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Design, synthesis & structure-activity relationships of a new class of antihuman enterovirus D68 & A71 agents.
Future Medicinal Chemistry 2018 June 2
AIM: No antiviral medications are currently approved to treat enterovirus (EV)-associated disease or prevent EV infection.
METHODS: In this study, a series of probenecid derivatives were designed via a rational strategy and synthesized to obtain more potent anti-EV agents.
RESULTS: Compounds 8 and 24 exhibited the most potent activity against EV D68 and A71, with half maximal effective concentration (EC50 ) values of 2.49/2.09 and 2.59/2.41 μM, respectively, and revealed a broad inhibition spectrum toward other EV strains, with high selectivity indices. Additionally, compounds 8 and 24 showed good stability in rat serum, with half-lives of 48.39 and 60.26 min, respectively.
CONCLUSION: Compounds 8 and 24 are the promising candidates for the development of new agents against EV D68 and A71 viruses.
METHODS: In this study, a series of probenecid derivatives were designed via a rational strategy and synthesized to obtain more potent anti-EV agents.
RESULTS: Compounds 8 and 24 exhibited the most potent activity against EV D68 and A71, with half maximal effective concentration (EC50 ) values of 2.49/2.09 and 2.59/2.41 μM, respectively, and revealed a broad inhibition spectrum toward other EV strains, with high selectivity indices. Additionally, compounds 8 and 24 showed good stability in rat serum, with half-lives of 48.39 and 60.26 min, respectively.
CONCLUSION: Compounds 8 and 24 are the promising candidates for the development of new agents against EV D68 and A71 viruses.
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