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.
Bioorg Med Chem
; 15(22): 7087-97, 2007 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-17869116
ABSTRACT
A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, substituted at the 2-position with piperidines bearing quaternary ammonium salt side chains, were synthesized and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Pseudomonas aeruginosa
/
Infecções por Pseudomonas
/
Proteínas da Membrana Bacteriana Externa
/
Compostos de Amônio Quaternário
/
Antibacterianos
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Japão