Claims for Patent: 9,181,257

Summary for Patent: 9,181,257

Title:	Inhibitors of Bruton's tyrosine kinase
Abstract:	Disclosed herein are pyrazolo[3,4-d]pyrimidines 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.
Inventor(s):	Lee Honigberg, Erik Verner, Zhengying Pan
Assignee:	Pharmacyclics LLC
Application Number:	US14/080,640
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,181,257
Patent Claims:	1. A compound of Formula (A) having the structure: wherein: A is N; R1 is L2-(substituted or unsubstituted heteroaryl), or L2-(substituted or unsubstituted aryl), where L2 is a bond, O, S, —S(═O), —S(═O)2, C(═O), -(substituted or unsubstituted C1-C6 alkyl), or -(substituted or unsubstituted C2-C6 alkenyl); R2 and R3 are independently selected from H or lower alkyl; R4 is L3-X-L4-G, wherein, L3 is optional, and when present is a bond, or an optionally substituted or unsubstituted alkyl; X is a bond; L4 is a substituted or unsubstituted nitrogen containing heterocycle; or L3, X and L4 taken together form a nitrogen containing heterocyclic ring; and G is a Michael acceptor moiety; or a pharmaceutically acceptable solvate, hydrate, or salt thereof. 2. The compound of claim 1, wherein G is bound to a nitrogen atom in L4. 3. The compound of claim 2, wherein G is bound to a nitrogen atom in L4 to form a substituted acrylamide. 4. The compound of claim 3, wherein R1 is L2-substituted aryl; and L2 is a bond. 5. The compound of claim 4, wherein R2 and R3 are independently H. 6. The compound of claim 5, wherein L3 is optionally substituted or unsubstituted alkyl. 7. The compound of claim 6, wherein L3 is methylene and L4 is pyrrolidine or piperidine. 8. The compound of claim 5, wherein the compound of Formula (A) has the structure of Formula (B): wherein: Y and R12 taken together form a 4-, 5-, or 6-membered heterocyclic ring; each Ra is independently H, halogen, —CF3, —CN, —NO2, OH, NH2, -La-(substituted or unsubstituted alkyl), -La-(substituted or unsubstituted alkenyl), -La-(substituted or unsubstituted heteroaryl), or -La-(substituted or unsubstituted aryl), wherein La is a bond, O, S, —S(═O), —S(═O)2, NH, C(O), CH2, —NHC(O)O, —NHC(O), or —C(O)NH; and G together with the nitrogen atom to which it is bound forms a substituted acrylamide; or a pharmaceutically acceptable solvate, hydrate, or salt thereof. 9. The compound of claim 8, wherein each Ra is independently H, halogen, -La-(substituted or unsubstituted heteroaryl), or -La-(substituted or unsubstituted aryl), wherein La is O, —NHC(O), or —C(O)NH. 10. The compound of claim 9, wherein each Ra is independently H, F, or -La-(substituted or unsubstituted aryl), wherein La is O. 11. The compound of claim 10, wherein one Ra is F, and one Ra is —O-(unsubstituted phenyl). 12. The compound of claim 10, wherein one Ra is —O-(substituted phenyl) and —O-(substituted phenyl) is substituted with one or more F. 13. The compound of claim 8, wherein Y and R12 taken together form a piperidine ring. 14. The compound of claim 8, wherein Y and R12 taken together form a pyrrolidine ring.