Anti-influenza virus activities of 2-alkoxyimino-n-(2-isoxazolin-3-ylmethyl)acetamides.
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 microg/mL in vitro.
Kai
H
H
Aburahi Laboratories, Shionogi & Co., Ltd., Koka-cho, Koka-gun, 520-3423, Shiga, Japan. hiroyuki.kai@shionogi.co.jp
Matsumoto
H
H
Hattori
N
N
Takase
A
A
Fujiwara
T
T
Sugimoto
H
H
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D007555:Isoxazoles