7-Oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamides: synthesis and biological activity of a new class of highly potent inhibitors of human cytomegalovirus DNA polymerase.
We report a new class of non-nucleoside antivirals, the 7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamides, some of which possess remarkable potency versus a broad spectrum of herpesvirus DNA polymerases and excellent selectivity compared to human DNA polymerases. A critical factor in the level of activity is hypothesized to be conformational restriction of the key 2-aryl-2-hydroxyethylamine sidechain by an adjacent methyl group.
Larsen
Scott D
SD
Pfizer Global Research and Development, 2800 Plymouth Rd., Ann Arbor, MI 48105, USA. scott.d.larsen@pfizer.com
Zhang
Zhijun
Z
DiPaolo
Brian A
BA
Manninen
Peter R
PR
Rohrer
Douglas C
DC
Hageman
Michael J
MJ
Hopkins
Todd A
TA
Knechtel
Mary L
ML
Oien
Nancee L
NL
Rush
Bob D
BD
Schwende
Francis J
FJ
Stefanski
Kevin J
KJ
Wieber
Janet L
JL
Wilkinson
Karen F
KF
Zamora
Kathyrn M
KM
Wathen
Michael W
MW
Brideau
Roger J
RJ
D003587:Cytomegalovirus / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D011725:Pyridines; C023666:pyridine