17,20(Z)-Dehydro Vitamin D Analogs and Their Uses
First Claim
1. A compound having the formula:
- where Y1 and Y2, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, where R11 and R12 are each hydrogen or taken together are a methylene group, where R6 and R7, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or R6 and R7 when taken together may represent the group —
(CH2)x—
where x is an integer from 2 to 5, or R6 and R7 when taken together may represent the group ═
CR8R9 where R8 and R9, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or when taken together R8 and R9 may represent the group —
(CH2)x—
where x is an integer from 2 to 5, and where the group R represents a side chain represented by the structure where the side chain and 17-ene double bond is in the Z configuration and where Z in the above side chain structure is selected from Y, —
OY, —
CH2OY, —
C≡
CY and —
CH═
CHY, where the double bond in the side chain may have the cis or trans geometry, and where Y is selected from hydrogen, methyl, —
COR5 and a radical of the structure;
where m and n, independently, represent the integers from 0 to 5, where R1 is selected from hydrogen, deuterium, hydroxy, protected hydroxy, fluoro, trifluoromethyl, and C1-5-alkyl, which may be straight chain or branched and, optionally, bear a hydroxy or protected-hydroxy substituent, and where each of R2, R3, and R4, independently, is selected from deuterium, deuteroalkyl, hydrogen, fluoro, trifluoromethyl and C1-5 alkyl, which may be straight-chain or branched, and optionally, bear a hydroxy or protected-hydroxy substituent, and where R1 and R2, taken together, represent an oxo group, or an alkylidene group having a general formula CkH2k—
where k is an integer, the group ═
CR2R3, or the group —
(CH2)p—
, where p is an integer from 2 to 5, and where R3 and R4, taken together, represent an oxo group, or the group —
(CH2)q—
, where q is an integer from 2 to 5, and where R5 represents hydrogen, hydroxy, protected hydroxy, or C1-5 alkyl and wherein any of the CH-groups at positions 20, 22, or 23 in the side chain may be replaced by a nitrogen atom, or where any of the groups —
CH(CH3)—
, —
(CH2)m—
, —
CR1R2—
or —
(CH2)n—
at positions 20, 22, and 23, respectively, may be replaced by an oxygen or sulfur atom.
0 Assignments
0 Petitions
Accused Products
Abstract
This invention discloses 17,20(Z)-dehydro vitamin D analogs, and specifically 17(Z)-1α,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 and pharmaceutical uses therefor. This compound exhibits pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. This compound also may be used to treat autoimmune disorders and inflammatory diseases in humans as well as renal osteodystrophy and obesity. This compound also has significant calcemic activity making it a therapeutic agent for the treatment or prophylaxis of osteoporosis, osteomalacia, renal osteodystrophy and hypoparathyroidism.
-
Citations
98 Claims
-
1. A compound having the formula:
-
where Y1 and Y2, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, where R11 and R12 are each hydrogen or taken together are a methylene group, where R6 and R7, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or R6 and R7 when taken together may represent the group —
(CH2)x—
where x is an integer from 2 to 5, or R6 and R7 when taken together may represent the group ═
CR8R9 where R8 and R9, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or when taken together R8 and R9 may represent the group —
(CH2)x—
where x is an integer from 2 to 5, and where the group R represents a side chain represented by the structurewhere the side chain and 17-ene double bond is in the Z configuration and where Z in the above side chain structure is selected from Y, —
OY, —
CH2OY, —
C≡
CY and —
CH═
CHY, where the double bond in the side chain may have the cis or trans geometry, and where Y is selected from hydrogen, methyl, —
COR5 and a radical of the structure;
where m and n, independently, represent the integers from 0 to 5, where R1 is selected from hydrogen, deuterium, hydroxy, protected hydroxy, fluoro, trifluoromethyl, and C1-5-alkyl, which may be straight chain or branched and, optionally, bear a hydroxy or protected-hydroxy substituent, and where each of R2, R3, and R4, independently, is selected from deuterium, deuteroalkyl, hydrogen, fluoro, trifluoromethyl and C1-5 alkyl, which may be straight-chain or branched, and optionally, bear a hydroxy or protected-hydroxy substituent, and where R1 and R2, taken together, represent an oxo group, or an alkylidene group having a general formula CkH2k—
