DEUTERIUM-ENRICHED AMOXICILIN
The present application describes deuterium-enriched amoxicilin, 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 19 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 19 is at least 5%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 19 is selected from 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%, (k) 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 5 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 6 -R 9 is selected from at least 25%, at least 50%, at least 75%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 10 is selected from 100%.
6 . 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%, 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-5 of Table 1.
8 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 6-10 of Table 2.
9 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 19 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 19 is at least 5%.
10 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 1 -R 19 is selected from 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%, (k) at least 63%, at least 68%, at least 74%, at least 79%, at least 84%, at least 89%, at least 95%, and 100%.
11 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 1 -R 5 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
12 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 6 -R 9 is selected from at least 25%, at least 50%, at least 75%, and 100%.
13 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 10 is selected from 100%.
14 . An isolated deuterium-enriched compound of claim 9 , wherein the compound is selected from compounds 1-5 of Table 1.
15 . An isolated deuterium-enriched compound of claim 9 , wherein the compound is selected from compounds 6-10 of Table 2.
16 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 19 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 19 is at least 5%.
17 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 1-5 of Table 1.
18 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 6-10 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 treatment of infections of the ear, nose, and throat, the genitourinary tract, the skin and skin structure, and the lower respiratory tract due to susceptible (only b-lactamase-negative) strains of Streptococcus spp. (a- and b-hemolytic strains only), S. pneumoniae, Staphylococcus spp., H. influenzae, E. coli, P. mirabilis , or E. faecalis , and/or acute, uncomplicated gonorrhea (ano-genital and urethral infections) due to N. gonorrhoeae 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.