Novel inhibitors of bacterial protein synthesis: structure-activity relationships for 1,8-naphthyridine derivatives incorporating position 3 and 4 variants.
Structure-activity relationships for a recently discovered novel ribosome inhibitor (NRI) class of antibacterials were investigated. Preliminary efforts to optimize protein synthesis inhibitory activity of the series through modification of positions 3 and 4 of the naphthyridone lead template resulted in the identification of several biochemically potent analogues. A lack of corresponding whole cell antibacterial activity is thought to be a consequence of poor cellular penetration as evidenced by the enhancement of activity observed for a lead analogue tested in the presence of a cell permeabilizing agent.
Clark
Richard F
RF
Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. rick.clark@abbott.com
Wang
Sanyi
S
Ma
Zhenkun
Z
Weitzberg
Moshe
M
Motter
Christopher
C
Tufano
Michael
M
Wagner
Rolf
R
Gu
Yu-Gui
YG
Dandliker
Peter J
PJ
Lerner
Claude G
CG
Chovan
Linda E
LE
Cai
Yingna
Y
Black-Schaefer
Candace L
CL
Lynch
Linda
L
Kalvin
Douglas
D
Nilius
Angela M
AM
Pratt
Steve D
SD
Soni
Niru
N
Zhang
Tianyuan
T
Zhang
Xiaolin
X
Beutel
Bruce A
BA
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000737:chemistry* / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D009287:Naphthyridines; D011500:Protein Synthesis Inhibitors