where k is an integer, the group ═
CR2R3, or the group —
(CH2)p—
, where p is an integer from 2 to 5, and where R3 and R4, taken together, represent an oxo group, or the group —
(CH2)q—
, where q is an integer from 2 to 5, and where R5 represents hydrogen, hydroxy, protected hydroxy, or C1-5 alkyl and wherein any of the CH-groups at positions 20, 22, or 23 in the side chain may be replaced by a nitrogen atom, or where any of the groups —
CH(CH3)—
, —
(CH2)m—
, —
CR1R2—
or —
(CH2)n—
at positions 20, 22, and 23, respectively, may be replaced by an oxygen or sulfur atom.- View Dependent Claims (2, 3, 4, 5, 6, 7)
-
-
8. A compound having the formula:
-
where Y1 and Y2, which may be the same or different, are each selected from hydrogen or a hydroxy-protecting group. - View Dependent Claims (9, 10, 11, 12, 13, 14)
-
-
15. 17(Z)-1α
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
- View Dependent Claims (17, 18)
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
-
16. A pharmaceutical composition containing an effective amount of 17(Z)-1α
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 together with a pharmaceutically acceptable excipient.
-
19. A method of treating psoriasis comprising administering to a subject with psoriasis an effective amount of a 17(20)-dehydro vitamin D analog having the formula:
-
where Y1 and Y2, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, where R11 and R12 are each hydrogen or taken together are a methylene group, where R6 and R7, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or R6 and R7 when taken together may represent the group —
(CH2)x—
where x is an integer from 2 to 5, or R6 and R7 when taken together may represent the group ═
CR8R9 where R8 and R9, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or when taken together R8 and R9 may represent the group —
(CH2)x—
where x is an integer from 2 to 5, and where the group R represents a side chain represented by the structurewhere the side chain and 17-ene double bond is in the Z configuration and where Z in the above side chain structure is selected from Y, —
OY, —
CH2OY, —
C≡
CY and —
CH═
CHY, where the double bond in the side chain may have the cis or trans geometry, and where Y is selected from hydrogen, methyl, —
COR5 and a radical of the structure;
where m and n, independently, represent the integers from 0 to 5, where R1 is selected from hydrogen, deuterium, hydroxy, protected hydroxy, fluoro, trifluoromethyl, and C1-5-alkyl, which may be straight chain or branched and, optionally, bear a hydroxy or protected-hydroxy substituent, and where each of R2, R3, and R4, independently, is selected from deuterium, deuteroalkyl, hydrogen, fluoro, trifluoromethyl and C1-5 alkyl, which may be straight-chain or branched, and optionally, bear a hydroxy or protected-hydroxy substituent, and where R1 and R2, taken together, represent an oxo group, or an alkylidene group having a general formula CkH2k—
where k is an integer, the group ═
CR2R3, or the group —
(CH2)p—
, where p is an integer from 2 to 5, and where R3 and R4, taken together, represent an oxo group, or the group —
(CH2)q—
, where q is an integer from 2 to 5, and where R5 represents hydrogen, hydroxy, protected hydroxy, or C1-5 alkyl and wherein any of the CH-groups at positions 20, 22, or 23 in the side chain may be replaced by a nitrogen atom, or where any of the groups —
CH(CH3)—
, —
(CH2)m—
, —
CR1R2—
or —
(CH2)n—
at positions 20, 22, and 23, respectively, may be replaced by an oxygen or sulfur atom.- View Dependent Claims (20, 21, 22, 23, 24)
-
-
25. A method of treating psoriasis comprising administering to a subject with psoriasis an effective amount of 17(Z)-1α
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
- View Dependent Claims (26, 27, 28, 29, 30)
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
-
31. A method of treating a disease selected from the group consisting of leukemia, colon cancer, breast cancer, skin cancer or prostate cancer comprising administering to a subject with said disease an effective amount of a 17(20)-dehydro vitamin D analog having the formula:
