Next, we examined protein binding of all compounds, a
feature that can be clinically relevant in the context of possible
drug−drug interactions or in view of the “therapeutic window”.
As shown in Table 3, our results suggest that all compounds do
not or only to a small extent bind to albumin (0−38%). As a
general trend, protein binding appears to increase with higher
lipophilicity. Not surprisingly, data obtained with human
plasma (only available for amidine 6, guanidine 7) reveals
higher protein binding due to the presence of several other
plasma proteins (i.e., α1-acidic glycoprotein). In the literature,
protein binding of 5 is stated with 3% and 1 with 42%.37 Thus,
with regard to protein binding, the herein presented oseltamivir
derivatives exhibit an almost identical profile as the approved
drug 1.