Benzimidazole derivatives as ITK inhibitors

1. A compound of Formula (IA):

wherein:

(i) when Z is N, then ring B is:

wherein:

Z 1 , Z 2 , and Z 3 are CH (or C if substituted with R 1 or R 2 ) or Z 1 , Z 2 , and Z 3 are independently N or CH (or C if substituted with R 1 or R 2 ) provided that only one of Z 1 , Z 2 , and Z 3 is N; and

(ii) when Z is C , then ring B is:

wherein:

Z 2 and Z 3 are CH (or C if substituted with R 1 or R 2 ) or Z 2 and Z 3 are independently N or CH (or C if substituted with R 1 or R 2 ) provided that only one of Z 2 and Z 3 is N;

R 1 is hydrogen, hydroxyalkyl, alkoxyalkyl, —NR 3 COR 4 , —CONR 3 R 5 , -(alkylene)-NR 3 R 5 (where each R 3 is hydrogen, or alkyl, R 4 is alkyl, haloalkyl, cycloalkyl, optionally substituted aryl or optionally substituted heteroaryl, and each R 5 is hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, acyl, cycloalkylalkyl, or heterocyclylalkyl optionally substituted with one, two, or three substituents independently selected from alkyl, halo, hydroxy, alkoxy, hydroxyalkyl, or alkoxyalkyl; or R 3 and R 5 together with the nitrogen atom to which they are attached form heterocycloamino or spiroheterocycloamino wherein the heterocycloamino ring is optionally substituted with one, two, or three substituents independently selected from alkyl, halo, hydroxyl, alkoxy, hydroxyalkyl, or alkoxyalkyl), —NR 6 R 7 (where R 6 is hydrogen or alkyl and R 7 is hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, or acyl, or R 6 and R 7 together with the nitrogen atom to which they are attached form heterocyclyl optionally substituted with one or two substituents independently selected from alkyl, halo, hydroxyl, hydroxyalkyl, or alkoxyalkyl), or —OR 8 (where R 8 is hydroxyalkyl, alkoxyalkyl, or heterocyclylalkyl optionally substituted with one, two, or three substituents independently selected from alkyl, halo, hydroxyalkyl, or alkoxyalkyl);

R 2 is hydrogen, alkyl, cycloalkyl, cyano, alkoxy, hydroxy, halo, haloalkyl, or haloalkoxy;

Ar is 5-CHF 2 thien-2-yl or a five membered heteroaryl ring substituted with optionally substituted heteroaryl;

X is alkylene, cycloalkylene,

(where Z 4 is bond or alkylene, and ring A is heterocycloamino optionally substituted with one or two substituents independently selected from alkyl, hydroxy, or fluoro), -alkylene-O—, -cycloalkylene-NR a —, or -(alkylene)-NR a -(where each R a is hydrogen, alkyl or cycloalkyl);

Y is —CO — or —SO 2 —;

R b is hydrogen, cyano, nitro, halo, haloalkyl, haloalkoxy, alkylthio, or alkylsulfonyl;

R c is hydrogen, alkyl, haloalkoxy, substituted alkyl, cycloalkyl, cycloalkyleneNR d1 R e or cycloalkylene(alkylene)NR d1 R e (where each R d1 and R e are independently hydrogen, alkyl, or cycloalkyl), alkoxyalkyloxyalkyl, or 3 to 6 membered saturated monocyclic heterocyclyl containing one or two heteroatoms selected from N, O, or S and optionally substituted with one or two substituents independently selected from hydroxy, alkyl or fluoro; and

R d is hydrogen or alkyl, or R b and R d together form a bond; provided that when R b is other than hydrogen, then R c is not hydrogen and R d is hydrogen;

and/or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 having the structure (I):

wherein:

(i) when Z is N, then ring B is:

wherein:

Z 1 , Z 2 , and Z 3 are CH (or C if substituted with R 1 or R 2 ) or Z 1 , Z 2 , and Z 3 are independently N or CH (or C if substituted with R 1 or R 2 ) provided that only one of Z 1 , Z 2 , and Z 3 is N; and

(ii) when Z is C , then ring B is:

wherein:

Z 2 and Z 3 are CH (or C if substituted with R 1 or R 2 ) or Z 2 and Z 3 are independently N or CH (or C if substituted with R 1 or R 2 ) provided that only one of Z 2 and Z 3 is N;

