초록 ▼

Disclosed herein are compounds of Formula (I) that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Method

Disclosed herein are compounds of Formula (I) that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

대표청구항 ▼

1. A compound having the structure of Formula (II): wherein: X is a bond, C1-C4alkylene, C2-C4alkenylene, C2-C4alkynylene, or C1-C4heteroalkylene;Y is substituted or unsubstituted cycloalkylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, or substituted or unsu

1. A compound having the structure of Formula (II): wherein: X is a bond, C1-C4alkylene, C2-C4alkenylene, C2-C4alkynylene, or C1-C4heteroalkylene;Y is substituted or unsubstituted cycloalkylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, or substituted or unsubstituted heterocycloalkylene;Z is C(═O), C(═S), S(═O), S(═O)2, NR4C(═O), NR4S(═O), or NR4S(═O)2;R1 and R2 are each independently H, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted C1-C4alkyl, or substituted or unsubstituted C3-C6cycloalkyl; or R1 and R2 are taken together with the nitrogen to which they are attached to form a heterocycloalkyl ring;each R3 is independently halogen, C1-C4alkyl, —CF3, —CN, —NO2, —NH2, —OH, or —OCH3;R4 is H, C1-C4alkyl, or C1-C6heteroalkyl; andm is 1-3; ora pharmaceutically acceptable solvate, or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1, wherein X is a bond; Y is substituted or unsubstituted heterocycloalkylene; and Z is C(═O). 3. The compound of claim 2, wherein each R3 is independently —F, —Cl, —CH3, or —OCH3. 4. The compound of claim 3, wherein R1 and R2 are each independently substituted or unsubstituted C1-C4alkyl, or substituted or unsubstituted C3-C6cycloalkyl. 5. The compound of claim 4, wherein R1 and R2 are each CH3. 6. The compound of claim 4, wherein R1 is CH3 and R2 is C3-C4cycloalkyl. 7. The compound of claim 1, wherein X is a bond; Y is substituted or unsubstituted phenylene; and Z is NR4C(═O). 8. The compound of claim 7, wherein each R3 is independently —F, —Cl, —CH3, or —OCH3. 9. The compound of claim 8, wherein R1 and R2 are each independently substituted or unsubstituted C1-C4alkyl, or substituted or unsubstituted C3-C6cycloalkyl. 10. The compound of claim 1, wherein X is a bond; Y is substituted or unsubstituted C3-C6cycloalkylene; and Z is NR4C(═O). 11. The compound of claim 10, wherein each R3 is independently —F, —Cl, —CH3, or —OCH3. 12. The compound of claim 1, wherein X is a bond; Y is substituted or unsubstituted heteroarylene; and Z is NR4C(═O). 13. The compound of claim 12, wherein each R3 is independently —F, —Cl, —CH3, or —OCH3. 14. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1 or a pharmaceutically acceptable salt, or pharmaceutically acceptable solvate thereof.