DEUTERIUM-ENRICHED LINEZOLID
The present application describes deuterium-enriched linezolid, 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 20 are independently selected from H and D; and the abundance of deuterium in R 1 -R 20 is at least 5%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 20 is selected from at least 5% , at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 is 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 4 is selected from at least 33%, at least 67%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 10 -R 12 is selected from at least 33%, at least 67%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 5 -R 9 and R 13 -R 20 is selected from at least 8%, at least 15%, at least 23%, at least 31%, at least 38%, at least 46%, at least 54%, at least 62%, at least 69%, at least 77%, at least 85%, at least 92%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 and R 2 -R 4 is selected from at least 25%, at least 50%, at least 75%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 and R 10 -R 12 is selected from at least 25%, at least 50%, at least 75%, and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 , R 5 -R 9 , and R 13 -R 20 is selected from at least 7% , at least 14%, at least 21%, at least 29%, at least 36%, at least 43%, at least 50%, at least 57%, at least 64%, at least 71%, at least 79%, at least 86%, at least 93%, and 100%.
10 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 4 and R 10 -R 12 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
11 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 4 , R 5 -R 9 and R 13 -R 20 is selected from at least 6% , at least 13%, at least 19%, at least 25%, at least 31%, at least 38%, at least 44%, at least 50%, at least 56%, at least 63%, at least 69%, at least 75%, at least 81%, at least 88%, at least 94%, and 100%.
12 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 5 -R 9 , R 10 -R 12 , and R 13 -R 20 is selected from at least 6%, at least 13%, at least 19%, at least 25%, at least 31%, at least 38%, at least 44%, at least 50%, at least 56%, at least 63%, at least 69%, at least 75%, at least 81%, at least 88%, at least 94%, and 100%.
13 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 , R 2 -R 4 and R 10 -R 12 is selected from at least 14%, at least 29%, at least 43%, at least 57%, at least 71%, at least 86%, and 100%.
14 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 , R 2 -R 4 , R 5 -R 9 , and R 13 -R 20 is selected from at least 6%, 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%.
15 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 , R 5 -R 9 , R 10 -R 12 , and R 13 -R 20 is selected from at least 6%, 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%.
16 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 4 , R 5 -R 9 , R 10 -R 12 , and R 13 -R 20 is selected from at least 5%, at least 11% 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%.
17 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-11 of Table 1.
18 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 12-23 of Table 2.
19 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 20 are independently selected from H and D; and the abundance of deuterium in R 1 -R 20 is at least 5%.
20 . An isolated deuterium-enriched compound of claim 19 , wherein the compound is selected from compounds 1-11 of Table 1.
21 . An isolated deuterium-enriched compound of claim 19 , wherein the compound is selected from compounds 12-23 of Table 2.
22 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 20 are independently selected from H and D; and the abundance of deuterium in R 1 -R 20 is at least 5%.
23 . A mixture of deuterium-enriched compounds of claim 22 , wherein the compounds are selected from compounds 1-11 of Table 1.
24 . A mixture of deuterium-enriched compounds of claim 22 , wherein the compounds are selected from compounds 12-23 of Table 2.
25 . 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.
26 . A method for treating infections caused by multi-resistant 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.