Certain substituted amides, method of making, and method of use thereof

1. A method for treating a patient suffering from B cell lymphoma, B-cell leukemia, or rheumatoid arthritis comprising administering to the patient an effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof, or a mixture thereof, wherein

X is chosen from N and CR 2 ;

Y is chosen from N and CR 3′ ;

Z is chosen from N and CR 3 ; provided that only one of X, Y and Z is N;

W is N;

V is CH;

R 1 is chosen from:

R 2 is chosen from H, CH 3 , F, Cl, CN, OCH 3 , OH and CF 3 ;

R 2′ is chosen from H and F;

R 3 is chosen from H, CH 3 , CF 3 , F, Cl, CN and OCH 3 ;

R 3′ is chosen from H, CH 3 , F, Cl, CN and OCH 3 ;

R 4 is

m is chosen from 0 and 1;

n is chosen from 0 and 1;

R 5 is chosen from H, C 1 -C 6 alkyl, and C 3 -C 6 cycloalkyl, wherein said alkyl is optionally substituted with one or more substituents chosen from OH, F, and OCH 3 ;

R 6 is chosen from H and C 1 -C 6 alkyl; or R 5 and R 6 are optionally taken together with the nitrogen atom to which they are attached to form a 4- to 6-membered cyclic ring having 0-1 additional N, S or O, wherein the optional additional ring nitrogen is optionally substituted with C 1 -C 3 alkyl and said cyclic ring is optionally substituted with OH;

R 7 is chosen from H, C 1 -C 6 alkyl, and C 3 -C 6 cycloalkyl, wherein said alkyl is optionally substituted with one or more substituents chosen from OH and O(C 1 -C 4 alkyl); or R 6 and R 7 are optionally taken together with the —N(R 5 )C(R 9 )(CH 2 ) n ═O)N(R 8 )— group through the respective nitrogen atoms to which they are directly attached to form a 6-membered cyclic ring;

R 8 is chosen from H and C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with one or more substituents chosen from OH, F, and OCH 3 ; or R 7 and R 8 are optionally taken together with the nitrogen atom to which they are attached to form a 4- to 6-membered cyclic ring having 0-1 additional N, S or O, wherein the optional additional ring nitrogen is optionally substituted with C 1 -C 3 alkyl and said cyclic ring is optionally substituted with OH;

R 9 is chosen from H and CH 3 ;

R 10 is chosen from OH, H and C 1 -C 3 alkyl optionally substituted with N(R 9 ) 2 ;

R 11 is chosen from H, CH 3 and CF 3 ; and

R 12 is C 1 -C 3 alkyl.

2. The method of claim 1 , wherein R 11 is CH 3 .

3. The method of claim 2 , wherein W is N and V is CH.

4. The method of claim 3 , wherein X is CR 2 .

5. The method of claim 3 , wherein X is N.

6. The method of claim 3 , wherein Y is CR 3′ .

7. The method of claim 3 , wherein Y is N.

8. The method of claim 3 , wherein Z is CR 3 .

9. The method of claim 3 , wherein Z is N.

10. The method of claim 3 , wherein the compound is:

11. The method of claim 1 , wherein R 2′ is F.

12. The method of claim 1 , wherein R 2′ is H.

13. The method of claim 12 , wherein R 1 is chosen from:

R 2 is chosen from H, CH 3 , F, and Cl;

R 3 is chosen from H, CH 3 , F, and Cl;

R 3′ is chosen from H, CH 3 , F and Cl;

R 5 is chosen from H and C 1 -C 6 alkyl;

R 6 is chosen from H and C 1 -C 6 alkyl; or R 5 and R 6 are optionally taken together with the nitrogen atom to which they are attached to form a 6-membered cyclic ring having 0-1 additional N, S or O, wherein the optional additional ring nitrogen is optionally substituted with C 1 -C 3 alkyl;

R 8 is chosen from H and C 1 -C 6 alkyl; or R 7 and R 8 are optionally taken together with the nitrogen atom to which they are attached to form a 4- to 6-membered cyclic ring having 0-1 additional N, S or O, wherein the optional additional ring nitrogen is optionally substituted with C 1 -C 3 alkyl;

R 10 is chosen from H or C 1 -C 3 alkyl; and

R 11 is CH 3 .