-
where Y1 and Y2, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, where R11 and R12 are each hydrogen or taken together are a methylene group, where R6 and R7, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or R6 and R7 when taken together may represent the group —
(CH2)x—
where x is an integer from 2 to 5, or R6 and R7 when taken together may represent the group ═
CR8R9 where R8 and R9, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or when taken together R8 and R9 may represent the group —
(CH2)x—
where x is an integer from 2 to 5, and where the group R represents a side chain represented by the structurewhere the side chain and 17-ene double bond is in the Z configuration and where Z in the above side chain structure is selected from Y, —
OY, —
CH2OY, —
C≡
CY and —
CH═
CHY, where the double bond in the side chain may have the cis or trans geometry, and where Y is selected from hydrogen, methyl, —
COR5 and a radical of the structure;
where m and n, independently, represent the integers from 0 to 5, where R1 is selected from hydrogen, deuterium, hydroxy, protected hydroxy, fluoro, trifluoromethyl, and C1-5-alkyl, which may be straight chain or branched and, optionally, bear a hydroxy or protected-hydroxy substituent, and where each of R2, R3, and R4, independently, is selected from deuterium, deuteroalkyl, hydrogen, fluoro, trifluoromethyl and C1-5 alkyl, which may be straight-chain or branched, and optionally, bear a hydroxy or protected-hydroxy substituent, and where R1 and R2, taken together, represent an oxo group, or an alkylidene group having a general formula CkH2k—
where k is an integer, the group =CR2R3, or the group —
(CH2)p—
, where p is an integer from 2 to 5, and where R3 and R4, taken together, represent an oxo group, or the group —
(CH2)q—
, where q is an integer from 2 to 5, and where R5 represents hydrogen, hydroxy, protected hydroxy, or C1-5 alkyl and wherein any of the CH-groups at positions 20, 22, or 23 in the side chain may be replaced by a nitrogen atom, or where any of the groups —
CH(CH3)—
, —
(CH2)m—
, —
CR1R2—
or —
(CH2)n—
at positions 20, 22, and 23, respectively, may be replaced by an oxygen or sulfur atom.- View Dependent Claims (32, 33, 34, 35)
-
-
36. A method of treating a disease selected from the group consisting of leukemia, colon cancer, breast cancer, skin cancer or prostate cancer comprising administering to a subject with said disease an effective amount of 17(E)-1α
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
- View Dependent Claims (37, 38, 39, 40)
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
-
41. A method of treating an autoimmune disease selected from the group consisting of multiple sclerosis, lupus, diabetes mellitus, hot versus graft rejection, and rejection of organ transplants, comprising administering to a subject with said disease an effective amount of a 17(20)-dehydro vitamin D analog having the formula:
-
where Y1 and Y2, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, where R1l and R12 are each hydrogen or taken together are a methylene group, where R6 and R7, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or R6 and R7 when taken together may represent the group —
(CH2)x—
where x is an integer from 2 to 5, or R6 and R7 when taken together may represent the group ═
CR8R9 where R8 and R9, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or when taken together R8 and R9 may represent the group —
(CH2)x—
where x is an integer from 2 to 5, and where the group R represents a side chain represented by the structurewhere the side chain and 17-ene double bond is in the Z configuration and where Z in the above side chain structure is selected from Y, —
OY, —
CH2OY, —
C≡
CY and —
CH═
CHY, where the double bond in the side chain may have the cis or trans geometry, and where Y is selected from hydrogen, methyl, —
COR5 and a radical of the structure;
where m and n, independently, represent the integers from 0 to 5, where R1 is selected from hydrogen, deuterium, hydroxy, protected hydroxy, fluoro, trifluoromethyl, and C1-5-alkyl, which may be straight chain or branched and, optionally, bear a hydroxy or protected-hydroxy substituent, and where each of R2, R3, and R4, independently, is selected from deuterium, deuteroalkyl, hydrogen, fluoro, trifluoromethyl and C1-5 alkyl, which may be straight-chain or branched, and optionally, bear a hydroxy or protected-hydroxy substituent, and where R1 and R2, taken together, represent an oxo group, or an alkylidene group having a general formula CkH2k—
