Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the same
Provided are 4′-arylmethoxy isoindoline compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.
1. A compound of formula (I):
or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
X is C═0 or CH 2 ;
R 1 is —Y—R 3 ;
R 2 is H or (C 1 -C 6 )alkyl;
Y is: 6 to 10 membered aryl optionally substituted with one or more halogen;
R 3 is: —(CH 2 ) n -aryl, —O—(CH 2 ) n -aryl or —(CH 2 ) n —O-aryl, wherein the aryl is optionally substituted with one or more: (C 1 -C 6 )alkyl, itself optionally substituted with one or more halogen; (C 1 -C 6 )alkoxy, itself substituted with one or more halogen; oxo; amino; carboxyl; cyano; hydroxyl; halogen; 6 to 10 membered aryl or heteroaryl, optionally substituted with one or more (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or halogen; —CONH 2 ; or —COO—(C 1 -C 6 )alkyl, wherein the alkyl may be optionally substituted with one or more halogen;
—(CH 2 ),-heterocycle, —O—(CH 2 ) n -heterocycle or —(CH 2 ) n , —O-heterocycle, wherein the heterocycle is optionally substituted with one or more: (C 1 -C 6 )alkyl, itself optionally substituted with one or more halogen; (C 1 -C 6 )alkoxy, itself substituted with one or more halogen; oxo; amino; carboxyl; cyano; hydroxyl; halogen; 6 to 10 membered aryl or heteroaryl, optionally substituted with one or more (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or halogen; —CONH 2 ; or —COO—(C 1 -C 6 )alkyl, wherein the alkyl may be optionally substituted with one or more halogen; or
—(CH 2 ) n -heteroaryl, —O—(CH 2 ) n -heteroaryl or —(CH 2 ) n —O-heteroaryl, wherein the heteroaryl is optionally substituted with one or more: (C 1 -C 6 )alkyl, itself optionally substituted with one or more halogen; (C 1 -C 6 )alkoxy, itself substituted with one or more halogen; oxo; amino; carboxyl; cyano; hydroxyl; halogen; 6 to 10 membered aryl or heteroaryl, optionally substituted with one or more (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or halogen; —CONH 2 ; or —COO—(C 1 -C 6 )alkyl, wherein the alkyl may be optionally substituted with one or more halogen; and
n is 0, 1, 2 or 3.
2. The compound of claim 1 , wherein X is CH 2 .
3. The compound of claim 1 , wherein Y is phenyl, and R 3 is —(CH 2 ) n -heterocycle.
4. The compound of claim 1 , which is:
or a pharmaceutically acceptable salt or stereoisomer thereof.
5. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof.
6. A deuterium-enriched compound of the formula:
or a pharmaceutically acceptable salt or stereoisomer thereof.
7. A pharmaceutical composition comprising a compound of claim 6 , or a pharmaceutically acceptable salt or stereoisomer thereof.