Crystalline forms of (s)-2-ethylbutyl 2-(((s)-(((2r,3s,4r,5r)-5-(4-aminopyrrolo[2,1-f] [1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy) (phenoxy) phosphoryl)amino)propanoate
The present invention relates to novel salts and crystalline forms of (S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate for use in treating viral infections. In some embodiments, the viral infection is caused by a virus selected from the group consisting of Arenaviridae, Coronaviridae, Filoviridae, Flaviviridae, and Paramyxoviridae.
1. A pharmaceutical composition comprising a crystalline form of (S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo [2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy) phosphoryl)amino)propanoate, wherein the crystalline form is characterized by an X-ray powder diffraction (XRPD) pattern having peaks at 22.3°, 16.9°, and 16.2°±0.2° 2−θ and one to three additional therapeutic agents.
2. The pharmaceutical composition of claim 1 , wherein the additional therapeutic agents are each active against a virus selected from the group consisting of Arenaviridae, Coronaviridae, Filoviridae, Flaviviridae, and Paramyxoviridae.
3. The pharmaceutical composition of claim 2 , wherein the additional therapeutic agents are each active against Lassa virus.
4. The pharmaceutical composition of claim 2 , wherein the additional therapeutic agents are each active against Junin virus.
5. The pharmaceutical composition of claim 2 , wherein the additional therapeutic agents are each active against MERS virus.
6. The pharmaceutical composition of claim 2 , wherein the additional therapeutic agents are each active against SARS virus.
7. The pharmaceutical composition of claim 2 , wherein the additional therapeutic agents are each active against ebolavirus.
8. The pharmaceutical composition of claim 2 , wherein the additional therapeutic agents are each active against Marburg virus.
9. The pharmaceutical composition of claim 2 , wherein the additional therapeutic agents are each active against Zika virus.
10. The pharmaceutical composition of claim 2 , wherein the additional therapeutic agents are each active against respiratory syncytial virus.
11. A pharmaceutical composition comprising a crystalline form of (S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo [2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy) phosphoryl)amino)propanoate, wherein the crystalline form is characterized by an X-ray powder diffraction (XRPD) pattern having peaks at 22.3°, 16.9°, and 16.2°±0.2° 2−θ and a pharmaceutically acceptable excipient, wherein the pharmaceutical composition is in a unit dosage form.
12. A pharmaceutical composition comprising a crystalline form of (S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo [2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy) phosphoryl)amino)propanoate, wherein the crystalline form is characterized by an X-ray powder diffraction (XRPD) pattern having peaks at 22.3°, 16.9°, and 16.2°±0.2° 2−θ, prepared by combining a therapeutically effective amount of the crystalline form with a pharmaceutically acceptable excipient.
13. A method for treating a viral infection in a human, the method comprising administering to a human in need thereof a therapeutically effective amount of a crystalline form of (S)-2-ethylbutyl 2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo [2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy) phosphoryl)amino)propanoate, wherein the crystalline form is characterized by an X-ray powder diffraction (XRPD) pattern having peaks at 22.3°, 16.9°, and 16.2°±0.2° 2−θ.
14. The method for treating a virus infection in a human of claim 13 wherein the viral infection is caused by a virus selected from the group consisting of Arenaviridae, Coronaviridae, Filoviridae, Flaviviridae, and Paramyxoviridae.
15. The method of claim 14 , wherein the viral infection is caused by the Arenaviridae virus.
16. The method of claim 15 , wherein the Arenaviridae virus is Lassa virus or Junin virus.
17. The method of claim 14 , wherein the viral infection is caused by the Coronaviridae virus.
18. The method of claim 17 , wherein the Coronaviridae virus is MERS virus or SARS virus.
19. The method of claim 14 , wherein the viral infection is cause by the Filoviridae virus.
20. The method of claim 19 , wherein the Filoviridae virus is ebolavirus or Marburg virus.
21. The method of claim 14 , wherein the viral infection is cause by the Flaviviridae virus.
22. The method of claim 21 , wherein the Flaviviridae virus is Zika virus.