Inhibitors of bruton's tyrosine kinase

1. A compound having the structure of Formula (IV):

wherein:

T is a bond;

Y and Z together with the carbon atom to which they are attached form a C 2 -C 10 heterocycloalkyl, optionally substituted with at least one X;

wherein when Y and Z together with the carbon atom to which they are attached form a nitrogen atom-containing C 2 -C 10 heterocycloalkyl the nitrogen atom of the C 2 -C 10 heterocycloalkyl is substituted with W and the carbon atoms of the C 2 -C 10 heterocycloalkyl are optionally substituted with at least one X;

W is selected from C(═O)O-J, C(═O)NR 2 -J, C(═NR 2 )-J, —C(═NR 2 )NR 2 -J, C(═N—OR 3 )-J, C(═S)-J, S(═O) v -J, S(═O) v O-J;

X is F, Cl, Br, I, —CN, —NO 2 , —OR 3 , —N(R 2 ) 2 , —SR 2 , —C 1 -C 6 alkyl, —C(═O)R 2 , —OC(═)R 2 , —NR 2 C(═O)N(R 2 ) 2 , —C(═O)N(R 2 ) 2 , —C(═NR 2 )N(R 2 ) 2, —C(═N—OR 2 )N(R 2 ) 2, —C(═S)R 2 , —S(═O) v R 2 , —OS(═O) v R 2 , —NR 2 C(═O)OR 2 , —NR 2 S(═O) v R 2 ;

J is methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, or tert-butyl optionally substituted with at least one R 1 ;

v is 1 or 2;

R b is NH 2 ;

R 1 is selected from F, Cl, Br, I, —CN, —NO 2 , —SR 2 , —OR 3 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, —OC 1 -C 6 haloalkyl, C 1 -C 6 heteroalkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 heterocycloalkyl, phenyl, —NR 2 S(═O) 2 R 2 , —S(═O) 2 N(R 2 ) 2 , —C(═O)CF 3 , —C(═O)NR 2 S(═O) 2 R 2 , —S(═O) 2 NR 2 C(═O)R 2 , —NR 2 C(═O)R 8 , —NR 2 C(═O)N(R 2 ) 2 , —CO 2 R 2 , —OC(═O)R 2 , —OC(═O)R 2 , —C(═O)N(R 2 ) 2 , —OS(═O) 2 R 2 , —OS(═O) 2 OR 2 , —S(═O)R 2 , —S(═O) 2 R 2 , and —SO 3 H;

R 2 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, or C 3 -C 6 cycloalkyl;

R 3 is H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, or SO 3 H;

each R 6 is independently selected from H, —OR 3 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, —OC 1 -C 6 haloalkyl, C 1 -C 6 heteroalkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 heterocycloalkyl, phenyl, —NR 2 S(═O) 2 R 2 , —S(═O) 2 N(R 2 ) 2 , —C(═O)CF 3 , —C(═O)NR 2 S(═O) 2 R 2 , —S(═O) 2 NR 2 C(═O)R 2 , —N(R 2 ) 2 , wherein optionally the two R 2 groups of N(R 2 ) 2 and the nitrogen atom to which they are attached form a C 2 -C 6 heterocycloalkyl ring, —NR 2 C(═O)R 2 , —NR 2 C(═O)N(R 2 ) 2 , —CO 2 R 2 , —C(═O)R 2 , —OC(═O)R 2 , —C(═O)N(R 2 ) 2 , —OS(═O) 2 R 2 , —OS(═O) 2 OR 2 , —S(═O)R 2 , —S(═O) 2 R 2 , and —SO 3 H, wherein at least one R 6 is —OH;

R 8 is an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 2 -C 6 alkenyl, an optionally substituted C 2 -C 6 alkynyl, or an optionally substituted C 3 -C 6 cycloalkyl; or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 wherein W is C(═O)J.

3. The compound of claim 2 wherein J is substituted with at least one R 1 .

4. The compound of claim 3 wherein R 1 is selected from F, Cl, Br, I, —CN, —NO 2 , —SR 2 , —OR 3 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, —OC 1 -C 6 haloalkyl, C 1 -C 6 heteroalkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 heterocycloalkyl.

5. The compound of claim 2 wherein Y and Z together with the carbon atom to which they are attached form a nitrogen atom-containing C 2 -C 10 heterocycloalkyl selected from:

6. The compound of claim 5 wherein C 2 -C 10 heterocycloalkyl is

7. The compound of claim 1 wherein J is substituted with one R 1 .

8. The compound of claim 1 wherein J is substituted with two R 1 .

9. The compound of claim 7 wherein R 1 is selected from F, Cl, Br, I, —CN, and —OR 3 .

10. A pharmaceutical formulation comprising a therapeutically effective amount of a compound of claim 1 , and a pharmaceutically acceptable excipient.

11. The compound of claim 6 wherein C 2 -C 10 heterocycloalkyl is

12. The compound of claim 11 wherein J is ethyl optionally substituted with at least one R 1 ; and R 1 is selected from F, Cl, Br, I, —CN, —SR 2 , and —OR 3 .

13. The compound of claim 12 wherein J is unsubstituted ethyl.

14. The compound of claim 12 wherein J is —CH(OH)CH 2 (OH).