14. The method of claim 1 , wherein said compound is selected from:

N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenyl amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluorophenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1-(Ethyl(isopropyl)amino)-2-((2-methoxyethyl)(methyl)amino)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1,2-Bis(4-ethylpiperazin-1-yl)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1,2-Bis(4-ethyl piperazin-1-yl)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1-Ethyl-4-methyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetra hydrobenzo[b]thiophene-2-carboxamide;

4-tert-Butyl-N-(3-(6-(4-(1-ethyl-4-methyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydro pyrazin-2-yl)-2-methylphenyl)benzamide;

(S)—N-(3-(6-(4-(3-(Dimethyl amino)-2-(isopropyl(methyl)amino)-3-oxopropyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(3-(Dimethylamino)-1-(isopropyl(methyl)amino)-3-oxopropyl)phenyl amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methyl phenyl)-4,5,6,7-tetrahydro benzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1-Amino-2-morpholino-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4-tert-butylbenzamide;

N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenyl amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetra hydrobenzo[b]thiophene-2-carboxamide;

4-tert-Butyl-N-(3-(6-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)benzamide;

N-(3-(6-(4-(2-Amino-1-(isopropyl(methyl)amino)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydro pyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(2-Methyl-3-(4-methyl-6-(4-(1-methyl-3-oxopiperazin-2-yl)phenylamino)-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(2-(Dimethylamino)-1-(isopropyl(methyl)amino)-2-oxoethyl)phenyl amino)-4-methyl-5-oxo-4,5-dihydro pyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

4-tert-Butyl-N-(3-(6-(4-(2-(dimethylamino)-1-(isopropyl(methyl)amino)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)benzamide;

N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenyl amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2,5-difluorophenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

(S)-4-tert-Butyl-N-(3-(6-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)benzamide;

(R)-4-tert-Butyl-N-(3-(6-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)benzamide;

N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenylamino)-5-oxo-4,5-dihydro pyrazin-2-yl)-2-methylphenyl)-4-(ethyl(methyl)amino)benzamide;

(R)—N-(3-(6-(4-(2-(Dimethylamino)-1-(isopropyl(methyl)amino)-2-oxoethyl)phenyl amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenyl amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4-(1-ethylcyclopropyl)benzamide;

4-tert-Butyl-N-(3-(6-(4-(1-(4-ethylpiperazin-1-yl)-2-morpholino-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)benzamide;

N-(3-(6-(4-(1-(4-Ethylpiperazin-1-yl)-2-morpholino-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydro pyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1-(4-ethylpiperazin-1-yl)-2-morpholino-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methyl phenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1,2-Bis(4-ethyl piperazin-1-yl)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4-tert-butylbenzamide;

4-tert-Butyl-N-(3-(6-(4-(2-(dimethylamino)-1-(4-ethylpiperazin-1-yl)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)benzamide;

N-(3-(6-(4-(2-(Dimethylamino)-1-(4-ethylpiperazin-1-yl)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(2-(Dimethylamino)-1-(4-ethylpiperazin-1-yl)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydro pyrazin-2-yl)-2-methylphenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-2-carboxamide;

4-tert-Butyl-N-(3-(6-(4-(1-(4-ethylpiperazin-1-yl)-2-((2-methoxyethyl)(methyl)amino)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)benzamide;

N-(3-(6-(4-(1-(4-Ethylpiperazin-1-yl)-2-((2-methoxyethyl)(methyl)amino)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methyl phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1-(4-Ethylpiperazin-1-yl)-2-((2-methoxyethyl)(methyl)amino)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydro pyrazin-2-yl)-2-methylphenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1-Isopropyl-4-methyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenyl amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-5-fluoro-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(2-Chloro-3-(6-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenyl amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4-(ethyl(methyl)amino)benzamide;

