RESUMO
As part of a systematic study of the effects of chemical modifications on the antiinflammatory activity of 17,21-bis(acetyloxy)-2-bromo-6beta,9-difluoro-11beta-hydroxypregna-1,4-diene-3,20-dione (halopredone acetate, Topicon), a new potent antiinflammatory, a series of derivatives of 2-bromo-6beta-fluoropregna-1,4-diene-3,20-dione was prepared for pharmacological screening. Different synthetic approaches are described. All the synthesized compounds had topical antiinflammatory activity, with no side effects, but were lower in activity than halopredone acetate. Most of them showed topical antiinflammatory activity comparable to that of fluocinolone acetonide. Only two of the synthesized compounds were found to have systemic anti-inflammatory activity comparable to that of betamethasone.
Assuntos
Anti-Inflamatórios/síntese química , Pregnanodionas/síntese química , Animais , Peso Corporal/efeitos dos fármacos , Catálise , Fenômenos Químicos , Química , Rotação Ocular , Tamanho do Órgão/efeitos dos fármacos , Pregnanodionas/farmacologia , RatosRESUMO
A toxicological study of 17,21-bis(acetyloxy)-2-bromo-6beta,9-difluoro-11beta-hydroxypregna-1,4-dien-3,20-dione(halopredone acetate; Topicon), a new topical antiinflammatory steroid, administered a laboratory animals, was carried out in order to evaluate the safety of this compound. Halopredone acetate compared favorably with either hydrocortisone acetate or potent synthetic corticoids in acute and subacute toxicity studies in mice and rats. This compound did not induce gastric ulcers in rats after repeated administration and did not have any teratogenic effect in rats and rabbits. Also, repeated daily application for 4 months to the skins of mice from two different strains was well-tolerated.
Assuntos
Anti-Inflamatórios/toxicidade , Pregnadienos/toxicidade , Administração Tópica , Animais , Animais Recém-Nascidos , Carcinógenos , Feminino , Dose Letal Mediana , Masculino , Camundongos , Gravidez , Coelhos , Ratos , Baço/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Teratogênicos , Timo/efeitos dos fármacos , Fatores de TempoRESUMO
The special and general pharmacology of N1-piperonyl-N4-3,7,11-trimethyl-2,6,10-dodecatrienylpiperazine (U-27) is reported. According to the results of the animal experiments the compound turned out to be a well tolerated gastric antisecretory drug devoid of anticholinergic activity. The compound was able to prevent hypersecretion induced by pylorus ligature in rat and guinea pig. Its duration of action was remarkable and no tolerance occurred after a repeated treatment. The compound displayed also an interesting activity on several experimental ulcers.
