13alpha-Estrone and its 3-methyl or benzyl ether were halogenated in ring A with N-bromo-
or N-iodosuccinimide or 1,3-dibromo-5,5-dimethylhydantoin as electrophile triggers.
The chemo- and regioselectivities of the reactions depended greatly on the nature
of the substituent on C-3. Bromination of the ethers led to 2- and 4-regioisomers.
Bis-halogenation occurred only in the case of the phenolic derivative. Iodination
and bromination resulted in similar products, except that the 3-benzyl ether could
not be iodinated under the applied conditions. The potential inhibitory action of
the new halogenated 13alpha-estrones on human 17beta-hydroxysteroid dehydrogenase
1 activity was investigated via in vitro radiosubstrate incubation. Some compounds
proved to be effective inhibitors, with IC50 values in the submicromolar range.
