9H-pyrimido[4,5-B]indoles, 9H-pyrido[4',3':4,5]pyrrolo[2,3-D]pyridines, and 9H 1,3,6,9 tetraaza-fluorenes as CHK1 kinase function inhibitors

A compound of the following formula, or a pharmaceutically acceptable salt thereof:

• wherein:
• either:
• Y is CR6A and Z is N;
• or:
• Y is N and Z is CR7A;
• —R4A is independently -Q1, -Q2, -Q3, or -Q4;
• —R2A is independently —H or -G1;
• —R5A is independently —H or -G2;
• —R6A is independently —H or -G3;
• and
• —R7A is independently —H or -G3;
• and wherein:
• -Q1 is independently —NH2, —NHRW1, or —NRW12;
• wherein:
• each —RW1 is independently:
• —RX1, —RX2, —RX3, —RX4, —RX5, —RX6, —RX7, —RX8,
• -LX-RX4, -LX-RX5, -LX-RX6, -LX-RX7, or -LX-RX8;
• wherein:
• each —RX1 is saturated aliphatic C1-6alkyl;
• each —RX2 is aliphatic C2-6alkenyl;
• each —RX3 is aliphatic C2-6alkynyl;
• each —RX4 is saturated C3-6cycloalkyl;
• each —RX5 is C3-6cycloalkenyl;
• each —RX6 is non-aromatic C3-7heterocyclyl;
• each —RX7 is C6-10carboaryl;
• each —RX8 is C5-10heteroaryl;
• each -Lx- is saturated aliphatic C1-3alkylene;
• and wherein:
• each C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkenyl, non-aromatic C3-7heterocyclyl, C6-10carboaryl, C5-10heteroaryl, and C1-3alkylene is optionally substituted with one or more substituents —RX9, wherein each —RX9 is independently:
• —F, —Cl, —Br, —I,
• —RY1,
• —CF3,
• —OH,
• —ORY1,
• —OCF3,
• —SH,
• —SRY1,
• —CN,
• —NO2,
• —NH2, —NHRY1, —NRY12, —NRY2RY3,
• —C(═O)OH,
• —C(═O)ORY1,
• —C(═O)NH2, —C(═O)NHRY1, —C(═O)NRY12, —C(═O)NRY2RY3,
• -LY-OH, -LY-ORY1,
• -LY-NH2, -LY-NHRY1, -LY-NRY12, or -LY-NRY2RY3;
• wherein:
• each —RY1 is independently saturated aliphatic C1-4alkyl, phenyl, or benzyl;
• each -LY- is saturated aliphatic C1-5alkylene;
• and
• in each group —NRY2RY3, RY2 and RY3, taken together with the nitrogen atom to which they are attached, form a 5-, 6-, or 7-membered non-aromatic ring having exactly 1 ring heteroatom or exactly 2 ring heteroatoms, wherein one of said exactly 2 ring heteroatoms is N, and the other of said exactly 2 ring heteroatoms is independently N or O;
• -Q2 is —NRW2RW3, wherein RW2 and RW3, taken together with the nitrogen atom to which they are attached, form a 5-, 6-, or 7-membered non-aromatic ring having exactly 1 ring heteroatom or exactly 2 ring heteroatoms, wherein one of said exactly 2 ring heteroatoms is N, and the other of said exactly 2 ring heteroatoms is independently N or O;
• -Q3 is:
• wherein:
• m is independently 0 or 1;
• n is independently 0, 1 or 2;
• each —RP is independently saturated aliphatic C1-3alkyl or —CF3;
• —RQ is independently:
