An exhaustive conformational evaluation of the HIV-1 inhibitor BMS-378806 through theoretical calculations and nuclear magnetic resonance spectroscopy

BMS-378806 (1) is an azaindole derivative known to interfere with the HIV-1 entry process by targeting the viral gp120 envelope glycoprotein and inhibiting its interaction to cellular CD4 receptors. To give a detailed comprehension of its conformational features, a theoretical study of 1 was performed at the B3LYP/6-31G(d) level of calculation. Tenths of populated conformations were located and grouped into four families corresponding to the possible arrangements at the two planar amido functions. In agreement with these results, the high-field 1H NMR spectrum of 1, recorded at 248 K, showed four distinct series of signals easily attributable to each family, thus confirming on experimental grounds the very high degree of conformational mobility of the compound.