Biomedical subjects

Dennis Keith

Publications and source records attributed to Dennis Keith.

6 recordsLinked to original sources

PubMed2004

Potent and selective inhibitors of bacterial methionyl tRNA synthetase derived from an oxazolone-dipeptide scaffold.

The preparation and structure-activity relationships (SARs) of potent and selective small molecule inhibitors of bacterial methionyl-tRNA synthetase (MetRS) derived from an oxazolone-dipeptide scaffold are described. Examples combine Staphylococcus aureus MetRS (SaMetRS) potency with selectivity over human MetRS. As a result of the SAR expansion compound 14a was identified, as a potent SaMetRS inhibitor (IC(50)=18 nM) having moderate inhibition of MetRS derived from Enterococci faecalis (IC(50)=3.51 microM).

Bacteria↗

PubMed2004

A series of spirocyclic analogues as potent inhibitors of bacterial phenylalanyl-tRNA synthetases.

We have identified a series of spirocyclic furan and pyrrolidine inhibitors of Enterococcus faecalis and Staphylococcus aureus phenylalanyl-tRNA synthetases. The most potent analogue 1b showed IC50=5 nM (E. faecalis PheRS) and IC50=2 nM (S. aureus PheRS) with high selectivity over the human enzyme. The crystal X-ray structure of analogue 1b was determined.

Anti-Bacterial Agents↗

PubMed2004

A series of heterocyclic inhibitors of phenylalanyl-tRNA synthetases with antibacterial activity.

A series of novel heterocyclic analogues have been synthesized and evaluated for their ability to inhibit phenylalanyl-t-RNA synthetases and act as antibacterial agents. Several analogues have good antibacterial activity against Staphylococcus aureus.

Anti-Bacterial Agents↗

PubMed2003

Synthesis and biological activity of N-Acylated ornithine analogues of daptomycin.

N-Acylated ornithine analogues of daptomycin were synthesized and tested for their antibacterial efficacy.

Animals↗

PubMed2003

Array synthesis of novel lipodepsipeptide.

Synthetic array technology was utilized to rapidly synthesize and analyze a diverse set of reductive alkylation analogues of daptomycin. Analysis of the array suggested the use of polar functionality such as sulfonamides or amide or polar spaces such as piperazine would beneficially affect activity.

Alkylation↗

PubMed2003

Discovery of a potent and selective series of pyrazole bacterial methionyl-tRNA synthetase inhibitors.

Starting with a micromolar lead identified from high-throughput screening, a series of pyrazoles were discovered with significantly improved potency on bacterial methionyl-tRNA synthetase and selectivity over human methionyl-tRNA synthetase.

Anti-Infective Agents↗