where k is an integer, the group ═
CR2R3, or the group —
(CH2)p—
, where p is an integer from 2 to 5, and where R3 and R4, taken together, represent an oxo group, or the group —
(CH2)q—
, where q is an integer from 2 to 5, and where R5 represents hydrogen, hydroxy, protected hydroxy, or C1-5 alkyl and wherein any of the CH-groups at positions 20, 22, or 23 in the side chain may be replaced by a nitrogen atom, or where any of the groups —
CH(CH3)—
, —
(CH2)m—
, —
CR1R2—
or —
(CH2)n—
at positions 20, 22, and 23, respectively, may be replaced by an oxygen or sulfur atom.- View Dependent Claims (42, 43, 44, 45)
-
-
46. A method of treating an autoimmune disease selected from the group consisting of multiple sclerosis, lupus, diabetes mellitus, host versus graft rejection, and rejection of organ transplants, comprising administering to a subject with said disease an effective amount of 17(Z)-1α
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
- View Dependent Claims (47, 48, 49, 50)
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
-
51. A method of treating an inflammatory disease selected from the group consisting of rheumatoid arthritis, asthma, and inflammatory bowel diseases, comprising administering to a subject with said disease an effective amount of a 17(20)-dehydro vitamin D analog having the formula:
-
where Y1 and Y2, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, where R11 and R12 are each hydrogen or taken together are a methylene group, where R6 and R7, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or R6 and R7 when taken together may represent the group —
(CH2)x—
where x is an integer from 2 to 5, or R6 and R7 when taken together may represent the group =CR8R9 where R8 and R9, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or when taken together R8 and R9 may represent the group —
(CH2)x—
where x is an integer from 2 to 5, and where the group R represents a side chain represented by the structurewhere the side chain and 17-ene double bond is in the Z configuration and where Z in the above side chain structure is selected from Y, —
OY, —
CH2OY, —
C≡
CY and —
CH═
CHY, where the double bond in the side chain may have the cis or trans geometry, and where Y is selected from hydrogen, methyl, —
COR5 and a radical of the structure;
where m and n, independently, represent the integers from 0 to 5, where R1 is selected from hydrogen, deuterium, hydroxy, protected hydroxy, fluoro, trifluoromethyl, and C1-5-alkyl, which may be straight chain or branched and, optionally, bear a hydroxy or protected-hydroxy substituent, and where each of R2, R3, and R4, independently, is selected from deuterium, deuteroalkyl, hydrogen, fluoro, trifluoromethyl and C1-5 alkyl, which may be straight-chain or branched, and optionally, bear a hydroxy or protected-hydroxy substituent, and where R1 and R2, taken together, represent an oxo group, or an alkylidene group having a general formula CkH2k—
where k is an integer, the group ═
CR2R3, or the group —
(CH2)p—
, where p is an integer from 2 to 5, and where R3 and R4, taken together, represent an oxo group, or the group —
(CH2)q—
, where q is an integer from 2 to 5, and where R5 represents hydrogen, hydroxy, protected hydroxy, or C1-5 alkyl and wherein any of the CH-groups at positions 20, 22, or 23 in the side chain may be replaced by a nitrogen atom, or where any of the groups —
CH(CH3)—
, —
(CH2)m—
, —
CR1R2—
or —
(CH2)n—
at positions 20, 22, and 23, respectively, may be replaced by an oxygen or sulfur atom.- View Dependent Claims (52, 53, 54, 55)
-
-
56. A method of treating an inflammatory disease selected from the group consisting of rheumatoid arthritis, asthma, and inflammatory bowel diseases, comprising administering to a subject with said disease an effective amount of 17(Z)-1α
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
- View Dependent Claims (57, 58, 59, 60)
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
-
