RESUMO
The synthesis and anticonvulsant activity of 1-aryl-7,8-methylenedioxy-1,2,3,5-tetrahydro-4H-2,3-benzodiazepin-4-(thi)ones (4a-d) and their 3-N-alkylcarbamoyl derivatives (4e-h) are reported. The new compounds possess marked anticonvulsant properties, comparable to those of the dehydro analogues 3 and higher than that of GYKI 52466 (1). Noteworthy, compound 4c shows a longer-lasting anticonvulsant activity. Electrophysiological experiments show that derivative 4c is less effective than 1 and 3c to reduce the KA-evoked currents in cerebellar granule neurons.
Assuntos
Anticonvulsivantes/síntese química , Benzodiazepinas , Receptores de AMPA/antagonistas & inibidores , Animais , Ansiolíticos/farmacologia , Anticonvulsivantes/farmacologia , Camundongos , Camundongos Endogâmicos DBARESUMO
There is increasing evidence of the potential therapeutic utility of glutamate receptor antagonists in the treatment of several neurodegenerative disorders, including stroke and epilepsy. In the last few years noncompetitive AMPA receptor antagonists have received considerable attention due to their therapeutic potentiality. The discovery of GYKI 52466, the prototype of noncompetitive AMPA receptor antagonists endowed with anticonvulsant and neuroprotective properties, induced growing interest on 2,3-benzodiazepine derivatives. This review covers the chemistry and pharmacology of this important class of AMPA receptor antagonists.
Assuntos
Ansiolíticos/síntese química , Benzodiazepinas/síntese química , Benzodiazepinas/farmacologia , Antagonistas de Aminoácidos Excitatórios/síntese química , Antagonistas de Aminoácidos Excitatórios/farmacologia , Receptores de AMPA/antagonistas & inibidores , Ansiolíticos/química , Ansiolíticos/uso terapêutico , Benzodiazepinas/química , Desenho de Fármacos , Antagonistas de Aminoácidos Excitatórios/química , Humanos , Modelos Moleculares , Estrutura Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Relação Estrutura-AtividadeRESUMO
A series of 1H,3H-thiazolo[4,3-b]quinazolines (2a-i) were synthesized and evaluated for their in vitro antitumour activity against ca. 60 human tumour cell lines. They exhibited moderate (2c, 2d, 2f and 2g) to strong (2a, 2b, 2e, 2h and 2i) cell-growth inhibition at a concentration of 10(-4) M, but weak activity at lower concentrations. Only 1-(2,6-dichlorophenyl)-1H,3H-thiazolo[4,3-b]quinazoline (2h) possesses a significant growth inhibitory activity on 22 cell lines at a concentration of 10(-5) M.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Quinazolinas/síntese química , Quinazolinas/farmacologia , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Quinazolinas/química , Células Tumorais CultivadasRESUMO
We isolated corticosteroid-binding globulin from human plasma and used the isolated protein as the antigen in raising antibodies in rabbits. The resulting antiserum was used to develop an RIA with which we can determine the globulin in as little as 0.007 microL of serum, although we routinely use, after appropriate dilution, 0.02 microL. The mean concentration of corticosteroid-binding globulin in the serum of 40 normal subjects was 32.4 (SD 4.2) mg/L. The correlation (r) between results with this RIA and those by an established binding assay was 0.94.
