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[摘要]：Structural optimization of salicylamide-based hemagglutinin (HA) inhibitor 1 resulted in the identification of cis-3-(5-hydroxy-1,3,3-timethylcyclohexylmethylamino)benzenesulfonamide 28 and its derivatives as potent anti-influenza agents. The lead compound 28 and its 2-chloro analogue 40 can effectively prevent cytopathic effects (CPE) caused by infection of influenza A/Weiss/43 strain (H1N1) with EC(50) values of 210 and 86 nM, respectively. Mechanism of action studies indicate that 40 and its analogues inhibit the virus fusion with host endosome membrane by binding to HA and stabilizing the prefusion HA structure. With significantly improved metabolic stability, the reported series represents the first generation of orally bioavailable HA inhibitors that have a good selectivity window and potential for further development as novel anti-influenza agents. |
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