N-(3-(6-(4-(1-(Ethyl(isopropyl)amino)-2-morpholino-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydro pyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(1-(Ethyl(isopropyl)amino)-2-(4-ethylpiperazin-1-yl)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methyl phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-(3-(6-(4-(2-(Dimethylamino)-1-(ethyl(isopropyl)amino)-2-oxoethyl)phenyl amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-{3-[6-({4-[2-(Azetidin-1-yl)-1-(morpholin-4-yl)-2-oxo ethyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydro pyrazin-2-yl]-2-methylphenyl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{2-Methyl-3-[4-methyl-6-({4-[(methylcarbamoyl)(morpholin-4-yl)methyl]phenyl}amino)-5-oxo-4,5-dihydropyrazin-2-yl]phenyl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{3-[6-({4-[2-(Azetidin-1-yl)-1-[ethyl(propan-2-yl)amino]-2-oxoethyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydro pyrazin-2-yl]-2-methylphenyl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{3-[6-({4-[(Dimethyl carbamoyl)[ethyl(propan-2-yl)amino]methyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-{3-[6-({4-[1-(azetidin-1-yl)-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydro pyrazin-2-yl]-2-methyl phenyl}-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-5-oxo-4,5-dihydro pyrazin-2-yl)-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{3-[6-({4-[Azetidin-1-yl(dimethylcarbamoyl)methyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-[2-Methyl-3-(4-methyl-5-oxo-6-{[4-(1,2,4-trimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4,5-dihydropyrazin-2-yl)phenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[5-Chloro-3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{3-[6-({4-[Azetidin-1-yl(dimethylcarbamoyl)methyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4-tert-butylbenzamide;

N-{3-[6-({4-[Azetidin-1-yl(dimethylcarbamoyl)methyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-(3-{6-[(4-{Azetidin-1-yl[(2-hydroxyethyl)(methyl)carbamoyl]methyl}phenyl)amino]-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl}-2-methylphenyl)-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{2-Methyl-3-[4-methyl-6-({4-[4-methyl-3-oxo-1-(propan-2-yl)piperazin-2-yl]phenyl}amino)-5-oxo-4,5-dihydropyrazin-2-yl]phenyl}-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-{3-[6-({4-[(4-Ethyl piperazin-1-yl)[(2-hydroxy ethyl)(methyl)carbamoyl]methyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-{3-[6-({4-[(Diethyl carbamoyl)(4-ethylpiperazin-1-yl)methyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydro pyrazin-2-yl]-2-methyl phenyl}-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

4-tert-Butyl-N-(3-{6-[(4-{[ethyl(methyl)carbamoyl](4-ethylpiperazin-1-yl)methyl}phenyl)amino]-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl}-2-methylphenyl)benzamide;

4-tert-Butyl-N-{3-[6-({4-[(diethylcarbamoyl)(4-ethylpiperazin-1-yl)methyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}benzamide;

N-[3-(6-{[4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-N-methyl-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

4-tert-Butyl-N-(2-methyl-3-{4-methyl-6-[(4-{1-[methyl(propan-2-yl)amino]-2-(morpholin-4-yl)-2-oxoethyl}phenyl)amino]-5-oxo-4,5-dihydropyrazin-2-yl}phenyl)benzamide;

N-{3-[6-({4-[2-(Azetidin-1-yl)-1-[methyl(propan-2-yl)amino]-2-oxoethyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4-tert-butylbenzamide;

N-{3-[6-({4-[1-(Azetidin-1-yl)-2-(morpholin-4-yl)-2-oxoethyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-(3-{6-[(4-{Azetidin-1-yl[(2-hydroxyethyl)(methyl)carbamoyl]methyl}phenyl)amino]-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl}-2-methylphenyl)-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

4-tert-Butyl-N-(2-methyl-3-{4-methyl-6-[(4-{1-[methyl(propan-2-yl)amino]-2-(4-methylpiperazin-1-yl)-2-oxoethyl}phenyl)amino]-5-oxo-4,5-dihydropyrazin-2-yl}phenyl)benzamide;

N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenyl amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4-(1-methylcyclopropyl)benzamide;

N-(3-(6-(4-(1-Ethyl-4-methyl-3-oxopiperazin-2-yl)phenyl amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-2-carboxamide;

4-tert-Butyl-N-(3-(6-(4-(1-isopropyl-4-methyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)benzamide;

