DEUTERIUM-ENRICHED OCTREOTIDE
The present application describes deuterium-enriched octreotide, 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 66 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 66 is at least 2%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 66 is selected from at least 2%, at least 3%, at least 8%, at least 12%, at least 17%, at least 21%, at least 26%, at least 30%, at least 35%, at least 39%, at least 44%, at least 48%, at least 53%, at least 58%, at least 62%, at least 67%, at least 71%, at least 76%, at least 80%, at least 85%, at least 89%, at least 94%, at least 98%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 15 is selected from at least 7%, at least 13%, at least 20%, at least 27%, at least 33%, at least 40%, at least 47%, at least 53%, at least 60%, at least 67%, at least 73%, at least 80%, at least 87%, at least 93%, and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 19 -R 23 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 30 -R 34 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 38 -R 42 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 44 -R 51 is selected from at least 13%, at least 25%, at least 38%, at least 50%, at least 63%, at least 75%, at least 88%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 52 -R 56 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 60 -R 65 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
10 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-8 of Table 1.
11 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 9-16 of Table 2.
12 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 66 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 66 is at least 2%.
13 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 1 -R 66 is selected from at least 2%, at least 3%, at least 8%, at least 12%, at least 17%, at least 21%, at least 26%, at least 30%, at least 35%, at least 39%, at least 44%, at least 48%, at least 53%, at least 58%, at least 62%, at least 67%, at least 71%, at least 76%, at least 80%, at least 85%, at least 89%, at least 94%, at least 98%, and 100%.
14 . An isolated deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 1-8 of Table 1.
15 . An isolated deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 9-16 of Table 2.
16 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 66 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 66 is at least 2%.
17 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 1-8 of Table 1.
18 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 9-16 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 acromegaly 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.