Deuterium-enriched atorvastatin
The present application describes deuterium-enriched atorvastatin, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.
1. A deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 35 are independently selected from H and D; and the abundance of deuterium in R 32 -R 35 is 100%.
2. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 35 is 100% and the abundance of deuterium in R 1 -R 35 is selected from 20%, 26%, 31%, 37%, 43%, 49%, 54%, 60%, 66%, 71%, 77%, 83%, 89%, 94%, and 100%.
3. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 35 is 100% and the abundance of deuterium in R 5 -R 6 is selected from 50% and 100%.
4. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 35 is 100% and the abundance of deuterium in R 22 -R 35 is selected from 21%, 29%, 36%, 43%, 50%, 57%, 64%, 71%, 79%, 86%, 93%, and 100%.
5. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 35 is 100% and the abundance of deuterium in R 7 -R 35 is selected from 21%, 28%, 34%, 41%, 48%, 55%, 62%, 69%, 76%, 83%, 90%, 97%, and 100%.
6. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 35 is 100% and the abundance of deuterium in R 5 -R 6 and R 22 -R 35 is selected from 19%, 25%, 31%, 38%, 44%, 50%, 56%, 63%, 69%, 75%, 81%, 88%, 94%, and 100%.
7. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 35 is 100% and the abundance of deuterium in R 5 -R 35 is selected from 19%, 26%, 32%, 39%, 45%, 52%, 58%, 65%, 71%, 77%, 84%, 90%, 97%, and 100%.
8. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 35 is 100% and the abundance of deuterium in R 13 -R 14 is selected from 50% and 100%.
9. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 35 is 100% and the abundance of deuterium in R 5 -R 6 and R 8 -R 9 is selected from 25%, 50%, 75%, and 100%.
10. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 35 is 100% and the abundance of deuterium in R 22 -R 26 is selected from 20%, 40%, 60%, 80%, and 100%.
11. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 35 is 100% and the abundance of deuterium in R 15 -R 21 is selected from 14%, 29%, 43%, 57%, 71%, 86%, and 100%.
12. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 35 is 100% and the abundance of deuterium in R 5 -R 14 is selected from 10%, 20%, 30%, 40%, and 50%, 60%, 70%, 80%, 90%, and 100%.
13. A deuterium-enriched compound of claim 1 , wherein the compound is selected from a compound of Table 1 or a pharmaceutically acceptable salt thereof:
wherein when one of R 1 -R 31 is present, it is selected from H or D.
14. A deuterium-enriched compound of claim 1 , wherein the compound is selected from a compound of Table 2 or a pharmaceutically acceptable salt thereof:
15. An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 35 are independently selected from H and D; and the abundance of deuterium in R 32 -R 35 is 100%.
16. A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 35 are independently selected from H and D; and the abundance of deuterium in R 32 -R 35 is 100%.
17. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt form thereof.
18. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt form thereof.
19. A deuterium-enriched compound of claim 13 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
20. A deuterium-enriched compound of 13 , wherein the compound is:
or a pharmaceutically acceptable salt thereof, wherein R 1 -R 21 are selected from H and D.
21. A deuterium-enriched compound of 13 , wherein the compound is:
or a pharmaceutically acceptable salt thereof, wherein R 1 -R 6 are selected from H and D.
22. A deuterium-enriched compound of claim 13 , wherein the compound is:
or a pharmaceutically acceptable salt thereof, wherein R 5 -R 6 are selected from H and D.
23. A deuterium-enriched compound of claim 13 , wherein the compound is:
or a pharmaceutically acceptable salt thereof, wherein R 5 -R 6 and R 11 are selected from H and D.
24. A deuterium-enriched compound of claim 13 , wherein the compound is:
or a pharmaceutically acceptable salt thereof, wherein R 1 -R 4 are selected from H and D.
25. A deuterium-enriched compound of claim 13 , wherein the compound is:
or a pharmaceutically acceptable salt thereof, wherein R 1 -R 4 and R 11 are selected from H and D.
26. A deuterium-enriched compound of claim 13 , wherein the compound is:
or a pharmaceutically acceptable salt thereof, wherein R 1 -R 31 are selected from H and D.
27. A deuterium-enriched compound of claim 14 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
28. A deuterium-enriched compound of claim 14 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
29. A deuterium-enriched compound of claim 14 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
30. A deuterium-enriched compound of claim 14 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
31. A deuterium-enriched compound of claim 14 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
32. A deuterium-enriched compound of 14 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
33. A deuterium-enriched compound of claim 14 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
34. A deuterium-enriched compound of claim 14 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
35. A deuterium-enriched compound of claim 14 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
36. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 2 or a pharmaceutically acceptable salt form thereof.
37. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 3 or a pharmaceutically acceptable salt form thereof.
38. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 4 or a pharmaceutically acceptable salt form thereof.
39. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 5 or a pharmaceutically acceptable salt form thereof.
40. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 6 or a pharmaceutically acceptable salt form thereof.
41. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 7 or a pharmaceutically acceptable salt form thereof.
42. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 8 or a pharmaceutically acceptable salt form thereof.
43. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 9 or a pharmaceutically acceptable salt form thereof.
44. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 10 or a pharmaceutically acceptable salt form thereof.
45. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 11 or a pharmaceutically acceptable salt form thereof.
46. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 12 or a pharmaceutically acceptable salt form thereof.
47. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 13 or a pharmaceutically acceptable salt form thereof.
48. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 14 or a pharmaceutically acceptable salt form thereof.
49. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 15 or a pharmaceutically acceptable salt form thereof.
50. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 16 or a pharmaceutically acceptable salt form thereof.
51. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 19 or a pharmaceutically acceptable salt form thereof.
52. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 20 or a pharmaceutically acceptable salt form thereof.
53. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 21 or a pharmaceutically acceptable salt form thereof.
54. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 22 or a pharmaceutically acceptable salt form thereof.
55. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 23 or a pharmaceutically acceptable salt form thereof.
56. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 24 or a pharmaceutically acceptable salt form thereof.
57. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 25 or a pharmaceutically acceptable salt form thereof.
58. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 25 or a pharmaceutically acceptable salt form thereof.
59. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 27 or a pharmaceutically acceptable salt form thereof.
60. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 28 or a pharmaceutically acceptable salt form thereof.
61. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 29 or a pharmaceutically acceptable salt form thereof.
62. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 30 or a pharmaceutically acceptable salt form thereof.
63. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 31 or a pharmaceutically acceptable salt form thereof.
64. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 32 or a pharmaceutically acceptable salt form thereof.
65. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 33 or a pharmaceutically acceptable salt form thereof.
66. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 34 or a pharmaceutically acceptable salt form thereof.
67. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 35 or a pharmaceutically acceptable salt form thereof.
68. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 2 or a pharmaceutically acceptable salt form thereof.
69. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 3 or a pharmaceutically acceptable salt form thereof.
70. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 4 or a pharmaceutically acceptable salt form thereof.
71. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 5 or a pharmaceutically acceptable salt form thereof.
72. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 6 or a pharmaceutically acceptable salt form thereof.
73. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 7 or a pharmaceutically acceptable salt form thereof.
74. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 8 or a pharmaceutically acceptable salt form thereof.
75. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 9 or a pharmaceutically acceptable salt form thereof.
76. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 10 or a pharmaceutically acceptable salt form thereof.
77. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 11 or a pharmaceutically acceptable salt form thereof.
78. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 12 or a pharmaceutically acceptable salt form thereof.
79. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 13 or a pharmaceutically acceptable salt form thereof.
80. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 14 or a pharmaceutically acceptable salt form thereof.
81. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 15 or a pharmaceutically acceptable salt form thereof.
82. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 16 or a pharmaceutically acceptable salt form thereof.
83. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 19 or a pharmaceutically acceptable salt form thereof.
84. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 20 or a pharmaceutically acceptable salt form thereof.
85. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 21 or a pharmaceutically acceptable salt form thereof.
86. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 22 or a pharmaceutically acceptable salt form thereof.
87. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 23 or a pharmaceutically acceptable salt form thereof.
88. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 24 or a pharmaceutically acceptable salt form thereof.
89. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 25 or a pharmaceutically acceptable salt form thereof.
90. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 25 or a pharmaceutically acceptable salt form thereof.
91. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 27 or a pharmaceutically acceptable salt form thereof.
92. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 28 or a pharmaceutically acceptable salt form thereof.
93. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 29 or a pharmaceutically acceptable salt form thereof.
94. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 30 or a pharmaceutically acceptable salt form thereof.
95. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 31 or a pharmaceutically acceptable salt form thereof.
96. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 32 or a pharmaceutically acceptable salt form thereof.
97. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 33 or a pharmaceutically acceptable salt form thereof.
98. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 34 or a pharmaceutically acceptable salt form thereof.
99. A method for treating a disease selected from dyslipidaemia and/or combined hyperlipidemia comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 35 or a pharmaceutically acceptable salt form thereof.