RESUMO
Basic derivatives of 6,7-dihydroindolo[1,7-ab][1]benzazepine and 6H-indolo[7,1-cd][1,5]benzoxazepine incorporating the imipramine basic side chain were synthesized and screened for antidepressant activity in mice. With few exceptions, the compounds unsubstituted at C-2 antagonized reserpine-induced ptosis and hypothermia showing negligible anticholinergic and antihistaminic properties. The compound 1-[2-(N-methyl-N-benzylamino)ethyl]-6,7-dihydroindolo[1,7-ab][1]benzazepine had the highest toxicity-activity ratio.
Assuntos
Antidepressivos/síntese química , Benzazepinas/síntese química , Animais , Antidepressivos/farmacologia , Antidepressivos/toxicidade , Benzazepinas/farmacologia , Benzazepinas/toxicidade , Blefaroptose/prevenção & controle , Temperatura Corporal/efeitos dos fármacos , Depressão Química , Cobaias , Íleo/efeitos dos fármacos , Técnicas In Vitro , Indóis/síntese química , Indóis/farmacologia , Indóis/toxicidade , Dose Letal Mediana , Masculino , Camundongos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Reserpina/antagonistas & inibidoresRESUMO
A series of 4-alkyl-8,9-dihydro[1]benzazepino[3,2,1-jk][1,4]benzodiazepin-1(2H)-ones and brominated derivatives was synthesized. Two approaches for the synthesis of 4-alkyl[1]benzazepino[3,2,1-jk][1,4]benzodiazepin-1(2H)-ones and brominated derivatives are described. All compounds were evaluated for CNS activity. None showed significant activity. The results obtained indicate that in the case of the 1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one a phenyl group at the 1 position causes a fall in CNS activity not only when it is free but also when fused to the benzodiazepine system.
