DEUTERIUM-ENRICHED SILDENAFIL
The present application describes deuterium-enriched sildenafil, 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 30 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 30 is at least 3%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 30 is selected from at least 3%, at least 7%, , at least 13%, etc. 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%.
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 5 -R 6 is selected from at least 50% and at least 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 3 and R 7 -R 30 is selected from at least 4%, at least 8%, at least 15%, at least 23%, at least 31%, at least 38%, at least 46%, at least 50%, at least 58%, at least 65%, at least 73%, at least 81%, at least 88%, at least 96%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 and R 5 -R 6 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 1 , R 2 -R 3 , and R 7 -R 30 is selected from at least 4%, at least 7%, at least 15%, at least 22%, at least 30%, at least 37%, at least 44%, at least 52%, at least 59%, at least 67%, at least 74%, at least 81%, at least 89%, at least 96%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 3 , R 5 -R 6 , and R 7 -R 30 is selected from at least 4%, 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 92%, and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 4 is selected from at least 50%, and 100%.
10 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 5 -R 11 is selected from at least 14%, at least 29%, at least 43%, at least 57%, at least 71%, at least 86%, and 100%.
11 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 12 -R 14 is selected from at least 33%, at least 67%, and 100%.
12 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 26 -R 30 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
13 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 15 -R 22 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%.
14 . 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%.
15 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-13 of Table 1.
16 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 14-26 of Table 2.
17 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 30 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 30 is at least 3%.
18 . An isolated deuterium-enriched compound of claim 17 , wherein the compound is selected from compounds 1-3 of Table 1.
19 . An isolated deuterium-enriched compound of claim 17 , wherein the compound is selected from compounds 14-26 of Table 2.
20 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 30 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 30 is at least 3%.
21 . A mixture of deuterium-enriched compounds of claim 20 , wherein the compounds are selected from compounds 1-13 of Table 1.
22 . A mixture of deuterium-enriched compounds of claim 20 , wherein the compounds are selected from compounds 14-26 of Table 2.
23 . 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.
24 . A method for treating a disease selected from male erectile dysfunction and pulmonary arterial hypertension 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.