Three diazabicyclo analogs of BMS-378806, in which theaxial methyl group present on its piperazine ring is replaced by a carbon bridge, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane and-nonane derivatives maintained a significant infectivity reduction power, whereas the diazabicycloheptane derivative was much less effective. A modeling study allowed to relate the antiviral activity to the conformational preferences of the compounds. Moreover, similarly to BMS-378806, theoretical calculations predict the existence of different conformational families corresponding to the possible arrangements at the two planar amido functions of the compounds. High-field 1H NMR spectra confirm these results, as they show two distinct series of signals. A viral neutralization assay on a panel of six HIV-related pseudoviruses allowed the determination of the antiviral activity of three diazabicyclo analogs of BMS-378806, in which the axial methyl group on its piperazine ring is replaced by a carbon bridge. The diazabicyclooctane and-nonane derivatives show a significant infectivity reduction power that is related to their conformational preference.
Modeling and Spectroscopic Studies of Synthetic Diazabicyclo Analogs of the HIV-1 Inhibitor BMS-378806 and Evaluation of Their Antiviral Activity / L. Legnani, D.R. Colombo, E. Cocchi, L.P. Solano, S. Villa, L. Lopalco, V. Asti, L. Diomede, F. Marinone Albini, L. Toma. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1434-193X. - 2011:2(2011), pp. 287-294. [10.1002/ejoc.201001073]
Modeling and Spectroscopic Studies of Synthetic Diazabicyclo Analogs of the HIV-1 Inhibitor BMS-378806 and Evaluation of Their Antiviral Activity
D.R. ColomboSecondo
;L.P. Solano;S. Villa;
2011
Abstract
Three diazabicyclo analogs of BMS-378806, in which theaxial methyl group present on its piperazine ring is replaced by a carbon bridge, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane and-nonane derivatives maintained a significant infectivity reduction power, whereas the diazabicycloheptane derivative was much less effective. A modeling study allowed to relate the antiviral activity to the conformational preferences of the compounds. Moreover, similarly to BMS-378806, theoretical calculations predict the existence of different conformational families corresponding to the possible arrangements at the two planar amido functions of the compounds. High-field 1H NMR spectra confirm these results, as they show two distinct series of signals. A viral neutralization assay on a panel of six HIV-related pseudoviruses allowed the determination of the antiviral activity of three diazabicyclo analogs of BMS-378806, in which the axial methyl group on its piperazine ring is replaced by a carbon bridge. The diazabicyclooctane and-nonane derivatives show a significant infectivity reduction power that is related to their conformational preference.File | Dimensione | Formato | |
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