química , Propanolaminas/farmacologia , Fármacos Anti-HIV/química , Benzilaminas/química , Linhagem Celular , Humanos , Propanolaminas/química , Relação Estrutura-AtividadeRESUMO
As far as linear N-Boc-polyamines conjugates elicited remarkable anti-HIV activity, the synthesis and anti-HIV properties of cyclic N-Boc-polyamines conjugates such as tetraazamacrocycle-nucleoside were studied. These new conjugates include an ester linkage between the two moieties. They were synthesized using Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate coupling reagent, in the case of N-alkyl polyazamacrocycle derivatives, or through direct condensation of the acyl chloride derivative with nucleoside in the case of N-acyl polyazamacrocycle compounds. None of the new conjugates presented anti-HIV activity greater than that of the corresponding parent nucleosides.