Deuterium-enriched piperidinyl-methyl-purine amines and related compounds and their use in treating diseases and conditions
The invention provides deuterium-enriched piperidinyl-methyl-purine amines and related compounds, pharmaceutical compositions, their use for inhibiting NSD2, and their use in the treatment of a disease or condition, such as cancer.
1 . A compound represented by Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is H or D, provided that the abundance of deuterium in R 1 is at least 75%;
R 2 is H or D, provided that the abundance of deuterium in R 2 is at least 75%;
R 3 is H or D, provided that the abundance of deuterium in R 3 is at least 75%; and
R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , and R 21 are H.
2 . The compound of claim 1 , wherein the compound is represented by Formula I-A:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is H or D, provided that the abundance of deuterium in R 1 is at least 75%;
R 2 is H or D, provided that the abundance of deuterium in R 2 is at least 75%;
R 3 is H or D, provided that the abundance of deuterium in R 3 is at least 75%; and
R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , and R 21 are H.
3 . The compound of claim 2 , wherein the compound is a compound of Formula I-A.
4 . A compound selected from
and a pharmaceutically acceptable salt thereof.
5 . The compound of claim 4 , wherein the compound is
6 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
7 . A pharmaceutical composition comprising a compound of claim 4 and a pharmaceutically acceptable carrier.
8 . A pharmaceutical composition comprising a compound of claim 5 and a pharmaceutically acceptable carrier.
9 . A method for treating a disease or condition mediated by nuclear SET domain-containing protein 2 (NSD2), comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 to treat the disease or condition, wherein the disease or condition is prostate cancer or lung cancer.
10 . A method for treating a disease or condition mediated by nuclear SET domain-containing protein 2 (NSD2), comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 4 to treat the disease or condition, wherein the disease or condition is prostate cancer or lung cancer.
11 . A method for treating a disease or condition mediated by nuclear SET domain-containing protein 2 (NSD2), comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 5 to treat the disease or condition, wherein the disease or condition is prostate cancer or lung cancer.
12 . The method of claim 9 , wherein said disease or condition mediated by NSD2 is prostate cancer.
13 . The method of claim 10 , wherein said disease or condition mediated by NSD2 is prostate cancer.
14 . The method of claim 11 , wherein said disease or condition mediated by NSD2 is prostate cancer.
15 . The method of claim 9 , wherein said disease or condition mediated by NSD2 is lung cancer.
16 . The method of claim 10 , wherein said disease or condition mediated by NSD2 is lung cancer.
17 . The method of claim 11 , wherein said disease or condition mediated by NSD2 is lung cancer.
18 . The method of claim 10 , wherein said disease or condition mediated by NSD2 is non-small cell lung cancer.
19 . A method of inhibiting the activity of nuclear SET domain-containing protein 2 (NSD2), comprising contacting a NSD2 with an effective amount of a compound of claim 1 to inhibit the activity of said NSD2.
20 . A method of inhibiting the activity of nuclear SET domain-containing protein 2 (NSD2), comprising contacting a NSD2 with an effective amount of a compound of claim 4 to inhibit the activity of said NSD2.