Compounds that are ERK inhibitors

1. A compound of formula 1.0:

or the pharmaceutically acceptable salts thereof, wherein:

Y 1 , Y 2 , and Y 3 are each independently selected from the group consisting of:

—CH═, —N═ and —CR 9 ═;

z is 1 to 3;

X 1 is selected from the group consisting of: ═O, ═S, ═NOR 50 , —N(R 50 ) 2 (wherein each R 50 is independently selected), —N(R 51 )C(O)R 50 and —OR 50 ;

Q is a substituent selected from the group consisting of:

Each Q 1 represents a ring independently selected from the group consisting of:

cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl, wherein said substituted rings are substituted with 1 to 3 substituents independently selected from the group consisting of: halo and the R 10 moieties; provided that when Q 1 is aryl, heteroaryl, substituted aryl or substituted heteroaryl then the carbon atoms at the ring junction are not substituted;

Q 2 represents a ring independently selected from the group consisting of:

heterocycloalkyl and substituted heterocycloalkyl wherein said substituted rings are substituted with 1 to 3 substituents independently selected from the group consisting of: halo and the R 10 moieties;

Z 1 represents —(C(R 24 ) 2 ) w — wherein each R 24 is independently selected from the group consisting of: H, alkyl and F, and wherein w is 1, 2 or 3;

Z 2 is selected from the group consisting of: —N(R 44 )—, —O— and —C(R 46 ) 2 —;

m is 1 to 6;

n is 1 to 6;

p is 0 to 6;

t is 0, 1, or 2;

R 1 is selected from the group consisting of:

(1) —CN,

(2) —NO 2 ,

(3) —OR 10 ,

(4) —SR 10 ,

(5) —N(R 10 ) 2 ,

(6) R 10 ,

(7) —C(O)R 10 ,

(8) —(C(R 30 ) 2 ) n —NR 32 —C(O)—R 10 ,

(9) —(C(R 30 ) 2 ) n —NR 32 —S(O) t —R 10 ,

(10) —(C(R 30 ) 2 n —NR 32 —C(O)—N(R 32 )—R 10 ,

(12) —CF 3 ,

(13) —C(O)OR 10 ,

(14) —(C(R 30 ) 2 ) n R 13 ,

(15) alkenyl,

(16) —NR 32 —C(O)—R 14 ,

wherein each R 10 is independently selected,

wherein each a 10 is independently selected,

(20) —C(O)—NR 32 —(C(R 30 ) 2 ) p —OR 10 ,

(21) —C(O)N(R 10 ) 2 wherein each R 10 is independently selected,

(22) —C(O)—NR 32 —C(R 18 ) 3 wherein each R 18 is independently selected from the group consisting of: R 10 and —C(O)OR 19 , and R 19 is selected from the group consisting of:alkyl and substituted arylalkyl,

(23) —C(O)—NR 32 —(C(R 30 ) 2 ) n —C(O)—N(R 10 ) 2 ,

(24) heterocycloalkenyl,

 and (26) arylalkenyl-;

R 2 is selected from the group consisting of:

(1) H,

(2) —CN,

(3) halo,

(4) alkyl,

(5) substituted alkyl wherein said substituted alkyl is substituted with 1 to 3 substitutents selected from the group consisting of: (a) —OH, (b) —O-alky, (c) —O-alkyl substituted with 1 to 3 F atoms, and (d) —N(R 40 ) 2 wherein each R 40 is independently selected from the group consisting of: (i) H, (ii) C 1 -C 3 alkyl, (iii) —CF 3 , and (e) halo,

(6) alkynyl,

(7) alkenyl,

(8) —(CH 2 ) m R 11 ,

(9) —N(R 26 ) 2 ,

(10) —OR 23 ,

(11) —N(R 26 )C(O)R 42 ,

(12) cycloalkyl,

(13) cycloalkylalkyl,

(15) —O-(substituted alkyl) wherein said substituted alkyl is substituted with 1 to 3 F atoms,

(16) —S(O) t -alkyl,

(17) —C(O)-alkyl,

wherein each alkyl is independently selected,

which each alkyl is independently selected,

wherein each alkyl is independently selected,

(22) —N(R 48 )—C(O)—R 48 wherein each R 48 is independently selected from the group consisting of: H and alkyl, and

(23) —C(O)-alkyl; and

each R 3 , R 4 , R 5 , R 6 and R 7 is independently selected from the group consisting of: (1) H, (2) alkenyl, (3) substituted alkenyl, (4) alkyl, (5) substituted alkyl, (6) cycloalkyl, (7) substituted cycloalkyl, (8) cycloalkylalkyl-, (9) substituted cycloalkylalkyl-, (10) heterocycloalkyl, (11) substituted heterocycloalkyl, (12) heterocycloalkylalkyl-, (13) substituted heterocycloalkylalkyl-, (14) —C(O)R 10 , (15) arylheteroaryl-, (16) substituted arylheteroaryl-, (17) heteroarylaryl-, (18) substituted heteroarylaryl-, (19) aryl, (20) substituted aryl, (21) heteroaryl, (22) substituted heteroaryl, (23) heteroarylheteroaryl-, (24) substituted heteroarylheteroaryl-, (25) arylaminoheteroaryl-, (26) substituted arylaminoheteroaryl-, (27) arylalkynyl-, (28) substituted arylalkynyl-, (29) heteroarylalkynyl-, (30) substituted heteroarylalkynyl-, and (31) benzoheteroaryl;

