Vitamin d3 analogues for the prevention and treatment of bone disorders
AssigneesK.U. Leuven Research & Development, Universiteit Gent
InventorsRoger Bouillon, Annemieke Verstuyf, Pierre De Clercq, Maurits Vandewalle
Life of this patent
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Abstract
Novel vitamin D analogues are useful for making pharmaceutical compositions for the prevention or treatment of bone disorders such as osteoporosis
Claims12
A method for preventing or treating bone loss in humans comprising administering to a human an effective amount of a compound having the structural formula:
- or a diastereomer thereof.
A method for preventing or treating osteoporosis in humans comprising administering to a human an effective amount of a compound having the formula:
- or a diastereomer thereof.
A method for preventing or treating a bone disorder in a human, said disorder being chosen from the group consisting of bone loss, osteomalacia, renal osteodystrophy and osteoporosis, without inducing hypercalcemia in a human, comprising administering an effective amount of a compound having the structural formula:
- or a diastereomer thereof.
A method for the prevention or treatment of a bone disorder in a mammal comprising administering an effective amount of a vitamin D3 analogue selected from the group consisting of:
- (1R,3R)-5-{(E)-3-((1S,3R)-3-((1S,4R)-4-hydroxy-1,5-dimethylhexyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)cyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1S,4S)-4-hydroxy-1,5-dimethylhexyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylene-cyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1S,4R)-4-hydroxy-1,5-dimethylhexyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylene-cyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1S)-6,6,6-trifluoro-5-hydroxy-1-methyl-5-trifluoromethyl-3-hexynyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylenecyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1R)-6,6,6-trifluoro-5-hydroxy-1-methyl-5-trifluoromethyl-3-hexynyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylenecyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1R)-5-hydroxy-1,5-dimethyl-3-hexynyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylenecyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1S)-6,6,6-trifluoro-5-hydroxy-1-methyl-5-(trifluoromethyl)hexyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylenecyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1R)-6,6,6-trifluoro-5-hydroxy-1-methyl-5-(trifluoromethyl)hexyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylenecyclohexane-1,3-diol,
- (1R,3R)-5-((E)-3-((1S,3R)-3-((1R)-6,6,6-trifluoro-5-hydroxy-1-methyl-5-trifluoromethyl-3-hexynyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)cyclohexane-1,3-diol, and
- (1R,3R)-5-((E)-3-((1S,3R)-3-((1S)-5-ethyl-5-hydroxy-1-methylheptyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)cyclohexane-1,3-diol.
A method for preventing or treating a bone disorder in a human without inducing hypercalcemia in a human, comprising administering a therapeutically effective amount of a vitamin D3 analogue selected from the group consisting of:
- (1R,3R)-5-{(E)-3-((1S,3R)-3-((1S,4R)-4-hydroxy-1,5-dimethylhexyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)cyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1S,4S)-4-hydroxy-1,5-dimethylhexyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylene-cyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1S,4R)-4-hydroxy-1,5-dimethylhexyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylene-cyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1S)-6,6,6-trifluoro-5-hydroxy-1-methyl-5-trifluoromethyl-3-hexynyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylenecyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1R)-6,6,6-trifluoro-5-hydroxy-1-methyl-5-trifluoromethyl-3-hexynyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylenecyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1R)-5-hydroxy-1,5-dimethyl-3-hexynyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylenecyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1S)-6,6,6-trifluoro-5-hydroxy-1-methyl-5-(trifluoromethyl)hexyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylenecyclohexane-1,3-diol,
- (1R,3S)-5-((Z,2E)-3-((1S,3R)-3-((1R)-6,6,6-trifluoro-5-hydroxy-1-methyl-5-(trifluoromethyl)hexyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)-4-methylenecyclohexane-1,3-diol,
- (1R,3R)-5-((E)-3-((1S,3R)-3-((1R)-6,6,6-trifluoro-5-hydroxy-1-methyl-5-trifluoromethyl-3-hexynyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)cyclohexane-1,3-diol, and
- (1R,3R)-5-((E)-3-((1S,3R)-3-((1S)-5-ethyl-5-hydroxy-1-methylheptyl)-2,2,3-trimethylcyclopentyl)-2-propenylidene)cyclohexane-1,3-diol.
A compound selected from the group consisting of:
- (2E,4S) methyl 4-((1R,3R)-3-(tert-butyldiphenylsilyloxymethyl)-1,2,2-trimethylcyclopentyl)pent-2-enoate,
- (2E,4S)-4-((1R,3R)-3-(tert-butyldiphenylsilyloxymethyl)-1,2,2-trimethyl-cyclopentyl)pent-2-en-1-ol,
- (2E,4S)-4-((1R,3R)-3-(tert-butyldiphenylsilyloxymethyl)-1,2,2-trimethyl-cyclopentyl)pent-2-enal,
- (3S,4E,6S)-6-((1R,3R)-3-(tert-butyldiphenylsilyloxymethyl)-1,2,2-trimethyl-cyclopentyl)-2-methylhept-4-en-3-ol,
- (3R,4E,6S)-6-((1R,3R)-3-(tert-butyldiphenylsilyloxymethyl)-1,2,2-trimethyl-cyclopentyl)-2-methylhept-4-en-3-ol,
- (3R,6S)-6-((1R,3R)-3-(tert-butyldiphenylsilyloxymethyl)-1,2,2-trimethyl-cyclopentyl)-2-methylheptan-3-ol,
- (1R,3R)-(3-((1S,4R)-4-(tert-butyldiphenylsilyloxymethyl)-1,5-dimethyl-hexyl)-2,2,3-trimethylcyclopentyl)methanol,
- (1R,3R)-(3-((1S,4R)-4-(tert-butyldiphenylsilyloxymethyl)-1,5-dimethyl-hexyl)-2,2,3-trimethyl)cyclopentanecarbaldehyde,
- (3S,6S)-6-((1R,3R)-3-(tert-butyldiphenylsilyloxymethyl)-1,2,2-trimethyl-cyclopentyl)-2-methylheptan-3-ol,
- (1R,3R)-(3-((1S,4S)-4-(tert-butyldiphenylsilyloxymethyl)-1,5-dimethylhexyl)-2,2,3-trimethylcyclopentyl)methanol, and
- (1R,3R)-(3-((1S,4S)-4-(tert-butyldiphenylsilyloxymethyl)-1,5-dimethylhexyl)-2,2,3-trimethyl)cyclopentanecarbaldehyde.
Dependencies are inferred from the claim text.