Structure-activity relationships of novel potent MurF inhibitors

Yu Gui Gu; Alan S Florjancic; Richard F Clark; Tianyuan Zhang; Curt S Cooper; David D Anderson; Claude G Lerner; J Owen McCall; Yingna Cai; Candace L Black-Schaefer; Geoffrey F Stamper; Philip J Hajduk; Bruce A Beutel

doi:10.1016/j.bmcl.2003.09.073

Structure-activity relationships of novel potent MurF inhibitors

Bioorg Med Chem Lett. 2004 Jan 5;14(1):267-70. doi: 10.1016/j.bmcl.2003.09.073.

Authors

Yu Gui Gu¹, Alan S Florjancic, Richard F Clark, Tianyuan Zhang, Curt S Cooper, David D Anderson, Claude G Lerner, J Owen McCall, Yingna Cai, Candace L Black-Schaefer, Geoffrey F Stamper, Philip J Hajduk, Bruce A Beutel

Affiliation

¹ Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064, USA. [email protected]

PMID: 14684340
DOI: 10.1016/j.bmcl.2003.09.073

Abstract

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.

MeSH terms

Bacterial Proteins / antagonists & inhibitors*
Bacterial Proteins / metabolism
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Peptide Synthases / antagonists & inhibitors*
Peptide Synthases / metabolism
Peptidoglycan / biosynthesis
Structure-Activity Relationship

Substances

Bacterial Proteins
Enzyme Inhibitors
Peptidoglycan
Peptide Synthases
UDP-N-acetylmuramoylalanyl-D-glutamyllysine-D-alanyl-D-alanine ligase