SUBSTITUTED 6,5-FUSED BICYCLIC HETEROARYL COMPOUNDS
The present invention relates to substituted 6,5-fused bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof.
1 . A method of treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (Ib) or a pharmaceutically acceptable salt thereof:
wherein
X 2 is N or CH;
X 3 is CR 8 ;
X 4 is C;
Y 1 is CH;
Y 3 is CR 11 ;
R 6 is phenyl or a 5 to 6-membered heteroaryl selected from the group consisting of pyridinyl, pyrazolyl, pyrimidinyl, and furyl, wherein the phenyl and 5 to 6-membered heteroaryl are optionally substituted with one or more -Q 2 -T 2 , in which Q 2 is a C 1 -C 3 alkyl linker or a bond, and T 2 is unsubstituted 4 to 7-membered heterocycloalkyl;
R 7 is C 1 -C 6 alkyl or cyclopentyl;
R 8 is H or methyl or ethyl; and
R 11 is H.
2 . The method of claim 1 , wherein R 6 is pyridinyl optionally substituted with one or more -Q 2 -T 2 .
3 . The method of claim 2 , wherein X 2 is CH.
4 . The method of claim 3 , wherein T 2 is azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isoxazolidinyl, triazolidinyl, tetrahyrofuranyl, piperidinyl, 1,2,3,6-tetrahydropyridinyl, piperazinyl, tetrahydro-2H-pyranyl, 3,6-dihydro-2H-pyranyl, or morpholinyl.
5 . The method of claim 4 , wherein T 2 is piperazinyl.
6 . The method of claim 5 , wherein R 7 is methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, s-pentyl, or n-hexyl.
7 . The method of claim 6 , wherein R 7 is s-butyl.
8 . The method of claim 7 , wherein R 11 is H.
9 . The method of claim 8 , wherein R 8 is methyl.
10 . The method of claim 9 , wherein the compound has R configuration.
11 . The method of claim 9 , wherein the compound has S configuration.
12 . (canceled)
13 . The method of claim 1 , wherein the cancer is leukemia or lymphoma.
14 . The method of claim 13 , wherein the leukemia is selected from the group consisting of chronic lymphocytic leukemia, chronic myelogenous leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, hairy cell leukemia, chronic myelogenous leukemia, and acute myeloid leukemia.
15 . The method of claim 1 , wherein the cancer is lymphoma.
16 . The method of claim 15 , wherein the lymphoma is selected from the group consisting of B-cell lymphoma, diffuse large B-cell lymphoma, germinal center B cell-like lymphoma, cutaneous T-cell lymphoma, AIDS-related lymphoma, nervous system lymphoma, follicular lymphoma, and non-Hodgkin lymphoma.
17 . The method of claim 16 , wherein the lymphoma is B-cell lymphoma.
18 . The method of claim 16 , wherein the lymphoma is diffuse large B-cell lymphoma.
19 . The method of claim 16 , wherein the lymphoma is follicular lymphoma.
20 . The method of claim 16 , wherein the lymphoma is non-Hodgkin lymphoma.
21 . The method of claim 1 , wherein Q 2 is a C 1 -C 3 alkyl linker.
22 . A compound of Formula (Ib) or a pharmaceutically acceptable salt thereof:
wherein
X 2 is N or CH;
X 3 is CR 8 ;
X 4 is C;
Y 1 is CH;
Y 3 is CR 11 ;
R 6 is phenyl or a 5 to 6-membered heteroaryl selected from the group consisting of pyridinyl, pyrazolyl, pyrimidinyl, and furyl, wherein the phenyl and 5 to 6-membered heteroaryl are optionally substituted with one or more -Q 2 -T 2 , in which Q 2 is a C 1 -C 3 alkyl linker, and T 2 is unsubstituted 4 to 7-membered heterocycloalkyl;
R 7 is C 1 -C 6 alkyl or cyclopentyl;
R 8 is H or methyl or ethyl; and
R 11 is H.