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

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

wherein:

either: Y is CR 6A and Z is N;

or: Y is N and Z is CR 7A ;

—R 4A is independently -Q 1 , -Q 2 , -Q 3 , or -Q 4 ;

—R 2A is independently —H or -G 1 ;

—R 5A is independently —H or -G 2 ;

—R 6A is independently —H or -G 3 ; and

—R 7A is independently —H or -G 3 ;

and wherein:

-Q 1 is independently —NH 2 , —NHR W1 , or —NR W1 2 ;

wherein:

each —R W1 is independently:

—R X1 , —R X2 , —R X3 , —R X4 , —R X5 , —R X6 , —R X7 , —R X8 ,

-L X -R X4 , -L X -R X5 , -L X -R X6 , -L X -R X7 , or -L X -R X8 ;

wherein:

each —R X1 is saturated aliphatic C 1-6 alkyl;

each —R X2 is aliphatic C 2-6 alkenyl;

each —R X3 is aliphatic C 2-6 alkynyl;

each —R X4 is saturated C 3-6 cycloalkyl;

each —R X5 is C 3-6 cycloalkenyl;

each —R X6 is non-aromatic C 3-7 heterocyclyl;

each —R X7 is C 6-10 carboaryl;

each —R X8 is C 5-10 heteroaryl;

each -L x - is saturated aliphatic C 1-3 alkylene;

and wherein:

each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl, non-aromatic C 3-7 heterocyclyl, C 6-10 carboaryl, C 5-10 heteroaryl, and C 1-3 alkylene is optionally substituted with one or more substituents —R X9 , wherein each —R X9 is independently:

—F, —Cl, —Br, —I,

—R Y1 ,

—CF 3 ,

—OH,

—OR Y1 ,

—OCF 3 ,

—SH,

—SR Y1 ,

—CN,

—NO 2 ,

—NH 2 , —NHR Y1 , —NR Y1 2 , —NR Y2 R Y3 ,

—C(═O)OH,

—C(═O)OR Y1 ,

—C(═O)NH 2 , —C(═O)NHR Y1 , —C(═O)NR Y1 2 , —C(═O)NR Y2 R Y3 ,

-L Y -OH, -L Y -OR Y 1,

-L Y -NH 2 , -L Y -NHR Y1 , -L Y -NR Y1 2 , or -L Y -NR Y2 R Y3 ;

wherein:

each —R Y1 is independently saturated aliphatic C 1-4 alkyl, phenyl, or benzyl;

each -L Y - is saturated aliphatic C 1-5 alkylene; and

in each group —NR Y2 R Y3 , R Y2 and R Y3 , 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;

-Q 2 is —NR W2 R W3 , wherein R W2 and R W3 , 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;

-Q 3 is:

wherein:

m is independently 0 or 1;

n is independently 0, 1 or 2;

each —R P is independently saturated aliphatic C 1-3 alkyl or —CF 3 ;

—R Q is independently:

-L R -NH 2 , -L R -NHR R , -L R -NR R 2 ,

-L R -OH, -L R -OR R ,

—C(═O)OH, —C(═O)OR R ,

—C(═O)NH 2 , —C(═O)NHR R , —C(═O)NR R 2 ,

-L R -C(═O)OH, -L R -C(═O)OR R ,

-L R -C(═O)NH 2 , -L R -C(═O)NHR R , -L R -C(═O)NR R 2 , or

-L R -CN;

wherein:

each -L R - is saturated aliphatic C 1-3 alkylene; and

each —R R is saturated aliphatic C 1-3 alkyl;

-Q 4 is independently:

—NH-L T -NH 2 , —NH-L T -NHR T1 , —NH-L T -NR T1 2 , —NH-L T -NR T2 R T3 , —NR T1 -L T -NH 2 , —NR T1 -L T -NHR T1 , —NR T1 -L T -NR T1 2 , —NR-L T -NR T2 R T3 ;

