Claims
- 1. An optically active phenethanolamine of the formula ##STR11## wherein: R.sub.1 is hydrogen or fluorine;
- R.sub.2 is hydrogen, methyl or ethyl;
- R.sub.3 is hydroxy, C.sub.1 -C.sub.4 alkanoyloxy, aminocarbonyl, methylaminocarbonyl or C.sub.1 -C.sub.2 alkoxycarbonyl;
- with the limitation that when R.sub.2 is hydrogen, R.sub.3 is aminocarbonyl, methylaminocarbonyl or C.sub.1 -C.sub.2 alkoxycarbonyl;
- .sub.* C is an asymmetric carbon atom having the R absolute sterochemical configuration;
- .sub.**.sup.C is an asymmetric carbon atom when R.sub.2 is methyl or ethyl, and when asymmetric is of the S absolute stereochemical configuration; and
- the non-toxic pharmaceutically acceptable acid addition salts thereof.
- 2. A compound of claim 1 wherein R.sub.2 is hydrogen.
- 3. A compound of claim 2 wherein R.sub.1 is hydrogen.
- 4. The compound of claim 3, said compound being R-N-(2-phenyl-2-hydroxyethyl)-3-(4-methoxycarbonylphenyl)propylamine.
- 5. The compound of claim 3, said compound being R-N-(2-phenyl-2-hydroxyethyl)-3-(4-aminocarbonylphenyl)propylamine.
- 6. A compound of claim 1 wherein R.sub.2 is methyl or ethyl.
- 7. A compound of claim 6 wherein R.sub.3 is hydroxy, aminocarbonyl, methylaminocarbonyl or C.sub.1 -C.sub.2 alkoxycarbonyl.
- 8. The compound of claim 7, said compound being R,S-N-(2-phenyl-2-hydroxyethyl)-1-methyl-3-(4-methylaminocarbonylphenyl)propylamine.
- 9. The compound of claim 7, said compound being R,S-N-(2-phenyl-2-hydroxyethyl)-1-methyl-3-(4-hydroxyphenyl)propylamine.
- 10. The compound of claim 7, said compound being R,S-N-(2-phenyl-2-hydroxyethyl)-1-methyl-3-(4-aminocarbonylphenyl)propylamine.
- 11. The compound of claim 7, said compound being R,S-N-(2-phenyl-2-hydroxyethyl)-1-ethyl-3-(4-hydroxyphenyl)propylamine.
- 12. The compound of claim 7, said compound being R,S-N-(2-phenyl-2-hydroxyethyl)-1-ethyl-3-(4-aminocarbonylphenyl)propylamine.
- 13. A compound of claim 7 as a pharmaceutically acceptable acid addition salt.
- 14. The compound of claim 13, said compound being R,S-N-(2-phenyl-2-hydroxyethyl)-1-methyl-3-(4-hydroxyphenyl)propylaminium chloride.
- 15. The compound of claim 13, said compound being R,S-N-(2-phenyl-2-hydroxyethyl)-1-methyl-3-(4-aminocarbonylphenyl)propylaminium chloride.
- 16. The compound of claim 7, said compound being R,S-N-[2-(2-fluorophenyl)-2-hydroxyethyl]-1-methyl-3-(4-aminocarbonylphenyl)propylamine.
- 17. The compound of claim 7, said compound being R,S-N-[2-(2-fluorophenyl)-2-hydroxyethyl]-1-methyl-3-(4-hydroxyphenyl)propylamine.
- 18. The compound of claim 7, said compound being R,S-N-[2-(2-fluorophenyl)-2-hydroxyethyl]-1-ethyl-3-(4-aminocarbonylphenyl)propylamine.
- 19. The compound of claim 7, said compound being R,S-N-[2-(2-fluorophenyl)-2-hydroxyethyl]-1-methyl-3-(4-methylaminocarbonylphenyl)propylamine.
- 20. The compound of claim 6, said compound being R,S-N-(2-phenyl-2-hydroxyethyl)-1-methyl-3-(4-acetoxyphenyl)propylamine.
- 21. The compound of claim 6, said compound being R,S-N-(2-phenyl-2-hydroxyethyl)-1-methyl-3-(4-isobutyroxyphenyl)propylamine.
- 22. A pharmaceutical formulation useful in the control of weight in obese animals comprising as active principle an amount effective for controlling weight of an optically active phenethanolamine of claim 1 provided that when R.sub.1 is hydrogen, R.sub.3 is other than aminocarbonyl or methylaminocarbonyl in combination with a suitable pharmaceutical carrier therefor.
- 23. A pharmaceutical formulation according to claim 22 wherein the active principle is an R,S-isomer of a compound having the formula ##STR12## wherein: R.sub.1 is hydrogen or fluorine;
- R.sub.2 is methyl or ethyl;
- R.sub.3 is hydroxy, aminocarbonyl, methylaminocarbonyl or C.sub.1 -C.sub.2 alkoxycarbonyl, and the pharmaceutically acceptable acid addition salts thereof.
- 24. The formulation of claim 23 wherein the active principle is R,S-N-[2-(2-fluorophenyl)-2-hydroxyethyl]-1-methyl-3-(4-hydroxyphenyl)propylamine.
- 25. The formulation of claim 23 wherein the active principle is R,S-N-[2-(2-fluorophenyl)-2-hydroxyethyl]-1-methyl-3-(4-aminocarbonylphenyl)propylamine.
- 26. A method for effecting weight control in an obese animal in need of treatment which comprises administering to such animal an amount effective for controlling weight of a compound of claim 1 provided that when R.sub.1 is hydrogen, R.sub.3 is other than aminocarbonyl or methylaminocarbonyl.