• -LR-NH2, -LR-NHRR, -LR-NRR2,
• -LR-OH, -LR-ORR,
• —C(═O)OH, —C(═O)ORR,
• —C(═O)NH2, —C(═O)NHRR, —C(═O)NRR2,
• -LR-C(═O)OH, -LR-C(═O)ORR,
• -LR-C(═O)NH2, -LR-C(═O)NHRR, -LR-C(═O)NRR2, or
• -LR-CN;
• wherein:
• each -LR- is saturated aliphatic C1-3alkylene;
• and
• each —RR is saturated aliphatic C1-3alkyl;
• -Q4 is independently:
• —NH-LT-NH2, —NH-LT-NHRT1, —NH-LT-NRT12, —NH-LT-NRT2RT3, —NRT1-LT-NH2, —NRT1-LT-NHRT1, —NRT1-LT-NRT12, —NR-LT-NRT2RT3;
• —NH-LT-NHC(═O)RT1, —NH-LT-N(RT1)C(═O)RT1,
• —N(RT1)-LT-NHC(═O)RT1, or —N(RT1)-LT-N(RT1)C(═O)RT1,
• wherein:
• each -LT- is saturated aliphatic C1-6alkylene;
• each —RT1 is independently:
• —RU1, —RU2, —RU3, —RU4, —RU5, —RU6, —RU7, —RU8,
• wherein:
• each —RU1 is saturated aliphatic C1-6alkyl;
• each —RU2 is aliphatic C2-6alkenyl;
• each —RU3 is aliphatic C2-6alkynyl;
• each —RU4 is saturated C3-6cycloalkyl;
• each —RU5 is C3-6cycloalkenyl;
• each —RU6 is non-aromatic C3-7heterocyclyl;
• each —RU7 is C6-10-carboaryl;
• each —RU8 is C5-10heteroaryl;
• each -LU- is saturated aliphatic C1-3alkylene;
• and wherein:
• each C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkenyl, non-aromatic C3-7heterocyclyl, C6-10-carboaryl, C5-10heteroaryl, and C1-3alkylene is optionally substituted with one or more substituents —RU9, wherein each —RU9 is independently:
• —F, —Cl, —Br, —I,
• —Rv1,
• —CF3,
• —OH,
• —ORV1,
• —OCF3,
• —SH,
• —SRV1,
• —CN,
• —NO2,
• —NH2, —NHRV1, —NRV12, —NRV2RV3,
• —C(═O)OH,
• —C(═O)ORV1,
• —C(═O)NH2, —C(═O)NHRV1, —C(═O)NRV12, —C(═O)NRV2RV3,
• -LV-OH, -LV-ORV1,
• -LV-NH2, -LV-NHRV1, -LV-NRV12, or -LV-NRV2RV3;
• wherein:
• each —RV1 is independently saturated aliphatic C1-4alkyl, phenyl, or benzyl;
• each -LV- is saturated aliphatic C1-5alkylene;
• and
• in each group —NRV2RV3, RV2 and RV3, taken together with the nitrogen atom to which they are attached, form a 5-, 6-, or 7-membered non-aromatic ring having exactly 1 ring heteroatom or exactly 2 ring heteroatoms, wherein one of said exactly 2 ring heteroatoms is N, and the other of said exactly 2 ring heteroatoms is independently N or O;
• and
• in each group —NRT2RT3, RT2 and RT3, taken together with the nitrogen atom to which they are attached, form a 5-, 6-, or 7-membered non-aromatic ring having exactly 1 ring heteroatom or exactly 2 ring heteroatoms, wherein one of said exactly 2 ring heteroatoms is N, and the other of said exactly 2 ring heteroatoms is independently N or O;
• and wherein:
• -G1 is independently:
• —F, —Cl, —Br, —I,
• —RA1,
• —CF3,
• —OH,
• -LA-OH,
• —ORA1,
• -LA-ORA1,
• —OCF3,
• —SH,
• —SRA1,
• —CN,
• —NO2,
