1H-pyrazolo[3,4-
Provided herein are compounds according to Formulas (I) or (II) and pharmaceutically acceptable salts thereof, and compositions comprising the same, for use in various methods, including treating cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease, osteoarthritis, idiopathic pulmonary fibrosis and neurological conditions/disorders/diseases.
1. A method of treating a bone or cartilage disease in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof:
wherein:
R 1 is H;
R 2 is independently selected from the group consisting of H and —(C 1-9 alkyl) n N(R 9 ) 2 ;
R 3 is H;
R 4 is independently selected from the group consisting of -aryl(R 13 ) q , -furyl(R 15 ) q , and -thiophenyl(R 15 ) q ;
R 5 is H;
each R 8 is a substituent attached to the heterocyclyl ring and independently selected from the group consisting of H, halide, and —C 1-4 alkyl;
each R 9 is independently selected from the group consisting of H, —C 1-9 alkyl, —(C 1-3 alkyl) n carbocyclyl and —(C 1-9 alkyl)N(R 16 ) 2 ;
each R 13 is 1-2 substituents each attached to the aryl ring and independently selected from the group consisting of H, halide, —(C 1-3 alkyl) n heterocyclyl(R 8 ) q , —(C 1-9 alkyl) n N(R 9 ) 2 and —(C 1-9 alkyl) n NHSO 2 R 18 ;
each R 15 is a substituent attached to the heteroaryl ring and independently selected from the group consisting of H, lower alkyl, halide, —CF 3 , CN, and —C(═O)(C 1-3 alkyl);
each R 16 is independently selected from the group consisting of H and lower alkyl;
each R 18 is a lower alkyl;
A is C;
each q is independently an integer of 1 or 2; and
each n is independently an integer of 0 or 1.
2. The method of claim 1 , wherein the R 4 aryl is phenyl.
3. The method of claim 1 , wherein the R 13 heterocyclyl is selected from the group consisting of azetidinyl(R 8 ) q , pyrrolidinyl(R 8 ) q , piperidinyl(R 8 ) q , piperazinyl(R 8 ) q , and morpholinyl(R 8 ) q .
4. The method of claim 1 , wherein R 2 is H.
5. The method of claim 1 , wherein R 2 is —(C 1-9 alkyl) n N(R 9 ) 2 .
6. The method of claim 5 , wherein R 2 is —CH 2 N(R 9 ) 2 or —N(R 9 ) 2 .
7. The method of claim 6 , wherein R 9 is independently selected from the group consisting of H, Me, Et, n-propyl, isopropyl, and —CH 2 carbocyclyl.
8. The method of claim 7 , wherein R 4 is phenyl(R 13 ) q .
9. The method of claim 7 , wherein R 4 is -furyl(R 15 ) q .
10. The method of claim 7 , wherein R 4 is -thiophenyl(R 15 ) q .
11. The method of claim 8 , wherein R 13 is one substituent attached to the phenyl ring and the substituent is a fluorine atom.
12. The method of claim 8 , wherein R 13 is two substituents each attached to the phenyl ring and the substituents are a fluorine atom and —N(R 9 ) 2 , wherein R 9 is independently selected from the group consisting of H and —CH 2 CH 2 N(R 16 ) 2 , and wherein R 16 is independently selected from the group consisting of H, Me, and Et.
13. The method of claim 8 , wherein R 13 is two substituents each attached to the phenyl ring and the substituents are a fluorine atom and —(CH 2 ) n NHSO 2 R 18 , wherein R 9 is independently selected from the group consisting of Me and Et.
14. The method of claim 10 , wherein R 15 is one substituent attached to the thiophenyl ring and the substituents are selected from the group consisting of H, F, Me, and —C(═O)Me.
15. The method of claim 1 , wherein the compound of Formula (I) has a structure selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
16. The method of claim 1 , having a structure selected from the group consisting of:
pharmaceutically acceptable salt thereof.
17. The method of claim wherein the bone or cartilage disease is osteoarthritis.
18. The method of claim 1 , wherein the bone or cartilage disease is osteochondrodysplasia.
19. The method of claim 1 , wherein the subject is a human.
20. The method of claim 1 , wherein the subject is a non-human mammal.
21. A method of treating osteoarthritis in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound having a structure selected from the group consisting of:
pharmaceutically acceptable salt thereof.
22. A method of treating osteochondrodysplasia in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound having a structure selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.