Design and synthesis of 4-alkyl-2-amino(acetamino)-6-aryl-1,3-thiazine derivatives as influenza neuraminidase inhibitors.
With a convenient and economical method, two series of 1,3-thiazine derivatives 1 and 2 were synthesized, and their neuraminidase (NA) inhibitory activities were evaluated. The pharmacological results showed that most of the compounds have potent NA inhibitory activity. Especially, 1g exhibited the best activity against influenza virus A (H1N1) NA (IC50=29.06 µg/mL), and its crystal structure was determined by single-crystal X-ray diffraction. The preliminary biological assay indicated that 1,3-thiazine could be used as a core structure to design novel influenza NA inhibitors.
College of Chemistry and Chemical Engineering, Hunan University, Changsha, China.
Wan
W
Li
Lin
L
Xia
Aixi
A
Hu
Ailin
A
Liu
Junmei
J
Peng
Weiqing
W
Tan
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D013843:Thiazines; D009439:Neuraminidase
1,3-Thiazine; Crystal structure; Neuraminidase inhibitor; Synthesis