Isoindole-imide compounds, compositions, and uses thereof
The invention relates to isoindole-imide compounds and pharmaceutically acceptable salts, hydrates, solvates, clathrates, enantiomers, diastereomers, racemates, or mixtures of stereoisomers thereof, pharmaceutical compositions comprising these isoindole-imide compounds, and methods for reducing the level of cytokines and their precursors in mammals. In particular, the invention pertains to isoindole-imide compounds that are potent inhibitors of the production of TNF-α in mammals. The isoindole-imides described herein are useful for treating or preventing diseases or disorders in mammals, for example, cancers, such as solid tumors and blood-born tumors; heart disease, such as congestive heart failure; osteoporosis; and genetic, inflammatory; allergic; and autoimmune diseases.
1. A compound of the formula:
or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
X is CH 2 or C═O;
n is 0 or 1;
R 1 is C(O)R 3 ;
R 2 is H or methyl; and
R 3 is: (C 1 -C 8 )alkyl, optionally substituted with one or more substituents selected from a group consisting of halogen, N 3 , —S—(C 1 -C 8 )alkyl, aryl and OH; or
aryl, optionally substituted with one or more substituents selected from a group consisting of (C 1 -C 8 )alkyl, —O—(C 1 -C 8 )alkyl, halogen, CF 3 and NO 2 .
2. The compound of claim 1 , wherein X is CH 2 .
3. The compound of claim 1 , wherein R 3 is (C 1 -C 8 )alkyl, optionally substituted with one or more substituents selected from a group consisting of halogen, N 3 , —S—(C 1 -C 8 )alkyl, aryl and OH.
4. The compound of claim 3 , wherein the compound is:
5. The compound of claim 1 , wherein R 3 is aryl, optionally substituted with one or more substituents selected from a group consisting of (C 1 -C 8 )alkyl, —O—(C 1 -C 8 )alkyl, halogen, CF 3 and NO 2 .
6. The compound of claim 5 , wherein R 3 is phenyl, optionally substituted with one or more substituents selected from a group consisting of (C 1 -C 8 )alkyl, —O—(C 1 -C 8 )alkyl, halogen, CF 3 and NO 2 .
7. The compound of claim 6 , wherein the compound is:
8. A compound, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the compound is: