Solid forms of an HIV capsid inhibitor
The present disclosure relates to pharmaceutically acceptable salts, cocrystals, and crystalline forms thereof, of a compound which is N—((S)-1-(3-(4-chloro-3-(methylsulfonamido)-1-(2,2,2-trifluoroethyl)-1H-indazol-7-yl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2- ((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide, which is useful in the treatment of a Retroviridae viral infection including an infection caused by the HIV virus.
1. A crystalline form of N—((S)-1-(3-(4-chloro-3-(methylsulfonamido)-1-(2,2,2-trifluoroethyl)-1H-indazol-7-yl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide sodium salt, which is crystalline Form I.
2. The crystalline form of claim 1 , wherein the crystalline Form I has at least three XRPD peaks, in terms of 2-theta±0.2°, selected from 5.6°, 6.6°, 10.9°, 13.4°, 16.8°, 17.1°, 21.8°, 24.1°, and 26.9°.
3. The crystalline form of claim 1 , wherein the crystalline Form I is characterized by an XRPD pattern substantially as shown in FIG. 1 .
4. The crystalline form of claim 1 , wherein the crystalline Form I is characterized by a DSC thermogram having a melting onset of about 218° C.
5. The crystalline form of claim 1 , wherein the crystalline Form I is characterized by a DSC thermogram substantially as shown in FIG. 2 .
6. A crystalline form of N—((S)-1-(3-(4-chloro-3-(methylsulfonamido)-1-(2,2,2-trifluoroethyl)-1H-indazol-7-yl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide sodium salt, which is crystalline Form II.
7. The crystalline form of claim 6 , wherein the crystalline Form II has at least three XRPD peaks, in terms of 2-theta±0.2°, selected from 5.4°, 7.0°, 11.1°, 17.7°, 19.2°, 21.2°, 22.6°, 24.0°, and 27.7°.
8. The crystalline form of claim 6 , wherein the crystalline Form II is characterized by an XRPD pattern substantially as shown in FIG. 3 .
9. The crystalline form of claim 6 , wherein the crystalline Form II is characterized by a DSC thermogram having a melting onset of about 222° C.
10. The crystalline form of claim 6 , wherein the crystalline Form II is characterized by a DSC thermogram substantially as shown in FIG. 4 .
11. A crystalline form of N—((S)-1-(3-(4-chloro-3-(methylsulfonamido)-1-(2,2,2-trifluoroethyl)-1H-indazol-7-yl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide sodium salt, which is crystalline Form III.
12. The crystalline form of claim 11 , wherein the crystalline Form III has at least three XRPD peaks, in terms of 2-theta±0.2°, selected from 5.9°, 7.1°, 11.6°, 15.4°, 17.2°, 18.4°, 19.5°, 22.2°, and 27.2°.
13. The crystalline form of claim 11 , wherein the crystalline Form III is characterized by an XRPD pattern substantially as shown in FIG. 5 .
14. The crystalline form of claim 11 , wherein the crystalline Form III is characterized by a DSC thermogram having a melting onset of about 213° C.
15. The crystalline form of claim 11 , wherein the crystalline Form III is characterized by a DSC thermogram substantially as shown in FIG. 6 .
16. A pharmaceutical composition comprising the crystalline form of claim 1 , and at least one pharmaceutically acceptable excipient.
17. A pharmaceutical composition comprising the crystalline form of claim 6 , and at least one pharmaceutically acceptable excipient.
18. A pharmaceutical composition comprising the crystalline form of claim 11 , and at least one pharmaceutically acceptable excipient.
19. A method of treating or preventing a human immunodeficiency virus (HIV) infection comprising administering a therapeutically effective amount of the crystalline form of claim 3 to a subject in need thereof.
20. The method of claim 19 , wherein the method comprises administering the crystalline form in combination with one, two, three, or four additional therapeutic agents.