Corticoid 17-(alkyl carbonates) and processes for their preparation
AssigneeHoechst Aktiengesellschaft
InventorsUlrich Stache, Werner Fritsch, Hans G. Alpermann
Life of this patent
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Abstract
What is disclosed is corticoid 17-(alkyl carbonates) of the formula ##STR1## as defined in the specification, which compounds can be used in veterinary therapy and human therapy, in the form of suspensions, ointments, creams, sprays and the like, for the treatment of inflammatory dermatoses of very diverse cause.
Claims22
A compound selected from the group consisting of compounds of the formula ##STR17## wherein A is ##STR18## or C.dbd.O, and compounds of the formula ##STR19## wherein Y is hydrogen, fluorine, or chlorine;
- Z is hydrogen, chlorine, fluorine, or methyl;
- R.sub.3 is hydrogen, fluorine, .alpha.-methyl, monofluoromethyl, or difluoromethyl;
- R.sub.2 is alkyl having 1 to 8 carbon atoms;
- and
- R.sub.1 is acyl of the formula ##STR20## wherein R.sub.4 is hydrogen, alkyl having 1 to 10 carbon atoms, or cycloalkyl having 3 to 8 carbon atoms and n is a number from 0 to 4, or
- R.sub.1 is carbonyloxyalkyl of the formula ##STR21## wherein n is 0 or 1 and R.sub.4 is as earlier defined except that R.sub.4 is other than hydrogen when n is 0, or R.sub.1 is ##STR22## wherein R.sub.5 is alkyl having 1 to 4 carbon atoms, phenyl, methylphenyl, ethylphenyl, fluorophenyl, bromophenyl, or chlorophenyl.
A method for making a compound selected from the group consisting of compounds of the formula ##STR28## and compounds of the formula ##STR29## or C.dbd.O;
- Y is hydrogen, fluorine, or methyl;
- Z is hydrogen, chlorine, fluorine, or methyl
- R.sub.3 is hydrogen, fluorine, .alpha.-methyl, monofluoromethyl, or difluoromethyl;
- R.sub.2 is alkyl having 1 to 8 carbon atoms;
- and
- R.sub.1 is acyl of the formula ##STR30## wherein R.sub.4 is hydrogen, alkyl having 1 to 10 carbon atoms, or cycloalkyl having 3 to 8 carbon atoms and n is a number from 0 to 4, which method comprises hydrolyzing with weak acid a corticosteroid 17, 21-(dialkyl-orthocarbonate) of the formula ##STR31## respectively, to form the corresponding 17-(monoalkyl carbonate)-21-hydroxy compound, and then esterifying the 21-hydroxy group by reaction thereof with a halide or anhydride of a carboxylic acid of the formula ##STR32##
A method for making a compound selected from the group consisting of the compounds of the formula ##STR34## and compounds of the formula ##STR35## or C.dbd.O;
- Y is hydrogen, fluorine, or methyl;
- Z is hydrogen, chlorine, fluorine, or methyl
- R.sub.3 is hydrogen, fluorine, .alpha.-methyl, monofluoromethyl, or difluoromethyl;
- R.sub.2 is alkyl having 1 to 8 carbon atoms;
- and
- R.sub.1 is carbonyloxyalkyl of the formula ##STR36## wherein n is 0 or 1 and R.sub.4 is hydrogen, alkyl having 1 to 10 carbon atoms, or cycloalkyl having 3 to 8 carbon atoms except that R.sub.4 is other than hydrogen if n is 0, which method comprises hydrolyzing with weak acid a corticosteroid 17, 21-(dialkylorthocarbonate) of the formula ##STR37## respectively, to form the corresponding 17-(monoalkyl carbonate)-21-hydroxy compound, and then esterifying the 21-hydroxy group by reaction thereof with a halogenoformate of the formula ##STR38##
A method for making a compound selected from the group consisting of compounds of the formula ##STR40## and compounds of the formula ##STR41## or C.dbd.O;
- Y is hydrogen, fluorine, or methyl;
- Z is hydrogen, chlorine, fluorine, or methyl
- R.sub.3 is hydrogen, fluorine, .alpha.-methyl, monofluoromethyl;
- or difluoromethyl;
- R.sub.2 is alkyl having 1 to 8 carbon atoms;
- and R.sub.1 is ##STR42## wherein R.sub.5 is alkyl having 1 to 4 carbon atoms, phenyl, methylphenyl, ethylphenyl, fluorophenyl, bromophenyl, or chlorophenyl, which method comprises hydrolyzing with weak acid a corticosteroid 17,21-(dialkyl-orthocarbonate) of the formula ##STR43## respectively, to form the corresponding 17-(monoalkyl carbonate)-21-hydroxy compound, and then esterifying the 21-hydroxy group by reaction thereof with a sulfonic acid halide of the formula ##STR44##
Dependencies are inferred from the claim text.