RESUMO
Obesity is a major clinical problem in the western world, and many molecular targets have been explored in the search for effective therapeutic agents. One of these, antagonism of the cannabinoid 1 (CB1) receptor, rose to prominence following reports demonstrating the positive modulation of food intake by the CB1 antagonist, rimonabant (3) (SR141716A). In the present study, various diaryl-pyrazole derivatives containing cycloalkyl building blocks were synthesized and tested for CB1 receptor binding affinities. Thorough structure-activity relationship (SAR) studies to optimize the pyrazole substituents led to several novel CB1 antagonists with K(i) Assuntos
Pirazóis/química
, Pirazóis/farmacologia
, Receptor CB1 de Canabinoide/antagonistas & inibidores
, Animais
, Fármacos Antiobesidade/síntese química
, Fármacos Antiobesidade/química
, Fármacos Antiobesidade/farmacologia
, Peso Corporal/efeitos dos fármacos
, Bovinos
, Desenho de Fármacos
, Ingestão de Alimentos/efeitos dos fármacos
, Humanos
, Lipídeos/sangue
, Pirazóis/síntese química
, Ratos
, Relação Estrutura-Atividade