Compounds and methods for modulating Bruton's Tyrosine Kinase

A compound having the formula:

• wherein,
• R1 is independently halogen, —OR1D, or unsubstituted C1-C4 alkyl;
• z1 is an integer from 0 to 5;
• R2 is independently halogen;
• z2 is an integer from 0 to 4;
• R3 is hydrogen or —NH2;
• Y1 is N or C(R4);
• R4 is hydrogen, halogen, —CX43, —CHX42, —CH2X4, —OCX43, —OCH2X4, —OCHX42, —CN, —SOn4R4D, —SOv4NR4AR4B, —NHC(O)NR4AR4B, —N(O)m4, —NR4AR4B, —C(O)R4C, —C(O)—OR4C, —C(O)NR4AR4B, —OR4D, —NR4ASO2R4D, —NR4AC(O)R4C, —NR4AC(O)OR4C, —NR4AOR4C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• Y2 is N;
• L1 is a bond or unsubstituted methylene;
• L2 is a substituted or unsubstituted heterocycloalkylene;
• E is
• R15 is hydrogen, halogen, —CX153, —CHX152, —CH2X15, —CN, —SOn15R15D, —SOv15NR15AR15B, NHNR15AR15B, —ONR15AR15B, —NHC═(O)NHNR15AR15B, —NHC(O)NR15AR15B, —N(O)m15, —NR15AR15B, —C(O)R15C, —C(O)—OR15C, —C(O)NR15AR15B, —OR15D, —NR15ASO2R15D, —NR15AC(O)R15C, —NR15AC(O)OR15C, —NR15AOR15C, —OCX153, —OCHX152, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl;
• R16 is hydrogen, halogen, —CX163, —CHX162, —CH2X16, —CN, —SOn16R16D, —SOv16NR16AR16B, NHNR16AR16B, —ONR16AR16B, —NHC═(O)NHNR16AR16B, —NHC(O)NR16AR16B, —N(O)m16, —NR16AR16B, —C(O)R16C, —C(O)—OR16C, —C(O)NR16AR16B, —OR16D, —NR16ASO2R16D, —NR16AC(O)R16C, —NR16AC(O)OR16C, —NR16AOR16C, —OCX163, —OCHX162, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl;
• R17 is hydrogen, halogen, —CX173, —CHX172, —CH2X17, —CN, —SOn17R17D, —SOv17NR17AR17B, NHNR17AR17B, —ONR17AR17B, —NHC═(O)NHNR17AR17B, —NHC(O)NR17AR17B, —N(O)m17, —NR17AR17B, —C(O)R17C, —C(O)—OR17C, —C(O)NR17AR17B, —OR17D, —NR17ASO2R17D, —NR17AC(O)R17C, —NR17AC(O)OR17C, —NR17AOR17C, —OCX173, —OCHX172, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl;
• each R1D, R4A, R4B, R4C, R4D, R15A, R15B, R15C, R15D, R16A, R16B, R16C, R16D, R17A, R17B, R17C, and R17D is independently hydrogen, —CX3, —CN, —COOH, —CONH2, —CHX2, —CH2X, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R4A and R4B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R15A and R15B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R16A and R16B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• R17A and R17B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
• each X, X4, X15, X16, and X17 is independently —F, —Cl, —Br, or —I;
• n4, n15, n16, and n17 are independently an integer from 0 to 4;
• and
• m4, m15, m16, m17, v4, v15, v16, and v17 are independently an integer from 1 to 2.