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 compound, or pharmaceutically acceptable salt thereof, having the structure of Formula I:
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 compound of claim 1 , wherein the R 4 aryl is phenyl.
3. The compound 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 compound of claim 1 , wherein R 2 is H.
5. The compound of claim 1 , wherein R 2 is —(C 1-9 alkyl) n N(R 9 ) 2 .
6. The compound of claim 5 , wherein R 2 is —CH 2 N(R 9 ) 2 or —N(R 9 ) 2 .
7. The compound 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 compound of claim 7 , wherein R 4 is phenyl(R 13 ) q .
9. The compound of claim 7 , wherein R 4 is -furyl(R 15 ) q .
10. The compound of claim 7 , wherein R 4 is -thiophenyl(R 15 ) q .
11. The compound of claim 8 , wherein R 13 is one substituent attached to the phenyl ring and the substituent is a fluorine atom.
12. The compound 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 compound 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 compound 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 compound 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. A compound having a structure selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
17. A pharmaceutical composition comprising a therapeutically effective amount of a compound, or pharmaceutically acceptable salt thereof, having the structure of Formula I:
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;
each n is independently an integer of 0 or 1; and
a pharmaceutically acceptable excipient.
18. The pharmaceutical composition of claim 1 , wherein the R 4 aryl is phenyl.
19. The pharmaceutical composition 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 .
20. The pharmaceutical composition of claim 17 , wherein R 2 is H.
21. The pharmaceutical composition of claim 17 , wherein R 2 is —(C 1-9 alkyl) n N(R 9 ) 2 .
22. The pharmaceutical composition of claim 21 , wherein R 2 is —CH 2 N(R 9 ) 2 or —N(R 9 ) 2 .
23. The pharmaceutical composition of claim 22 , wherein R 9 is independently selected from the group consisting of H, Me, Et, n-propyl, isopropyl, and —CH 2 carbocyclyl.
24. The pharmaceutical composition of claim 23 , wherein R 4 is phenyl(R 13 ) q .
25. The pharmaceutical composition of claim 23 , wherein R 4 is -thiophenyl(R 15 ) q .
26. The pharmaceutical composition of claim 24 , wherein R 13 is one substituent attached to the phenyl ring and the substituent is a fluorine atom.
27. The pharmaceutical composition of claim 24 , 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.
28. The pharmaceutical composition of claim 24 , 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.
29. The pharmaceutical composition of claim 25 , wherein R 15 is one substituent attached to the phenyl and the substituents are selected from the group consisting of H, F, Me, and —C(═O)Me.
30. A pharmaceutical composition comprising a therapeutically effective amount of a compound having the structure of:
pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable excipient.