RESUMO
The synthesis of 10-piperazinyl-4H-thieno[3,2-b][1,5]benzodiazepines is described. The activity of these compounds has been assessed on the basis of their ability to produce hypothermia in mice and block a conditioned avoidance response (CAR) and produce catalepsy in rats, and the results are compared with various classical and nonclassical neuroleptic drugs. A number of compounds (6, 17, 21, and 22) demonstrate potency greater than clozapine and also show low degree of catalepsy. It is believed that this profile of activity, unlike standard neuroleptics, is associated with the relative lack of extrapyramidal side effects in the clinic. The corresponding 9-piperazinyl-4H-thieno[1,4]benzodiazepines (12 and 35, limited analogues prepared in the respective series, were inactive.
Assuntos
Antipsicóticos/síntese química , Benzodiazepinas/síntese química , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Benzodiazepinas/farmacologia , Temperatura Corporal/efeitos dos fármacos , Catalepsia/induzido quimicamente , Humanos , Dose Letal Mediana , Camundongos , Piperazinas/síntese química , Piperazinas/farmacologia , RatosRESUMO
The relatively rapid formation of pyrazoline adducts is a serious side reaction in the esterification of 15-oxo-PGF2alpha with ethereal diazomethane under conditions used routinely in the chemical derivatization of prostaglandins.