Bioorganic and Medicinal Chemistry Letters p. 3257 - 3261 (2004)
Update date:2022-08-04
Topics:
Pace, Paola
Nizi, Emanuela
Pacini, Barbara
Pesci, Silvia
Matassa, Victor
De Francesco, Raffaele
Altamura, Sergio
Summa, Vincenzo
Screening of the in-house sample collection for compounds with HCV NS5B RNA dependent RNA polymerase inhibition led to the identification of a new lead. Afterwards, we discovered that the screening lead, rather than containing the expected structure 1, was comprised of roughly a 1:1 mixture of meconic acid 2 and its monoethyl ester 3, with all inhibitory potency residing with 3. We propose that this compound shares critical common features for activity with α,γ-diketoacids inhibitors previously discovered by our group. SAR around this molecule will be presented to provide an improved basis for structure-based ligand design.
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