N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

(S)—N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

(R)—N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide; and

(S)-(+)-N-(3-(6-(4-(2-(Dimethylamino)-1-(isopropyl(methyl)amino)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-N-methyl-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-(3-{6-[(4-{1-[ethyl(methyl)amino]-2-(4-ethylpiperazin-1-yl)-2-oxoethyl}phenyl)amino]-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl}-2-methylphenyl)-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-6-[ethyl(methyl)amino]pyridine-3-carboxamide;

N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluoro-5-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{3-[6-({4-[2-(azetidin-1-yl)-1-[methyl(propan-2-yl)amino]-2-oxoethyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)phenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(4-ethyl-1-methyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(4-ethyl-1-methyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2,5-dimethylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[5-chloro-3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{3-[6-({4-[(dimethylcarbamoyl)(morpholin-4-yl)methyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{3-[6-({4-[(diethylcarbamoyl)(morpholin-4-yl)methyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-(3-{6-[(4-{[ethyl(methyl)carbamoyl](morpholin-4-yl)methyl}phenyl)amino]-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl}-2-methylphenyl)-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-(3-{6-[(4-{[(2-hydroxyethyl)(methyl)carbamoyl](morpholin-4-yl)methyl}phenyl)amino]-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl}-2-methylphenyl)-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{3-[6-({4-[2-(3-hydroxyazetidin-1-yl)-1-(morpholin-4-yl)-2-oxoethyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{3-[6-({4-[(dimethylcarbamoyl)(morpholin-4-yl)methyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-{3-[6-({4-[(diethylcarbamoyl)(morpholin-4-yl)methyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-{3-[6-({4-[2-(azetidin-1-yl)-1-(morpholin-4-yl)-2-oxoethyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-{2-methyl-3-[4-methyl-6-({4-[(methylcarbamoyl)(morpholin-4-yl)methyl]phenyl}amino)-5-oxo-4,5-dihydropyrazin-2-yl]phenyl}-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-(3-{6-[(4-{[ethyl(methyl)carbamoyl](morpholin-4-yl)methyl}phenyl)amino]-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl}-2-methylphenyl)-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-(3-{6-[(4-{[(2-hydroxyethyl)(methyl)carbamoyl](morpholin-4-yl)methyl}phenyl)amino]-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl}-2-methylphenyl)-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

N-{3-[6-({4-[2-(3-hydroxyazetidin-1-yl)-1-(morpholin-4-yl)-2-oxoethyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}-4H,5H,6H,7H,8H-cyclohepta[b]thiophene-2-carboxamide;

4-tert-butyl-N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-2-methoxybenzamide;

N-[2-chloro-3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-5-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2,6-dimethylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-5-methoxy-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2,6-difluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[5-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-6-fluoro-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[2,6-dichloro-3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)phenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[6-chloro-3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[2-chloro-5-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)phenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[2-chloro-3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-6-fluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[2-cyano-5-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)phenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[4-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-6-fluoropyridin-2-yl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

4-tert-butyl-N-{3-[6-({4-[(S)-(dimethylcarbamoyl) [methyl(propan-2-yl)amino]methyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}benzamide;

4-tert-butyl-N-{3-[6-({4-[(R)-(dimethylcarbamoyl)[methyl(propan-2-yl)amino]methyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-methylphenyl}benzamide;

4-tert-butyl-N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-N-[3-(dimethylamino)propyl]benzamide;

N-[6-chloro-3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[5-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)pyridin-3-yl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[6-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)pyridin-2-yl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[2-chloro-3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-6-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[6-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-3-fluoropyridin-2-yl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[6-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-5-fluoropyridin-2-yl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-7-oxo-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-7-hydroxy-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

4-tert-butyl-N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-2-methylbenzamide;

N-[3-(6-{[4-(1-ethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-6-fluoro-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(1-ethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2,6-difluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(1-ethyl-4-methyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2,6-difluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[5-(6-{[4-(4-ethyl-1-methyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

4-tert-butyl-N-[6-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)pyridin-2-yl]benzamide;

N-[5-(6-{[4-(1-ethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[5-(6-{[4-(1,4-diethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(4-ethyl-1-methyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2,6-difluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[5-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluorophenyl]-7,7-difluoro-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[5-(6-{[4-(1-ethyl-4-methyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[6-(6-{[4-(1-ethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-3-fluoropyridin-2-yl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[6-(6-{[4-(4-ethyl-1-methyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-3-fluoropyridin-2-yl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[6-(6-{[4-(1-ethyl-4-methyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-3-fluoropyridin-2-yl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[6-(6-{[4-(1,4-diethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-3-fluoropyridin-2-yl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-diethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-6-fluoro-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(4-ethyl-1-methyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-6-fluoro-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{5-[6-({4-[(2R)-1,4-dimethyl-3-oxopiperazin-2-yl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-fluorophenyl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-diethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2,6-difluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{5-[6-({4-[(2S)-1,4-dimethyl-3-oxopiperazin-2-yl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-fluorophenyl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{6-[6-({4-[(2S)-1,4-dimethyl-3-oxopiperazin-2-yl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-3-fluoropyridin-2-yl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{6-[6-({4-[(2R)-1,4-dimethyl-3-oxopiperazin-2-yl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-3-fluoropyridin-2-yl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[2-fluoro-5-(4-methyl-6-{[4-(4-methyl-3-oxopiperazin-2-yl)phenyl]amino}-5-oxo-4,5-dihydropyrazin-2-yl)phenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluoro-6-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(1-ethyl-4-methyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-6-fluoro-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[5-(6-{[4-(2,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluorophenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{5-[6-({4-[2-(azetidin-1-yl)-1-(dimethylamino)-2-oxoethyl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]-2-fluorophenyl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-{2-fluoro-5-[6-({4-[1-(2-hydroxyethyl)-4-methyl-3-oxopiperazin-2-yl]phenyl}amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl]phenyl}-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[5-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluorophenyl]-4,4-difluoro-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide;

N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl]-4-hydroxy-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide; and

N-[3-(5-{[5-(1,4-dimethyl-3-oxopiperazin-2-yl)pyridin-2-yl]amino}-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide.

15. The method of claim 1 , wherein an effective amount of said compound is administered intravenously, intramuscularly, or parenterally.

16. The method of claim 1 , wherein an effective amount of said compound is administered orally.

17. The method of claim 1 , further comprising administering to the patient an effective amount of a second active agent.

18. A method of claim 1 , wherein said compound is of Formula IX:

wherein

R 1 is chosen from:

R 2 is H, CH 3 , F, or Cl;

R 3 is H, CH 3 , F, or Cl;

R 3′ is H, CH 3 , F, or Cl;

R 4 is

m is 0 or 1;

n is 0 or 1;

R 5 is H or C 1 -C 6 alkyl;

R 6 is H or C 1 -C 6 alkyl; or R 5 and R 6 are optionally taken together with the nitrogen atom to which they are attached to form a 6-membered cyclic ring having 0-1 additional N, S or O, wherein the optional additional ring nitrogen is optionally substituted with C 1 -C 3 alkyl;

R 7 is H or C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with one or more substituents chosen from OH and O(C 1 -C 4 alkyl); or R 6 and R 7 are optionally taken together with the —N(R 5 )C(R 9 )(CH 2 ) n C(═O)N(R 8 )— group through the respective nitrogen atoms to which they are directly attached to form a 6-membered cyclic ring;

R 8 is H or C 1 -C 6 alkyl; or R 7 and R 8 are optionally taken together with the nitrogen atom to which they are attached to form a 4- to 6-membered cyclic ring having 0-1 additional N, S or O, wherein the optional additional ring nitrogen is optionally substituted with C 1 -C 3 alkyl;

R 9 is H or CH 3 ; and

R 10 is H or C 1 -C 3 alkyl.

19. The method of claim 14 , wherein said compound is N-(3-(6-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide.

20. The method of claim 14 , wherein said compound is (R)—N-(3-(6-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl amino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide.

21. The method of claim 14 , wherein said compound is N-[3-(6-{[4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenyl]amino}-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-fluoro-6-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide.