The identification and characterization of hydrazinyl urea-based antibacterial agents through combinatorial chemistry.
An effort to identify novel inhibitors of peptidoglycan synthesis with antibacterial activity resulted in the discovery of a series of biaryl urea-based antibacterial agents through isolation of a by-product from a mixture-based combinatorial library of semi-carbazones and subsequent parallel synthesis efforts. The compounds were shown to possess broad spectrum antibacterial activity against gram-positive drug resistant pathogens, and showed apparent specificity for disruption of the bacterial cell wall biosynthesis pathway.
Wilson
L J
LJ
Procter & Gamble Pharmaceuticals, Healthcare Research Center, Mason, OH 45040, USA. lwilson3@prius.jnj.com
Morris
T W
TW
Wu
Q
Q
Renick
P J
PJ
Parker
C N
CN
Davis
M C
MC
McKeever
H D
HD
Hershberger
P M
PM
Switzer
A G
AG
Shrum
G
G
Sunder
S
S
Jones
D R
DR
Soper
S S
SS
Dobson
R L
RL
Burt
T
T
Morand
K L
KL
Stella
M
M
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D002473:Cell Wall / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D006834:Hydrazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D006834:Hydrazines; C029424:hydrazine; D014508:Urea