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.
The monoethyl ester of meconic acid is an active site inhibitor of HCV NS5B RNA-dependent RNA polymerase / P. Pace, E. Nizi, B. Pacini, S. Pesci, V. Matassa, R. De Francesco, S. Altamura, V. Summa. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 14:12(2004), pp. 3257-3261. [10.1016/j.bmcl.2004.03.087]
The monoethyl ester of meconic acid is an active site inhibitor of HCV NS5B RNA-dependent RNA polymerase
R. De Francesco;
2004
Abstract
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.File | Dimensione | Formato | |
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