Substituted imidazopyridinyl-aminopyridine compounds
The present invention relates to substituted imidazopyridinyl-aminopyridine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted imidazopyridinyl-aminopyridine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.
1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
X is NR N R N ′, OR O , or SR S ;
R O and R S are each independently unsubstituted or substituted C 6 -C 10 aryl;
R N is (CH 2 ) m R hc ;
R N ′ is H;
m is 1, 2, 3 or 4; and
R hc is unsubstituted or substituted heterocycle comprising one 6-member ring and 1 or 2 heteroatoms selected from N, O and S.
2. The compound of claim 1 , wherein X is NR N R N ′; m is 1 or 2; and R hc is unsubstituted or substituted heterocycle selected from the group consisting of pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isoxazolidinyl, triazolidinyl, tetrahyrofuranyl, piperidinyl, piperazinyl, and morpholinyl.
3. The compound of claim 1 , wherein X is OR O ; and R O is unsubstituted phenyl or phenyl substituted with a substituent selected from the group consisting of hydroxyl, halogen, cyano, nitro, unsubstituted or substituted amino, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkoxy, and unsubstituted or substituted heterocycle comprising one 5- or 6-member ring and 1-3 heteroatoms selected from N, O and S.
4. The compound of claim 1 , wherein X is OR S ; and R S is unsubstituted phenyl or phenyl substituted with a substituent selected from the group consisting of hydroxyl, halogen, cyano, nitro, unsubstituted or substituted amino, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkoxy, and unsubstituted or substituted heterocycle comprising one 5- or 6-member ring and 1-3 heteroatoms selected from N, O and S.
5. The compound of claim 1 , selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
6. A compound of formula II:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is (CH 2 ) o —OH or C(O)R 2 ;
R 1 ′ is H; or
R 1 and R 1 ′, together with the nitrogen atom to which they are attached, form a ring selected from the group consisting of
wherein the nitrogen atom indicated by “**” is the nitrogen atom to which R 1 and R 1 ′ are attached;
o is 1, 2, 3 or 4;
R 2 is
tert-butyl, unsubstituted or substituted C 3 -C 8 carbocycle, or unsubstituted or substituted heterocycle comprising one 6-member ring and 1 or 2 heteroatoms selected from N, O and S;
n is 0, 1, 2 or 3;
R 10 is H, unsubstituted or substituted C 1 -C 6 alkyl, or C(O)R 11 ;
R 11 is unsubstituted or substituted C 1 -C 6 alkyl;
R C and R C ′, for each occurrence, are independently H or unsubstituted methyl;
R 3 is NR 12 R 12 ′, C(O)NR 6 R 6 ′, NR 7 ′C(O)R 7 , or NR 7 ′S(O) 2 R 7 ;
R 6 and R 6 ′ are each independently H or unsubstituted or substituted C 1 -C 6 alkyl, or R 6 and R 6 ′, together with the nitrogen atom to which they are attached, form an unsubstituted or substituted heterocycle comprising one 5- or 6-member ring and optionally 1 or 2 additional heteroatoms selected from N, O and S;
R 7 is unsubstituted or substituted C 1 -C 6 alkyl;
R 7 ′ is H or unsubstituted or substituted C 1 -C 6 alkyl;
R 12 and R 12 ′ are each H, or R 12 and R 12 ′, together with the nitrogen atom to which they are attached, form an unsubstituted or substituted heterocycle comprising one 6-member ring and optionally 1 or 2 additional heteroatoms selected from N, O and S;
R 4 is C(O)R 8 or S(O) 2 R r ;
R r is unsubstituted or substituted C 1 -C 6 alkyl;
R 8 is unsubstituted or substituted C 2 -C 6 alkyl, or unsubstituted or substituted C 3 -C 8 carbocycle;
R 5 and R 5 ′ are each independently H, unsubstituted or substituted C 1 -C 6 alkyl, or C(O)NR 9 R 9 ′, provided that R 5 and R 5 ′ are not both H;
R 9 and R 9 ′ are each independently H or unsubstituted or substituted C 1 -C 6 alkyl;
R aza is H or OH;
R p is C(O)NR q R q′ ; and
R q and R q ′ are each independently H or unsubstituted or substituted C 1 -C 6 alkyl.
7. The compound of claim 6 , wherein R 1 and R 1 ′, together with the nitrogen atom to which they are attached, form
8. The compound of claim 6 , wherein R 1 and R 1 ′, together with the nitrogen atom to which they are attached, form
9. The compound of claim 6 , wherein R 1 ′ is H and R 1 is (CH 2 ) o —OH.
10. The compound of claim 6 , wherein R 1 ′ is H and R 1 is C(O)R 2 .
11. The compound of claim 10 , wherein R 2 is
n is 0 or 1; R C and R C ′ are each unsubstituted methyl; R 10 is H, methyl, ethyl, propyl, or C(O)R 11 ; and R 11 is methyl, ethyl, or propyl.
12. The compound of claim 10 , wherein R 2 is tert-butyl or unsubstituted or substituted C 3 -C 8 carbocycle selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl.
13. The compound of claim 10 , wherein R 2 is unsubstituted or substituted heterocycle selected from the group consisting of pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isoxazolidinyl, triazolidinyl, tetrahyrofuranyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, and dioxanyl.
14. The compound of claim 6 , selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
15. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a salt thereof, and a pharmaceutically acceptable carrier or excipient.
16. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 6 , or a salt thereof, and a pharmaceutically acceptable carrier or excipient.