Discovery of (E)-1-amino-4-phenylbut-3-en-2-ol derivatives as novel neuraminidase inhibitors

Abstract Neuraminidase has been considered as an important target for designing agents against influenza viruses. In a discovery of anti-influenza agents with epigoitrin as the initial lead compound, a series of 1-amino-2-alkanols were synthesized and biologically evaluated. The in vitro evaluation indicated that ( E )-1-amino-4-phenylbut-3-en-2-ol ( C1 ) had better inhibitory activities than 2-amino-1-arylethan-1-ol derivatives. To our surprise, sulfonation of C1 with 4-methoxybenzenesulfonyl chloride afforded more active inhibitor II with up to 6.4 μM IC 50 value against neuraminidase. Furthermore, docking of inhibitor II into the active site of NA found that the H atoms in both NH 2 and OH groups of inhibitor II were the key factors for potency. Molecular docking research did not explained very well the observed structure-activity relationship (SAR) from amino acid residue level, but also aided the discovery of ( E )-1-amino-4-phenylbut-3-en-2-ol derivatives as novel and potent NA inhibitors.