2',6'-DIOXO-3'-DEUTERO-PIPERDIN-3-YL-ISOINDOLINE COMPOUNDS
The present application describes 2-(2′,6′-dioxo-3′-deutero-piperidin-3′-yl)isoindoles, deuterated derivatives thereof, stereoisomers thereof, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.
1 - 3 . (canceled)
4 . A deuterium-enriched compound having the following formula or a stereoisomer or pharmaceutically acceptable salt thereof:
wherein:
R 8 is selected from H and D;
R 8a is —OR 12a
one of X and Y is C═O and the other is selected from CH 2 , CHD, and CD 2 C═O;
Z is H or D, provided that the abundance of deuterium in Z is at least 30%;
R 1 -R 7 are independently selected from H and D;
R 12a is CH 2 —R a —R b —R c ;
R a is selected from aryl, (C 1 -C 6 )heterocycloalkyl, and (C 2 -C 9 )heteroaryl, wherein R a is optionally substituted with 1-3 halogen;
R b is selected from (CH 2 ) m , O(CH 2 ) m , and (CH 2 ) m O;
m is selected from 0-3;
R c is selected from aryl, (C 1 -C 6 )heterocycloalkyl, and (C 2 -C 9 )heteroaryl;
wherein a hydrogen atom present in any of the substituents is optionally replaced by deuterium.
5 - 24 . (canceled)
25 . The deuterium-enriched compound of claim 4 , wherein X is C═O.
26 . The deuterium-enriched compound of claim 4 , wherein R a is aryl.
27 . The deuterium-enriched compound of claim 25 , wherein R a is aryl.
28 . The deuterium-enriched compound of claim 26 , wherein said aryl is phenyl.
29 . The deuterium-enriched compound of claim 27 , wherein said aryl is phenyl.
30 . The deuterium-enriched compound of claim 27 , wherein R b is (CH 2 ) m .
31 . The deuterium-enriched compound of claim 29 , wherein R b is (CH 2 ) m .
32 . The deuterium-enriched compound of claim 27 , wherein R c is (C 1 -C 6 )heterocycloalkyl.
33 . The deuterium-enriched compound of claim 30 , wherein R c is (C 1 -C 6 )heterocycloalkyl.
34 . The deuterium-enriched compound of claim 31 , wherein R c is (C 1 -C 6 )heterocycloalkyl.
35 . The deuterium-enriched compound of claim 33 , wherein (C 1 -C 6 )heterocycloalkyl is morpholinyl.
36 . The deuterium-enriched compound of claim 34 , wherein (C 1 -C 6 )heterocycloalkyl is morpholinyl.
37 . The deuterium-enriched compound of claim 33 , wherein the abundance of deuterium in Z is at least 90%.
38 . The deuterium-enriched compound of claim 34 , wherein the abundance of deuterium in Z is at least 90%.
39 . The deuterium-enriched compound of claim 36 , wherein the abundance of deuterium in Z is at least 90%.
40 . The deuterium-enriched compound of claim 33 , wherein R 1 -R 7 are H, and R 8 is H.
41 . The deuterium-enriched compound of claim 34 , wherein R 1 -R 7 are H, and R 8 is H.
42 . The deuterium-enriched compound of claim 36 , wherein R 1 -R 7 are H, and R 8 is H.
43 . The deuterium-enriched compound of claim 39 , wherein R 1 -R 7 are H, and R 8 is H.
44 . A pharmaceutical composition comprising a deuterium-enriched compound of claim 1 and one or more excipients.
45 . A pharmaceutical composition comprising a deuterium-enriched compound of claim 33 and one or more excipients.
46 . A pharmaceutical composition comprising a deuterium-enriched compound of claim 34 and one or more excipients.
47 . A pharmaceutical composition comprising a deuterium-enriched compound of claim 43 and one or more excipients.
48 . A method of treating systemic lupus erythematosus, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 to treat systemic lupus erythematosus.
49 . The method of claim 48 , wherein the compound is a compound of claim 33 .
50 . The method of claim 48 , wherein the compound is a compound of claim 43 .
51 . A method of treating a disorder selected from the group consisting of scleroderma and sarcoidosis, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 to treat the disorder.