SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINES AS BRUTON'S TYROSINE KINASE MODULATORS
The invention is fused heterocyclic compounds of formula (I), and salts thereof, compositions thereof, and methods of use therefor. In particular, disclosed herein are certain fused heterocyclic compounds that can be useful for inhibiting protein kinase, including Bruton's tyrosine kinase (Btk), and for treating disorders mediated thereby.
1 .- 15 . (canceled)
16 . A method of treating a disease in a subject comprising administering to the subject a compound having the following structure:
wherein the disease is mantle cell lymphoma (MCL); and
the compound is administered at a dose of 160 mg twice a day (BID) or 320 mg once a day (QD).
17 . The method of claim 16 , wherein the subject is an adult patient.
18 . The method of claim 16 , wherein the subject has received at least one prior therapy.
19 . The method of claim 16 , wherein the subject is an adult patient; and the adult patient has received at least one prior therapy.
20 . A method of treating a disease in a subject comprising administering to the subject a compound having the following structure:
wherein the disease is Waldenstrom's macroglobulinemia (WM); and
the compound is administered at a dose of 160 mg twice a day (BID) or 320 mg once a day (QD).
21 . The method of claim 20 , wherein the subject is an adult patient.
22 . The method of claim 20 , wherein the subject has received at least one prior therapy.
23 . The method of claim 20 , wherein the subject is an adult patient; and the adult patient has received at least one prior therapy.
24 . A method of treating a disease in a subject comprising administering to the subject a compound having the following structure:
wherein the disease is chronic lymphocytic leukemia (CLL); and
the compound is administered at a dose of 160 mg twice a day (BID) or 320 mg once a day (QD).
25 . The method of claim 24 , wherein the subject is an adult patient.
26 . The method of claim 24 , wherein the subject has received at least one prior therapy.
27 . The method of claim 24 , wherein the subject is an adult patient; and the adult patient has received at least one prior therapy.
28 . A method of treating a disease in a subject comprising administering to the subject a compound having the following structure:
wherein the disease is small lymphocytic lymphoma (SLL); and
the compound is administered at a dose of 160 mg twice a day (BID) or 320 mg once a day (QD).
29 . The method of claim 28 , wherein the subject is an adult patient.
30 . The method of claim 28 , wherein the subject has received at least one prior therapy.
31 . The method of claim 28 , wherein the subject is an adult patient; and the adult patient has received at least one prior therapy.
32 . A method of treating a disease in a subject comprising administering to the subject a compound having the following structure:
wherein the disease is follicular lymphoma (FL); and
the compound is administered at a dose of 160 mg twice a day (BID) or 320 mg once a day (QD).
33 . The method of claim 32 , wherein the subject is an adult patient.
34 . The method of claim 32 , wherein the subject has received at least one prior therapy.
35 . The method of claim 32 , wherein the subject is an adult patient; and the adult patient has received at least one prior therapy.
36 . A method of treating a disease in a subject comprising administering to the subject a compound having the following structure:
wherein the disease is marginal zone lymphoma (MZL); and
the compound is administered at a dose of 160 mg twice a day (BID) or 320 mg once a day (QD).
37 . The method of claim 36 , wherein the subject is an adult patient.
38 . The method of claim 36 , wherein the subject has received at least one prior therapy.
39 . The method of claim 36 , wherein the subject is an adult patient; and the adult patient has received at least one prior therapy.
40 . A method of treating a disease in a subject comprising administering to the subject a compound having the following structure:
wherein the disease is diffuse large B cell lymphoma (DLBCL); and
the compound is administered at a dose of 160 mg twice a day (BID) or 320 mg once a day (QD).
41 . The method of claim 40 , wherein the subject is an adult patient.
42 . The method of claim 40 , wherein the subject has received at least one prior therapy.
43 . The method of claim 40 , wherein the subject is an adult patient; and the adult patient has received at least one prior therapy.