Nitrogen-containing heterocyclic compound
View Patent ↗The present invention provides a nitrogen-containing heterocyclic compound represented by formula (I): {wherein W represents a nitrogen atom or —CH—; X represents —C(═O)— or —CHR 4 — (wherein R 4 represents a hydrogen atom, or the like}; R 1 represents a group represented by the following formula: [wherein Q 1 represents a nitrogen atom or —CR 8 — (wherein R 8 represents a hydrogen atom, substituted or unsubstituted lower alkyl, or the like). Q 2 represents —NR 15 — (wherein R 15 represents a hydrogen atom, or the like) and R 5 and R 6 may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, or the like]; and R 2 and R 3 may be the same or different and each represents a hydrogen atom, halogen, substituted or unsubstituted lower alkyl, or the like} or a pharmaceutically acceptable salt thereof, and the like.
1. A nitrogen-containing heterocyclic compound represented by formula (I):
wherein W represents —CH—;
X represents —CHR 4 — (wherein R 4 represents a hydrogen atom);
R 1 represents a group represented by the following formula:
{wherein Q 1 represents —CR 8 — (wherein R 8 represents a hydrogen atom),
Q 2 represents —NR 15 — (wherein R 15 represents a hydrogen atom),
R 5 represents methyl substituted with NR 35b R 36b (wherein R 35b and R 36b may be the same or different and each represents a hydrogen atom, C 1-10 alkyl, C 1-10 alkyl substituted with hydroxy or C 1-10 alkoxy), pyrrolidin-1-ylmethyl, piperidin-1-ylmethyl, 4-(2-hydroxyethyl)piperazin-1-ylmethyl, piperazin-1-ylcarbonyl, or 4-methylpiperazin-1-yl, and
R 6 represents a hydrogen atom},
R 2 represents a hydrogen atom or C 1-10 alkoxy, and
R 3 represents hydroxy, halogen, or —OS(O) 2 R 24a (wherein R 24a represents C 1-10 alkyl, thienyl, pyridyl, amino, or dimethylamino),
or a pharmaceutically acceptable salt thereof.
2. The nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 5 is methyl substituted with NR 35a R 36a (wherein R 35a and R 36a may be the same or different and each represents a hydrogen atom or C 1-10 alkyl).
3. A nitrogen-containing heterocyclic compound represented by formula (Ia):
{wherein R 2A represents methoxy,
R 3A represents methylsulfonyloxy, and
R 5A represents (methylamino)methyl, (ethylamino)methyl, (propylamino)methyl, (2,2-dimethylethylamino)methyl, (cyclopropylamino)methyl, (cyclohexylamino)methyl, (dimethylamino)methyl, (diethylamino)methyl, [di(2-hydroxyethyl)amino]methyl, (2-methoxyethylamino)methyl, [di(2-methoxyethyl)amino]methyl, pyrrolidin-1-ylmethyl, piperidinomethyl, (4-piperidinopiperidino)methyl, morpholinomethyl, 4-methylpiperazin-1-ylmethyl or 4-(2-hydroxyethyl)piperazin-1-ylmethyl},
or a pharmaceutically acceptable salt thereof.
4. A pharmaceutical composition comprising, as an active ingredient, the nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof described in claim 3 together with a pharmaceutically acceptable carrier.
5. The nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof according to claim 1 or 2 , wherein R 2 is methoxy.
6. The nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof according to claim 1 or 2 , wherein R 3 is methylsulfonyloxy.
7. The nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof according to claim 5 , wherein R 3 is methylsulfonyloxy.
8. A nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-(methylaminomethyl)indol-2-yl]isoindolinone,
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-(ethylaminomethyl)indol-2-yl]isoindolinone,
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-(1-propylaminomethyl)indol-2-yl]isoindolinone,
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-(cyclopropylaminomethyl)indol-2-yl]isoindolinone,
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-(cyclohexylaminomethyl)indol-2-yl]isoindolinone, and
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-(2-methoxyethylaminomethyl)indol-2-yl]isoindolinone.
9. A nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof, wherein the compound is:
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-(dimethylaminomethyl)indol-2-yl]isoindolinone, or
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-(diethylaminomethyl)indol-2-yl]isoindolinone.
10. A nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof, wherein the compound is:
4-Methanesulfonyloxy-5-methoxy-7-{1H-5-[di(2-hydroxyethyl)aminomethyl]indol-2-yl}isoindolinone, or
4-Methanesulfonyloxy-5-methoxy-7-{1H-5-[di(2-methoxyethyl)aminomethyl]indol-2-yl}isoindolinone.
11. A nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-(pyrrolidin-1-ylmethyl)indol-2-yl]isoindolinone,
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-(piperidinomethyl)indol-2-yl]isoindolinone,
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-(4-piperidinopiperidinomethyl)indol-2-yl] isoindolinone,
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-(morpholinomethyl)indol-2-yl]isoindolinone,
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-(4-methylpyperazin-1-ylmethyl)indol-2-yl]isoindolinone, and
4-Methanesulfonyloxy-5-methoxy-7-[1H-5-[4-(2-hydroxyethyl)pyperazin-1-ylmethyl]indol-2-yl}isoindolinone.
12. A pharmaceutical composition comprising, as an active ingredient, the nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof described in any one of claim 8 to 11 together with a pharmaceutically acceptable carrier.
13. A method for inhibiting a protein kinase comprising a step of administering the nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof described in any one of claims 1 , 2 , 3 , 8 , 9 , 10 or 11 .
14. A method for inhibiting a fibroblast growth factor receptor comprising a step of administering the nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof described in any one of claims 1 , 2 , 3 , 8 , 9 , 10 or 11 .
15. A method for inhibiting an Aurora comprising a step of administering the nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof described in any one of claims 1 , 2 , 3 , 8 , 9 , 10 or 11 .
16. A method for inhibiting a fms-like tyrosine kinase 3 comprising a step of administering the nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof described in any one of claims 1 , 2 , 3 , 8 , 9 , 10 or 11 .
17. A method for treating a hematopoietic tumor comprising a step of administering the nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof described in any one of claims 1 , 2 , 3 , 8 , 9 , 10 or 11 .
18. A method for treating leukemia, myeloma, or lymphoma comprising a step of administering the nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof described in any one of claims 1 , 2 , 3 , 8 , 9 , 10 or 11 .
19. A method for treating multiple myeloma comprising a step of administering the nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof described in any one of claims 1 , 2 , 3 , 8 , 9 , 10 or 11 .
20. A method for treating stomach cancer comprising a step of administering the nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof described in any one of claims 1 , 2 , 3 , 8 , 9 , 10 or 11 .
21. A method for treating colon cancer comprising a step of administering the nitrogen-containing heterocyclic compound or the pharmaceutically acceptable salt thereof described in any one of claims 1 , 2 , 3 , 8 , 9 , 10 or 11 .