61. A method of treating a skin condition selected from the group consisting of wrinkles, lack of adequate skin firmness, lack of adequate dermal hydration and insufficient sebum secretion which comprises administering to a subject with said skin condition an effective amount of a 17(20)-dehydro vitamin D analog having the formula:
-
where Y1 and Y2, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, where R11 and R12 are each hydrogen or taken together are a methylene group, where R6 and R7, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or R6 and R7 when taken together may represent the group —
(CH2)x—
where x is an integer from 2 to 5, or R6 and R7 when taken together may represent the group ═
CR8R9 where R8 and R9, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or when taken together R8 and R9 may represent the group —
(CH2)x—
where x is an integer from 2 to 5, and where the group R represents a side chain represented by the structurewhere the side chain and 17-ene double bond is in the Z configuration and where Z in the above side chain structure is selected from Y, —
OY, —
CH2OY, —
C≡
CY and —
CH═
CHY, where the double bond in the side chain may have the cis or trans geometry, and where Y is selected from hydrogen, methyl, —
COR5 and a radical of the structure;
where m and n, independently, represent the integers from 0 to 5, where R1 is selected from hydrogen, deuterium, hydroxy, protected hydroxy, fluoro, trifluoromethyl, and C1-5-alkyl, which may be straight chain or branched and, optionally, bear a hydroxy or protected-hydroxy substituent, and where each of R2, R3, and R4, independently, is selected from deuterium, deuteroalkyl, hydrogen, fluoro, trifluoromethyl and C1-5 alkyl, which may be straight-chain or branched, and optionally, bear a hydroxy or protected-hydroxy substituent, and where R1 and R2, taken together, represent an oxo group, or an alkylidene group having a general formula CkH2k—
where k is an integer, the group ═
CR2R3, or the group —
(CH2)p—
, where p is an integer from 2 to 5, and where R3 and R4, taken together, represent an oxo group, or the group —
(CH2)q—
, where q is an integer from 2 to 5, and where R5 represents hydrogen, hydroxy, protected hydroxy, or C1-5 alkyl and wherein any of the CH-groups at positions 20, 22, or 23 in the side chain may be replaced by a nitrogen atom, or where any of the groups —
CH(CH3)—
, —
(CH2)m—
, —
CR1R2—
or —
(CH2)n—
at positions 20, 22, and 23, respectively, may be replaced by an oxygen or sulfur atom.- View Dependent Claims (62, 63, 64, 65, 66)
-
-
67. A method of treating a skin condition selected from the group consisting of wrinkles, lack of adequate skin firmness, lack of adequate dermal hydration and insufficient sebum secretion which comprises administered to a subject with said skin condition an effective amount of 17(Z)-1α
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
- View Dependent Claims (68, 69, 70, 71, 72)
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
-
73. A method of treating renal osteodystrophy comprising administering to a subject with renal osteodystrophy an effective amount of a 17(20)-dehydro vitamin D analog having the formula:
-
where Y1 and Y2, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, where R11 and R12 are each hydrogen or taken together are a methylene group, where R6 and R7, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or R6 and R7 when taken together may represent the group —
(CH2)x—
where x is an integer from 2 to 5, or R6 and R7 when taken together may represent the group ═
CR8R9 where R8 and R9, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or when taken together R8 and R9 may represent the group —
(CH2)x—
where x is an integer from 2 to 5, and where the group R represents a side chain represented by the structurewhere the side chain and 17-ene double bond is in the Z configuration and where Z in the above side chain structure is selected from Y, —
OY, —
CH2OY, —
C≡
CY and —
CH═
CHY, where the double bond in the side chain may have the cis or trans geometry, and where Y is selected from hydrogen, methyl, —
COR5 and a radical of the structure;
