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MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 7: highly soluble and in vivo active quaternary ammonium analogue D13-9001, a potential preclinical candidate.
TLDR
Attachment of the charged entity using an N-ethylcarbamoyloxy linker led to the discovery of the highly soluble compound 22 (D13-9001), which maintained good potency in vitro and displayed excellent activity in vivo in a rat pneumonia model of P. aeruginosa. Expand
MexAB-OprM-specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 1: discovery and early strategies for lead optimization.
TLDR
The identification of a series of compounds that specifically inhibit efflux by the MexAB-OprM pump system in Pseudomonas aeruginosa is described and efforts to improve solubility and reduce serum protein binding by the introduction of polar groups are discussed. Expand
Inhibitors of bacterial efflux pumps as adjuvants in antibiotic treatments and diagnostic tools for detection of resistance by efflux.
TLDR
Inhibition of efflux pumps appears to be (i) a promising strategy for restoring the activity of existing antibiotics, and (ii) a useful method to detect the presence ofefflux determinants in clinical isolates. Expand
Inhibitors of Bacterial Efflux Pumps as Adjuvants in Antibacterial Therapy and Diagnostic Tools for Detection of Resistance by Efflux
TLDR
Inhibition of efflux pumps appears to be (i) a promising strategy for restoring the activity of existing antibiotics, and (ii) a useful method to detect the presence ofefflux determinants in clinical isolates. Expand
Conformationally-restricted analogues of efflux pump inhibitors that potentiate the activity of levofloxacin in Pseudomonas aeruginosa.
Conformational restriction of the ornithine residue of the efflux pump inhibitor D-ornithine-D-homophenylalanine-3-aminoquinoline (MC-02,595, 2) furnished bioisosteric proline derivatives that wereExpand
MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 2: achieving activity in vivo through the use of alternative scaffolds.
TLDR
Use of alternative scaffolds upon which the key elements for pump inhibition were arrayed gave second generation leads with greatly improved physical properties and activity in the potentiation of antibacterial quinolones (levofloxacin and sitafl oxacin) versus Pseudomonas aeruginosa in vivo. Expand
MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 6: exploration of aromatic substituents.
TLDR
By incorporating hydrophilic substituents onto the aryl nucleus, it is found a morpholine analogue that possessed improved solubility, retained activity in vitro, and displayed potentiation activity in vivo in a rat model of P. aeruginosa pneumonia. Expand
In Vivo Antibacterial Activity of RWJ-54428, a New Cephalosporin with Activity against Gram-Positive Bacteria
TLDR
These studies show that RWJ-54428 is active in experimental mouse models of infection against gram-positive organisms, including strains resistant to earlier cephalosporins and penicillin G. Expand
Synthesis of novel tetracycline derivatives with substitution at the C-8 position
Abstract The C-8 functionalization of tetracycline derivatives via acid-catalyzed rearrangement of 7(or 9)azidotetracyclines is described. These compounds are the first to be prepared from an intactExpand
Synthesis of 5,8‐dihydroxynaphtho[2,3‐c][1,2,5]thiadiazole‐6,9‐dione and 6,9‐dihydroxybenzo[g]quinoxaline‐5,10‐dione
The synthesis of 5,8-dihydroxynaphtho[2,3-c][1,2,5]thiadiazole-4,9-dione 3, 6,9-dihydroxybenzo[g]quinoxaline-5,10-dione 4, and their lesser oxygenated analogs via Friedel-Crafts and Diels-AlderExpand
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