Design, Synthesis, Inhibitory Activity, and SAR Studies of Hydrophobic Phenylacetic Acid Derivatives as Neuraminidase Inhibitors

Introduction: A series of hydrophobic phenylacetic acid derivatives introducing an aromatic lipophilic side chain at C-3 amino and an acetyl or isopropionyl at C-4 amino were synthesized and evaluated for their ability to inhibit neuraminidase (NA) of influenza A virus. Methods: All compounds were synthesized in good yields starting from commercially available 2-(4- aminophenyl) acetic acid using a suitable synthetic strategy. Results: These compounds showed potent inhibitory activity against influenza A NA. Several compounds with alkylated amino group showed moderate NA subtype selectivity, among which compound (7i) displayed the best. Conclusion: Compound (7i) activity against H5N1 was more than 10 times better than H9N2, and could be used as lead compounds in the future.