Claims for Patent: 4,138,581

Summary for Patent: 4,138,581

Title:	3(Hydroxy or hydroxymethyl)-4(hydroxy)-.alpha.-(aminomethyl)benzyl alcohols
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.
Inventor(s):	Minatoya; Hiroaki (East Greenbush, NY), Tullar; Benjamin F. (Laurel Park, NC), Conway; Walter D. (Amherst, NY)
Assignee:	Sterling Drugs Inc. (New York, NY)
Application Number:	05/654,700
Patent Claims:	1. An ester of 3,4-dihydroxy-alpha-(amino- and N-substituted amino-methyl)benzyl alcohol having the formula ##STR13## wherein R is hydrogen, alkyl having 1-4 carbon atoms, or cycloalkyl having 3-6 carbon atoms; R' is hydrogen or ethyl; Y is an acyl member which is alkanoyl having 1-22 carbon atoms, alkenoyl having one or two double bonds and having 4-22 carbon atoms, cycloalkyl--C.sub.n H.sub.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.sub.n H.sub.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, halo, or trifluoromethyl; and Y.sup.1 and Y.sup.2 are the same or different and are hydrogen or one of the acyl members defined by Y, at least one of Y and Y.sup.1 being Z--C.sub.n H.sub.2n --CO-- or a pharmaceutically acceptable acid-addition salt thereof. 2. A compound according to claim 1, wherein Y and Y.sup.1 are the same or different and each is Z--C.sub.n H.sub.2n --CO--. 3. A compound according to claim 2 wherein Y.sup.2 and R' are hydrogen. 4. A compound according to claim 2 wherein n is zero. 5. A compound having the formula ##STR14## wherein R is hydrogen, alkyl having 1-4 carbon atoms, or cycloalkyl having 3-6 carbon atoms; R' is hydrogen or ethyl; Y and Y.sup.1 are the same or different and each is Z--C.sub.n H.sub.2n --CO-- wherein n is zero, and Z is phenyl or phenyl substituted by 1-3 members of the group consisting of alkyl having 1-4 carbon atoms, halo or trifluoromethyl or a pharmaceutically acceptable acid-addition salt thereof. 6. A compound according to claim 5 wherein R' is hydrogen. 7. A compound according to claim 6 wherein R is isopropyl. 8. A compound according to claim 5 wherein R' is ethyl. 9. A compound according to claim 8 wherein R is tertbutyl. 10. A compound having the formula ##STR15## wherein Y and Y.sup.1 are the same or different and each is Z--C.sub.n H.sub.2n --CO-- wherein n is zero, and Z is phenyl or phenyl substituted by 1-3 members of the group consisting of alkyl having 1-4 carbon atoms, halo, or trifluoromethyl or a pharmaceutically acceptable acid-addition salt thereof. 11. A compound according to claim 10 wherein each of Y and Y.sup.1 is alkylbenzoyl. 12. A compound according to claim 11 wherein alkylbenzoyl is toluyl. 13. A compound according to claim 1 wherein one of Y and Y.sup.1 is Z--C.sub.n H.sub.2n --CO-- and the other is alkanoyl. 14. A compound according to claim 13 wherein n is zero. 15. A compound having the formula ##STR16## wherein R is hydrogen, alkyl having 1-4 carbon atoms, or cycloalkyl having 3-6 carbon atoms; R' is hydrogen or ethyl; one of Y and Y.sup.1 is an acyl member which is alkanoyl having 1-22 carbon atoms, and the other is Z--C.sub.n H.sub.2n --CO-- wherein n is zero, and Z is phenyl or phenyl substituted by 1-3 members of the group consisting of alkyl having 1-4 carbon atoms, halo, or trifluoromethyl or a pharmaceutically acceptable acid-addition salt thereof. 16. A compound according to claim 15 wherein R'is hydrogen. 17. A compound according to claim 15 wherein R' is ethyl. 18. A compound having the formula ##STR17## wherein one of Y and Y.sup.1 is an acyl member which is alkanoyl having 1-22 carbon atoms, and the other is Z--C.sub.n H.sub.2n --CO-- wherein n is zero, and Z is phenyl or phenyl substituted by 1-3 members of the group consisting of alkyl having 1-4 carbon atoms, halo, or trifluoromethyl or a pharmaceutically acceptable acid-addition salt thereof. 