R 1 is hydrogen, hydroxyalkyl, alkoxyalkyl, —NR 3 COR 4 , —CONR 3 R 5 , -(alkylene)-NR 3 R 5 (where each R 3 is hydrogen, or alkyl, R 4 is cycloalkyl, optionally substituted aryl or optionally substituted heteroaryl, and each R 5 is hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, acyl, or heterocyclylalkyl optionally substituted with one or two substituents independently selected from alkyl, halo, hydroxyalkyl, or alkoxyalkyl; or R 3 and R 5 together with the nitrogen atom to which they are attached form heterocycloamino or spiroheterocycloamino wherein the heterocycloamino ring is optionally substituted with one or two substituents independently selected from alkyl, halo, hydroxyalkyl, or alkoxyalkyl), —NR 6 R 7 (where R 6 is hydrogen or alkyl and R 7 is hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, or acyl, or R 6 and R 7 together with the nitrogen atom to which they are attached form heterocyclyl optionally substituted with one or two substituents independently selected from alkyl, halo, hydroxyl, hydroxyalkyl, or alkoxyalkyl), or —OR 8 (where R 8 is hydroxyalkyl, alkoxyalkyl, or heterocyclylalkyl optionally substituted with one or two substituents independently selected from alkyl, halo, hydroxyalkyl, or alkoxyalkyl);

R 2 is hydrogen, alkyl, cycloalkyl, cyano, alkoxy, hydroxy, halo, haloalkyl, or haloalkoxy;

X is alkylene, cycloalkylene,

or

(where Z 4 is bond or alkylene, and ring A is heterocycloamino optionally substituted with one or two substituents independently selected from alkyl, hydroxy, or fluoro), -alkylene-O—, -cycloalkylene-NR a —, or -(alkylene)-NR a -(where each R a is hydrogen, alkyl or cycloalkyl);

Y is —CO — or —SO 2 —;

R b is hydrogen, cyano, nitro, halo, haloalkyl, haloalkoxy, alkylthio, or alkylsulfonyl;

R c is hydrogen, alkyl, haloalkoxy, substituted alkyl, cycloalkyl, cycloalkyleneNR d1 R e or cycloalkylene(alkylene)NR d1 R e (where each R d1 and R e are independently hydrogen, alkyl, or cycloalkyl), or 3 to 6 membered saturated monocyclic heterocyclyl containing one or two heteroatoms selected from N, O or S and optionally substituted with one or two substituents independently selected from hydroxy, alkyl or fluoro; and

R d is hydrogen, alkyl, or R b and R d together form a bond; provided that when R b is other than hydrogen, then R c is not hydrogen and R d is hydrogen;

or a pharmaceutically acceptable salt thereof.

3. The compound or a pharmaceutically acceptable salt thereof of claim 2 wherein the compound of Formula (I) has the structure (Ia):

4. The compound or a pharmaceutically acceptable salt thereof of claim 3 wherein Z 1 , Z 2 , and Z 3 are CH (or C if substituted with R 2 ).

5. The compound or a pharmaceutically acceptable salt thereof of claim 2 wherein the compound of Formula (I) has the structure (Ib):

6. The compound or a pharmaceutically acceptable salt thereof of claim 5 wherein Z 1 and Z 3 are CH (or C if substituted with R 2 ).

7. The compound or a pharmaceutically acceptable salt thereof of claim 2 wherein R b and R c are hydrogen.

8. The compound or a pharmaceutically acceptable salt thereof of claim 2 wherein R b is cyano and R c is alkyl, substituted alkyl, cycloalkyl, or 3 to 6 membered saturated monocyclic heterocyclyl containing one or two heteroatoms selected from N, O, or S and optionally substituted with one or two substituents independently selected from hydroxy, alkyl or fluoro.

9. The compound or a pharmaceutically acceptable salt thereof of claim 8 wherein R c is alkyl.

10. The compound or a pharmaceutically acceptable salt thereof of claim 8 wherein R c is cycloalkyl.

11. The compound or a pharmaceutically acceptable salt thereof of claim 8 wherein R c is substituted alkyl.

12. The compound or a pharmaceutically acceptable salt thereof Of claim 8 wherein R c is alkyl substituted with hydroxy, alkoxy, —NRR′ (where R is hydrogen, alkyl, hydroxyalkyl, or alkoxyalkyl and R′ is hydrogen or alkyl) or heterocyclyl which is optionally substituted with one or two groups independently selected from alkyl or hydroxyl.

