Quinazolin-2-ylamino-quinazolin-4-ols as novel non-nucleoside inhibitors of bacterial DNA polymerase III.
High throughput screening led to the discovery of a novel series of quinazolin-2-ylamino-quinazolin-4-ols as a new class of DNA polymerase III inhibitors. The inhibition of chromosomal DNA replication results in bacterial cell death. The synthesis, structure-activity relationships and functional activity are described.
Guiles
Joseph
J
Replidyne, Inc., 1450 Infinite Dr., Louisville, CO 80027, USA. joe.guiles@comcast.net
Sun
Xicheng
X
Critchley
Ian A
IA
Ochsner
Urs
U
Tregay
Ming
M
Stone
Kim
K
Bertino
Jennifer
J
Green
Louis
L
Sabin
Rob
R
Dean
Frank
F
Dallmann
H Garry
HG
McHenry
Charles S
CS
Janjic
Nebojsa
N
D016923:Cell Death; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004247:DNA / Q000737:chemistry; D004258:DNA Polymerase III / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D015394:Molecular Structure; D011799:Quinazolines / Q000737:chemistry*; D013297:Streptococcus pyogenes / Q000201:enzymology; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011799:Quinazolines; D004247:DNA; D004258:DNA Polymerase III