Claims for Patent: 4,242,334

Summary for Patent: 4,242,334

Title:	Corticoid 17-(alkyl carbonates) and processes for their preparation
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.
Inventor(s):	Ulrich Stache, Werner Fritsch, Hans G. Alpermann
Assignee:	Sanofi Aventis Deutschland GmbH
Application Number:	US05/930,194
Patent Claims:	1. A compound selected from the group consisting of compounds of the formula ##STR17## wherein A is ##STR18## or C═O, and compounds of the formula ##STR19## wherein Y is hydrogen, fluorine, or chlorine;Z is hydrogen, chlorine, fluorine, or methyl; R3 is hydrogen, fluorine, α-methyl, monofluoromethyl, or difluoromethyl; R2 is alkyl having 1 to 8 carbon atoms; and R1 is acyl of the formula ##STR20## wherein R4 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 R1 is carbonyloxyalkyl of the formula ##STR21## wherein n is 0 or 1 and R4 is as earlier defined except that R4 is other than hydrogen when n is 0, or R1 is ##STR22## wherein R5 is alkyl having 1 to 4 carbon atoms, phenyl, methylphenyl, ethylphenyl, fluorophenyl, bromophenyl, or chlorophenyl. 2. A compound as in claim 1 wherein R1 is ##STR23## and R4 is hydrogen. 3. A compound as in claim 1 wherein R1 is ##STR24## and R4 is alkyl having 1 to 10 carbon atoms. 4. A compound as in claim 1 of the formula ##STR25## 5. A compound as in claim 1 of the formula ##STR26## 6. A compound as in claim 1 of the formula ##STR27## 7. A compound as in claim 1 which is prednisolon-17-ethyl-carbonate-21-propionate. 8. A compound as in claim 1 which is prednisolon-17-ethyl-carbonate-21-acetate. 9. A compound as in claim 1 which is prednisolon-17-n-propyl-carbonate-21-propionate. 10. A compound as in claim 1 which is prednisolon-17-n-propyl-carbonate-21-acetate. 11. A compound as in claim 1 which is cortisol-17-ethyl-carbonate-21-propionate. 12. A compound as in claim 2 which is cortisol-17-n-propyl-carbonate-21-propionate. 13. A pharmaceutical composition for the treatment of inflammatory dermatosis which comprises an effective amount of a compound as in claim 1 and a pharmaceutically-acceptable carrier therefor. 14. The method of treating inflammatory dermatosis in a human or animal suffering therefrom which method comprises locally or topically administering an effective amount of a compound as in claim 1. 15. 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═O; Y is hydrogen, fluorine, or methyl;Z is hydrogen, chlorine, fluorine, or methyl R3 is hydrogen, fluorine, α-methyl, monofluoromethyl, or difluoromethyl; R2 is alkyl having 1 to 8 carbon atoms; and R1 is acyl of the formula ##STR30## wherein R4 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## 16. A method as in claim 15 wherein A is ##STR33## and the hydroxy group thereof is then oxidized to a keto group. 17. 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═O; Y is hydrogen, fluorine, or methyl;Z is hydrogen, chlorine, fluorine, or methyl R3 is hydrogen, fluorine, α-methyl, monofluoromethyl, or difluoromethyl; R2 is alkyl having 1 to 8 carbon atoms; and R1 is carbonyloxyalkyl of the formula ##STR36## wherein n is 0 or 1 and R4 is hydrogen, alkyl having 1 to 10 carbon atoms, or cycloalkyl having 3 to 8 carbon atoms except that R4 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## 18. A method as in claim 17 wherein A is ##STR39## and the hydroxy group thereof is then oxidized to a keto group. 19. 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═O; Y is hydrogen, fluorine, or methyl;Z is hydrogen, chlorine, fluorine, or methyl R3 is hydrogen, fluorine, α-methyl, monofluoromethyl; or difluoromethyl; R2 is alkyl having 1 to 8 carbon atoms; and R1 is ##STR42## wherein R5 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## 20. A method as in claim 19 wherein A is ##STR45## and the hydroxy group thereof is then oxidized to a keto group. 21. A compound as in claim 1 wherein R1 is carbonyloxyalkyl of the formula ##STR46## 22. A compound as in claim 1 wherein R1 is ##STR47##