Modeling and Spectroscopic Studies of Synthetic Diazabicyclo Analogs of the HIV‐1 Inhibitor BMS‐378806 and Evaluation of Their Antiviral Activity

Three diazabicyclo analogs of BMS-378806, in which the axial 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 1 H NMR spectra confirm these results, as they show two distinct series of signals.