13. The compound or a pharmaceutically acceptable salt thereof of claim 8 wherein R c is 3 to 6 membered saturated monocyclic heterocyclyl containing one or two heteroatoms selected from N, O, or S and optionally substituted with one or two substituents independently selected from hydroxy, alkyl or fluoro.

14. The compound or a pharmaceutically acceptable salt thereof of claim 2 wherein —X—Y— is

15. The compound or a pharmaceutically acceptable salt thereof of claim 2 wherein —X—Y— is

16. The compound or a pharmaceutically acceptable salt thereof of claim 2

wherein —X—Y— is

17. The compound or a pharmaceutically acceptable salt thereof of claim 2 wherein R 1 is hydrogen, —NR 3 COR 4 , or -(alkylene)-NR 3 R 5 where R 3 is hydrogen or alkyl, R 4 is optionally substituted aryl or heteroaryl, and R 5 is hydrogen, alkyl, haloalkyl, or acyl or R 3 and R 5 together with the nitrogen atom to which they are attached form heterocycloamino optionally substituted with one or two substituents independently selected from alkyl, halo, hydroxyalkyl, or alkoxyalkyl.

18. The compound or a pharmaceutically acceptable salt thereof of claim 17 wherein R 1 is hydrogen.

19. The compound or a pharmaceutically acceptable salt thereof of claim 17 wherein R 1 is -(alkylene)-NR 3 R 5 where R 3 is hydrogen or alkyl and R 5 is hydrogen, alkyl, haloalkyl, or acyl.

20. The compound or a pharmaceutically acceptable salt thereof of claim 17 wherein R 1 is (S)-CH 2 N(COCF 3 )CH(CH 3 )C(CH 3 ) 3 , (S)-CH 2 NHCH(CH 3 )C(CH 3 ) 3 , or (S)-CH 2 N(CH 3 )CH(CH 3 )C(CH 3 ) 3 , preferably (S)-CH 2 NHCH(CH 3 )C(CH 3 ) 3 .

21. The compound or a pharmaceutically acceptable salt thereof of claim 2 wherein R 2 is hydrogen.

22. A compound selected from:

N-(1-(1-acryloylpiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)-4-chlorobenzamide;

N-(1-(1-acryloylpiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)nicotinamide;

N-(1-(1-acryloylpiperidin-3-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)-4-chlorobenzamide;

4-chloro-N-(1-(1-(2-cyano-4-methylpent-2-enoyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide;

N-(1-(1-(2-cyano-4-methylpent-2-enoyl)piperidin-3-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)nicotinamide;

N-(1-(1-acryloylpiperidin-3-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)nicotinamide;

4-chloro-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide;

N-(1-((1-acryloylpyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-4-chlorobenzamide;

N-(1-(1-(2-cyano-4-methylpent-2-enoyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)nicotinamide;

N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2(3H)-ylidene)nicotinamide;

N-(1-((1-acryloylpyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2(3H)-ylidene)nicotinamide;

(S)-N-(1-(1-acryloylpiperidin-4-yl)-5-(((3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-4-chlorobenzamide;

4-chloro-N-(1-(1-(2-cyano-4-methylpent-2-enoyl)piperidin-3-yl)-5-((N-((S)-3,3-dimethylbutan-2-yl)-2,2,2-trifluoroacetamido)methyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide;

N-(1-(1-acryloylpiperidin-3-yl)-5-((N-((S)-3,3-dimethylbutan-2-yl)-2,2,2-trifluoroacetamido)methyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-4-chlorobenzamide;

4-chloro-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((N-((S)-3,3-dimethylbutan-2-yl)-2,2,2-trifluoroacetamido)methyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide;

N-(1-((1-acryloylpyrrolidin-2-yl)methyl)-5-((N-((S)-3,3-dimethylbutan-2-yl)-2,2,2-trifluoroacetamido)methyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-4-chlorobenzamide;

4-chloro-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)(methyl)amino)methyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide;

4-chloro-N-(1-(1-(2-cyano-4-methylpent-2-enoyl)piperidin-3-yl)-5-((((S)-3,3-dimethylbutan-2-yl)(methyl)amino)methyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide;

N-(1-(1-(2-cyano-4-methylpent-2-enoyl)piperidin-3-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide

N-(1-(1-acryloylpiperidin-3-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

N-(1-(1-(2-cyano-4-(dimethylamino)-4-methylpent-2-enoyl)piperidin-3-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

N-(1-(1-(4-(dimethylamino)but-2-enoyl)piperidin-3-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

4-chloro-N-(1-(1-(2-cyano-4-methylpent-2-enoyl)piperidin-3-yl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide;

N-(1-(1-(4-amino-2-cyano-4-methylpent-2-enoyl)piperidin-3-yl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-4-chlorobenzamide;

4-chloro-N-(1-(1-(2-cyano-4-methyl-4-(methylamino)pent-2-enoyl)piperidin-3-yl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)benzamide;

4-chloro-N-(1-(1-(2-cyano-4-(dimethylamino)-4-methylpent-2-enoyl)piperidin-3-yl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)benzamide;

N-(1-(1-acryloylpiperidin-3-yl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-4-chlorobenzamide;

4-chloro-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)benzamide;

N-(1-((1-(4-amino-2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-4-chlorobenzamide;

4-chloro-N-(1-((1-(2-cyano-4-methyl-4-(methylamino)pent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)benzamide;

4-chloro-N-(1-((1-(2-cyano-4-(dimethylamino)-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)benzamide;

4-chloro-N-(1-((1-(2-cyano-4-ethoxy-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)benzamide;

N-(1(1-acryloylpyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-4-chlorobenzamide;

N-(1-(((R)-1-acryloylpyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-4-chlorobenzamide;

4-chloro-N-(1-(1-(2-cyano-4,4-dimethylpent-2-enoyl)piperidin-3-yl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)benzamide;

4-chloro-N-(1-((1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)benzamide;

N-(1((1-acryloylpyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-4-(difluoromethyl)benzamide;

N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-4-(difluoromethyl)benzamide;

N-(1-((1-acryloylpyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

N-(1-((1-(2-cyano-4-methylpent-2-enoyl)azetidin-3-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

(R)-N-(1-((1-(4-amino-2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methyl-4-morpholinopent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

(S)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

N-(1-((1-(4-amino-2-cyano-4-methylpent-2-enoyl)azetidin-3-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

(S)-N-(1((1-(4-amino-2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

(S)-N-(1-((1-(2-cyano-4-methyl-4-morpholinopent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

N-(1-(2-(2-cyano-4-methylpent-2-enamido)ethyl)-1H-benzo [d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

N-(1-((1-(2-cyano-4-methyl-4-morpholinopent-2-enoyl)azetidin-3-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

N-(1-(2-(4-amino-2-cyano-4-methylpent-2-enamido)ethyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

N-(1-(2-(2-cyano-4-methyl-4-morpholinopent-2-enamido)ethyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(S)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(2-(2-cyano-N,4-dimethylpent-2-enamido)ethyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

N-(1-(2-(2-cyano-N,4-dimethyl-4-morpholinopent-2-enamido)ethyl)-1H-benzo[d]imidazol-2-yl)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide;

N-(1-(((S)-1-acryloylpyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-4-chlorobenzamide;

N-(1-(((R)-1-acryloylpyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-4-chlorobenzamide;

N-(1-(((R)-1-acryloylpyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(2-cyano-3-cyclopropylacryloyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(2-cyano-3-(3-methyloxetan-3-yl)acryloyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(2-cyano-4-ethoxy-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-(dimethylamino)-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-acryloylpyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(2-(2-cyano-N,4,4-trimethylpent-2-enamido)ethyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)isoxazole-5-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)benzamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-3-(trifluoromethyl)benzamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-3-methylbenzamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-3,4-difluorobenzamide;

(R)-N-(1-((1-(2-cyano-5-hydroxy-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide.