where m and n, independently, represent the integers from 0 to 5, where R1 is selected from hydrogen, deuterium, hydroxy, protected hydroxy, fluoro, trifluoromethyl, and C1-5-alkyl, which may be straight chain or branched and, optionally, bear a hydroxy or protected-hydroxy substituent, and where each of R2, R3, and R4, independently, is selected from deuterium, deuteroalkyl, hydrogen, fluoro, trifluoromethyl and C1-5 alkyl, which may be straight-chain or branched, and optionally, bear a hydroxy or protected-hydroxy substituent, and where R1 and R2, taken together, represent an oxo group, or an alkylidene group having a general formula CkH2k—
where k is an integer, the group ═
CR2R3, or the group —
(CH2)p—
, where p is an integer from 2 to 5, and where R3 and R4, taken together, represent an oxo group, or the group —
(CH2)q—
, where q is an integer from 2 to 5, and where R5 represents hydrogen, hydroxy, protected hydroxy, or C1-5 alkyl and wherein any of the CH-groups at positions 20, 22, or 23 in the side chain may be replaced by a nitrogen atom, or where any of the groups —
CH(CH3)—
, —
(CH2)m—
, —
CR1R2—
or —
(CH2)n—
at positions 20, 22, and 23, respectively, may be replaced by an oxygen or sulfur atom.- View Dependent Claims (74, 75, 76, 77)
-
-
78. A method of treating renal osteodystrophy comprising administering to a subject with renal osteodystrophy an effective amount of 17(E)-1α
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
- View Dependent Claims (79, 80, 81, 82)
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
-
83. A method of treating or preventing obesity of an animal, inhibiting adipocyte differentiation, inhibiting SCD-1 gene transcription, and/or reducing body fat in an animal comprising administering to an animal in need thereof an effective amount of a 17(20)-dehydro vitamin D analog having the formula:
-
where Y1 and Y2, which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, where R11 and R12 are each hydrogen or taken together are a methylene group, where R6 and R7, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or R6 and R7 when taken together may represent the group —
(CH2)x—
where x is an integer from 2 to 5, or R6 and R7 when taken together may represent the group ═
CR8R9 where R8 and R9, which may be the same or different, are each selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, fluoroalkyl, hydroxy and alkoxy, or when taken together R8 and R9 may represent the group —
(CH2)x—
where x is an integer from 2 to 5, and where the group R represents a side chain represented by the structurewhere the side chain and 17-ene double bond is in the Z configuration and where Z in the above side chain structure is selected from Y, —
OY, —
CH2OY, —
C≡
CY and —
CH═
CHY, where the double bond in the side chain may have the cis or trans geometry, and where Y is selected from hydrogen, methyl, —
COR5 and a radical of the structure;
where m and n, independently, represent the integers from 0 to 5, where R1 is selected from hydrogen, deuterium, hydroxy, protected hydroxy, fluoro, trifluoromethyl, and C1-5-alkyl, which may be straight chain or branched and, optionally, bear a hydroxy or protected-hydroxy substituent, and where each of R2, R3, and R4, independently, is selected from deuterium, deuteroalkyl, hydrogen, fluoro, trifluoromethyl and C1-5 alkyl, which may be straight-chain or branched, and optionally, bear a hydroxy or protected-hydroxy substituent, and where R1 and R2, taken together, represent an oxo group, or an alkylidene group having a general formula CkH2k—
where k is an integer, the group ═
CR2R3, or the group —
(CH2)p—
, where p is an integer from 2 to 5, and where R3 and R4, taken together, represent an oxo group, or the group —
(CH2)q—
, where q is an integer from 2 to 5, and where R5 represents hydrogen, hydroxy, protected hydroxy, or C1-5 alkyl and wherein any of the CH-groups at positions 20, 22, or 23 in the side chain may be replaced by a nitrogen atom, or where any of the groups —
CH(CH3)—
, —
(CH2)m—
, —
CR1R2—
or —
(CH2)n—
at positions 20, 22, and 23, respectively, may be replaced by an oxygen or sulfur atom.- View Dependent Claims (84, 85, 86, 87, 88, 89, 90)
-
-
91. A method of treating or preventing obesity of an animal, inhibiting adipocyte differentiation, inhibiting SCD-1 gene transcription, and/or reducing body fat in an animal comprising administering to an animal in need thereof an effective amount of 17(Z)-1α
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
- View Dependent Claims (92, 93, 94, 95, 96, 97, 98)
- ,25-dihydroxy-17(20)-dehydro-2-methylene-19-nor-vitamin D3 having the formula;
Specification