1,5-naphthyridine derivatives and MELK inhibitors containing the same

A compound represented by formula (I) or a pharmaceutically acceptable salt thereof:

• wherein,
• X1 is selected from the group consisting of a direct bond, —NR12—, —O—, and —S—;
• R12 is selected from the group consisting of a hydrogen atom, C1-C6 alkyl and C3-C10 cycloalkyl;
• Q1 is selected from the group consisting of C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, 3- to 10-membered non-aromatic heterocyclyl, (C3-C10 cycloalkyl)-C1-C6 alkyl, (C6-C10 aryl)-C1-C6 alkyl, (5- to 10-membered heteroaryl)-C1-C6 alkyl, and (3- to 10-membered non-aromatic heterocyclyl)-C1-C6 alkyl;
• wherein Q1 is optionally substituted with one or more substituents independently selected from A1;
• X2 is selected from the group consisting of —CO—, —S—, —SO—, and —SO2—;
• R11 is selected from the group consisting of C1-C6 alkyl, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl;
• wherein R11 is optionally substituted with one or more substituents independently selected from A2;
• R5 is selected from the group consisting of a halogen atom, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl;
• wherein the cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from A3;
• R2, R3, and R4 are independently selected from the group consisting of a hydrogen atom, a halogen atom, and C1-C6 alkyl;
• A1 and A3 are independently selected from the group consisting of a halogen atom, cyano, —COOR13, —CONR14R15, formyl, (C1-C6 alkyl)carbonyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, nitro, —NR16R17, —OR18, —S(O)nR19, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl;
• wherein the alkylcarbonyl, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from A4;
• A2 is independently selected from the group consisting of a halogen atom, cyano, C3-C10 cycloalkyl, carboxy, formyloxy, (C1-C6 alkyl)carbonyloxy, hydroxy, C1-C6 alkoxy, amino, C1-C6 alkylamino, and di(C1-C6 alkyl)amino;
• R13, R14, and R15 are independently selected from the group consisting of a hydrogen atom, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl;
• wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from A4;
• or R14 and R15 together with the nitrogen atom to which they are attached form 3- to 10-membered nitrogen-containing heterocyclyl, which is optionally substituted with one or more substituents independently selected from A4;
• R16 and R18 are independently selected from the group consisting of a hydrogen atom, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, 3- to 10-membered non-aromatic heterocyclyl, and —COR20;
• wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from A4;
• R17 is selected from the group consisting of a hydrogen atom, and C1-C6 alkyl that is optionally substituted with one or more substituents independently selected from A4;
• or R16 and R17 together with the nitrogen atom to which they are attached form 3- to 10-membered nitrogen-containing heterocyclyl, which is optionally substituted with one or more substituents independently selected from A4;
• R19 is selected from the group consisting of C1-C6 alkyl, C3-C10 cycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl;
• wherein the alkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from A4;
• R20 is selected from the group consisting of a hydrogen atom, —NR14R15, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl;
• wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from A4;
• n is an integer independently selected from 0 to 2;
• A4 is independently selected from consisting of a halogen atom, cyano, —COOR21, —CONR22R23, formyl, (C1-C6 alkyl)carbonyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, nitro, —NR24R25, —OR26, —S(O)nR27, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl;
• wherein the alkylcarbonyl, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from A5;
• R21, R22, and R23 are independently selected from the group consisting of a hydrogen atom, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl;
• wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from A5;
• or R22 and R23 together with the nitrogen atom to which they are attached form 3- to 10-membered nitrogen-containing heterocyclyl, which is optionally substituted with one or more substituents independently selected from A5;
• R24 and R26 are independently selected from the group consisting of a hydrogen atom, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, 3- to 10-membered non-aromatic heterocyclyl, and —COR28;
• wherein the alkyl, alkenyl, alkynyl cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from A5;
• R25 is selected from the group consisting of a hydrogen atom, and C1-C6 alkyl that is optionally substituted with one or more substituents independently selected from A5;
• or R24 and R25 together with the nitrogen atom to which they are attached form 3- to 10-membered nitrogen-containing heterocyclyl, which is optionally substituted with one or more substituents independently selected from A5;
• R27 is selected from the group consisting of C1-C6 alkyl, C3-C10 cycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl;
• wherein the alkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from A5;
• R28 is independently selected from the group consisting of a hydrogen atom, —NR22R23, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl;
• wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from A5;
• A5 is independently selected from consisting of a halogen atom, cyano, —COOR31, —CONR32R33, formyl, (C1-C6 alkyl)carbonyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, nitro, —NR34R35, —OR36, —S(O)nR37, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl;
• wherein the alkylcarbonyl, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from A6;
• R31, R32, and R33 are independently selected from the group consisting of a hydrogen atom, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl;
• wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from A6;
• or R32 and R33 together with the nitrogen atom to which they are attached form 3- to 10-membered nitrogen-containing heterocyclyl, which is optionally substituted with one or more substituents independently selected from A6;
• R34 and R36 are independently selected from the group consisting of a hydrogen atom, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, 3- to 10-membered non-aromatic heterocyclyl, and —COR38;
• wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from A6;
• R35 is selected from the group consisting of a hydrogen atom, and C1-C6 alkyl that is optionally substituted with one or more substituents independently selected from A6;
• or R34 and R35 together with the nitrogen atom to which they are attached form 3- to 10-membered nitrogen-containing heterocyclyl, which is optionally substituted with one or more substituents independently selected from A6;
• R37 is selected from the group consisting of C1-C6 alkyl, C3-C10 cycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl;
• wherein the alkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from A6;
• R38 is independently selected from the group consisting of a hydrogen atom, —NR32R33, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl;
• wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from A6;
• A6 is independently selected from consisting of a halogen atom, cyano, carboxy, —COOR41, —CONR42R43, formyl, (C1-C6 alkyl)carbonyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, nitro, —NR44R45, —OR46, S(O)nR47, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl;
• wherein the alkylcarbonyl, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from the group consisting of a halogen atom, hydroxy, C1-C6 alkoxy, amino, C1-C6 alkylamino, and di(C1-C6 alkyl)amino;
• R41, R42, and R43 are independently selected from the group consisting of a hydrogen atom, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl;
• wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more substituents independently selected from the group consisting of a halogen atom, hydroxy, C1-C6 alkoxy, amino, C1-C6 alkylamino, and di(C1-C6 alkyl)amino;
• R44 and R46 are independently selected from the group consisting of a hydrogen atom, C1-C6 alkyl, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, 3- to 10-membered non-aromatic heterocyclyl, and —COR48;
• R45 is selected from the group consisting of a hydrogen atom, and C1-C6 alkyl;
• R47 is selected from the group consisting of C1-C6 alkyl, C3-C10 cycloalkyl, C6-C10 aryl, and 5- to 10-membered heteroaryl;
• and
• R48 is independently selected from the group consisting of C1-C6 alkyl, C3-C10 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered non-aromatic heterocyclyl.