Migrastatins and uses thereof
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
1. A compound of formula I:
or a pharmaceutically acceptable salt thereof; wherein:
i. R 1 is hydrogen and is a single bond; or
ii. R 1 is C 1-3 aliphatic optionally substituted with one or more halogens and is a (Z)—double bond; and
R 2 is C 1-3 aliphatic;
R 3 and R 5 are each independently —C 1-3 aliphatic; and
R 4 is-T-Y;
-T- is a C 1-3 bivalent saturated or unsaturated, straight or branched, hydrocarbon chain; and
—Y is selected from —CO 2 R or —C(O)N(R) 2 ; wherein
each R is independently —H or C 1-3 aliphatic.
2. The compound of claim 1 , wherein
i. is a (Z)— double bond and R 1 is C 1-3 aliphatic substituted with one or more halogens; or
ii. R 4 is -T-Y wherein -T- is CH 2 .
3. The compound of claim 2 , wherein
i. R 1 is —CF 3 ; or
ii. R 4 is -T-Y wherein -T- is CH 2 and —Y is —CO 2 H.
4. The compound of claim 1 , wherein the compound is of formula II:
or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen.
5. The compound of claim 1 , wherein the compound is of formula II-a:
or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen.
6. The compound of claim 1 , wherein R 1 is hydrogen R 4 is -T-Y wherein -T- is —CH 2 —, and is a single bond.
7. The compound of claim 1 , wherein R 1 is C 1-3 aliphatic substituted with one or more halogens, R 4 is -T-Y wherein -T- is —CH 2 —, and is a (Z)— double bond.
8. The compound of claim 1 , wherein R 1 is C 1-3 aliphatic, R 4 is -T-Y wherein -T- is —CH 2 —, and is a (Z)—double bond.
9. The compound of claim 7 , wherein R 1 is —CF 3 .
10. The compound of claim 8 , wherein R 1 is methyl.
11. The compound of claim 1 , wherein the compound is selected from:
or a pharmaceutically acceptable salt thereof.
12. A pharmaceutical composition comprising a compound of claim 1 or 11 and a pharmaceutically acceptable carrier.
13. A compound selected from:
or a pharmaceutically acceptable salt thereof.
14. The compound of claim 1 , wherein the compound is of formula III:
or a pharmaceutically acceptable salt thereof, wherein R 1 is C 1-3 aliphatic substituted with one or more halogens.
15. The compound of claim 1 , wherein the compound is of formula IV:
or a pharmaceutically acceptable salt thereof, wherein R 1 is C 1-3 aliphatic.
16. The compound of claim 1 , wherein the compound is of formula III-a:
or a pharmaceutically acceptable salt thereof, wherein R 1 is C 1-3 aliphatic substituted with one or more halogens.
17. The compound of claim 1 , wherein the compound is of formula IV-a:
or a pharmaceutically acceptable salt thereof, wherein R 1 is C 1-3 aliphatic.
18. The compound of claim 4 , having the structure depicted below:
or a pharmaceutically acceptable salt thereof.
19. The compound of claim 4 , having the structure depicted below:
or a pharmaceutically acceptable salt thereof.
20. The compound of claim 4 , having the structure depicted below:
or a pharmaceutically acceptable salt thereof.
21. The compound of claim 14 , wherein R 1 is —CF 3 .
22. The compound of claim 21 , having the structure depicted below:
or a pharmaceutically acceptable salt thereof.
23. The compound of claim 15 , wherein R 1 is methyl.
24. The compound of claim 23 , having the structure depicted below:
or a pharmaceutically acceptable salt thereof.
25. A pharmaceutical composition comprising a compound of claim 13 and a pharmaceutically acceptable carrier.