24 HYDROXYVITAMIN D, ANALOGS AND USES THEREOF
First Claim
Patent Images
1. A method of achieving an effect in a patient in need thereof comprising administering an effective amount of a vitamin D compound wherein the effect is treating bone loss, treating hyperproliferation, or modulating the immune or inflammatory response, and wherein said vitamin D compound is a compound of formula (I):
- wherein Z is a side chain of formula IIB;
wherein R5 and R6 are each hydrogen or taken together form a double bond between C-22 and C-23, R3 is hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 is lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl; and
R1 and R2 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl, lower fluoroalkenyl, lower cycloalkyl or taken together with the carbon to which they are bonded form a C3-C8 cyclocarbon ring;
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; and
X is hydrogen, lower alkyl or lower fluoroalkyl.
0 Assignments
0 Petitions
Accused Products
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.
-
Citations
94 Claims
-
1. A method of achieving an effect in a patient in need thereof comprising administering an effective amount of a vitamin D compound wherein the effect is treating bone loss, treating hyperproliferation, or modulating the immune or inflammatory response, and wherein said vitamin D compound is a compound of formula (I):
-
wherein Z is a side chain of formula IIB;
wherein R5 and R6 are each hydrogen or taken together form a double bond between C-22 and C-23, R3 is hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 is lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl; and
R1 and R2 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl, lower fluoroalkenyl, lower cycloalkyl or taken together with the carbon to which they are bonded form a C3-C8 cyclocarbon ring;
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; and
X is hydrogen, lower alkyl or lower fluoroalkyl.- View Dependent Claims (2, 3, 4, 5, 6, 7, 8)
-
-
9. A method of achieving an effect in a patient in need thereof comprising administering an effective amount of a vitamin D compound wherein the effect is treating bone loss, treating hyperparathyroidism, treating hyperproliferation, or modulating the immune or inflammatory response, and wherein said vitamin D compound is a compound of formula (I):
-
wherein Z is a side chain of formula IIA;
wherein a dotted line along the side chain represents an optional additional C—
C bond;
m is 0 or 1;
R5 and R6 are each hydrogen or taken together form a double bond between C-22 and C-23, R3 is hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 is lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl; and
R1 and R2 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl, lower fluoroalkenyl, lower cycloalkyl or taken together with the carbon to which they are bonded form a C3-C8 cyclocarbon ring;
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; and
X is hydrogen, lower alkyl or lower fluoroalkyl.- View Dependent Claims (10, 11, 12, 13, 14, 15)
-
-
16. A method of achieving an effect in a patient in need thereof comprising administering an effective amount of a previtamin D compound, wherein the effect is treating bone loss, treating hyperproliferation, or modulating the immune or inflammatory response, wherein said previtamin D compound is a compound of formula (III):
-
wherein Z is a side chain of formula IIA, IIB, IIC, IID, IIE or IIF;
wherein a dotted line along the side chain represents an optional additional C—
C bond;
m is zero or an integer which is 1;
n is an integer which is 1 or 2;
q is zero or an integer which is 1 or 2;
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;
R5 and R6 are each hydrogen or taken together form a double bond between C-22 and C-23, R3, R9 and R10 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl; and
R1 and R2 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl, lower fluoroalkenyl, lower cycloalkyl or taken together with the carbon to which they are bonded form a C3-C8 cyclocarbon ring;
Y is a methyl group or hydrogen; and
X is hydrogen, lower alkyl or lower fluoroalkyl.- View Dependent Claims (17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)
-
-
30. A method of treating hyperparathyroidism comprising administering an effective amount of a previtamin D compound, wherein said previtamin D compound is a compound of formula (III):
-
wherein Z is a side chain of formula IIA, IIC, or IIE;
wherein a dotted line along the side chain represents an optional additional C—
C bond;
m is zero or an integer which is 1;
n is an integer which is 1 or 2;
q is zero or an integer which is 1 or 2;
