Salts and solid form of a BTK inhibitor
Disclosed herein are processes for preparing 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile free base (compound (I)), salts of compound (I) and solid state form of said salts. Also disclosed herein are pharmaceutical compositions comprising such salts and solid state form thereof and methods of treating cancer, autoimmune, and inflammatory diseases using compound (I) or a pharmaceutically acceptable salt thereof.
1. A method of treating at least one inflammatory and/or autoimmune disease selected from thrombotic thrombocytopenic purpura, polyarteritis nodosa, cutaneous lupus, cutaneous form of systemic sclerosis (CREST), mixed connective tissue disease, cryoglobulinemia, primary biliary sclerosis, sclerosing cholangitis, Al urticaria, IgA nephropathy, lupus nephritis, granulomatosis with polyangiitis, and pemphigus vulgaris in a mammal, comprising administering to said mammal a pharmaceutical composition comprising:
at least one compound selected from (E) isomer, (Z) isomer, and a mixture of (E) and (Z) isomers of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile; and/or
at least one pharmaceutically acceptable salt of any of the foregoing compounds; and
at least one pharmaceutically acceptable carrier or excipient.
2. The method of claim 1 , wherein the at least one inflammatory and/or autoimmune disease is acute, and further wherein the pharmaceutical composition is administered in place of or in combination with corticosteroid therapy, optionally in combination with at least one noncorticosteroidal immunosuppressive and/or antiinflammatory agent.
3. The method of claim 1 , wherein the pharmaceutical composition is administered in place of or in combination with corticosteroid maintenance therapy, and optionally in combination with at least one noncorticosteroidal immunosuppressive and/or antiinflammatory agent.
4. The method of claim 1 , wherein the pharmaceutical composition comprises at least one compound which is a substantially pure (E) or (Z) isomer of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile, and/or
at least one pharmaceutically acceptable salt of said compound; and
at least one pharmaceutically acceptable carrier or excipient,
and wherein the mammal is a human.
5. The method of claim 4 , wherein at least about 85% w/w of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile or at least about 85% w/w of a pharmaceutically acceptable salt of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile is the (E) isomer.
6. The method of claim 1 , wherein:
the pharmaceutical composition is administered to a human; and
the at least one disease is pemphigus vulgaris.
7. The method of claim 1 , wherein the pharmaceutical composition is optionally administered in combination with at least one immunosuppressive agent selected from interferon alpha, interferon gamma, cyclophosphamide, tacrolimus, mycophenolate mofetil, methotrexate, dapsone, sulfasalazine, azathioprine, an anti-CD20 agent, anti-TNFalpha agent, anti-IL6 agent toward ligand or its receptors, anti-IL17 agent to ligand or its receptors, anti-IL1 agent to ligand or its receptors, anti-IL2 agent to ligand or its receptors, anti-CD2 agent, anti-CD3 agent, anti-CD80/86 agent, anti-sphingosine-1-phosphate receptor agent, anti-C5 agent, anti-mTOR agent, anti-calcineurin agent, anti-BAFF/BlyS agent, leflunomide, and teriflunomide.
8. The method of claim 1 , wherein the pharmaceutical composition is optionally administered in combination with rituximab, ofatumumab, obinutuzumab, or veltuzumab, or a biosimilar version thereof.
9. The method of claim 1 , wherein the at least one pharmaceutically acceptable salt is a sulfonic acid or carboxylic acid salt of at least one compound selected from (E) isomer, (Z) isomer, and a mixture of (E) and (Z) isomers of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]-pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile.
10. The method of claim 1 , wherein the at least one pharmaceutically acceptable salt is an amorphous form of a pharmaceutically acceptable salt of at least one compound selected from (E) isomer, (Z) isomer, and a mixture of (E) and (Z) isomers of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]-pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile.