4′-O-substituted isoindoline derivatives and compositions comprising and methods of using the same
Provided are 4′-O substituted 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:
or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
Y is C=O or CH 2 ; and
R 1 is heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl or heterocyclylcarbonyl;
and where R 1 is optionally substituted with one or more groups selected from alkoxy, halo, alkyl, carboxy, alkylaminocarbonyl, alkoxycarbonyl, nitro, amine, nitrile, haloalkyl, hydroxy, and alkylsulfonyl.
2. The compound of claim 1 , wherein Y is C=O.
3. The compound of claim 1 , wherein Y is CH 2 .
4. The compound of claim 1 , wherein R 1 is heteroarylalkyl.
5. The compound of claim 1 , wherein the aryl group in R 1 is a 5 or 6 membered monocyclic heteroaryl group containing 1-3 heteroatoms selected from O, N and S.
6. The compound of claim 1 , wherein the heteroayl group in R 1 is a bicyclic heteroaryl group.
7. The compound of claim 1 , wherein R 1 is substituted with one or more substituents selected from alkoxy, halo, alkyl and alkylsulfonyl.
8. The compound of claim 1 , wherein R 1 substituted with one or two substituents selected from methoxy, chloro, bromo, fluoro, methyl and methylsulfonyl.
9. The compound of claim 1 , wherein R 1 is substituted with one or more substituents selected from nitro, amino, haloalkyl, nitrile, or hydroxy.
10. The compound of claim 1 , wherein R 1 is quinolymethyl benzofurylmethyl, benzothienylmethyl, furylmethyl or thienylmethyl.
11. The compound of claim 1 , wherein R 1 is 3 -quinolylmethyl, 2-quinolylmethyl, 2-benzofurylmethyl, 2-benzothienylmethyl, 3-chlorothien-2-ylmethyl, 4-fluorobenzothien-2-ylmethyl, 2-furylmethyl, or 5-chlorothien-2-ylmethyl.
12. The compound of claim 1 , wherein the compound has formula:
and wherein R 5 is heteroaryl, optionally substituted with one, two or three groups seleted from alkyl, halo, alkoxy, carboxy, alkylaminocarbonyl, alkoxycarbonyl, nitro, amine, nitrile, haloalkyl, hydroxy, and alkylsulfonyl; and n 1 is 0-5.
13. The compound of claim 12 , wherein R 5 is selected from furyl, thienyl, benzofuryl, benzothienyl and quinolyl, optionally substituted with one or two groups selected from methyl, methoxy, chloro, fluoro, bromo and methylsulfonyl.
14. The compound of claim 12 , wherein the compound has formula
15. The compound of claim 1 , selected from:
and pharmaceutically acceptable salts or stereoisomers thereof.
16. The compound of claim 1 , selected from:
and pharmaceutically acceptable salts or stereoisomers thereof.
17. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof.
18. A single unit dosage form comprising a compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof.
19. The single unit dosage form of claim 18 , which is suitable for oral or parenteral administration.
20. The single unit dosage form of claim 19 , which is suitable for oral administration.
21. The single unit dosage form of claim 20 , which is a tablet or a capsule.