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Details for Patent: 5,321,018
| Title: | Use of 1.alpha.-hydroxylated-19-nor-vitamin D compounds to treat psoriasis |
| Abstract: | A novel use for 1.alpha.-hydroxylated-19-nor-vitamin D compounds to treat psoriasis inasmuch as these compounds when administered to humans are converted to a metabolite, such as a 1.alpha.,25-dihydroxylated compound, which metabolite in vitro will cause differentiation in a human cell line. |
| Inventor(s): | DeLuca; Hector F. (Deerfield, WI) |
| Assignee: | Wisconsin Alumni Research Foundation (Madison, WI) |
| Filing Date: | Nov 20, 1992 |
| Application Number: | 07/987,258 |
| Claims: | 1. A method for treating psoriasis which comprises administering to a patient an effective amount of a compound of the formula: ##STR9## where X and Y are each selected from the group consisting of hydrogen, acyl, alkylsilyl and alkoxyalkyl, and where U is selected from a side chain of the formula ##STR10## wherein R.sub.1 and R.sub.2 are each selected from the group consisting of alkyl, deuteroalkyl, hydroxyalkyl and fluoroalkyl, or, when taken together represent the group--(CH.sub.2).sub.m --where m is an integer having a value of from 2 to 5, R.sub.3 is selected from the group consisting of hydrogen, deuterium, hydroxy, fluorine, O-acyl, alkyl, hydroxyalkyl and fluoroalkyl, R.sub.6 is selected from the group consisting of hydrogen, deuterium, fluorine, alkyl, hydroxyalkyl and fluoroalkyl, or, R.sub.3 and R.sub.6 taken together represent double-bonded oxygen or double-bonded carbon, R.sub.4 and R.sub.5 are each selected from the group consisting of hydrogen, deuterium, hydroxy, O-acyl, fluorine and alkyl, or, R.sub.4 and R.sub.5 taken together form a carbon-carbon double bond or a carbon-carbon triple bond, and wherein n is an integer having a value of from 1 to 5 and wherein the carbon at any one of positions 20, 22, or 23 in the side chain may be replaced by an O, S, or N atom with the proviso that when n is 1 then R.sub.1 and R.sub.2 must both be methyl. 2. The method of claim 1 wherein said compound is 1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 3. The method of claim 1 wherein said compound is 1.alpha.-hydroxy-19-nor-24,24-difluoro-vitamin D.sub.3. 4. The method of claim 1 wherein said compound is 1.alpha.-hydroxy-19-nor-26,27-hexadeutero-vitamin D.sub.3. 5. The method of claim 1 wherein said compound is 1.alpha.-hydroxy-19-nor-26,27-hexafluorovitamin D.sub.3. 6. The method of claim 1 wherein said compound is 1.alpha.-hydroxy-19-nor-vitamin D.sub.2. 7. The method of claim 1 wherein the compound is 24-homo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 8. The method of claim 1 wherein the compound is 24-dihomo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 9. The method of claim 1 wherein the compound is 24-trihomo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 10. The method of claim 1 wherein the compound is 26,27-dimethyl-24-dihomo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 11. The method of claim 1 wherein the compound is 26,27-dimethyl-24-trihomo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 12. The method of claim 1 wherein the compound is 26,27-diethyl-24-dihomo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 13. The method of claim 1 wherein the compound is 26,27-diethyl-24-trihomo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 14. The method of claim 1 wherein the compound is 26,27-dipropyl-24-dihomo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 15. The method of claim 1 wherein the compound is 26,27-dipropyl-24-trihomo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 16. The method of claim 1 wherein the compound is 24-homo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 17. The method of claim 1 wherein the compound is 24-dihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 18. The method of claim 1 wherein the compound is 24-trihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 19. The method of claim 1 wherein the compound is 26,27-dimethyl-24-dihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 20. The method of claim 1 wherein the compound is 26,27-dimethyl-24-trihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 21. The method of claim 1 wherein the compound is 26,27-diethyl-24-dihomo-1.alpha.hydroxy-19-nor-vitamin D.sub.3. 22. The method of claim 1 wherein the compound is 26,27-diethyl-24-trihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 23. The method of claim 1 wherein the compound is 26,27-dipropyl-24-dihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 24. The method of claim 1 wherein the compound is 26,27-dipropyl-24-trihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 25. The method of claim 1 wherein the compound is 1.alpha.-hydroxy-19-nor-24 epi-vitamin D.sub.2. 26. The method of claim 1 wherein said effective amount comprises about 0.01 .mu.g/day to about 100 .mu.g/day of said compound. 27. A composition for use in the treatment of psoriasis which comprises an effective amount of a compound of the formula: ##STR11## where X and Y are each selected from the group consisting of hydrogen, acyl, alkylsilyl and alkoxyalkyl, and where U is selected from a side chain of the formula ##STR12## wherein R.sub.1 and R.sub.2 are each selected from the group consisting of alkyl, deuteroalkyl, hydroxyalkyl and fluoroalkyl, or, when taken together represent the group--(CH.sub.2).sub.m --where m is an integer having a value of from 2 to 5, R.sub.3 is selected from the group consisting of hydrogen, deuterium, hydroxy, fluorine, O-acyl, alkyl, hydroxyalkyl and fluoroalkyl, R.sub.6 is selected from the group consisting of hydrogen, deuterium, fluorine, alkyl, hydroxyalkyl and fluoroalkyl, or, R.sub.3 and R.sub.6 taken together represent double-bonded oxygen or double-bonded carbon, R.sub.4 and R.sub.5 are each selected from the group consisting of hydrogen, deuterium, hydroxy, O-acyl, fluorine and alkyl, or, R.sub.4 and R.sub.5 taken together form a carbon-carbon double bond or a carbon-carbon triple bond, and wherein n is an integer having a value of from 1 to 5 and wherein the carbon at any one of positions 20, 22, or 23 in the side chain may be replaced by an O, S, or N atom with the proviso that when n is 1 then R.sub.1 and R.sub.2 must both be methyl. 28. The composition of claim 27 wherein said compound is 1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 29. The composition of claim 27 wherein said compound is 1.alpha.-hydroxy-19-nor-24,24-difluoro-vitamin D.sub.3. 30. The composition of claim 27 wherein said compound is 1.alpha.-hydroxy-19-nor-26,27-hexadeutero-vitamin D.sub.3. 31. The composition of claim 27 wherein said compound is 1.alpha.-hydroxy-19-nor-26,27-hexafluorovitamin D.sub.3. 32. The composition of claim 27 wherein said compound is 1.alpha.-hydroxy-19-nor-vitamin D.sub.2. 33. The composition of claim 27 wherein the compound is 24-homo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 34. The composition of claim 27 wherein the compound is 24-dihomo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 35. The composition of claim 27 wherein the compound is 24-trihomo-1.alpha.-hydroxy-19-nor-22dehydrovitamin D.sub.3. 36. The composition of claim 27 wherein the compound is 26,27-dimethyl-24-dihomo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 37. The composition of claim 27 wherein the compound is 26,27-dimethyl-24-trihomo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 38. The composition of claim 27 wherein the compound is 26,27-diethyl-24-dihomo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 39. The composition of claim 27 wherein the compound is 26,27-diethyl-24-trihomo-1.alpha.-hydroxy-19-nor-22-dehydrovitamin D.sub.3. 40. The composition of claim 27 wherein the compound is 26,27-dipropyl-24-dihomo-1.alpha.-hydroxy-19-nor22-dehydrovitamin D.sub.3. 41. The composition of claim 27 wherein the compound is 26,27-dipropyl-24-trihomo-1.alpha.-hydroxy-19-nor22-dehydrovitamin D.sub.3. 42. The composition of claim 27 wherein the compound is 24-homo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 43. The composition of claim 27 wherein the compound is 24-dihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 44. The composition of claim 27 wherein the compound is 24-trihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 45. The composition to claim 27 wherein the compound is 26,27-dimethyl-24-dihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 46. The composition of claim 27 wherein the compound is 26,27-dimethyl-24-trihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 47. The composition of claim 27 wherein the compound is 26,27-diethyl-24-dihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 48. The composition of claim 27 wherein the compound is 26,27-diethyl-24-trihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 49. The composition of claim 27 wherein the compound is 26,27-dipropyl-24-dihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 50. The composition of claim 27 wherein the compound is 26,27-dipropyl-24-trihomo-1.alpha.-hydroxy-19-nor-vitamin D.sub.3. 51. The composition of claim 27 wherein the compound is 1.alpha.-hydroxy-19-nor-24 epi-vitamin D.sub.2. 52. The composition of claim 27 wherein said effective amount is between about 0.01 .mu.g to about 100 .mu.g per gram of the composition. 53. A method of treating psoriasis which comprises administering to a patient an effective amount of 1.alpha.-hydroxylated-19-nor-vitamin D compound which compound upon administering to humans is converted to a metabolite and said metabolite in vitro will cause differentiation of promelocytes to monocytes in a cell line selected from a group consisting of a U937 cell line, an HL60 cell line and a M1 cell line. |
