Structure-activity relationships of bioisosteres of a carboxylic acid in a novel class of bacterial translation inhibitors.
The discovery and initial optimization of a novel anthranilic acid derived class of antibacterial agents which suffered from extensive protein binding has been previously reported. The structure-activity relationships around the carboxylic acid substituent are described herein. This acid was replaced by several alternative functional groups in attempts to retain bioactivity while reducing protein binding. Only groups with an acidic proton retained activity, and analogs containing those groups maintained the protein binding inherent to this class of antibacterial agents.
Ruble
J Craig
JC
Medicinal Chemistry, Pharmacia Corporation, 301 Henrietta Street, Kalamazoo, MI 49001, USA.
Wakefield
Brian D
BD
Kamilar
Gregg M
GM
Marotti
Keith R
KR
Melchior
Earline
E
Sweeney
Michael T
MT
Zurenko
Gary E
GE
Romero
Donna L
DL
D001419:Bacteria / Q000187:drug effects* / Q000235:genetics; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D014176:Protein Biosynthesis / Q000187:drug effects*; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids