We have located links that may give you full text access.
Novel oral anti-influenza prodrug candidate AV5075S.
OBJECTIVES: Development of a novel drug candidate with improved activity against influenza virus neuraminidase (NA) compared with currently available therapeutics.
METHODS: Synthesized compounds were evaluated in vitro and in vivo. Three-dimensional molecular docking was successfully applied to classify compounds within the series by inhibitory potency. Stability was investigated in blood samples and in animal models. A pharmacokinetic study was performed in dogs and rats using peroral and intravenous administration.
RESULTS: A novel highly potent drug candidate [(3R,4R,5S)-4-(2,2-difluoroacetylamino)-5-amino-3-(1-ethyl-propoxy)-cyclohex-1-enecarboxylic acid; AV5027] and its prodrug ethyl ester (AV5075S) were synthesized and tested. AV5027 and AV5075S exhibit picomolar activity against influenza virus NA. AV5075S inhibited NA in a model of pneumonia using mouse-adapted A/Aichi/2/68 (H3N2) virus significantly more strongly than oseltamivir phosphate. A general metabolic pathway was constructed for the parent compound based on experimental results and theoretical analyses.
CONCLUSIONS: AV5075S can be reasonably regarded as a novel 'next in class' oral drug candidate for the treatment of influenza.
METHODS: Synthesized compounds were evaluated in vitro and in vivo. Three-dimensional molecular docking was successfully applied to classify compounds within the series by inhibitory potency. Stability was investigated in blood samples and in animal models. A pharmacokinetic study was performed in dogs and rats using peroral and intravenous administration.
RESULTS: A novel highly potent drug candidate [(3R,4R,5S)-4-(2,2-difluoroacetylamino)-5-amino-3-(1-ethyl-propoxy)-cyclohex-1-enecarboxylic acid; AV5027] and its prodrug ethyl ester (AV5075S) were synthesized and tested. AV5027 and AV5075S exhibit picomolar activity against influenza virus NA. AV5075S inhibited NA in a model of pneumonia using mouse-adapted A/Aichi/2/68 (H3N2) virus significantly more strongly than oseltamivir phosphate. A general metabolic pathway was constructed for the parent compound based on experimental results and theoretical analyses.
CONCLUSIONS: AV5075S can be reasonably regarded as a novel 'next in class' oral drug candidate for the treatment of influenza.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app