DEUTERIUM-ENRICHED TIGECYCLINE
The present application describes deuterium-enriched tigecycline, 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 39 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 39 is at least 3%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 39 is selected from at least 3%, at least 5%, at least 11%, at least 16%, at least 21%, at least 26%, at least 32%, at least 37%, at least 42%, at least 47%, at least 53%, at least 58%, at least 63%, at least 68%, at least 74%, at least 79%, at least 84%, at least 89%, at least 95%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 8 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%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 9 -R 19 is selected from at least 9%, at least 18%, at least 27%, at least 36%, at least 45%, at least 56%, at least 64%, at least 73%, at least 82%, at least 91%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 20 and R 27 -R 33 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%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 21 -R 26 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 34 -R 39 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds I-6 of Table 1.
9 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 7-12 of Table 2.
10 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 39 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 39 is at least 3%.
11 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 1 -R 39 is selected from at least 3%, at least 5%, at least 11%, at least 16%, at least 21%, at least 26%, at least 32%, at least 37%, at least 42%, at least 47%, at least 53%, at least 58%, at least 63%, at least 68%, at least 74%, at least 79%, at least 84%, at least 89%, at least 95%, and 100%.
12 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 1 -R 8 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%.
13 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 9 -R 19 is selected from at least 9%, at least 18%, at least 27%, at least 36%, at least 45%, at least 56%, at least 64%, at least 73%, at least 82%, at least 91%, and 100%.
14 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 20 and R 27 -R 33 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%.
15 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 21 -R 26 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
16 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 34 -R 39 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
17 . An isolated deuterium-enriched compound of claim 10 , wherein the compound is selected from compounds 1-6 of Table 1.
18 . An isolated deuterium-enriched compound of claim 10 , wherein the compound is selected from compounds 7-12 of Table 2.
19 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 39 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 39 is at least 3%.
20 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 1 -R 39 is selected from at least 3%, at least 5%, at least 11%, at least 16%, at least 21%, at least 26%, at least 32%, at least 37%, at least 42%, at least 47%, at least 53%, at least 58%, at least 63%, at least 68%, at least 74%, at least 79%, at least 84%, at least 89%, at least 95%, and 100%.
21 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 1 -R 8 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%.
22 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 9 -R 19 is selected from at least 9%, at least 18%, at least 27%, at least 36%, at least 45%, at least 56%, at least 64%, at least 73%, at least 82%, at least 91%, and 100%.
23 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 20 and R 27 -R 33 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%.
24 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 21 -R 26 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
25 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 34 -R 39 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
26 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 1-6 of Table 1.
27 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 7-12 of Table 2.
28 . 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.
29 . A method for treating a disease selected from Gram-positive bacteria and/or Gram-negative bacteria 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.