Toxicological studies on halopredone acetate.

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.

Derivatives of 2-bromo-6beta-fluoropregna-1,4-diene-3,20-dione and their antiinflammatory activity.

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.

Pharmacological properties of n1-piperonyl-n4-3,7,11-trimethyl-2,6,10-dodecatrienyl-piperazine, a new non-anticholinergic gastric antisecretory agent.

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.