A new class of the HCV NS5b RNA-dependent RNA polymerase inhibitors, the dihyroxypyrimidinecarboxylic acid derivative, was designed from a diketoacid and meconic acid derivative discovered by screening. Mechanism of action and essential moieties required for activity were identified. The corresponding N-methylpyrimidinone was also prepared; both classes are novel, reversible, and selective inhibitors of the HCV NS5b polymerase with improved druglike characteristics.
HCVNS5b RNA-dependent RNA polymerase inhibitors: From alpha,gamma-diketoacids to 4,5-dihydroxypyrimidine- or 3-methyl-5-hydroxypyrimidinonecarboxylic acids : design and synthesis / V. Summa, A. Petrocchi, V.G. Matassa, M. Taliani, R. Laufer, R. De Francesco, S. Altamura, P. Pace. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 47:22(2004), pp. 5336-5339.
|Titolo:||HCVNS5b RNA-dependent RNA polymerase inhibitors: From alpha,gamma-diketoacids to 4,5-dihydroxypyrimidine- or 3-methyl-5-hydroxypyrimidinonecarboxylic acids : design and synthesis|
|Parole Chiave:||Virus NS5B polymerase; hepatitis-C; thiophene-2-carboxylic acids; nonnucleoside inhibitors; poten inhibitors; replication; discovery; identification; derivatives; therapy|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore BIO/19 - Microbiologia Generale
|Data di pubblicazione:||2004|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/jm0494669|
|Appare nelle tipologie:||01 - Articolo su periodico|