Inhibitors of bruton's tyrosine kinase

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

• wherein:
• T is a bond, C1-C6alkylene, or C3-C6cycloalkylene;
• Y and Z are each independently selected from H, C2-C6alkenyl, C3-C10cycloalkyl, C1-C6heteroalkyl, C2-C6heteroalkenyl, C4-C10heterocycloalkenyl and C2-C10heterocycloalkyl, wherein C1-C6alkyl, C2-C6alkenyl, C3-C10cycloalkyl, C1-C6heteroalkyl, C2-C6-heteroaklenyl, C4-C10heterocycloalkenyl and C2-C10heterocycloalkyl are optionally substituted with at least one R1;
• or
• Y and Z together with the carbon atom to which they are attached form a C3-C10cycloalkyl, C2-C10heterocycloalkyl, C4-C10heterocycloalkenyl, aryl, or heteroaryl, wherein C3-C10cycloalkyl, C2-C10heterocycloalkyl, C4-C10heterocycloalkenyl, aryl, or heteroaryl, are 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 C2-C10heterocycloalkyl or C4-C10heterocycloalkenyl, the nitrogen atom of the C2-C10heterocycloalkyl or C4-C10heterocycloalkenyl is optionally substituted with W and the carbon atoms of the C2-C10heterocycloalkyl or C4-C10heterocycloalkenyl are optionally substituted with at least one X;
• W is selected from J, C(═O)-J, C(═O)O-J, C(═O)NR2-J, C(═NR2)-J, —C(═NR2)NR2-J, C(═N—OR3)-J, C(═S)-J, S(═O)v-J, S(═O)vO-J;
• X is F, Cl, Br, I, —CN, —NO2, —OR3, —N(R2)2, —SR2, —C1-C6alkyl, —C(═O)R2, —OC(═)R2, —NR2C(═O)R5, —NR2C(═O)N(R2)2, —C(═O)N(R2)2, —C(═NR2)N(R2)2, —C(═N—OR2)N(R2)2, —C(═S)R2, —S(═O)vR2, —OS(═O)vR2, —NR2C(═O)OR2, —NR2S(═O)vR2;
• J is —C1-C6alkyl, C3-C6cycloalkyl, —C2-C6alkene, C2-C6heterocycloalkyl, aryl, or heteroaryl optionally substituted with at least one R1;
• v is 1 or 2;
• Rb is NH2, OH, OSO3H or NHSO3H, halogen, —CN, —NO2, —SR2, optionally substituted C1-C6alkyl;
• N(R2)2 or NHR7;
• R1 is selected from F, Cl, Br, I, —CN, —NO2, —SR2, —OR3, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, —OC1-C6haloalkyl, C1-C6heteroalkyl, C3-C6cycloalkyl, C2-C6heterocycloalkyl, heteroaryl, phenyl, —NR2S(═O)2R2, —S(═O)2N(R2)2, —C(═O)CF3, —C(═O)NR2S(═O)2R2, —S(═O)2NR2C(═O)R2, —N(R2)2, wherein optionally the two R2 groups of N(R2)2 and the nitrogen atom to which they are attached form a C2-C6 heterocycloalkyl ring, —NR2C(═O)R2, —NR2C(═O)R8, —NR2C(═O)N(R2)2, —CO2R2, —C(═O)R2, —OC(═O)R2, —C(═O)N(R2)2), —OS(═O)2R2, —OS(═O)2OR2, —S(═O)R2, —S(═O)2R2, —SO3H, and at least one amino acid fragment;
• R2 is H, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or C3-C6cycloalkyl;
• R3 is H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, or SO3H;
• R6 is selected from H, F, Cl, Br, I, —CN, —NO2, —SR2, —OR3, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, —OC1-C6haloalkyl, C1-C6heteroalkyl, C3-C6cycloalkyl, C2-C6heterocycloalkyl, phenyl, —NR2S(═O)2R2, —S(═O)2N(R2)2, —C(═O)CF3, —C(═O)NR2S(═O)2R2, —S(═O)2NR2C(═O)R2, —N(R2)2, wherein optionally the two R2 groups of N(R2)2 and the nitrogen atom to which they are attached form a C2-C6 heterocycloalkyl ring, —NR2C(═O)R2, —NR2C(═O)N(R2)2, C(═O)R2, —OC(═O)R2, —C(═O)N(R2)2, —OS(═O)2R2, —OS(═O)2OR2, —S(═O)R2, —S(═O)2R2, —SO3H, and at least one amino acid fragment;
• wherein each R6 cannot all be H;
• R7 is an amino protecting group;
• R8 is an optionally substituted C1-C6alkyl, an optionally substituted C2-C6alkenyl, an optionally substituted C2-C6alkynyl, or an optionally substituted C3-C6cycloalkyl;
• or a pharmaceutically acceptable salt, solvate, or metabolite thereof.