• —NH2, —NHRA1, —NRA12, —NRA2RA3,
• -LA-NH2, -LA-NHRA1, -LA-NRA12, -LA-NRA2RA3,
• —C(═O)OH,
• —C(═O)ORA1,
• —C(═O)NH2, —C(═O)NHRA1, —C(═O)NRA12, —C(═O)NRA2RA3,
• —NHC(═O)RA1, —NRA1C(═O)RA1,
• —NHC(═O)ORA1, —NRA1C(═O)ORA1,
• —OC(═O)NH2, —OC(═O)NHRA1, —OC(═O)NRA12,
• —OC(═O)RA1,
• —C(═O)RA1,
• —NHC(═O)NH2, —NHC(═O)NHRA1,
• —NHC(═O)NRA12, —NHC(═O)NRA2RA3,
• —NRA1C(═O)NH2, —NRA1C(═O)NHRA1,
• —NRA1C(═O)NRA12, —NRA1C(═O)NRA2RA3,
• —NHS(═O)2RA1, —NRA1S(═O)2RA1,
• —S(═O)2NH2, —S(═O)2NHRA1, —S(═O)2NRA12, —S(═O)2NRA2RA3,
• —S(═O)RA1,
• —S(═O)2RA1,
• —OS(═O)2RA1, or
• —S(═O)2ORA1,
• wherein:
• each -LA- is saturated aliphatic C1-5alkylene;
• in each group —NRA2RA3, RA2 and RA3, taken together with the nitrogen atom to which they are attached, form a 5-, 6-, or 7-membered non-aromatic ring having exactly 1 ring heteroatom or exactly 2 ring heteroatoms, wherein one of said exactly 2 ring heteroatoms is N, and the other of said exactly 2 ring heteroatoms is independently N or O;
• each —RA1 is independently:
• —RB1, —RB2, —RB3, —RB4, —RB5, —RB6, —RB7, —RB8,
• -LB-RB4, -LB-RB5, -LB-RB6, -LB-RB7, or -LB-RB8;
• wherein:
• each —RB1 is saturated aliphatic C1-6alkyl;
• each —RB2 is aliphatic C2-6alkenyl;
• each —RB3 is aliphatic C2-6alkynyl;
• each —RB4 is saturated C3-6cycloalkyl;
• each —RB5 is C3-6cycloalkenyl;
• each —RB6 is non-aromatic C3-7heterocyclyl;
• each —RB7 is C6-10carboaryl;
• each —RB8 is C5-10heteroaryl;
• each -LB- is saturated aliphatic C1-3alkylene;
• and wherein:
• each C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkenyl, non-aromatic C3-7heterocyclyl, C6-10carboaryl, C5-10heteroaryl, and C1-3alkylene is optionally substituted with one or more substituents —RB9, wherein each —RB9 is independently:
• —F, —Cl, —Br, —I,
• —RC1,
• —CF3,
• —OH,
• —ORC1,
• —OCF3,
• —SH,
• —SRC1,
• —CN,
• —NO2,
• —NH2, —NHRC1, —NRC12, —NRC2RC3,
• —C(═O)OH,
• —C(═O)ORC1,
• —C(═O)NH2, —C(═O)NHRC1, —C(═O)NRC12, —C(═O)NRC2RC3,
• -LC-OH, -LC-ORC1,
• -LC-NH2, -LC-NHRC1, -LC-NRC12, or -LC-NRC2RC3;
• wherein:
• each —RC1 is independently saturated aliphatic C1-4alkyl, phenyl, or benzyl;
• each -LC- is saturated aliphatic C1-5alkylene;
• and
• in each group —NRC2RC3, RC2 and RC3, taken together with the nitrogen atom to which they are attached, form a 5-, 6-, or 7-membered non-aromatic ring having exactly 1 ring heteroatom or exactly 2 ring heteroatoms, wherein one of said exactly 2 ring heteroatoms is N, and the other of said exactly 2 ring heteroatoms is independently N or O;
• -G2 is independently:
• —F, —Cl, —Br, —I,
• —RE1,
• —CF3,
• —OH,
• -LE-OH,
• —ORE1,
