Migrastatin analogs and uses thereof
The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof, compositions thereof, and methods for the use thereof in the treatment of various disorders including cancer, metastasis and disorders involving increased angiogenesis, wherein R 1 -R 6 , R a -R c , Q, Y 1 , Y 2 and n are as defined herein.
1. A compound of formula:
or a pharmaceutically acceptable salt thereof;
wherein X 1 is CH 2 , NH or O;
Y 1 and Y 2 are independently OH, C(R Y ) 3 or Y 1 and Y 2 taken together with the carbon atom to which they are attached are —C═O, wherein R Y is halo;
the bond is a single bond or a double bond;
R 3 is lower alkyl;
R 4 is OH;
R 5 is H or lower alkyl; and
R 6 is H or lower alkyl.
2. The compound of claim 1 , wherein X 1 is O.
3. The compound of claim 1 , wherein the bond is a single bond.
4. The compound of claim 1 , wherein Y 1 and Y 2 taken together with the carbon atom to which they are attached are —C═O.
5. The compound of claim 1 , wherein R 3 is methyl.
6. The compound of claim 1 , wherein R 5 is methyl.
7. The compound of claim 1 , wherein R 6 is methyl.
8. The compound of claim 2 , wherein Y 1 and Y 2 taken together with the carbon atom to which they are attached are —C═O.
9. The compound of claim 8 , wherein the bond is a single bond.
10. The compound of claim 9 , wherein R 3 , R 5 , and R 6 are lower alkyl.
11. A compound selected from: