DEUTERIUM-ENRICHED BUPRENORPHINE
The present application describes deuterium-enriched buprenorphine, 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 4 , are independently selected from H and D; and
the abundance of deuterium in R 1 -R 41 is at least 2% provided that when R 27 and R 29 are D, then at least one other R is D; and provided that when R 35 -R 36 and R 38 -R 39 are D, then at least one other R is D.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 41 is selected from at least 2%, provided that when R 27 and R 29 are D, then at least one other R is D. The abundance can also be at least 5%, at least 10%, at least 15%, at least 20%, at least 24%, at least 29%, at least 34%, at least 39%, at least 44%, at least 49%, at least 54%, at least 59%, at least 63%, at least 68%, at least 73%, at least 78%, at least 83%, at least 88%, at least 93%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 is selected from at least 50% and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 10 and R 26 -R 34 is selected from at least 6%, provided that when R 27 and R 29 are D, then at least one other R is D. The abundance can also be at least 12%, at least 18%, at least 24%, at least 29%, at least 35%, at least 41%, at least 47%, at least 53%, at least 59%, at least 65%, at least 71%, at least 76%, at least 82%, at least 88%, at least 94%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 11 -R 19 is selected from at least 11%, at least 22%, at least 33%, at least 44%, at least 56%, at least 67%, at least 78%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 20 -R 22 is selected from at least 33%, at least 67%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 23 -R 25 is selected from at least 33%, at least 67%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 35 -R 41 is selected from at least 14%, provided that when R 35 -R 36 and R 38 -R 39 are D, then at least one other R is D. The abundance can also be at least 29%, at least 43%, at least 57%, at least 71%, at least 86%, and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-7 of Table 1.
10 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 8-14 of Table 2.
11 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 41 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 41 is at least 2% provided that when R 27 and R 29 are D, then at least one other R is D; and provided that when R 35 -R 36 and R 38 -R 39 are D, then at least one other R is D.
12 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 1 -R 41 is selected from at least 2%, provided that when R 27 and R 29 are D, then at least one other R is D. The abundance can also be at least 5%, at least 10%, at least 15%, at least 20%, at least 24%, at least 29%, at least 34%, at least 39%, at least 44%, at least 49%, at least 54%, at least 59%, at least 63%, at least 68%, at least 73%, at least 78%, at least 83%, at least 88%, at least 93%, and 100%.
13 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 1 -R 2 is selected from at least 50% and 100%.
14 . An isolated deuterium-enriched compound of claim 11 , wherein the compound is selected from compounds 1-7 of Table 1.
15 . An isolated deuterium-enriched compound of claim 11 , wherein the compound is selected from compounds 8-14 of Table 2.
16 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 41 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 41 is at least 2% provided that when R 27 and R 29 are D, then at least one other R is D; and provided that when R 35 -R 36 and R 38 -R 39 are D, then at least one other R is D.
17 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 1-7 of Table 1.
18 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 8-14 of Table 2.
19 . 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.
20 . A method for treating a disease selected from moderate to severe pain, peri-operative analgesia, and/or opioid dependence 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.