• -LE-ORE1,
• —OCF3,
• —SH,
• —SRE1,
• —CN,
• —NO2,
• —NH2, —NHRE1, —NRE12, —NRE2RE3,
• -LE-NH2, -LE-NHRE1, -LE-NRE12, -LE-NRE2RE3,
• —C(═O)OH,
• —C(═O)ORE1,
• —C(═O)NH2, —C(═O)NHRE1, —C(═O)NRE12, —C(═O)NRE2RE3,
• —NHC(═O)RE1, —NRE1C(═O)RE1,
• —NHC(═O)ORE1, —NRE1C(═O)ORE1,
• —OC(═O)NH2, —OC(═O)NHRE1, —OC(═O)NRE12,
• —OC(═O)RE1,
• —C(═O)RE1,
• —NHC(═O)NH2, —NHC(═O)NHRE1,
• —NHC(═O)NRE12, —NHC(═O)NRE2RE3,
• —NRE1C(═O)NH2, —NRE1C(═O)NHRE1,
• —NRE1C(═O)NRE12, —NRE1C(═O)NRE2RE3,
• —NHS(═O)2RE1, —NRE1S(═O)2RE1,
• —S(═O)2NH2, —S(═O)2NHRE1, —S(═O)2NRE1 2, —S(═O)2NRE2RE3,
• —S(═O)RE1,
• —S(═O)2RE1,
• —OS(═O)2RE1, or
• —S(═O)2ORE1,
• wherein:
• each -LE- is saturated aliphatic C1-5alkylene;
• in each group —NRE2RE3, RE2 and RE3, taken together with the nitrogen atom to which they are attached, form a 5-, 6-, or 7-membered non-aromatic ring having exactly 1 ring heteroatom or exactly 2 ring heteroatoms, wherein one of said exactly 2 ring heteroatoms is N, and the other of said exactly 2 ring heteroatoms is independently N or O;
• each —RE1 is independently:
• —RF1, —RF2, —RE3, —RF4, —RF5, —RF6, —RF7, —RF8,
• -LF-RF4, -LF-RF5, -LF-RF6, -LF-RF7 or -LFRF8;
• wherein:
• each —RF1 is saturated aliphatic C1-6alkyl;
• each —RF2 is aliphatic C2-6alkenyl;
• each —RF3 is aliphatic C2-6alkynyl;
• each —RF4 is saturated C3-6cycloalkyl;
• each —RF5 is C3-6cycloalkenyl;
• each —RF6 is non-aromatic C3-7heterocyclyl;
• each —RF7 is C6-10carboaryl;
• each —RF8 is C5-10heteroaryl;
• each -LF- is saturated aliphatic C1-3alkylene;
• and wherein:
• each C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkenyl, non-aromatic C3-7heterocyclyl, C6-10carboaryl, C5-10heteroaryl, and C1-3alkylene is optionally substituted with one or more substituents —RF9, wherein each —RF9 is independently:
• —F, —Cl, —Br, —I,
• —RG1,
• —CF3,
• —OH,
• —ORG1,
• —OCF3,
• —SH,
• —SRG1,
• —CN,
• —NO2,
• —NH2, —NHRG1, —NRG12, —NRG2RG3,
• —C(═O)OH,
• —C(═O)ORG1,
• —C(═O)NH2, —C(═O)NHRG1, —C(═O)NRG12, —C(═O)NRG2RG3,
• -LG-OH, -LG-ORG1,
• -LG-NH2, -LG-NHRG1, -LG-NRG12, or -LG-NRG2RG3;
• wherein:
• each —RG1 is independently saturated aliphatic C1-4alkyl, phenyl, or benzyl;
• each -LG- is saturated aliphatic C1-5alkylene;
• and
• in each group —NRG2RG3, RG2 and RG3, taken together with the nitrogen atom to which they are attached, form a 5-, 6-, or 7-membered non-aromatic ring having exactly 1 ring heteroatom or exactly 2 ring heteroatoms, wherein one of said exactly 2 ring heteroatoms is N, and the other of said exactly 2 ring heteroatoms is independently N or O;
• -G3 is independently:
• —F, —Cl, —Br, —I,
