Structure-activity relationships of novel potent MurF inhibitors.
A novel class of MurF inhibitors was discovered and structure-activity relationship studies have led to several potent compounds with IC(50)=22 approximately 70 nM. Unfortunately, none of these potent MurF inhibitors exhibited significant antibacterial activity even in the presence of bacterial cell permeabilizers.
Gu
Yu Gui
YG
Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064, USA. yu-gui.y.gu@abbott.com
Florjancic
Alan S
AS
Clark
Richard F
RF
Zhang
Tianyuan
T
Cooper
Curt S
CS
Anderson
David D
DD
Lerner
Claude G
CG
McCall
J Owen
JO
Cai
Yingna
Y
Black-Schaefer
Candace L
CL
Stamper
Geoffrey F
GF
Hajduk
Philip J
PJ
Beutel
Bruce A
BA
D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D010453:Peptide Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010457:Peptidoglycan / Q000096:biosynthesis; D013329:Structure-Activity Relationship
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D010457:Peptidoglycan; D010453:Peptide Synthases; C060628:UDP-N-acetylmuramoylalanyl-D-glutamyllysine-D-alanyl-D-alanine ligase