In each case only [ 16a,l 7a-d] isoxazolidines were isolated. The pentacyclic adducts 16-19 were active topical antiinflammatory agents in mice, with 18 being more potent than any of the standard compounds tested. The hexacyclic adduct 20 was inactive in this assay.

The preparation and topical antiinflammatory potencies of a series of 7 alpha-halogeno-16-substituted-prednisolone derivatives are described. The 7 alpha-chloro, 7 alpha-bromo, and 7 alpha-iodo corticosteroids were obtained by addition of hydrogen halide to the 6,7-dehydro compounds. The extent of addition of HCl varied with substitution at C-11, while no addition of HF was observed at all. The 7 alpha-fluoro corticosteroids were prepared by reaction of the appropriate 7 beta-hydroxy compounds with N,N-diethyl(2-chloro-1,1,2-trifluoroethyl)amine. The 7 beta-hydroxy steroids were obtained, in turn, from the 6,7-dehydro compounds via the 6 beta,7 beta-dihydroxy derivatives. Antiinflammatory potencies were measured in mice by the Tonelli croton oil ear assay. The greatest effect of a 7 alpha-halogen was observed in the 16 alpha-methylprednisolone series, where 7 alpha-chloro and 7 alpha-bromo substitution increased potency 2.5- to 3.5-fold. Compounds 4b and 5b were equipotent to betamethasone dipropionate. 7 alpha-Halogen substitution in other series produced more variable effects and sometimes led to a reduction of antiinflammatory potency.

Die Steroide (I) und (IV) werden in die Pregnatriendione (III) und (V) übergeführt, die mit Nitronen und mit dem N‐Oxid (VII) die Cycloaddukte (VI) bzw. (VIII) ergeben.

Die Addition von Halogenwasserstoffen an die Trienone (I) ergibt die 7α‐Halogeno‐dienone (II).