• —RH1,
• —CF3,
• —OH,
• -LH-OH,
• —ORH1,
• -LH-ORH1,
• —OCF3,
• —SH,
• —SRH1,
• —CN,
• —NO2,
• —NH2, —NHRH1, —NRH12, —NRH2RH3,
• -LH-NH2, -LH-NHRH1, -LH-NRH12, -LH-NRH2RH3,
• —C(═O)OH,
• —C(═O)ORH1,
• —C(═O)NH2, —C(═O)NHRH1, —C(═O)NRH12, —C(═O)NRH2RH3,
• —NHC(═O)RH1, —NRH1C(═O)RH1,
• —NHC(═O)ORH1, —NRH1C(═O)ORH1,
• —OC(═O)NH2, —OC(═O)NHRH1, —OC(═O)NRH12,
• —OC(═O)RH1,
• —C(═O)RH1,
• —NHC(═O)NH2, —NHC(═O)NHRH1,
• —NHC(═O)NRH12, —NHC(═O)NRH2RH3,
• —NRH1C(═O)NH2, —NRH1C(═O)NHRH1,
• —NRH1C(═O)NRH12, —NRH1C(═O)NRH2RH3,
• —NHS(═O)2RH1, —NRH1S(═O)2RH1,
• —S(═O)2NH2, —S(═O)2NHRH1, —S(═O)2NRH12, —S(═O)2NRH2RH3,
• —S(═O)RH1,
• —S(═O)2RH1,
• —OS(═O)2RH1, or
• —S(═O)2ORH1,
• wherein:
• each -LH- is saturated aliphatic C1-5alkylene;
• in each group —NRH2RH3, RH2 and RH3, taken together with the nitrogen atom to which they are attached, form a 5-, 6-, or 7-membered non-aromatic ring having exactly 1 ring heteroatom or exactly 2 ring heteroatoms, wherein one of said exactly 2 ring heteroatoms is N, and the other of said exactly 2 ring heteroatoms is independently N or O;
• and
• each —RH1 is independently:
• —RJ1, —RJ2, —RJ3, —RJ4, —RJ5, —RJ6, —RJ7, —RJ8,
• -LJ-RJ4, -LJ-RJ5, -LJ-RJ6, -LJ-RJ7, or -LJ-RJ8;
• wherein:
• each —RJ1 is saturated aliphatic C1-6alkyl;
• each —RJ2 is aliphatic C2-6alkenyl;
• each —RJ3 is aliphatic C2-6alkynyl;
• each —RJ4 is saturated C3-6cycloalkyl;
• each —RJ5 is C3-6cycloalkenyl;
• each —RJ6 is non-aromatic C3-7heterocyclyl;
• each —RJ7 is C6-10carboaryl;
• each —RJ8 is C5-10heteroaryl;
• each -LJ- is saturated aliphatic C1-3alkylene;
• and wherein:
• each C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkenyl, non-aromatic C3-7heterocyclyl, C6-10carboaryl, C5-10heteroaryl, and C1-3alkylene is optionally substituted with one or more substituents —RJ9, wherein each —RJ9 is independently:
• —F, —Cl, —Br, —I,
• —RK1,
• —CF3,
• —OH,
• —ORK1,
• —OCF3,
• —SH,
• —SRK1,
• —CN,
• —NO2,
• —NH2, —NHRK1, —NRK12, NRK2RK3,
• —C(═O)OH,
• —C(═O)ORK1,
• —C(═O)NH2, —C(═O)NHRK1, —C(═O)NRK12, —C(═O)NRK2RK3,
• -LK-OH, -LK-ORK1,
• -LK-NH2, -LK-NHRK1, -LK-NRK12, or -LK-NRK2RK3;
• wherein:
• each —RK1 is independently saturated aliphatic C1-4alkyl, phenyl, or benzyl;
• each -LK- is saturated aliphatic C1-5alkylene;
• and
• in each group —NRK2RK3, RK2 and RK3, taken together with the nitrogen atom to which they are attached, form a 5-, 6-, or 7-membered non-aromatic ring having exactly 1 ring heteroatom or exactly 2 ring heteroatoms, wherein one of said exactly 2 ring heteroatoms is N, and the other of said exactly 2 ring heteroatoms is independently N or O.