title: Novel inhibitors of bacterial protein synthesis: structure-activity relationships for 1,8-naphthyridine derivatives incorporating position 3 and 4 variants.
abstract: 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.
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. rick.clark@abbott.com
authors.forename: Richard F
authors.initials: RF
authors.lastname: Clark
authors.forename: Sanyi
authors.initials: S
authors.lastname: Wang
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Ma
authors.forename: Moshe
authors.initials: M
authors.lastname: Weitzberg
authors.forename: Christopher
authors.initials: C
authors.lastname: Motter
authors.forename: Michael
authors.initials: M
authors.lastname: Tufano
authors.forename: Rolf
authors.initials: R
authors.lastname: Wagner
authors.forename: Yu-Gui
authors.initials: YG
authors.lastname: Gu
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dandliker
authors.forename: Claude G
authors.initials: CG
authors.lastname: Lerner
authors.forename: Linda E
authors.initials: LE
authors.lastname: Chovan
authors.forename: Yingna
authors.initials: Y
authors.lastname: Cai
authors.forename: Candace L
authors.initials: CL
authors.lastname: Black-Schaefer
authors.forename: Linda
authors.initials: L
authors.lastname: Lynch
authors.forename: Douglas
authors.initials: D
authors.lastname: Kalvin
authors.forename: Angela M
authors.initials: AM
authors.lastname: Nilius
authors.forename: Steve D
authors.initials: SD
authors.lastname: Pratt
authors.forename: Niru
authors.initials: N
authors.lastname: Soni
authors.forename: Tianyuan
authors.initials: T
authors.lastname: Zhang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhang
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Beutel
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D009287:Naphthyridines; D011500:Protein Synthesis Inhibitors