Nuclear transport modulators and uses thereof
The present invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the compounds of formula I or their pharmaceutically acceptable salts, and methods of using said compounds, salts and compositions in the treatment of various disorders associated with CRM1 activity.
1 . A pharmaceutical composition comprising a compound represented by structural formula IV:
or a pharmaceutically acceptable salt thereof, wherein:
R 2 is selected from optionally substituted heteroaryl and a pharmaceutically acceptable carrier.
2 . The pharmaceutical composition of claim 1 , wherein R 2 is an optionally substituted 5-6-membered heteroaryl having 1, 2 or 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur.
3 . The pharmaceutical composition of claim 2 , wherein R 2 is an optionally substituted 5-membered heteroaryl having 1, 2 or 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur.
4 . The pharmaceutical composition of claim 3 , wherein R 2 is an optionally substituted pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, or oxadiazolyl.
5 . The pharmaceutical composition of claim 2 , wherein R 2 is an optionally substituted 6-membered heteroaryl having 1, 2 or 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur.
6 . The pharmaceutical composition of claim 5 , wherein R 2 is an optionally substituted pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl or triazinyl.
7 . The pharmaceutical composition of claim 1 , wherein R 2 is optionally substituted with 1, 2 or 3 substituents independently selected from halogen, C 1 -C 4 alkyl, halo-C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 thioalkoxy, hydroxyl, amino, C 1 -C 4 alkylamino, C 1 -C 4 dialkylamino, sulfhydryl, cyano, C 6 aryl and C 5 -C 6 heteroaryl.
8 . The pharmaceutical composition of claim 7 , wherein R 2 is optionally substituted with 1, 2 or 3 substituents independently selected from fluoro, chloro, C 1 -C 4 alkyl, —CF 3 , amino and cyano.
9 . A method for treating a cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition of claim 1 , wherein the cancer is selected from multiple myeloma, diffuse large B-cell lymphoma, acute myeloid leukemia and follicular lymphoma.
10 . A method for promoting wound healing in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition of claim 2 .
11 . The method of claim 9 , wherein the cancer is multiple myeloma.
12 . The method of claim 9 , wherein the cancer is diffuse large B-cell lymphoma.
13 . The method of claim 9 , wherein the pharmaceutical composition is administered orally.
14 . A method for treating a cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition of claim 2 , wherein the cancer is prostate cancer.
15 . The method of claim 14 , wherein the pharmaceutical composition is administered orally.
16 . A method for treating myelodysplastic syndrome, the method comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition of claim 1 .
17 . The method of claim 16 , wherein the pharmaceutical composition is administered orally.