Crystalline form of (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide, preparation, and uses thereof
The present invention relates to a crystalline form of (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide for inhibiting Btk, methods of preparation thereof and pharmaceutical compositions, and use of the crystalline form above in the treatment of a disease, or in the manufacturing of a medicament for the treatment of a disease.
1. An amorphous form of Compound 1,
wherein the amorphous form has an enantiomeric excess value of at least 90%.
2. The amorphous form of claim 1 , wherein the amorphous form has a mid-point temperature of a glass transition temperature of about 79.7° C.
3. The amorphous form of claim 2 , wherein the amorphous form has an enantiomeric excess value of at least 97%.
4. The amorphous form of claim 3 , wherein the amorphous form has a purity of at least 99.3%.
5. The amorphous form of claim 4 , wherein the amorphous form has a purity of at least 99.5%.
6. A pharmaceutical composition comprising the amorphous form of claim 5 and a pharmaceutically acceptable excipient.
7. The pharmaceutical composition of claim 6 , wherein the composition is in a single unit form.
8. The pharmaceutical composition of claim 7 , wherein the single unit form comprises about 40 mg or about 80 mg of the amorphous form of Compound 1.
9. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition comprises about 160 mg of the amorphous form of Compound 1.
10. A method for treating a B-cell proliferative disease in a subject, comprising administering to the subject in need thereof the amorphous form of claim 1 , wherein the B-cell proliferative disease is selected from a group consisting of chronic lymphocytic leukemia, small lymphocytic lymphoma, mantle cell lymphoma, Waldenström's macroglobulinemia, marginal zone lymphoma, and follicular lymphoma.
11. The method of claim 10 , wherein the amorphous form of Compound 1 is administrated at a dose of 40 mg/day to 320 mg/day.
12. The method of claim 10 , wherein the amorphous form of Compound 1 is administered at a dose of 160 mg twice a day (BID).
13. The method of claim 10 , wherein the amorphous form of Compound 1 is administered at a dose of 320 mg once a day (QD).
14. The method of claim 10 , wherein the B-cell proliferative disease is chronic lymphocytic leukemia.
15. The method of claim 10 , wherein the B-cell proliferative disease is small lymphocytic lymphoma.
16. The method of claim 10 , wherein the B-cell proliferative disease is mantle cell lymphoma.
17. The method of claim 16 , wherein the subject has received at least one prior therapy.
18. The method of claim 10 , wherein the B-cell proliferative disease is Waldenström's macroglobulinemia.
19. The method of claim 10 , wherein the B-cell proliferative disease is marginal zone lymphoma.
20. The method of claim 19 , wherein the subject has received at least one prior therapy.
21. The method of claim 20 , wherein the marginal zone lymphoma is relapsed or refractory marginal zone lymphoma.
22. The method of claim 10 , wherein the B-cell proliferative disease is follicular lymphoma.
23. The method of claim 10 , wherein the amorphous form of Compound 1 is administered orally.
24. A lyophilized amorphous form of Compound 1,
25. The lyophilized amorphous form of claim 24 , wherein the lyophilized amorphous form has an enantiomeric excess value of at least 97%.
26. The lyophilized amorphous form of claim 25 , wherein the lyophilized amorphous form has a purity of at least 99.3%.
27. The lyophilized amorphous form of claim 26 , wherein the lyophilized amorphous form has a purity of at least 99.5%.