Choline salt forms of an HIV capsid inhibitor
The present disclosure relates to choline salts, 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 and prevention of a Retroviridae viral infection including an infection caused by the HIV virus.
1. A pharmaceutically acceptable salt, 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 N,N,N-trimethylethanolammonium salt.
2. A crystalline form of the salt of claim 1 .
3. The crystalline form of claim 2 , which is crystalline Form I.
4. The crystalline form of claim 3 , wherein the crystalline Form I has at least three XRPD peaks, in terms of 2-theta±0.2°, selected from 5.5°, 7.5°, 7.9°, 14.9°, 15.7°, 16.8°, 17.6°, 19.3°, and 22.4°.
5. The crystalline form of claim 3 , wherein the crystalline Form I is characterized by an XRPD pattern substantially as shown in FIG. 4 .
6. The crystalline form of claim 3 , wherein the crystalline Form I is characterized by a DSC thermogram having a melting onset of about 157° C.
7. The crystalline form of claim 3 , wherein the crystalline Form I is characterized by a DSC thermogram substantially as shown in FIG. 5 .
8. The crystalline form of claim 2 , which is crystalline Form II.
9. The crystalline form of claim 8 , wherein the crystalline Form II has at least three XRPD peaks, in terms of 2-theta±0.2°, selected from 7.5°, 9.6°, 14.0°, 14.9°, 16.1°, 16.9°, 20.8°, 21.0°, and 26.5°.
10. The crystalline form of claim 8 , wherein the crystalline Form II is characterized by an XRPD pattern substantially as shown in FIG. 6 .
11. The crystalline form of claim 8 , wherein the crystalline Form II is characterized by a DSC thermogram having a melting onset of about 147° C.
12. The crystalline form of claim 8 , wherein the crystalline Form II is characterized by a DSC thermogram substantially as shown in FIG. 7 .
13. The crystalline form of claim 2 , which is crystalline Form III.
14. The crystalline form of claim 13 wherein the crystalline Form III has at least three XRPD peaks, in terms of 2-theta±0.2°, selected from 7.8°, 8.1°, 8.3°, 15.0°, 15.7°, 16.7°, 20.0°, 21.1°, and 21.7°.
15. The crystalline form of claim 13 , wherein the crystalline Form III is characterized by an XRPD pattern substantially as shown in FIG. 8 .
16. The crystalline form of claim 13 , wherein the crystalline Form III is characterized by a DSC thermogram having a melting onset of about 144° C.
17. The crystalline form of claim 13 , wherein the crystalline Form III is characterized by a DSC thermogram substantially as shown in FIG. 9 .
18. A pharmaceutical composition comprising the pharmaceutically acceptable salt of claim 1 , and at least one pharmaceutically acceptable excipient.
19. A pharmaceutical composition comprising the crystalline form of claim 2 , and at least one pharmaceutically acceptable excipient.
20. A pharmaceutical composition comprising the crystalline form of claim 3 , and at least one pharmaceutically acceptable excipient.
21. A pharmaceutical composition comprising the crystalline form of claim 8 , and at least one pharmaceutically acceptable excipient.
22. A pharmaceutical composition comprising the crystalline form of claim 13 , and at least one pharmaceutically acceptable excipient.