INHIBITORS OF BRUTON'S TYROSINE KINASE
Described herein are irreversible kinase inhibitor compounds, methods for synthesizing such irreversible inhibitors, and methods for using such irreversible inhibitors in the treatment of diseases. Further described herein are methods, assays and systems for determining an appropriate irreversible inhibitor of a protein, including a kinase.
1 - 100 . (canceled)
101 . A kinase inhibitor having the structure of Formula (VII):
wherein:
is a substituted bicyclic heteroaromatic ring that binds to the active site ATP binding site of Bruton's tyrosine kinase (Btk), provided that
is not
where each represents a substitution other than H;
Y is an optionally substituted heterocycloalkylene;
Z is C(═O);
R 7 and R 8 taken together form a bond; and
R 6 is substituted or unsubstituted C 1 -C 4 alkyl; or
a pharmaceutically acceptable salt thereof.
102 . The kinase inhibitor of claim 101 , wherein
is substituted with
103 . The kinase inhibitor of claim 102 , wherein Y is
104 . The kinase inhibitor of claim 103 , wherein R 6 is CH 3 .
105 . A kinase inhibitor having the structure:
wherein:
is a substituted bicyclic heteroaromatic ring that binds to the active site ATP binding site of Bruton's tyrosine kinase (Btk), provided that
is not
where each represents a substitution other than H;
R 7 and R 8 taken together form a bond; and
R 6 is substituted or unsubstituted C 1 -C 4 alkyl; or a pharmaceutically acceptable salt thereof.
106 . The kinase inhibitor of claim 105 , wherein R 6 is CH 3 .
107 . A pharmaceutical formulation comprising the kinase inhibitor of claim 104 and a pharmaceutically acceptable excipient.
108 . The pharmaceutical formulation of claim 107 formulated for a route of administration selected from oral administration, parenteral administration, buccal administration, nasal administration, topical administration, or rectal administration.
109 . The pharmaceutical formulation of claim 107 formulated for oral administration.