—NH-L T -NHC(═O)R T1 , —NH-L T -N(R T1 )C(═O)R T1 ,

—N(R T1 )-L T -NHC(═O)R T1 , or —N(R T1 )-L T -N(R T1 )C(═O)R T1 ,

wherein:

each -L T - is saturated aliphatic C 1-6 alkylene;

each —R T1 is independently:

—R U1 , —R U2 , —R U3 , —R U4 , —R U5 , —R U6 , —R U7 , —R U8 ,

wherein:

each —R U1 is saturated aliphatic C 1-6 alkyl;

each —R U2 is aliphatic C 2-6 alkenyl;

each —R U3 is aliphatic C 2-6 alkynyl;

each —R U4 is saturated C 3-6 cycloalkyl;

each —R U5 is C 3-6 cycloalkenyl;

each —R U6 is non-aromatic C 3-7 heterocyclyl;

each —R U7 is C 6-10 -carboaryl;

each —R U8 is C 5-10 heteroaryl;

each -L U - is saturated aliphatic C 1-3 alkylene;

and wherein:

each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl, non-aromatic C 3-7 heterocyclyl, C 6-10 -carboaryl, C 5-10 heteroaryl, and C 1-3 alkylene is optionally substituted with one or more substituents —R U9 , wherein each —R U9 is independently:

—F, —Cl, —Br, —I,

—R v1 ,

—CF 3 ,

—OH,

—OR V1 ,

—OCF 3 ,

—SH,

—SR V1 ,

—CN,

—NO 2 ,

—NH 2 , —NHR V1 , —NR V1 2 , —NR V2 R V3 ,

—C(═O)OH,

—C(═O)OR V1 ,

—C(═O)NH 2 , —C(═O)NHR V1 , —C(═O)NR V1 2 , —C(═O)NR V2 R V3 ,

-L V -OH, -L V -OR V1 ,

-L V -NH 2 , -L V -NHR V1 , -L V -NR V1 2 , or -L V -NR V2 R V3 ;

wherein:

each —R V1 is independently saturated aliphatic C 1-4 alkyl, phenyl, or benzyl;

each -L V - is saturated aliphatic C 1-5 alkylene; and

in each group —NR V2 R V3 , R V2 and R V3 , 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 —NR T2 R T3 , R T2 and R T3 , 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:

-G 1 is independently:

—F, —Cl, —Br, —I,

—R A1 ,

—CF 3 ,

—OH,

-L A -OH,

—OR A1 ,

-L A -OR A1 ,

—OCF 3 ,

—SH,

—SR A1 ,

—CN,

—NO 2 ,

—NH 2 , —NHR A1 , —NR A1 2 , —NR A2 R A3 ,

-L A -NH 2 , -L A -NHR A1 , -L A -NR A1 2 , -L A -NR A2 R A3 ,

—C(═O)OH,

—C(═O)OR A1 ,

—C(═O)NH 2 , —C(═O)NHR A1 , —C(═O)NR A1 2 , —C(═O)NR A2 R A3 ,

—NHC(═O)R A1 , —NR A1 C(═O)R A1 ,

—NHC(═O)OR A1 , —NR A1 C(═O)OR A1 ,

—OC(═O)NH 2 , —OC(═O)NHR A1 , —OC(═O)NR A1 2 ,

—OC(═O)R A1 ,

—C(═O)R A1 ,

—NHC(═O)NH 2 , —NHC(═O)NHR A1 ,

—NHC(═O)NR A1 2 , —NHC(═O)NR A2 R A3 ,

—NR A1 C(═O)NH 2 , —NR A1 C(═O)NHR A1 ,

—NR A1 C(═O)NR A1 2 , —NR A1 C(═O)NR A2 R A3 ,

—NHS(═O) 2 R A1 , —NR A1 S(═O) 2 R A1 ,

—S(═O) 2 NH 2 , —S(═O) 2 NHR A1 , —S(═O) 2 NR A1 2 , —S(═O) 2 NR A2 R A3 ,

—S(═O)R A1 ,

—S(═O) 2 R A1 ,

—OS(═O) 2 R A1 , or

—S(═O) 2 OR A1 ,

wherein:

each -L A - is saturated aliphatic C 1-5 alkylene;

in each group —NR A2 R A3 , R A2 and R A3 , 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 —R A1 is independently:

—R B1 , —R B2 , —R B3 , —R B4 , —R B5 , —R B6 , —R B7 , —R B8 ,

-L B -R B4 , -L B -R B5 , -L B -R B6 , -L B -R B7 , or -L B -R B8 ;

wherein:

each —R B1 is saturated aliphatic C 1-6 alkyl;

each —R B2 is aliphatic C 2-6 alkenyl;

each —R B3 is aliphatic C 2-6 alkynyl;

each —R B4 is saturated C 3-6 cycloalkyl;

each —R B5 is C 3-6 cycloalkenyl;

each —R B6 is non-aromatic C 3-7 heterocyclyl;

each —R B7 is C 6-10 carboaryl;

each —R B8 is C 5-10 heteroaryl;

each -L B - is saturated aliphatic C 1-3 alkylene;

and wherein:

each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl, non-aromatic C 3-7 heterocyclyl, C 6-10 carboaryl, C 5-10 heteroaryl, and C 1-3 alkylene is optionally substituted with one or more substituents —R B9 , wherein each —R B9 is independently:

—F, —Cl, —Br, —I,

—R C1 ,

—CF 3 ,

—OH,

—OR C1 ,

—OCF 3 ,

—SH,

—SR C1 ,

—CN,

—NO 2 ,

—NH 2 , —NHR C1 , —NR C1 2 , —NR C2 R C3 ,

—C(═O)OH,

—C(═O)OR C1 ,

—C(═O)NH 2 , —C(═O)NHR C1 , —C(═O)NR C1 2 , —C(═O)NR C2 R C3 ,

-L C -OH, -L C -OR C1 ,

-L C -NH 2 , -L C -NHR C1 , -L C -NR C1 2 , or -L C -NR C2 R C3 ;

wherein:

each —R C1 is independently saturated aliphatic C 1-4 alkyl, phenyl, or benzyl;

each -L C - is saturated aliphatic C 1-5 alkylene; and

in each group —NR C2 R C3 , R C2 and R C3 , 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;

-G 2 is independently:

—F, —Cl, —Br, —I,

—R E1 ,

—CF 3 ,

—OH,

-L E -OH,

—OR E1 ,

-L E -OR E1 ,

—OCF 3 ,

—SH,

—SR E1 ,

—CN,

—NO 2 ,

—NH 2 , —NHR E1 , —NR E1 2 , —NR E2 R E3 ,

-L E -NH 2 , -L E -NHR E1 , -L E -NR E1 2 , -L E -NR E2 R E3 ,

—C(═O)OH,

—C(═O)OR E1 ,

—C(═O)NH 2 , —C(═O)NHR E1 , —C(═O)NR E1 2 , —C(═O)NR E2 R E3 ,

—NHC(═O)R E1 , —NR E1 C(═O)R E1 ,

—NHC(═O)OR E1 , —NR E1 C(═O)OR E1 ,

—OC(═O)NH 2 , —OC(═O)NHR E1 , —OC(═O)NR E1 2 ,

—OC(═O)R E1 ,

—C(═O)R E1 ,

—NHC(═O)NH 2 , —NHC(═O)NHR E1 ,

—NHC(═O)NR E1 2 , —NHC(═O)NR E2 R E3 ,

—NR E1 C(═O)NH 2 , —NR E1 C(═O)NHR E1 ,

—NR E1 C(═O)NR E1 2 , —NR E1 C(═O)NR E2 R E3 ,

—NHS(═O) 2 R E1 , —NR E1 S(═O) 2 R E1 ,

—S(═O) 2 NH 2 , —S(═O) 2 NHR E1 , —S(═O) 2 NR E1 2 , —S(═O) 2 NR E2 R E3 ,

—S(═O)R E1 ,

—S(═O) 2 R E1 ,

—OS(═O) 2 R E1 , or

—S(═O) 2 OR E1 ,

wherein:

each -L E - is saturated aliphatic C 1-5 alkylene;

in each group —NR E2 R E3 , R E2 and R E3 , 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 —R E1 is independently:

—R F1 , —R F2 , —R E3 , —R F4 , —R F5 , —R F6 , —R F7 , —R F8 ,

-L F -R F4 , -L F -R F5 , -L F -R F6 , -L F -R F7 or -L F R F8 ;

wherein:

each —R F1 is saturated aliphatic C 1-6 alkyl;

each —R F2 is aliphatic C 2-6 alkenyl;

each —R F3 is aliphatic C 2-6 alkynyl;

each —R F4 is saturated C 3-6 cycloalkyl;

each —R F5 is C 3-6 cycloalkenyl;

each —R F6 is non-aromatic C 3-7 heterocyclyl;

each —R F7 is C 6-10 carboaryl;

each —R F8 is C 5-10 heteroaryl;

each -L F - is saturated aliphatic C 1-3 alkylene;

and wherein:

each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl, non-aromatic C 3-7 heterocyclyl, C 6-10 carboaryl, C 5-10 heteroaryl, and C 1-3 alkylene is optionally substituted with one or more substituents —R F9 , wherein each —R F9 is independently:

—F, —Cl, —Br, —I,

—R G1 ,

—CF 3 ,

—OH,

—OR G1 ,

—OCF 3 ,

—SH,

—SR G1 ,

—CN,

—NO 2 ,

—NH 2 , —NHR G1 , —NR G1 2 , —NR G2 R G3 ,

—C(═O)OH,

—C(═O)OR G1 ,

—C(═O)NH 2 , —C(═O)NHR G1 , —C(═O)NR G1 2 , —C(═O)NR G2 R G3 ,

-L G -OH, -L G -OR G1 ,

-L G -NH 2 , -L G -NHR G1 , -L G -NR G1 2 , or -L G -NR G2 R G3 ;

wherein:

each —R G1 is independently saturated aliphatic C 1-4 alkyl, phenyl, or benzyl;

each -L G - is saturated aliphatic C 1-5 alkylene; and

in each group —NR G2 R G3 , R G2 and R G3 , 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;

-G 3 is independently:

—F, —Cl, —Br, —I,

—R H1 ,

—CF 3 ,

—OH,

-L H -OH,

—OR H1 ,

-L H -OR H1 ,

—OCF 3 ,

—SH,

—SR H1 ,

—CN,

—NO 2 ,

—NH 2 , —NHR H1 , —NR H1 2 , —NR H2 R H3 ,

-L H -NH 2 , -L H -NHR H1 , -L H -NR H1 2 , -L H -NR H2 R H3 ,

—C(═O)OH,

—C(═O)OR H1 ,

—C(═O)NH 2 , —C(═O)NHR H1 , —C(═O)NR H1 2 , —C(═O)NR H2 R H3 ,

—NHC(═O)R H1 , —NR H1 C(═O)R H1 ,

—NHC(═O)OR H1 , —NR H1 C(═O)OR H1 ,

—OC(═O)NH 2 , —OC(═O)NHR H1 , —OC(═O)NR H1 2 ,

—OC(═O)R H1 ,

—C(═O)R H1 ,

—NHC(═O)NH 2 , —NHC(═O)NHR H1 ,

—NHC(═O)NR H1 2 , —NHC(═O)NR H2 R H3 ,

—NR H1 C(═O)NH 2 , —NR H1 C(═O)NHR H1 ,

—NR H1 C(═O)NR H1 2 , —NR H1 C(═O)NR H2 R H3 ,

—NHS(═O) 2 R H1 , —NR H1 S(═O) 2 R H1 ,

—S(═O) 2 NH 2 , —S(═O) 2 NHR H1 , —S(═O) 2 NR H1 2 , —S(═O) 2 NR H2 R H3 ,

—S(═O)R H1 ,

—S(═O) 2 R H1 ,

—OS(═O) 2 R H1 , or

—S(═O) 2 OR H1 ,

wherein:

each -L H - is saturated aliphatic C 1-5 alkylene;

in each group —NR H2 R H3 , R H2 and R H3 , 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 —R H1 is independently:

—R J1 , —R J2 , —R J3 , —R J4 , —R J5 , —R J6 , —R J7 , —R J8 ,

-L J -R J4 , -L J -R J5 , -L J -R J6 , -L J -R J7 , or -L J -R J8 ;

wherein:

each —R J1 is saturated aliphatic C 1-6 alkyl;

each —R J2 is aliphatic C 2-6 alkenyl;

each —R J3 is aliphatic C 2-6 alkynyl;

each —R J4 is saturated C 3-6 cycloalkyl;

each —R J5 is C 3-6 cycloalkenyl;

each —R J6 is non-aromatic C 3-7 heterocyclyl;

each —R J7 is C 6-10 carboaryl;

each —R J8 is C 5-10 heteroaryl;

each -L J - is saturated aliphatic C 1-3 alkylene;

and wherein:

each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl, non-aromatic C 3-7 heterocyclyl, C 6-10 carboaryl, C 5-10 heteroaryl, and C 1-3 alkylene is optionally substituted with one or more substituents —R J9 , wherein each —R J9 is independently:

—F, —Cl, —Br, —I,

—R K1 ,

—CF 3 ,

—OH,

—OR K1 ,

—OCF 3 ,

—SH,

—SR K1 ,

—CN,

—NO 2 ,

—NH 2 , —NHR K1 , —NR K1 2 , NR K2 R K3 ,

—C(═O)OH,

—C(═O)OR K1 ,

—C(═O)NH 2 , —C(═O)NHR K1 , —C(═O)NR K1 2 , —C(═O)NR K2 R K3 ,

-L K -OH, -L K -OR K1 ,

-L K -NH 2 , -L K -NHR K1 , -L K -NR K1 2 , or -L K -NR K2 R K3 ;

wherein:

each —R K1 is independently saturated aliphatic C 1-4 alkyl, phenyl, or benzyl;

each -L K - is saturated aliphatic C 1-5 alkylene; and

in each group —NR K2 R K3 , R K2 and R K3 , 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.

2. A compound according to claim 1 , wherein:

Y is CR 6A and Z is N;

R 6A is —H;

—R 2A is —H; and

—R 5A is —H.

3. A compound according to claim 1 , wherein:

Y is N and Z is CR 7A ;

—R 7A is —H;

—R 2A is —H; and

—R 5A is —H.

4. A compound according to claim 1 , wherein —R 4A is -Q 1 .

5. A compound according to claim 2 , wherein —R 4A is -Q 1 .

6. A compound according to claim 3 , wherein —R 4A is -Q 1 .

7. A compound according to claim 1 , wherein —R 4A is -Q 2 .

8. A compound according to claim 2 , wherein —R 4A is -Q 2 .

9. A compound according to claim 3 , wherein —R 4A is -Q 2 .

10. A compound according to claim 1 , wherein —R 4A is -Q 3 .

11. A compound according to claim 2 , wherein —R 4A is -Q 3 .

12. A compound according to claim 3 , wherein —R 4A is -Q 3 .

13. A compound according to claim 1 , wherein —R 4A is -Q 4 .

14. A compound according to claim 2 , wherein —R 4A is -Q 4 .

15. A compound according to claim 3 , wherein —R 4A is -Q 4 .

16. A compound selected from the following compounds, or a pharmaceutically acceptable salt thereof:

17. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier or diluent.

18. A method of preparing a pharmaceutical composition comprising the step of admixing a compound according to claim 1 , and a pharmaceutically acceptable carrier or diluent.