19. A compound according to claim 18 wherein one of Y and Y.sup.1 is alkylbenzoyl. 20. A compound according to claim 19 wherein alkylbenzoyl is toluyl. 21. A compound according to claim 1 wherein one of Y and Y.sup.1 is Z--C.sub.n H.sub.2n --CO-- and the other is hydrogen. 22. A compound according to claim 21 wherein n is zero. 23. A compound according to claim 22 wherein Y.sup.2 is hydrogen. 24. A compound having the formula ##STR18## wherein R is hydrogen, alkyl having 1-4 carbon atoms, or cycloalkyl having 3-6 carbon atoms; R' is hydrogen or ethyl; Y is Z--C.sub.n H.sub.2n --CO-- wherein n is zero, and Z is phenyl or phenyl substituted by 1-3 members of the group consisting of alkyl having 1-4 carbon atoms, halo, or trifluoromethyl or a pharmaceutically acceptable acid-addition salt thereof. 25. A compound according to claim 24 wherein R' is ethyl. 26. A compound according to claim 24 wherein R' is hydrogen. 27. A compound according to claim 26 wherein R is tert-butyl. 28. A compound selected from the group consisting of: 3,4-bis(p-toluyloxy)-alpha-[1-(tert-butylamino)ethyl]benzyl alcohol hydrochloride, 3,4-bis(p-toluyloxy)-alpha-[1-(isopropylamino)ethyl]benzyl alcohol hydrochloride. 29. An ester of 3-hydroxymethyl-4-hydroxy-alpha-(amino-and N-substituted amino-methyl)benzyl alcohol having the formula ##STR19## wherein 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 an acyl member which is alkanoyl having 1-22 carbon atoms, alkenoyl having one or two double bonds and having 4-22 carbon atoms, cycloalkyl--C.sub.n H.sub.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.sub.n H.sub.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, halo, or trifluoromethyl; and Y.sup.1 and Y.sup.2 are the same or different and are hydrogen or one of the acyl members defined by Y, at least one of Y and Y.sup.1 being Z--C.sub.n H.sub.2n --CO-- or a pharmaceutically acceptable acid-addition salt thereof. 30. A compound according to claim 29 wherein Y.sup.2 is hydrogen. 31. A compound according to claim 30 wherein R' is alkyl. 32. A compound according to claim 30 wherein R' is hydrogen. 33. A compound according to claim 32 wherein R is alkyl. 34. A compound according to claim 33 wherein R is tert-butyl. 35. A compound according to claim 34 wherein Y and Y.sup.1 are the same or different and each is Z--C.sub.n H.sub.2n --CO--. 36. A compound according to claim 35 wherein n is zero. 37. A compound according to claim 34 wherein one of Y and Y.sup.1 is alkanoyl and the other is Z--C.sub.n H.sub.2n --CO--. 38. A compound according to claim 37 wherein n is zero. 39. A compound according to claim 34 wherein Y.sup.1 is hydrogen. 40. 3,4-Bis(p-toluyloxy)-alpha-[(isopropylamino)methyl]benzyl alcohol methanesulfonate according to claim 7. 41. 3-Benzoyloxy-4-p-toluyloxy-alpha-[(tert-butylamino)methyl]benzyl alcohol methanesulfonate according to claim 10. 42. 3,4-Bis(benzoyloxy)-alpha-[(tert-butylamino)methyl]benzyl alcohol hydrochloride according to claim 10. 43. 3,4-Bis(p-toluyloxy)-alpha-[(tert-butylamino)methyl]benzyl alcohol methanesulfonate according to claim 12. 44. 3,4-Bis(m-toluyloxy)-alpha-[(tert-butylamino)methyl]benzyl alcohol methanesulfonate according to claim 12. 45. 3-Acetoxy-4-p-toluyloxy-alpha-[(tert-butylamino)methyl]benzyl alcohol methanesulfonate according to claim 20. 46. 3-Hydroxy-4-m-toluyloxy-alpha-[(tert-butylamino)methyl]benzyl alcohol methanesulfonate according to claim 27.