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 having the structure: for use in treating viral infections. One crystalline form of the compound can be characterized by an X-ray powder diffraction (XRPD) pattern having peaks at 22.3°, 16.9°, and 16.2° 2-θ±0.2° 2-θ. 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 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 about 22.3°, 16.9°, and 16.2° 2-θ±0.2° 2-θ.
2. The crystalline form of claim 1 , characterized by a unit cell as determined by single crystal X-ray crystallography of the following dimensions: a=10.505 (2) Å; b=12.736 (3) Å; c=11.066 (2) Å; α=90°; β=100.105 (7)° and γ=90.
3. The crystalline form of claim 1 , characterized by a Differential Scanning Calorimetry (DSC) thermogram peak at 138° C.
4. A pharmaceutical composition comprising a crystalline form of claim 1 and a pharmaceutically acceptable excipient.
5. The crystalline form of claim 1 , wherein the X-ray powder diffraction (XRPD) pattern has further peaks at about 13.8° and 12.7° 2-θ±0.2° 2-θ.
6. The crystalline form of claim 1 , wherein the X-ray powder diffraction (XRPD) pattern has further peaks at about 22.5°, 10.6° and 14.5° 2-θ±0.2° 2-θ.
7. The crystalline form of claim 1 , wherein the X-ray powder diffraction (XRPD) pattern has peaks at about 22.3°, 16.9°, 16.2°, 13.8°, 12.7°, 22.5°, 10.6° and 14.5° 2-θ±0.2° 2-θ.
8. The crystalline form of claim 1 , characterized by one or more of the following:
an X-ray powder diffraction (XRPD) pattern further having peaks at about 22.3°, 16.9°, 16.2°, 13.8°, 12.7°, 22.5°, 10.6° and 14.5° 2-θ±0.2° 2-θ;
a Differential Scanning calorimetry (DSC) thermogram peak at 138° C.; and
a unit cell as determined by single crystal X-ray crystallography of the following dimensions: a=10.505 (2) Å; b=12.736 (3) Å; c=11.066 (2) Å; α=90°; β=100.105 (7)°; and γ=90.
9. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern as set forth in FIG. 5 .
10. The crystalline form of claim 1 , characterized by differential scanning calorimetry (DSC) pattern as set forth in FIG. 6 .
11. The crystalline form of claim 1 , characterized by thermogravimetric analysis (TGA) pattern as set forth in FIG. 7 .
12. The crystalline form of claim 1 , characterized by dynamic vapor sorption (DVS) pattern as set forth in FIG. 8 .