Anti-influenza Virus Activities of 2-Alkoxyimino-N-(2-isoxazolin-3-ylmethyl)acetamides

Abstract A series of 2-alkoxyimino- N -(2-isoxazolin-3-ylmethyl)acetamides and related compounds were synthesized and their antiviral activities against human influenza A virus were assessed. Studies of the structure–activity relationships revealed the strongest antiviral activity when position-5 of the isoxazoline ring was substituted with a tert -butyl group. When the alkoxyimino moiety was substituted with a methyl, ethyl, isopropyl or allyl group, good antiviral activity was obtained. Among the geometrical isomers at the oxime moiety, the E -isomers were more active than the Z -isomers. Among the compounds examined, ( E )-2-allyloxyimino-2-cyano- N -(5- tert -butyl-2-isoxazolin-3-ylmethyl)acetamide ( 1j ) was the most active inhibitor with an EC 50 of 3 μg/mL in vitro.