(R)-N-(1-((1-(4-amino-2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(S)-N-(1-(1-(4-amino-2-cyano-4-methylpent-2-enoyl)pyrrolidin-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-((1-(4-amino-2-cyano-4-methylpent-2-enoyl)azetidin-3-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(S)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(2-(2-cyano-N,4-dimethyl-4-morpholinopent-2-enamido)ethyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(2-(2-cyano-4-(dimethylamino)-N,4-dimethylpent-2-enamido)ethyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-((1-(2-cyano-4-(dimethylamino)-4-methylpent-2-enoyl)azetidin-3-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-((1-(2-cyano-4-methyl-4-morpholinopent-2-enoyl)azetidin-3-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-(hydroxymethyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((neopentylamino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-(morpholinomethyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((2,6-dimethylmorpholino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-(((2,2,2-trifluoroethyl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((4-methylpiperazin-1-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-6-((neopentylamino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-6-(morpholinomethyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-6-((2,6-dimethylmorpholino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-6-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-6-((((R)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(5-amino-2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((neopentylamino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1 (2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-(morpholinomethyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide; 97

N-(1-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((2,6-dimethylmorpholino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-3-(3-methyloxetan-3-yl)acryloyl)pyrrolidin-2-yl)methyl)-5-((neopentylamino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-3-(3-methyloxetan-3-yl)acryloyl)pyrrolidin-2-yl)methyl)-5-(morpholinomethyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(2-cyano-3-(3-methyloxetan-3-yl)acryloyl)pyrrolidin-2-yl)methyl)-5-((2,6-dimethylmorpholino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide,

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((isobutylamino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((isobutylamino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-3-(3-methyloxetan-3-yl)acryloyl)pyrrolidin-2-yl)methyl)-5-((isobutylamino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((3-methyloxetan-3-yl)methyl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((3-methyloxetan-3-yl)methyl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-3-(3-methyloxetan-3-yl)acryloyl)pyrrolidin-2-yl)methyl)-5-((((3-methyloxetan-3-yl)methyl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(5-(2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl)-1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(but-2-ynoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(but-2-ynoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-4-chlorobenzamide;

N-(1-(1-(but-2-ynoyl)piperidin-3-yl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(1-(but-2-ynoyl)piperidin-3-yl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-4-chlorobenzamide;

(R)-N-(1-((1-(2-cyano-3-(3-methyloxetan-3-yl)acryloyl)pyrrolidin-2-yl)methyl)-5-((neopentylamino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide.

(R)-N-(1-((1-(5-amino-2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-6-((neopentylamino)-methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-3-(3-methyloxetan-3-yl)acryloyl)pyrrolidin-2-yl)methyl)-6-((neopentylamino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-(((2-hydroxy-2-methylpropyl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-(((cyclopropylmethyl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-2-(5-(difluoromethyl)thiophene-2-carboxamido)-N-neopentyl-1H-benzo[d]imidazole-5-carboxamide;

(R)-1-((1-(2-cyano-3-(3-methyloxetan-3-yl)acryloyl)pyrrolidin-2-yl)methyl)-2-(5-(difluoromethyl)thiophene-2-carboxamido)-N-neopentyl-1H-benzo[d]imidazole-5-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((3-(2-hydroxypropan-2-yl)azetidin-1-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((3-hydroxyazetidin-1-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-(1-(2-cyano-4,4-dimethylpent-2-enoyl)piperidin-3-yl)-1H-benzo imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(S)-N-(1-(1-(2-cyano-4,4-dimethylpent-2-enoyl)piperidin-3-yl)-1H-benzo imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4,4-dimethyl-5-morpholinopent-2-enoyl)pyrrolidin-2-yl)methyl)-5-(hydroxymethyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-1-((1-acryloylpyrrolidin-2-yl)methyl)-2-(5-(difluoromethyl)thiophene-2-carboxamido)-N-neopentyl-1H-benzo[d]imidazole-5-carboxamide;

N-(3-(((R)-1-(2-cyano-4-(2-methoxyethoxy)-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-6-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-3H-imidazo[4,5-b]pyridin-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

1-(((R)-1-acryloylpyrrolidin-2-yl)methyl)-2-(5-(difluoromethyl)thiophene-2-carboxamido)-N-((S)-3,3-dimethylbutan-2-yl)-1H-benzo[d]imidazole-5-carboxamide;

(S)-N-(1-((1-(2-cyano-4,4-dimethylpent-2-enoyl)azetidin-3-yl)methyl)-5-(((3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

1-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-2-(5-(difluoromethyl)thiophene-2-carboxamido)-N-((S)-3,3-dimethylbutan-2-yl)-1H-benzo[d]imidazole-5-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-(3-hydroxypentan-3-yl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-((1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-3-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-ethoxy-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((neopentylamino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((neopentylamino)-methyl)-1H-benzo[d]imidazol-2-yl)isoxazole-5-carboxamide;

