Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 15, Issue 3, Pages 675-678Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2004.11.028
Keywords
HCV; inhibitor; NS5B; pteridine
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From compound library screening using an HCV NS5B RNA-dependent RNA polymerase enzymatic assay, we identified a pteridine hit compound with an IC50 of 15 muM. Our SAR studies were focused on the different groups at the 6- and 7-positions. substitutions at the 4-position, and replacement of N-1 or N-3 with carbon in the pteridine ring. We found that NH or OH at 4-position is critical for the inhibitory activity. Furthermore, a hydrophobic substituent at the 4-position may help compounds permeate through the cell membrane. (C) 2004 Elsevier Ltd. All rights reserved.
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