wherein said R 3 , R 4 , R 5 , R 6 and R 7 substituted groups (7), (9), (11), (13), (16), (18), (20), (22), (24), (26), (28) and (30) are substituted with 1 to 3 substituents independently selected from the group consisting of: —NH 2 , —NHR 20 , —N(R 20 ) 2 wherein each R 20 is independently selected, alkyl, alkenyl, halo, —C(O)—NH—R 28 , —C(O)OR 28 , —C(O)R 28 , and —OR 20 ;

wherein said R 3 , R 4 , R 5 , R 6 and R 7 substituted groups (3) and (5) are substituted with 1 to 3 substituents independently selected from the group consisting of: —NH 2 , halo, —C(O)—NH—R 28 , —C(O)OR 28 , and —C(O)R 28 ;

R 5A is selected from the group consisting of: halo, —OH, alkyl, —SR 52 , —O-alkyl;

R 8 is selected from the group consisting of: H, —OH, —N(R 10 ) 2 , —NR 10 C(O)R 12 , and alkyl;

each R 9 is independently selected from the group consisting of:halogen, —CN, —NO 2 , —OR 10 , —SR 10 , —N(R 10 ) 2 , and R 10 ;

each R 10 is independently selected from the group consisting of: H, alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, alkylheteroaryl-, alkylaryl-, substituted alkyl, substituted aryl, substituted arylalkyl, substituted heteroaryl, substituted heteroarylalkyl, substituted cycloalkyl, substituted cycloalkylalkyl, substituted heterocycloalkyl, substituted heterocycloalkylalkyl, substituted alkylheteroaryl-, substituted alkylaryl-, heterocycloalkenyl, and substituted heterocycloalkenyl, and wherein:

said R 10 substituted alkyl is substituted with 1 to 3 substituents independently selected from the group consisting of: —NH 2 , —NHR 20 , —NO 2 , —CN, —OR 26 , —C(O)—NH—R 26 , —C(O)OR 26 , and —C(O)R 26 , and

said R 10 substituted aryl, substituted arylalkyl, substituted heteroaryl, substituted heteroarylalkyl, substituted cycloalkyl, substituted cycloalkylalkyl, substituted heterocycloalkyl, substituted heterocycloalkylalkyl, substituted alkylheteroaryl- and substituted alkylaryl- are substituted with 1 to 3 substituents independently selected from the group consisting of: (1) —NH 2 , (2) —NO 2 , (3) —CN, (4) —OH, (5) —OR 20 , (6) —OCF 3 , (7) alkyl substituted with 1 to 3 independently selected halo atoms, (8) —C(O)R 38 , (9) alkyl, (10) alkenyl, (11) halo, (12) —C(O)—NH—R 26 , (13) —C(O)OR 38 , (14) —C(O)—NR 32 —(C(R 30 ) 2 ) n —N(R 38 ) 2 , (15) —S(O) t R 38 , (16) —C(O)—NR 32 —R 38 , (17) —NR 32 —C(O)—R 38 ,

 (19) —NHR 20 , (20) cycloalkyl, (21) —O-alkyl—O—R 20 , (22) hydroxyalkyl, (23) —N(R 20 ) 2 wherein each R 20 is independently selected, (24) —alkyl—OR 20 , (25) —O-alkyl—OH, (26) —NH(hydroxyalkyl), and (27) oxazolidinone;

R 11 is selected from the group consisting of: F, —OH, —CN, —OR 10 , —NHNR 1 R 10 , —SR 10 and heteroaryl;

R 12 is selected from the group consisting of: alkyl, aryl, heteroaryl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl and heterocycloalkylalkyl;

R 14 is selected from the group consisting of: alkyl, aryl, heteroaryl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, alkylheterocycloalkyl, heterocycloalkylalkyl-, alkylheteroaryl- and alkylaryl-;

R 15 is selected from the group consisting of: H, —OH, alkyl, aryl, heteroaryl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl and heterocycloalkylalkyl-, alkylheteroaryl- and alkylaryl-;

R 20 represents alkyl;

R 23 is selected from the group consisting of: H, alkyl, aryl, cycloalkyl, and cycloalkylalkyl-;

each R 26 is independently selected from the group consisting of: H and alkyl;

R 28 is alkyl;

each R 30 is independently selected from the group consisting of: H, alkyl, and F;

each R 32 is independently selected from the group consisting of: H and alkyl;

each R 35 is independently selected from the group consisting of: H and C 1 to C 6 alkyl;

