Substituted heterocyclic compounds
The present invention relates to substituted heterocyclic compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted heterocyclic 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, prodrug, or derivative thereof:
wherein:
is an optionally substituted heteroaryl or heterocycle selected from:
wherein “*” indicates the point of attachment of the optionally substituted heteroaryl or heterocycle;
n is 0, 1, 2 or 3, and each R 1 is independently selected from hydroxyl, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkoxyl, halogen, cyano, nitro, amino, unsubstituted or substituted C 1 -C 6 alkylamino, and unsubstituted or substituted di-C 1 -C 6 alkylamino;
m is 0, 1, 2, 3, 4, 5 or 6;
R 2 and R 2′ are each independently H, unsubstituted or substituted C 1 -C 9 alkyl, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation, unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, and optionally containing unsaturation, or -T r -R r ;
T r is unsubstituted or substituted C 1 -C 6 alkyl linker, or a bond;
R r is H, hydroxyl, unsubstituted or substituted C 1 -C 6 alkoxyl, amino, unsubstituted or substituted C 1 -C 6 alkylamino, unsubstituted or substituted di-C 1 -C 6 alkylamino, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation, or unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, and optionally containing unsaturation;
R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are each independently H, unsubstituted or substituted C 1 -C 6 alkyl, or unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation;
R 8 is H, unsubstituted or substituted C 1 -C 6 alkyl, —C(O)R 11 , —C(O)OR 11 , —C(O)NR 11 R 12 , or —S(O) 2 R 11 ;
R 9 and R 10 are each independently H, unsubstituted or substituted C 1 -C 6 alkyl, or -T q -R q ;
T q is unsubstituted or substituted C 1 -C 6 alkyl linker, or a bond;
R q is H, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle, or unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S;
R 11 and R 12 are each independently H, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle, or unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, or -T r -R t ;
T r is unsubstituted or substituted C 1 -C 6 alkyl linker, or a bond;
R t is H, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted C 1 -C 6 alkoxy, unsubstituted or substituted C 6 -C 10 aryloxy, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle, unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, —C(O)OR 13 , or —C(O)R 13 ; and
R 13 is H or unsubstituted or substituted C 1 -C 6 alkyl.
2. The compound of claim 1 , wherein
3. The compound of claim 1 , wherein
4. The compound of claim 1 , wherein said compound is a compound of Formula II or a pharmaceutically acceptable salt, prodrug, or derivative thereof:
wherein:
n is 0, 1, 2 or 3, and each R 1 is independently selected from hydroxyl, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkoxyl, halogen, cyano, nitro, amino, unsubstituted or substituted C 1 -C 6 alkylamino, and unsubstituted or substituted di-C 1 -C 6 alkylamino;
R 2 is H, unsubstituted or substituted C 1 -C 9 alkyl, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation, unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, and optionally containing unsaturation, or -T r -R r ;
R 3 , R 4 , R 5 , R 6 , and R 7 are each independently H, unsubstituted or substituted C 1 -C 6 alkyl, or unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation;
T r is unsubstituted or substituted C 1 -C 6 alkyl linker, or a bond; and
R r is H, hydroxyl, unsubstituted or substituted C 1 -C 6 alkoxyl, amino, unsubstituted or substituted C 1 -C 6 alkylamino, unsubstituted or substituted di-C 1 -C 6 alkylamino, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation, or unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, and optionally containing unsaturation.
5. The compound of claim 4 , wherein R 2 is C 1 -C 6 straight chain or C 3 -C 6 branched alkyl substituted with one or more groups, each of which can be the same or different, selected from hydroxyl, halogen, amino, unsubstituted or substituted C 1 -C 6 alkylamino, unsubstituted or substituted di-C 1 -C 6 alkylamino, unsubstituted or substituted C 1 -C 6 alkoxyl, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation, and unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, and optionally containing unsaturation.
6. The compound of claim 4 , wherein R 2 is unsubstituted or substituted phenyl or naphthyl.
7. The compound of claim 1 , wherein said compound is a compound of Formula III, or a pharmaceutically acceptable salt, prodrug, or derivative thereof:
wherein:
n is 0, 1, 2 or 3, and each R 1 is independently selected from hydroxyl, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkoxyl, halogen, cyano, nitro, amino, unsubstituted or substituted C 1 -C 6 alkylamino, and unsubstituted or substituted di-C 1 -C 6 alkylamino;
R 5 , R 6 , and R 7 are each independently H, unsubstituted or substituted C 1 -C 6 alkyl, or unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation;
R 9 and R 10 are each independently H, unsubstituted or substituted C 1 -C 6 alkyl, or -T q -R q ;
T q is unsubstituted or substituted C 1 -C 6 alkyl linker, or a bond; and
R q is H, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle, or unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S.
8. The compound of claim 7 , wherein n is 0.
9. The compound of claim 7 , wherein R q is heterocycle selected from pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isoxazolidinyl, triazolidinyl, tetrahyrofuranyl, piperidinyl, piperazinyl, and morpholinyl, and the like, and is optionally substituted.