(R)-N-(1-((1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((neopentylamino)methyl)-1H-benz[d]imidazol-2-yl)isoxazole-5-carboxamide;

(R)-N-(1-((1-(2-cyano-3-(3-methyloxetan-3-yl)acryloyl)pyrrolidin-2-yl)methyl)-5-((neopentylamino)methyl)-1H-benzo[d]imidazol-2-yl)isoxazole-5-carboxamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((neopentylamino)methyl)-1H-benzo[d]imidazol-2-yl)nicotinamide;

(R)-N-(1-((1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((neopentylamino)methyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)benzamide;

N-(1-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)isoxazole-5-carboxamide;

N-(1-(((R)-1-(2-cyano-4-ethoxy-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)isoxazole-5-carboxamide;

N-(1-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-3-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)isoxazole-5-carboxamide;

N-(1-(((R)-1-(2-cyano-4-ethoxy-4-methylpent-2-enoyl)pyrrolidin-3-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)isoxazole-5-carboxamide;

N-(1-(((S)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-3-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)isoxazole-5-carboxamide;

N-(1-(((S)-1-(2-cyano-4-ethoxy-4-methylpent-2-enoyl)pyrrolidin-3-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)isoxazole-5-carboxamide;

N-(1-(((S)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-3-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((S)-1-(2-cyano-4-ethoxy-4-methylpent-2-enoyl)pyrrolidin-3-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-3-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-(((R)-1-(2-cyano-4-ethoxy-4-methylpent-2-enoyl)pyrrolidin-3-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide; N-(1-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)benzamide;

N-(1-(((R)-1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)benzamide;

N-(1-(((R)-1-(2-cyano-4-ethoxy-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)benzamide;

(R)-N-(1-(1-(2-cyano-4,4-dimethylpent-2-enoyl)piperidin-3-yl)-5-(hydroxymethyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-((R)-1-(2-cyano-4-ethoxy-4-methylpent-2-enoyl)pyrrolidin-3-yl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(1-((R)-1-(2-cyano-4-methylpent-2-enoyl)pyrrolidin-3-yl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(3-(((R)-1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-6-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-3H-imidazo[4,5-b]pyridin-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

N-(3-(((R)-1-(2-cyano-4-ethoxy-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-6-((((S)-3,3-dimethylbutan-2-yl)amino)methyl)-3H-imidazo[4,5-b]pyridin-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

(R)-N-(3-((1-(2-cyano-4,4-dimethylpent-2-enoyl)pyrrolidin-2-yl)methyl)-6-((neopentylamino)methyl)-3H-imidazo[4,5-b]pyridin-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide; and

(R)-N-(3-((1-(2-cyano-4-ethoxy-4-methylpent-2-enoyl)pyrrolidin-2-yl)methyl)-6-((neopentylamino)methyl)-3H-imidazo[4,5-b]pyridin-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide;

an individual E or Z isomer thereof; or

a pharmaceutically acceptable salt of any of the above compounds.

23. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient.

24. A method of relieving or causing regression of asthma, allergic dermatitis, atopic dermatitis, or psoriasis in a patient which method comprises administering to the patient in need thereof, a pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

25. The compound or a pharmaceutically acceptable salt thereof of claim 3 wherein R b and R c are hydrogen.

26. The compound or a pharmaceutically acceptable salt thereof of claim 3 wherein R b is cyano and R c is alkyl, substituted alkyl, cycloalkyl, or 3 to 6 membered saturated monocyclic heterocyclyl containing one or two heteroatoms selected from N, O, or S and optionally substituted with one or two substituents independently selected from hydroxy, alkyl or fluoro.

27. The compound or a pharmaceutically acceptable salt thereof of claim 25 wherein —X—Y— is

28. The compound or a pharmaceutically acceptable salt thereof of claim 27 wherein R 2 is hydrogen.

29. N-(1-(((R)-1-acryloylpyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)-methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide; or a pharmaceutically acceptable salt thereof.

30. A pharmaceutical composition comprising N-(1-(((R)-1-acryloylpyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)-methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide; or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

31. The method of claim 24 wherein the pharmaceutical composition comprises N-(1-(((R)-1-acryloylpyrrolidin-2-yl)methyl)-5-((((S)-3,3-dimethylbutan-2-yl)amino)-methyl)-1H-benzo[d]imidazol-2-yl)-5-(difluoromethyl)thiophene-2-carboxamide; or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.