Inhibitors of bruton's tyrosine kinase and method of their use

A compound of Formula (I):

• wherein
• R1 is H;
• R2 is selected from the group consisting of:
• CH2-cyclohexyl, wherein the cyclohexyl is optionally substituted with OH;
• 3-hydroxyadamantan-1-yl;
• and C3-6cycloalkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of:
• OH, halogen, C1-6alkyl, C1-6haloalkyl, OC1-6alkyl, CN, NR6R7, NR8—C(O)H, NR8—C(O)—C1-6alkyl, NR8—C(O)—C1-6haloalkyl, NR8—C(O)—O—C1-6alkyl, NR8—C(O)—C1-6alk-OH, NR8—C(O)—C1-6alk-NR6R7, and NR8—C(O)—C(R3)═CR4(R5);
• wherein
• R3 is selected from the group consisting of:
• H, CN, halogen, C1-6 haloalkyl, and C1-6alkyl;
• R4 and R5 are each independently selected from the group consisting of:
• H;
• C0-6alk-NR6R7;
• C1-6alk-O—C1-6alkyl;
• C3-6cycloalkyl;
• heterocycloalkyl optionally substituted with C1-6alkyl;
• and -linker-PEG-Biotin;
• R6 and R7 are each independently selected from the group consisting of:
• H, C1-6alkyl, C(O)H, and CN;
• and
• R8 is H;
• or R1 and R2, together with the nitrogen atom to which they are attached, form a pyrrolidinyl ring optionally substituted with NR6R7, wherein R6 and R7 are each independently selected from the group consisting of H;
• C1-6alkyl;
• NR8—C(O)—C1-6alkyl;
• and NR8—C(O)—C(R3)═CR4(R5), wherein R3 is H or CN;
• R4 is H;
• and R5 is H or cyclopropyl;
• A is selected from the group consisting of:
• pyridyl;
• phenyl;
• pyrimidinyl;
• pyrazinyl;
• pyridin-2(1H)-one;
• and pyridazinyl;
• wherein the A is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of:
• halogen, C1-6alkyl, C1-6 haloalkyl, and OC1-6alkyl;
• E is selected from the group consisting of:
• O, a bond, and CH2;
• G is selected from the group consisting of:
• H;
• halogen;
• C1-6alkyl;
• C1-6haloalkyl;
• NH(C1-6alkyl);
• C3-6cycloalkyl;
• phenyl;
• pyrimidinyl;
• pyridyl;
• pyridazinyl;
• pyridin-2(1H)-one;
• heterocycloalkyl that contains an oxygen heteroatom;
• and phenyl-CH2—O-phenyl, wherein the —O-phenyl is substituted with CN;
• wherein the phenyl;
• pyridyl;
• pyridazinyl;
• and pyridin-2(1H)-one is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of:
• halogen, C1-6alkyl, C1-6haloalkyl, OC1-6haloalkyl, and OC1-6alkyl;
• and
• stereoisomers and isotopic variants thereof;
• and
• pharmaceutically acceptable salts thereof.