Isoindolinone compounds, and uses thereof

1 . A compound represented by structural formula (I):

or a pharmaceutically acceptable salt thereof,

wherein:

the moiety

 is C 3-8 cycloalkyl optionally substituted with 1 to 6 R a , 4 to 10 membered monocyclic or bicyclic heterocyclyl optionally substituted with 1 to 6 R a , having 1 to 3 heteroatoms selected from N, O, and S;

each R a is independently selected from hydrogen, halogen, hydroxyl, nitro, cyano, amino, mercapto, —COOH, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyloxy, C 2 -C 6 alkynyloxy, C 2 -C 6 alkanoyl, C 2 -C 6 alkylester, C 1 -C 6 thioalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, hydroxyC 1 -C 6 alkyl, aminoC 1 -C 6 alkyl, (mono- and di-C 1 -C 6 alkylamino)C 0 -C 4 alkyl, —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), —O—C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), —C 0 -C 4 alkyl-(phenyl), —C 0 -C 4 alkylOC(O)OC 1 -C 6 alkyl, —C 0 -C 4 alkylOC(O)C 1 -C 6 alkyl, —C 0 -C 4 alkylC(O)OC 1 -C 6 alkyl, C 0 -C 4 alkyl-(4- to 7-membered heterocycloalkyl) having 1, 2, or 3 heteroatoms independently chosen from N, O, and S, and C 0 -C 4 alkyl-(5- or 6-membered unsaturated or aromatic heterocycle) having 1, 2, or 3 heteroatoms independently chosen from N, O, and S, —C(O)OR 11 , —C 0 -C 4 alkylNR 11 R 12 , —C(O)NR 11 R 12 , —SO 2 R 11 , —SO 2 NR 11 R 12 , —OC(O)R 11 , and —C(NR 11 )NR 11 R 12 , wherein R 11 and R 12 are independently chosen from hydrogen, C 1 -C 6 alkyl, —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), and —O—C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl);

and wherein when moiety

 bears greater than or equal to two R a , two R a are optionally taken together with atoms to which they are bound to form a carbocyclyl or heterocyclyl ring;

the moiety

 is 6 to 18 membered aryl optionally substituted with 1 to 6 R b , 5 to 18 membered heteroaryl optionally substituted with 1 to 6 R b , having 1 to 3 heteroatoms selected from N, O, and S, each R b is independently selected from hydrogen, halogen, hydroxyl, nitro, cyano, amino, mercapto, —COOH, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyloxy, C 2 -C 6 alkynyloxy, C 2 -C 6 alkanoyl, C 2 -C 6 alkylester, C 1 -C 6 thioalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, hydroxyC 1 -C 6 alkyl, aminoC 1 -C 6 alkyl, (mono- and di-C 1 -C 6 alkylamino)C 0 -C 4 alkyl, —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), —O—C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), —C 0 -C 4 alkyl-(phenyl), —C 0 -C 4 alkylOC(O)OC 1 -C 6 alkyl, —C 0 -C 4 alkylOC(O)C 1 -C 6 alkyl, —C 0 -C 4 alkylC(O)OC 1 -C 6 alkyl, C 0 -C 4 alkyl-(4- to 7-membered heterocycloalkyl) having 1, 2, or 3 heteroatoms independently chosen from N, O, and S, and C 0 -C 4 alkyl-(5- or 6-membered unsaturated or aromatic heterocycle) having 1, 2, or 3 heteroatoms independently chosen from N, O, and S, —C(O)OR 11 , —C 0 -C 4 alkylNR 11 R 12 , —C(O)NR 11 R 12 , —SO 2 R 11 , —SO 2 NR 11 R 12 , —OC(O)R 11 , and —C(NR 11 )NR 11 R 12 , wherein R 11 and R 12 are independently chosen from hydrogen, C 1 -C 6 alkyl, —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), and —O—C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl);

and wherein when moiety

 bears greater than or equal to two R b , two R b are optionally taken together with atoms to which they are bound to form a carbocyclyl or heterocyclyl ring.

2 . The compound of claim 1 , wherein the compound is a compound represented by structural formula (I-1) or (I-2)

or a pharmaceutically acceptable salt thereof;

wherein

moiety

 and moiety

 are as defined in claim 1 .

3 . The compound of claim 1 , wherein the moiety

is selected from the group consisting of

wherein:

n, for each occurrence, is independently 0, 1, 2, 3, 4, 5, or 6;

X 1 , for each occurrence, is independently C, N, O, or S;

X 2 , for each occurrence, is independently C, N, O, or S;

X 3 , for each occurrence, is independently C, N, O, or S;

X 4 , for each occurrence, is independently C, N, O, or S;

X 5 , for each occurrence, is independently C, N, O, or S;

X 6 , for each occurrence, is independently C, N, O, or S; and

R a is as defined in claim 1 .

4 . The compound of claim 3 , wherein the moiety

is

wherein:

n, for each occurrence, is independently 0, 1, 2, 3, 4, 5, or 6;

X 1 , for each occurrence, is independently C, N, O, or S;

X 2 , for each occurrence, is independently C, N, O, or S;

X 3 , for each occurrence, is independently C, N, O, or S; and

R a , for each occurrence, is independently selected from H, F, Cl, Br, Me, CN, MeO, Et, CF 3 O,

CF 3 , and EtO—.

