INHIBITORS OF BRUTON'S TYROSINE KINASE FOR THE TREATMENT OF SOLID TUMORS

1 . A method for treating a disorder characterized by the presence or development of one or more solid tumors comprising administering to an individual in need thereof a composition containing a therapeutically effective amount of a compound that forms a covalent bond with a cysteine sidechain of a Bruton's tyrosine kinase (Btk) or a Bruton's tyrosine kinase homolog.

2 - 26 . (canceled)

27 . The method of claim 1 wherein the compound is an irreversible inhibitor of Btk.

28 . The method of claim 1 wherein the compound has the structure of Formula (VII):

wherein:

is a moiety that binds to the active site of Btk;

Y is an optionally substituted group selected from among alkylene, heteroalkylene, arylene, heteroarylene, heterocycloalkylene, cycloalkylene, alkylenearylene, alkyleneheteroarylene, alkylenecycloalkylene, and alkyleneheterocycloalkylene;

Z is C(═O), OC(═O), NHC(═O), NCH 3 C(═O), C(═S), S(═O) x , OS(═O) x , NHS(═O) x , where x is 1 or 2;

R 6 and R 8 are independently selected from among H, unsubstituted C 1 -C 4 alkyl, substituted C 1 -C 4 alkyl, unsubstituted C 1 -C 4 heteroalkyl, substituted C 1 -C 4 heteroalkyl, unsubstituted C 3 -C 6 cycloalkyl, substituted C 3 -C 6 cycloalkyl, unsubstituted C 2 -C 6 heterocycloalkyl, and substituted C 2 -C 6 heterocycloalkyl; or

R 6 and R 8 taken together form a bond;

R 7 is H, substituted or unsubstituted C 1 -C 4 alkyl, substituted or unsubstituted C 1 -C 4 heteroalkyl, C 1 -C 6 alkoxyalkyl, C 1 -C 8 alkylaminoalkyl, C 1 -C 8 hydroxyalkylaminoalkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted C 2 -C 8 heterocycloalkyl, substituted or unsubstituted heteroaryl, C 1 -C 4 alkyl(aryl), C 1 -C 4 alkyl(heteroaryl), C 1 -C 4 alkyl(C 3 -C 8 cycloalkyl), or C 1 -C 4 alkyl(C 2 -C 8 heterocycloalkyl); or a pharmaceutically active metabolite, or pharmaceutically acceptable solvate, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug thereof.

29 . The method of claim 28 , wherein

is a substituted fused biaryl moiety selected from

30 . The method of claim 28 , wherein:

Z is C(═O), NHC(═O), NCH 3 C(═O), or S(═O) 2 ;

each of R 6 and R 8 is H; or

R 6 and R 8 taken together form a bond.

31 . The method of claim 30 , wherein:

Y is a 4-, 5-, 6-, or 7-membered cycloalkylene ring; or

Y is a 4-, 5-, 6-, or 7-membered heterocycloalkylene ring; or

Y is a C 1 -C 4 alkylene, or 4-, 5-, 6-, or 7-membered heterocycloalkylene ring;

R 7 is H, substituted or unsubstituted C 1 -C 4 alkyl, substituted or unsubstituted C 1 -C 4 heteroalkyl, C 1 -C 6 alkoxyalkyl, C 1 -C 8 alkylaminoalkyl, C 1 -C 8 hydroxyalkylaminoalkyl, C 1 -C 8 alkoxyalkylaminoalkyl, C 1 -C 4 alkyl(aryl), C 1 -C 4 alkyl(heteroaryl), C 1 -C 4 alkyl(C 3 -C 8 cycloalkyl), or C 1 -C 4 alkyl(C 2 -C 8 heterocycloalkyl).

32 . The method of claim 31 wherein R 7 is H.

33 . The method of claim 28 , wherein the compound is a compound of Formula (I) having the structure:

34 . The method of claim 1 , wherein the disorder is a sarcoma, lymphoma, or carcinoma.

35 . The method of claim 1 , wherein the disorder is mammary ductal carcinoma, lobular carcinoma, an adenocarcinoma, small cell lung carcinoma, non-small cell lung carcinoma, a melanoma, or a combination thereof.

36 . The method of claim 1 , wherein the disorder is pancreatic cancer.

37 . A method for treating a disorder characterized by the presence or development of one or more solid tumors comprising administering to an individual in need thereof a composition containing a therapeutically effective amount of a compound that forms a covalent bond with a cysteine sidechain of a HER4.

38 . The method of claim 37 , wherein the disorder is mammary ductal carcinoma, lobular carcinoma, or a combination thereof.

39 . The method of claim 1 or claim 37 wherein the compound has a plasma half life of less than about 4 hours.

40 . The method of claim 39 wherein the plasma half life of the compound is less than about 3 hours.