Naphthalene carboxamides as inhibitors of human cytomegalovirus DNA polymerase.
ortho-Hydroxynaphthalene carboxamides have been identified as inhibitors of HCMV DNA polymerase. SAR investigations have demonstrated that both the amide and hydroxy functionalities are required for activity. Substitution on the naphthalene ring has led to inhibitors with submicromolar IC50s against HCMV polymerase. These compounds have been found to be >100-fold selective for inhibition of HCMV polymerase versus human alpha polymerase and display antiviral activity in a cell-based plaque reduction assay.
Vaillancourt
V A
VA
Pharmacia, Kalamazoo, MI 49007, USA. valerie.a.vaillancourt@am.pnu.com
Cudahy
M M
MM
Staley
S A
SA
Brideau
R J
RJ
Conrad
S J
SJ
Knechtel
M L
ML
Oien
N L
NL
Wieber
J L
JL
Yagi
Y
Y
Wathen
M W
MW
D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D003587:Cytomegalovirus / Q000201:enzymology*; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors; D004259:DNA-Directed DNA Polymerase; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009284:Naphthols / Q000737:chemistry / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014764:Viral Proteins
D000577:Amides; D004791:Enzyme Inhibitors; D009284:Naphthols; D019384:Nucleic Acid Synthesis Inhibitors; C109367:UL54 protein, Human herpesvirus 5; D014764:Viral Proteins; D004256:DNA Polymerase I; D004259:DNA-Directed DNA Polymerase