5 . The compound of claim 3 , wherein the moiety

is selected from

wherein, n, for each occurrence, is independently 0, 1, 2, 3, 4, or 5; and

R a is as defined in claim 3 .

6 . The compound of claim 1 , wherein the moiety

wherein

m, for each occurrence, is independently 0, 1, 2, 3, 4, or 5;

Y 1 , for each occurrence, is independently C, N, O, or S;

Y 2 , for each occurrence, is independently C, N, O, or S;

Y 3 , for each occurrence, is independently C, N, O, or S;

Y 4 , for each occurrence, is independently C, N, O, or S;

Y 5 , for each occurrence, is independently C, N, O, or S; and

R b is as defined in claim 1 .

7 . The compound of claim 6 , wherein the moiety

is

wherein

m, for each occurrence, is independently 0, 1, 2, 3, 4, or 5;

Y 1 , for each occurrence, is independently C, N, O, or S;

Y 2 , for each occurrence, is independently C, N, O, or S;

Y 3 , for each occurrence, is independently C, N, O, or S;

Y 4 , for each occurrence, is independently C, N, O, or S;

Y 5 , for each occurrence, is independently C, N, O, or S; and

R b for each occurrence is selected from H, F, Cl, Br, Me, CN, MeO, Et, CF 3 O,

 CF 3 , and EtO—.

8 . The compound of claim 6 , wherein the moiety

is selected from

wherein

m, for each occurrence, is independently 0, 1, 2, 3, 4, or 5; and

R b is as defined in claim 6 .

9 . The compound of claim 8 , wherein the moiety

is selected from

wherein

R b is as defined in claim 8 .

10 . The compound of claim 1 , wherein the compound is a compound represented by a structural formula selected from the following group: (II), (III), (IV), (V) and (VI)

or a pharmaceutically acceptable salt thereof,

wherein

m, for each occurrence, is independently 0, 1, 2, 3, 4, or 5;

n, for each occurrence, is independently 0, 1, 2, 3, 4, 5, or 6;

X 1 , for each occurrence, is independently C, N, O, or S;

X 2 , for each occurrence, is independently C, N, O, or S;

X 3 , for each occurrence, is independently C, N, O, or S;

X 4 , for each occurrence, is independently C, N, O, or S;

X 5 , for each occurrence, is independently C, N, O, or S;

X 6 , for each occurrence, is independently C, N, O, or S

Y 1 , for each occurrence, is independently C, N, O, or S;

Y 2 , for each occurrence, is independently C, N, O, or S;

Y 3 , for each occurrence, is independently C, N, O, or S;

Y 4 , for each occurrence, is independently C, N, O, or S;

Y 5 , for each occurrence, is independently C, N, O, or S; and

R a and R b are as defined in claim 1 .

11 . The compound of claim 10 , wherein the compound is a compound represented by structural formula (I-7) or (I-8)

or a pharmaceutically acceptable salt thereof;

wherein

m, n, R a and R b are as defined in claim 10 .

12 . The compound of claim 10 , wherein the compound is a compound represented by structural formula (I-9) or (I-10)

or a pharmaceutically acceptable salt thereof;

wherein

m, n, R a and R b are as defined in claim 10 .

13 . The compound of claim 1 , wherein, each R a is independently selected from hydrogen, halogen, hydroxyl, nitro, cyano, trifluoromethyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 heterocycloalkyl, —N—(C 1 -C 6 alkyl) 2 , C 1 -C 6 alkyl-C 1 -C 6 heterocycloalkyl.

14 . The compound of claim 1 , wherein, each R b is independently selected from hydrogen, halogen, hydroxyl, nitro, cyano, amino, mercapto, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, aminoC 1 -C 6 alkyl, (mono- and di-C 1 -C 6 alkylamino)C 0 -C 4 alkyl, —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), —O—C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), C 0 -C 4 alkyl-(4- to 7-membered heterocycloalkyl) having 1, 2, or 3 heteroatoms independently chosen from N, O, and S, and C 0 -C 4 alkyl-(5- or 6-membered unsaturated or aromatic heterocycle) having 1, 2, or 3 heteroatoms independently chosen from N, O, and S, —C(O)OR 11 , —C 0 -C 4 alkylNR 11 R 12 , —C(O)NR 11 R 12 , —SO 2 R 11 , —SO 2 NR 11 R 12 , —OC(O)R 11 , and —C(NR 11 )NR 11 R 12 , wherein R 11 and R 12 are independently chosen from hydrogen, C 1 -C 6 alkyl, —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), and —O—C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl).

15 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, which is:

16 . The compound of claim 1 , wherein, the compound is selected from

17 . The compound of claim 1 , wherein, the compound is selected from

18 . A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

19 . A method of treating a disorder in a subject in need thereof, comprising administering to a subject in need thereof a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the disorder comprises Acute lymphoblastic leukemia (ALL), Acute myelogenous leukemia (AML), Chronic lymphocytic leukemia (CLL), Chronic myelogenous leukemia (CML), Acute monocytic leukemia (AMOL), Hairy cell leukemia (HCL), T-cell prolymphocytic leukemia (T-PLL), Large granular lymphocytic leukemia, Adult T-cell leukemia and Chronic lymphocytic leukemia.