- 27. A method according to claim 26 wherein a compound of claim 1 is administered to a mature obese animal to effect a weight loss.
- 28. A method according to claim 26 wherein a compound of claim 1 is administered to an immature obese animal to prevent excessive weight gain.
- 29. A method according to claim 26 wherein the compound administered is the R,S-isomer of a compound of the formula ##STR13## wherein: R.sub.1 is hydrogen or fluorine;
- R.sub.2 is methyl or ethyl;
- R.sub.3 is hydroxy, aminocarbonyl, methylaminocarbonyl or C.sub.1 -C.sub.2 alkoxycarbonyl, and the pharmaceutically acceptable acid addition salts thereof.
- 30. A method for improving the quality of meat in livestock animals comprising administering an effective amount of a compound of claim 1 wherein R.sub.2 is hydrogen provided that when R.sub.1 is hydrogen, R.sub.3 is other than aminocarbonyl or methylaminocarbonyl.
- 31. The method of claim 30 wherein the animal species treated is swine.
- 32. A method for improving meat quality in swine comprising administering an effective amount of a compound of the formula ##STR14## wherein: R.sub.1 is hydrogen or fluorine;
- R.sub.3 is hydroxy, C.sub.1 -C.sub.4 alkanoyloxy, aminocarbonyl, methylaminocarbonyl or C.sub.1 -C.sub.2 alkoxycarbonyl; provided that when R.sub.1 is hydrogen, R.sub.3 is other than aminocarbonyl or methylaminocarbonyl and the pharmaceutically acceptable acid addition salts thereof.
- 33. The method of claim 32 wherein the compound administered is dl-N-(2-phenyl-2-hydroxyethyl)-3-(4-methoxycarbonylphenyl)propylamine.
- 34. A pharmecutical composition useful for the treatment of obesity in humans and animals which comprises an anti-obesity effective amount of a compound of the formula (II) ##STR15## or a pharmaceutically acceptable salt thereof, wherein R.sub.1 is hydrogen or fluorine, R.sub.2 and R.sub.3 are each hydrogen, R.sub.6 is hydrogen, R.sub.7 is hydrogen, methyl or ethyl, Y is C.sub.2 alkylene, X is a bond, R.sub.4 is carboxylic acid ester, and R.sub.5 is hydrogen, in combination with a pharmaceutically acceptable carrier.
- 35. A composition according to claim 34 wherein C(R.sub.6)R.sub.7 is CH(CH.sub.3).
- 36. A composition according to claim 34 wherein the compound is in the form of a single stereoisomer.
- 37. A composition according to claim 34 wherein the compound is in the form of a mixture of stereoisomers.
- 38. A composition according to claim 34 wherein the compound contains two centers of asymmetry and is used as a diastereoisomer free of the other diastereoisomer.
- 39. A composition according to claim 34 wherein R.sub.7 is hydrogen.
- 40. A composition according to claim 34 in oral administration form.
- 41. A composition according to claim 34 in a form suitable for administration by injection.
- 42. A composition according to claim 34 in unit dosage form, wherein each dosage unit contains from 0.01 to 100 milligrams of said compound.
- 43. A method of treating obesity in humans and animals which comprises administering to a human or animal in need thereof an anti-obesity effective amount of a composition of claim 34.
- 44. A method according to claim 43 wherein R.sub.1 is hydrogen.
- 45. A method according to claim 43 wherein C(R.sub.6)R.sub.7 is CH(CH.sub.3).
- 46. A method according to claim 43 wherein R.sub.4 is lower alkoxycarbonyl.
- 47. A method according to claim 46 wherein R.sub.4 is methoxycarbonyl or ethoxycarbonyl.
- 48. A method according to claim 43 wherein the compound is in the form of a single stereoisomer.
- 49. A method according to claim 43 wherein the compound is in the form of a mixture of stereoisomers.
- 50. A method according to claim 43 wherein the compound contains two centers of asymmetry and is used as a diastereoisomer free of the other diastereoisomer.
- 51. A method according to claim 43 wherein R.sub.7 is hydrogen.
- 52. A method according to claim 43 wherein the administration is oral.
- 53. A method according to claim 43 wherein administration is by injection.
CROSS-REFERENCE TO RELATED CASES
This application is a division of application Ser. No. 416,783, filed Sept. 10, 1982, now abandoned, which was a division of Ser. No. 96,361, filed Nov. 21, 1979, now U.S. Pat. No. 4,391,826, which was a continuation-in-part of Ser. No. 921,670, filed July 3, 1978, now abandoned.
US Referenced Citations (23)
Foreign Referenced Citations (6)
Number |
Date |
Country |
623286 |
Jul 1961 |
CAX |
006735 |
Jan 1980 |
EPX |
894396 |
Sep 1953 |
DEX |
6481871 |
Aug 1965 |
NLX |
6610530 |
Jan 1968 |
NLX |
673994 |
Mar 1967 |
ZAX |
Non-Patent Literature Citations (5)
Entry |
Goodman et al., The Pharm. Basis of Therapeutics, 8th Ed. MacMillan Chapter 24. |
Richards et al., Br. J. Clin. Pharmac. 1, 505-510 (1974). |
Wiemers Arch. Exper. Path U. Pharmakol Bd 213, S283-313 (1951). |
VanDijk et al., Recueil, vol. 92, 1281-1297 (1973). |
Moed et al. Recueil, vol. 74, 919-936 (1955). |
Divisions (2)
|
Number |
Date |
Country |
Parent |
416783 |
Sep 1982 |
|
Parent |
96361 |
Nov 1979 |
|
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
921670 |
Jul 1978 |
|