RESUMO
A series of pyrrolopyridine-substituted oxazolidinones containing various C-5 acetamide isosteres was synthesized and the structure-antibacterial activity relationships determined against a representative panel of susceptible and resistant Gram-positive bacteria.
Assuntos
Acetamidas/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Oxazolidinonas/química , Oxazolidinonas/farmacologia , Piridinas/química , Antibacterianos/química , Enterococcus/efeitos dos fármacos , Linezolida , Estrutura Molecular , Oxazolidinonas/síntese química , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
A novel series of 3,5-diarylisoxazole and 3,5-diaryl-1,2,4-oxadiazole IL-8 inhibitors has been identified. These compounds exhibit activity in an IL-8 binding assay as well as in a functional assay of IL-8 induced elastase release from neutrophils. In addition, one of the compounds exhibits oral activity in a rat adjuvant arthritis model.
Assuntos
Isoxazóis/química , Isoxazóis/farmacologia , Oxidiazóis/química , Oxidiazóis/farmacologia , Receptores de Interleucina-8A/antagonistas & inibidores , Administração Oral , Isoxazóis/administração & dosagem , Isoxazóis/síntese química , Oxidiazóis/administração & dosagem , Oxidiazóis/síntese química , Relação Estrutura-AtividadeRESUMO
A novel series of oxazolidinones containing a pyrroloaryl substituent was synthesized and screened against a representative panel of susceptible and resistant Gram-positive bacteria. Several members of this series were found to have antibacterial activity comparable to or better than linezolid.
Assuntos
Acetamidas/síntese química , Acetamidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Oxazolidinonas/síntese química , Oxazolidinonas/farmacologia , Acetamidas/química , Antibacterianos/química , Linezolida , Testes de Sensibilidade Microbiana , Oxazolidinonas/química , Relação Estrutura-AtividadeRESUMO
Oxazolidinone antibacterial agents, where the morpholino group of linezolid was replaced with an N-substituted piperidinyloxy moiety, were synthesized and shown to be active against a variety of resistant and susceptible Gram-positive organisms. The functionality attached to the piperidine nitrogen was varied extensively to determine the SAR for this series. One of the most potent compounds, 11, showed in vivo efficacy upon subcutaneous administration in a Staphylococcus aureus Smith murine systemic infection.