10. The compound of claim 7 , wherein R q is piperidinyl.
11. The compound of claim 1 , wherein said compound is a compound of Formula IV or a pharmaceutically acceptable salt, prodrug, or derivative thereof:
wherein:
n is 0, 1, 2 or 3, and each R 1 is independently selected from hydroxyl, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkoxyl, halogen, cyano, nitro, amino, unsubstituted or substituted C 1 -C 6 alkylamino, and unsubstituted or substituted di-C 1 -C 6 alkylamino;
m is 0, 1, 2, 3, 4, 5 or 6;
R 2 is H, unsubstituted or substituted C 1 -C 9 alkyl, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation, unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, and optionally containing unsaturation, or -T r -R r ;
T r is unsubstituted or substituted C 1 -C 6 alkyl linker, or a bond;
R r is H, hydroxyl, unsubstituted or substituted C 1 -C 6 alkoxyl, amino, unsubstituted or substituted C 1 -C 6 alkylamino, unsubstituted or substituted di-C 1 -C 6 alkylamino, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation, or unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, and optionally containing unsaturation; and
R 5 , R 6 , and R 7 are each independently H, unsubstituted or substituted C 1 -C 6 alkyl, or unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation.
12. The compound of claim 11 , wherein R 2 is unsubstituted or substituted phenyl or naphthyl.
13. The compound of claim 11 , wherein R 2 is phenyl or naphthyl substituted with one or more groups, each of which can be the same or different, selected from hydroxyl, halogen, nitro, cyano, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkoxyl, unsubstituted or substituted C 6 -C 10 aryloxyl, unsubstituted or substituted heteroaryloxyl, amino, unsubstituted or substituted C 1 -C 6 alkylamino, unsubstituted or substituted di-C 1 -C 6 alkylamino, unsubstituted or substituted C 1 -C 6 alkylcarbonyl, unsubstituted or substituted C 1 -C 6 alkoxylcarbonyl, unsubstituted or substituted C 6 -C 10 arylcarbonyl, unsubstituted or substituted C 1 -C 6 alkylaminocarbonyl, unsubstituted or substituted di-C 1 -C 6 alkylaminocarbonyl, unsubstituted or substituted C 6 -C 10 arylaminocarbonyl, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation, and unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, and optionally containing unsaturation.
14. The compound of claim 1 , wherein said compound is a compound of Formula V or a pharmaceutically acceptable salt, prodrug, or derivative thereof:
wherein
n is 0, 1, 2 or 3, and each R 1 is independently selected from hydroxyl, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkoxyl, halogen, cyano, nitro, amino, unsubstituted or substituted C 1 -C 6 alkylamino, and unsubstituted or substituted di-C 1 -C 6 alkylamino;
m is 0, 1, 2, 3, 4, 5 or 6;
R 2 is H, unsubstituted or substituted C 1 -C 9 alkyl, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation, unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, and optionally containing unsaturation, or -T r -R r ;
T r is unsubstituted or substituted C 1 -C 6 alkyl linker, or a bond;
R r is H, hydroxyl, unsubstituted or substituted C 1 -C 6 alkoxyl, amino, unsubstituted or substituted C 1 -C 6 alkylamino, unsubstituted or substituted di-C 1 -C 6 alkylamino, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation, or unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, and optionally containing unsaturation; and
R 5 , R 6 , and R 7 are each independently H, unsubstituted or substituted C 1 -C 6 alkyl, or unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation.
15. The compound of claim 14 , wherein R 2 is unsubstituted or substituted phenyl or naphthyl.
16. The compound of claim 14 , wherein R 2 is phenyl or naphthyl substituted with one or more groups, each of which can be the same or different, selected from hydroxyl, halogen, nitro, cyano, unsubstituted or substituted C 1 -C 6 alkyl, unsubstituted or substituted C 1 -C 6 alkoxyl, unsubstituted or substituted C 6 -C 10 aryloxyl, unsubstituted or substituted heteroaryloxyl, amino, unsubstituted or substituted C 1 -C 6 alkylamino, unsubstituted or substituted di-C 1 -C 6 alkylamino, unsubstituted or substituted C 1 -C 6 alkylcarbonyl, unsubstituted or substituted C 1 -C 6 alkoxylcarbonyl, unsubstituted or substituted C 6 -C 10 arylcarbonyl, unsubstituted or substituted C 1 -C 6 alkylaminocarbonyl, unsubstituted or substituted di-C 1 -C 6 alkylaminocarbonyl, unsubstituted or substituted C 6 -C 10 arylaminocarbonyl, unsubstituted or substituted C 6 -C 10 aryl, unsubstituted or substituted heteroaryl comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, unsubstituted or substituted C 3 -C 10 carbocycle optionally containing unsaturation, and unsubstituted or substituted heterocycle comprising 1 or 2,5- or 6-member rings and 1-4 heteroatoms selected from N, O and S, and optionally containing unsaturation.
17. A pharmaceutical composition comprising a compound of claim 1 and one or more pharmaceutically acceptable carriers.