RESUMO
Two series of compounds, 2 and 3, were synthesized and their binding affinities were evaluated for the human recombinant muscarinic M(1) receptor subtype expressed in CHO cells. Comparing their binding affinities for the NMS binding sites and the Oxo-M binding sites, they were assumed as agonists. In particular, compound 2e was a good ligand for the agonist binding sites with an IC(50) of 23 nM, which represents over 1585 times stronger binding than for the antagonist binding sites.
Assuntos
Compostos Aza/síntese química , Compostos Aza/metabolismo , Compostos Bicíclicos com Pontes/síntese química , Compostos Bicíclicos com Pontes/metabolismo , Receptores Muscarínicos/metabolismo , Animais , Células CHO , Cricetinae , Ligantes , Receptor Muscarínico M1RESUMO
A series of 3-(3-phenylisoxazol-5-yl)methylidene-1-azabicycles synthesized showed different binding characteristics to acetylcholine receptors depending on the substituents on the phenyl ring. Small polar substituents gave preferential binding affinity to nicotinic receptors, and large hydrophobic substituents to muscarinic receptors.
Assuntos
Compostos Aza/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Isoxazóis/química , Receptores Colinérgicos/química , Alcaloides/química , Azocinas , Ligação Competitiva , Estrutura Molecular , N-Metilescopolamina/química , Ligação Proteica , Quinolizinas , Receptores Muscarínicos/química , Receptores Nicotínicos/químicaRESUMO
Three-dimensional QSAR studies for two series of new oxazolidinone antibacterial agents were conducted using the comparative molecular field analysis (CoMFA). In vitro activities (MICs) of the compounds against methicillin-resistant Staphylococcus aureus 88 (MRSA 88) exhibited a strong correlation with their steric, electrostatic factors and lipophilicities.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Oxazóis/química , Oxazóis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
Two series of oxazolidinone derivatives having substituted isoxazoles were synthesized and tested for antibacterial activities against several Gram-positive strains including the resistant strains of Staphylococcus and Enterococcus, such as MRSA, CRSA, MSSA and VRE. Some of them showed in vitro activities (MIC) comparable or superior to the reference compound vancomycin.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Isoxazóis/química , Oxazóis/síntese química , Oxazóis/farmacologia , Antibacterianos/química , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Oxazóis/químicaRESUMO
The synthesis and in vitro synergies of 2 beta-alkenyl and oxyiminopenam sulfone derivatives are described. Most of the compounds synthesized exhibited good inhibitory activities and synergistic antibacterial activities with piperacillin and ceftriaxone, respectively, against several beta-lactamase producing strains. Particularly the 2 beta-alkenylpenam sulfone derivatives. 1e and 1g, showed good synergistic activity with ceftriaxone against Citrobacter freundi NIH 10018-68 and Proteus vulgaris 20. Also the compounds 2a, 2c, and 2f, 2 beta-oxyiminopenam sulfone derivatives, exhibited improved synergistic activity with piperacillin against Citrobacter freundi NIH 10018-68.