R 36 is selected from the group consisting of: H, alkyl, and —O-alkyl;

each R 38 is independently selected from the group consisting of: H, alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, alkylheteroaryl-, alkylaryl-, substituted alkyl, substituted aryl, substituted arylalkyl, substituted heteroaryl, substituted heteroarylalkyl, substituted cycloalkyl, substituted cycloalkylalkyl, substituted heterocycloalkyl, substituted heterocycloalkylalkyl, substituted alkylheteroaryl- and substituted alkylaryl-, and wherein:

said R 38 substituted alkyl is substituted with 1 to 3 substituents independently selected from the group consisting of: —NH 2 , —NO 2 , —CN, —OR 26 , halo, —C(O)—NH—R 28 , —C(O)OR 28 , and —C(O)R 28 , and

said R 38 substituted aryl, substituted arylalkyl, substituted heteroaryl, substituted heteroarylalkyl, substituted cycloalkyl, substituted cycloalkylalkyl, substituted heterocycloalkyl, substituted heterocycloalkylalkyl, substituted alkylheteroaryl- and substituted alkylaryl- are substituted with 1 to 3 substituents independently selected from the group consisting of: (1) —NH 2 , (2) —NO 2 , (3) —CN, (4) —OH, (5) —OR 20 , (6) —OCF 3 , (7) —CF 3 , (8) —C(O)OR 26 , (9) alkyl, (10) alkenyl, (11) halo, (12) —C(O)—NH—R 26 , (13) —C(O)OR 26 , (14)—C(O)—NR 32 —(C(R 30 ) n —N(R 26 ) 2 , (15) —S(O) t R 26 , (16) —C(O)N(R 32 )(R 26 ), (17) —NR 32 C(O)R 26 ,

 and (19) —NHR 20 ;

R 42 is selected from the group consisting of: alkyl, aryl, heteroaryl, and cycloalkyl;

R 44 is selected from the group consisting of: H, alkyl, cycloalkyl, and cycloalkylalkyl;

Each R 46 is independently selected from the group consisting of: H, alkyl, cycloalkyl, and cycloalkylalkyl;

Each R 50 is independently selected from the group consisting of H and alkyl;

R 51 is selected from the group consisting of H and alkyl; and

R 52 is —O-alkyl.

2. The compound of claim 1 wherein Q is 2.1.

3. The compound of claim 1 wherein Z 1 is —CH 2 —.

4. The compound of claim 1 wherein each R 3 , R 4 , R 6 , and R 7 is independently selected from the group consisting of: H and alkyl.

5. The compound of claim 4 wherein each R 3 , R 4 , R 6 , and R 7 is H; Q is 2.1; and the compound of formula 1.0 is:

6. The compound of claim 1 wherein R 1 is selected from the group consisting of:

 and wherein R 5 is selected from the group consisting of:

7. The compound of claim 1 wherein R 1 is phenyl or substituted phenyl.

8. The compound of claim 1 wherein R 1 is heteroaryl or substituted heteroaryl.

9. The compound of claim 6 wherein: Q is 2.1; each R 3 , R 4 , R 6 , and R 7 is H; and the compound of formula 1.0 is:

10. The compound of claim 9 wherein: R 1 is selected from the group consisting of:

and R 5 is selected from the group consisting of:

11. The compound of claim 1 wherein said compound is a compound of formula 1.4:

or the pharmaceutically acceptable salts thereof, wherein R 1 , R 2 and Q are independently selected, and wherein:

Q is:

R 1 is selected from the group consisting of:

R 2 is selected from the group consisting of: —O-alkyl and —S-alkyl; and

R 5 is selected from the group consisting of:

12. The compound of claim 11 wherein R 2 is —OCH 3 .

13. The compound of claim 11 wherein R 2 is —SCH 3 .

14. A compound selected from the group consisting of:

wherein R 50 is selected from the group consisting of: H and alkyl, wherein said alkyl is selected from methyl and ethyl,

wherein R 50 is selected from the group consisting of: H and alkyl, wherein said alkyl is selected from methyl and ethyl,

wherein R 50 is selected from the group consisting of: H and alkyl, wherein said alkyl is selected from methyl and ethyl,

wherein R 50 is selected from the group consisting of: H and alkyl, wherein said alkyl is selected from methyl and ethyl, and

and the pharmaceutically acceptable salts thereof.

15. A pharmaceutical composition comprising at least one compound of claim 1 and a pharmaceutically acceptable carrier.

16. The compound of claim 14 selected from the group consisting of:

wherein R 50 is selected from the group consisting of: H and alkyl, wherein said alkyl is selected from methyl and ethyl,

wherein R 50 is selected from the group consisting of: H and alkyl, wherein said alkyl is selected from methyl and ethyl,

wherein R 50 is selected from the group consisting of: H and alkyl, wherein said alkyl is selected from methyl and ethyl,

wherein R 50 is selected from the group consisting of: H and alkyl, wherein said alkyl is selected from methyl and ethyl, and

17. A compound selected from the group consisting of:

and the pharmaceutically acceptable salts thereof.

18. The compound of claim 17 selected from the group consisting of: