RESUMEN
Extension of the structure-activity relationship studies that led to the discovery of the nonsedating potent muscle relaxant, antiinflammatory, and analgesic agent (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 1, has given rise to (E)-2-(4-chloro-6-fluoro-1-indanylidene)-N-methylacetamide, 2. Compound 2 is a potent antiinflammatory and analgesic agent without centrally acting muscle relaxant activity.
Asunto(s)
Acetamidas/síntesis química , Analgésicos/síntesis química , Antiinflamatorios no Esteroideos/síntesis química , Indanos/síntesis química , Acetamidas/química , Acetamidas/farmacología , Analgésicos/química , Analgésicos/farmacología , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Hipnóticos y Sedantes/síntesis química , Hipnóticos y Sedantes/química , Hipnóticos y Sedantes/farmacología , Indanos/química , Indanos/farmacología , Ratones , Relajantes Musculares Centrales/síntesis química , Relajantes Musculares Centrales/química , Relajantes Musculares Centrales/farmacología , Ratas , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
The design of rigid cyclic analogues derived from cinnamamide 1, (E)-N-cyclopropyl-3-(3-fluorophenyl)prop-2-enamide, and beta-methylcinnamamide 2, (E)-N-cyclopropyl-3-(3-fluorophenyl)but-2-enamide, has led to the discovery of the potent, centrally acting muscle relaxant (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 17. Compound 17 also possesses potent antiinflammatory and analgesic activity. This paper describes the synthesis and the muscle relaxant, antiinflammatory, and analgesic structure-activity relationships of 17 and 67 of its analogues. Compound 17 has been taken into phase I clinical trials.