Esters of 3-(hydroxy or hydroxymethyl)-4-hydroxyphenyl aminomethyl ketones

Abstract

Mono-, di- and tri-esters of 3-(hydroxy or hydroxymethyl)-4-hydroxy-alpha-(aminomethyl)benzyl alcohols, obtained by methods involving reduction of the corresponding mono- and di-ester ketones, are useful for producing sympathomimetic effects, such as bronchodilation, of long duration with low cardiovascular stimulating effect, in warm-blooded mammals.

We claim: 
     
       1. A compound of the group consisting of: 3-(Y 1  -O-)-4-(Y-O-)phenyl (R-NH-)(R')methyl ketones having the formula ##STR6## and 3-(Y-O-CH 2  -)-4-(Y 1  -O-)phenyl (R-NH-) (R')methyl ketones having the formula ##STR7## .Iadd.wherein R, in Formula III, is tert-butyl or cycloalkyl having 3-6 carbon atoms; and in Formula IV is hydrogen, alkyl having 1-4 carbon atoms, or cycloalkyl having 3-6 carbon atoms; and .Iaddend. wherein, in each formula:   .[.R is hydrogen, alkyl having 1-4 carbon atoms, or cycloalkyl having 3-6 carbon atoms;.].   R' is hydrogen or alkyl having 1-3 carbon atoms;   Y' is hydrogen or an acyl member which is alkanoyl having 1-22 carbon atoms, cycloalkyl-C n  H 2n  --CO-- having a total of 4-10 carbon atoms of which 3-7 are ring carbon atoms in cycloalkyl and wherein n is zero, one, or two, 1- or 2-adamantanecarbonyl, phenoxyacetyl, naphthalenecarbonyl, or Z--C n  H 2n  --CO-- wherein n is zero, one or two and Z is phenyl or phenyl substituted by 1-3 members of the group consisting of alkyl having 1-4 carbon atoms, alkoxy having 1-4 carbon atoms, halo, or trifluoromethyl;   Y is one of the acyl members defined by Y 1 , at least one of Y and Y 1  being Z--C n  H 2n  --CO--; and   .[.wherein in Formula III at least one of Y and Y 1  contains no less than four carbon atoms when R is tert-butyl or cycloalkyl and no less than seven carbon atoms when R is hydrogen or alkyl other than tert-butyl; and in Formula IV at least one of Y and Y 1  contains no less than four carbon atoms; and.]. acid-addition salts thereof.   
     
     
       2. A 3-(Y 1  -O-)-4-(Y-O)phenyl(R-NH-)(R')methyl ketone according to claim 1. 
     
     
       3. A compound according to claim 2 wherein R' is hydrogen. .[.4. A compound 
     
     
        according to claim 3 wherein R is alkyl..]. 5. A compound according to 
     
     
        claim .[.4.]. .Iadd.3 .Iaddend.wherein R is tert-butyl. 6. A 3-(Y-O-CH 2  -)-4-(Y 1  -O-)phenyl (R-NH-) (R')methyl ketone 
     
     
        according to claim 1. 7. A compound according to claim 6 wherein R' is 
     
     
        hydrogen. 8. A compound according to claim 7 wherein R is alkyl. 9. A 
     
     
        compound according to claim 8 wherein R is tert-butyl. 10. A compound 
     
     
        according to claim 9 wherein one of Y and Y 1  is alkanoyl. 11. A 
     
     
        compound according to claim 9 wherein Y 1  is hydrogen. 12. A compound according to claim 5 wherein each of Y and Y 1  is Z-C n  H 2n   
     
     
        --CO--. 13. A compound according to claim 12 wherein n is zero. 14. A compound according to claim 13 wherein each of Y and Y 1  is 
     
     
        alkylbenzoyl. 15. A compound according to claim 14 wherein each of Y and 
     
     
        Y 1  is toluyl. 16. A compound according to claim 13 wherein each of Y 
     
     
        and Y 1  is anisoyl. 17. A compound according to claim 5 wherein one of 
     
     
        Y and Y 1  is alkanoyl and the other is Z--C n  H --CO--. 18. A 
     
     
        compound according to claim 17 wherein n is zero. 19. A compound according 
     
     
        to claim 18 wherein one of Y and Y 1  is alkylbenzoyl. 20. A compound 
     
     
        according to claim 19 wherein one of Y and Y 1  is toluyl. 21. A compound according to claim 18 wherein one of Y and Y 1  is anisoyl. 
     
     
            A compound according to claim 5 wherein Y 1  is hydrogen. 23. A 
     
     
        compound according to claim 22 wherein n is zero. 24. A compound according 
     
     
        to claim 23 wherein Y is toluyl. 25. A compound according to claim 23 
     
     
        wherein Y is anisoyl. 26. A compound according to claim 9 wherein each of 
     
     
        Y and Y 1  is Z--C n  H 2n  --CO--. 27. A compound according to claim 26 wherein n is zero.