RESUMO
Ring-cleaved pleuromutilin derivatives comprised of a [5.3.1] bicyclic core structure have been synthesized and evaluated in vitro as antibacterial agents. Four of the compounds described were found to have MICsAssuntos
Antibacterianos/síntese química
, Antibacterianos/química
, Antibacterianos/farmacologia
, Diterpenos/síntese química
, Diterpenos/química
, Diterpenos/farmacologia
, Testes de Sensibilidade Microbiana
, Compostos Policíclicos
, Staphylococcus aureus/efeitos dos fármacos
, Streptococcus pneumoniae/efeitos dos fármacos
, Relação Estrutura-Atividade
, Pleuromutilinas
RESUMO
Forty-five novel cephalosporin derivatives with activity against methicillin-resistant Staphylococcus aureus (MRSA) are described. The compounds contain novel cinnamic acid moieties at C-7 that were synthesized using a key Heck reaction followed by nucleophilic aromatic substitution reactions. The most active compound (41) displayed an MIC(90) against MRSA of 1.0 microg/mL, and a PD(50) of 0.8 mg/kg. Compound 14 was found to be very safe in a mouse model of acute toxicity.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Cefalosporinas/química , Cefalosporinas/farmacologia , Cinamatos/química , Cinamatos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Dose Letal Mediana , Resistência a Meticilina , Camundongos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/patogenicidade , Relação Estrutura-Atividade , Testes de Toxicidade AgudaRESUMO
Twenty-seven novel cephalosporin derivatives with activity against methicillin-resistant Staphylococcus aureus (MRSA) are described. The compounds contain novel acid moieties at C-7 that were synthesized using nucleophilic aromatic substitution reactions and Stille couplings. The most interesting compound (6) displayed an MIC(90) against MRSA of 3.7 microg/mL, and an average PD(50) of 3.9 mg/kg.
