24-Hydroxyvitamin D, analogs and uses thereof
First Claim
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1. A method of achieving an effect in a patient comprising administering an effective amount of a vitamin D compound which is a 24-hydroxyvitamin D or a 24-hydroxyprevitamin D wherein the effect is treating or preventing bone loss or bone mineral content, hyperparathyroidism, hyperproliferation, or modulating the immune and inflammatory responses.
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Abstract
The invention provides 24-hydroxyvitamin D compounds and methods for their use in the treatment and prophylaxis of hyperparathyroidism and hyperproliferative diseases, and in the modulation of the immune and inflammatory responses as well as the treatment of bone depletive disorders.
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Citations
27 Claims
- 1. A method of achieving an effect in a patient comprising administering an effective amount of a vitamin D compound which is a 24-hydroxyvitamin D or a 24-hydroxyprevitamin D wherein the effect is treating or preventing bone loss or bone mineral content, hyperparathyroidism, hyperproliferation, or modulating the immune and inflammatory responses.
- 11. A method of achieving an effect in a patient comprising administering an effective amount of a vitamin D compound which is a 24-hydroxyvitamin D or a 24-hydroxyprevitamin D wherein the effect is increasing or maintaining bone mass or bone mineral content, lowering or maintaining lowered parathyroid hormone level, inhibiting hyperproliferative effects, inducing or enhancing cell differentiation modulating immune response, and modulating inflammatory response.
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14. A method of treating a human to alleviate the pathological effects of osteoporosis, hyperparathyroidism, psoriasis, skin cancer, breast cancer, colon cancer, prostate cancer, prostatic hyperplasia and immune response imbalance and inflammatory response in balance, wherein the method comprises administering to the human a vitamin D compound which is a 24-hydroxyvitamin D or a 24-hydroxyprevitamin D wherein said compound is administered to the human in an amount sufficient to increase or maintain bone mass or bone mineral content, lower or maintain lowered parathyroid hormone level, inhibit hyperproliferative effects, induce or enhance cell differentiation, modulate immune response and modulate inflammatory response in the human.
- 15. A pharmaceutical composition comprising an effective amount of a substantially pure, synthesized a 24-hydroxyvitamin D or a 24-hydroxyprevitamin D and a pharmaceutically acceptable carrier, adjuvant or vehicle.
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19. A 24-hydroxyvitamin D compound which is a compound of formula (I):
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wherein Z represents a saturated or unsaturated, substituted or unsubstituted, straight-chain or branched C4-C18 hydrocarbon group in which the C-24 or equivalent position is hydroxylated;
Y is a methylene group if Y is double bonded to the A-ring or a methyl group or hydrogen if Y is single bonded provided that the compound of formula (I) is not 24-hydroxyvitamin D2; and
X is hydrogen, lower alkyl or lower fluoroalkyl provided that the compound of formula (I) is not 24-hydroxyvitamin D2.- View Dependent Claims (21, 22)
wherein n is an integer which is 1 or 2;
R 3 is hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
A is carbon, oxygen, sulfur or nitrogen;
r is 1 and s is zero when A is nitrogen;
r and s are 1 when A is carbon;
r and s are zero when A is sulfur or oxygen; and
R9 and R10 are independently hydrogen, lower alkyl, lower alkenyl, lower fluoroalkyl or lower fluoroalkenyl.
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22. The compound of
claim 19 wherein Z is a side chain of formula (IIE):-
wherein a dotted line along the side chain represents an optional additional C-C bond;
q is zero or an integer which is 1 or 2;
R3 is hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
A is carbon, oxygen, sulfur or nitrogen;
r is 1 and s is zero when A is nitrogen;
r and s are 1 when A is carbon;
r and s are zero when A is sulfur or oxygen; and
R9 and R10 are independently hydrogen, lower alkyl, lower alkenyl, lower fluoroalkyl or lower fluoroalkenyl.
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20. A 24-hydroxyprevitamin D which is a compound of formula (Ill):
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wherein Z represents a saturated or unsaturated, substituted or unsubstituted, straight-chain or branched C4-C18 hydrocarbon group in which the C-24 or equivalent position is hydroxylated;
Y is a methyl group or hydrogen; and
X is hydrogen, lower alkyl or lower fluoroalkyl.- View Dependent Claims (23, 24)
wherein n is an integer which is 1 or 2;
R3 is hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
A is carbon, oxygen, sulfur or nitrogen;
r is 1 and s is zero when A is nitrogen;
r and s are 1 when A is carbon;
r and s are zero when A is sulfur or oxygen;
R9 and R10 are independently hydrogen, lower alkyl, lower alkenyl, lower fluoroalkyl or lower fluoroalkenyl.
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24. The compound of
claim 20 , wherein Z is a side chain of formula (IIE):-
wherein a dotted line along the side chain represents an optional additional C-C bond;
q is zero or an integer which is 1 or 2;
R3 is hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
A is carbon, oxygen, sulfur or nitrogen;
r is 1 and s is zero when A is nitrogen;
r and s are 1 when A is carbon;
r and s are zero when A is sulfur or oxygen; and
R9 and R10 are independently hydrogen, lower alkyl, lower alkenyl, lower fluoroalkyl or lower fluoroalkenyl.
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25. As an article of manufacture, a tablet having a relatively high absorption rate for vitamin D as measured by blood level of vitamin D over time after ingestion, comprising a vitamin D compound which is 24-hydroxyvitamin D or 24-hydroxyprevitamin D and a pharmaceutically acceptable carrier, adjuvant or vehicle.
Specification