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;
R5 and R6 are each hydrogen or taken together form a double bond between C-22 and C-23, R3, R9 and R10 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl; and
R1 and R2 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl, lower fluoroalkenyl, lower cycloalkyl or taken together with the carbon to which they are bonded form a C3-C8 cyclocarbon ring;
Y is a methyl group or hydrogen; and
X is hydrogen, lower alkyl or lower fluoroalkyl.- View Dependent Claims (31, 32, 33, 34)
-
-
35. A method of achieving an effect in a patient in need thereof comprising administering an effective amount of a vitamin D compound, wherein the effect is increasing or maintaining bone mass or bone mineral content, inhibiting hyperproliferative effects, inducing or enhancing cell differentiation, and wherein the vitamin D compound is a compound of formula (I):
-
wherein Z is a side chain of formula IIA, IIB, IIC, IID, IIE or IIF;
wherein a dotted line along the side chain represents an optional additional C—
C bond;
m is zero or an integer which is 1;
n is an integer which is 1 or 2;
q is zero or an integer which is 1 or 2;
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;
R5 and R6 are each hydrogen or taken together form a double bond between C-22 and C-23, R3, R9 and R10 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl; and
R1 and R2 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl, lower fluoroalkenyl, lower cycloalkyl or taken together with the carbon to which they are bonded form a C3-C8 cyclocarbon ring;
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; and
X is hydrogen, lower alkyl or lower fluoroalkyl.- View Dependent Claims (36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47)
-
-
48. A method of lowering elevated parathyroid hormone levels or maintaining lowered parathyroid hormone levels in a patient in need thereof comprising administering an effective amount of a vitamin D compound, wherein the vitamin D compound is a compound of formula (I):
-
wherein Z is a side chain of formula IIA, IIC, or IIE;
wherein a dotted line along the side chain represents an optional additional C—
C bond;
m is zero or an integer which is 1;
n is an integer which is 1 or 2;
q is zero or an integer which is 1 or 2;
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;
R5 and R6 are each hydrogen or taken together form a double bond between C-22 and C-23, R3, R9 and R10 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl; and
R1 and R2 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl, lower fluoroalkenyl, lower cycloalkyl or taken together with the carbon to which they are bonded form a C3-C8 cyclocarbon ring;
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; and
X is hydrogen, lower alkyl or lower fluoroalkyl.- View Dependent Claims (49, 50, 51, 52)
-
-
53. A method of achieving an effect in a patient in need thereof comprising administering an effective amount of a previtamin D compound, wherein the effect is increasing or maintaining bone mass or bone mineral content, inhibiting hyperproliferative effects, inducing or enhancing cell differentiation, wherein said previtamin D compound is a compound of formula (III):
-
wherein Z is a side chain of formula IIA, IIB, IIC, IID, IIE or IIF;
wherein a dotted line along the side chain represents an optional additional C—
C bond;
m is zero or an integer which is 1;
n is an integer which is 1 or 2;
q is zero or an integer which is 1 or 2;
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;
R5 and R6 are each hydrogen or taken together form a double bond between C-22 and C-23, R3, R9 and R10 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl; and
R1 and R2 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl, lower fluoroalkenyl, lower cycloalkyl or taken together with the carbon to which they are bonded form a C3-C8 cyclocarbon ring;
Y is a methyl group or hydrogen; and
X is hydrogen, lower alkyl or lower fluoroalkyl.- View Dependent Claims (54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65)
-
-
66. A method of lowering elevated parathyroid hormone levels or maintaining lowered parathyroid hormone levels in a patient in need thereof comprising administering an effective amount of a previtamin D compound, wherein said previtamin D compound is a compound of formula (III):
-
wherein Z is a side chain of formula IIA, IIC or IIE;
wherein a dotted line along the side chain represents an optional additional C—
C bond;
m is zero or an integer which is 1;
n is an integer which is 1 or 2;
q is zero or an integer which is 1 or 2;
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;
R5 and R6 are each hydrogen or taken together form a double bond between C-22 and C-23, R3, R9 and R10 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl; and
R1 and R2 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl, lower fluoroalkenyl, lower cycloalkyl or taken together with the carbon to which they are bonded form a C3-C8 cyclocarbon ring;
Y is a methyl group or hydrogen; and
X is hydrogen, lower alkyl or lower fluoroalkyl.- View Dependent Claims (67, 68, 69, 70)
-
-
71. A pharmaceutical composition comprising an effective amount of a substantially pure, synthesized vitamin D compound and a pharmaceutically acceptable carrier, wherein the vitamin D compound is a compound of formula (I):
-
wherein Z is a side chain of formula IIA, IIB, IIC, IID, IIE or IIF;
wherein a dotted line along the side chain represents an optional additional C—
C bond;
m is zero or an integer which is 1;
n is an integer which is 1 or 2;
q is zero or an integer which is 1 or 2;
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;
R5 and R6 are each hydrogen or taken together form a double bond between C-22 and C-23, R3, R9 and R10 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl; and
R1 and R2 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl, lower fluoroalkenyl, lower cycloalkyl or taken together with the carbon to which they are bonded form a C3-C8 cyclocarbon ring;
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; and
X is hydrogen, lower alkyl or lower fluoroalkyl.- View Dependent Claims (72, 73, 74, 75, 76, 77, 78, 79, 80, 81)
-
-
82. A pharmaceutical composition comprising an effective amount of a substantially pure, synthesized previtamin D compound and a pharmaceutically acceptable carrier, wherein the previtamin D compound is a compound of formula (III):
-
wherein Z is a side chain of formula IIA, IIB, IIC, IID, IIE or IIF;
wherein a dotted line along the side chain represents an optional additional C—
C bond;
m is zero or an integer which is 1;
n is an integer which is 1 or 2;
q is zero or an integer which is 1 or 2;
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;
R5 and R6 are each hydrogen or taken together form a double bond between C-22 and C-23, R3, R9 and R10 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl; and
R1 and R2 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl, lower fluoroalkenyl, lower cycloalkyl or taken together with the carbon to which they are bonded form a C3-C8 cyclocarbon ring;
Y is a methyl group or hydrogen; and
X is hydrogen, lower alkyl or lower fluoroalkyl.- View Dependent Claims (83, 84, 85, 86, 87, 88, 89, 90, 91, 92)
-
-
93. An article of manufacture comprising a tablet or capsule comprising a vitamin D compound and a pharmaceutically acceptable carrier, wherein the vitamin D compound is a compound of formula (I):
-
wherein Z is a side chain of formula IIA, IIB, IIC, IID, IIE or IIF;
wherein a dotted line along the side chain represents an optional additional C—
C bond;
m is zero or an integer which is 1;
n is an integer which is 1 or 2;
q is zero or an integer which is 1 or 2;
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;
R5 and R6 are each hydrogen or taken together form a double bond between C-22 and C-23, R3, R9 and R10 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl; and
R1 and R2 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl, lower fluoroalkenyl, lower cycloalkyl or taken together with the carbon to which they are bonded form a C3-C8 cyclocarbon ring;
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; and
X is hydrogen, lower alkyl or lower fluoroalkyl.
-
-
94. An article of manufacture comprising a tablet or capsule comprising a previtamin D compound and a pharmaceutically acceptable carrier, wherein the previtamin D compound is a compound of formula (III):
-
wherein Z is a side chain of formula IIA, IIB, IIC, IID, IIE or IIF;
wherein a dotted line along the side chain represents an optional additional C—
C bond;
m is zero or an integer which is 1;
n is an integer which is 1 or 2;
q is zero or an integer which is 1 or 2;
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;
R5 and R6 are each hydrogen or taken together form a double bond between C-22 and C-23, R3, R9 and R10 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl;
R4 and R7 are independently lower alkyl, lower fluoroalkyl, lower alkenyl or lower fluoroalkenyl; and
R1 and R2 are independently hydrogen, lower alkyl, lower fluoroalkyl, lower alkenyl, lower fluoroalkenyl, lower cycloalkyl or taken together with the carbon to which they are bonded form a C3-C8 cyclocarbon ring;
Y is a methyl group or hydrogen; and
X is hydrogen, lower alkyl or lower fluoroalkyl.
-
Specification