Synthesis and activity of C2-substituted analogs of influenza neuraminidase inhibitor GS 4071

The influence of C2-substitution of GS 4071 on the influenza neuraminidase inhibitory activity was investigated. The introduction of lipophilic substituents (chloro, methyl, and methylthio) at the C2 position resulted in a significant decrease of the activity. This result indicates that at the enzyme active site there is limited hydrophobic pocket for group at the C2 position of GS 4071.