Add time:09/01/2019         Source:sciencedirect.com

A novel series of N-benzenesulfonyl matrinic amine/amide and matrinic methyl ether analogues were designed, synthesized and evaluated for their in vitro anti-coxsackievirus B3 (CVB3) activities. The structure–activity relationship (SAR) studies revealed that introduction of a suitable amide substituent on position 4′ could greatly enhance the antivirus potency. Compared to the lead compounds, the newly synthesized matrinic amide derivatives 21c–d and 21j exhibited stronger anti-CVB3 activities with lower micromolar IC50 from 2.5 μM to 2.7 μM, and better therapeutic properties with improved selectivity index (SI) from 63 to 67. The SAR results provided powerful information for further strategic optimization, and these top compounds were selected for the next evaluation as novel enterovirus inhibitors.

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