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

Patent metadata

Field	Value
Publication number	US-10836787-B2
Application number	US-201815964597-A
Country	US
Kind code	B2
Filing date	Apr 27, 2018
Priority date	May 1, 2017
Publication date	Nov 17, 2020
Grant date	Nov 17, 2020

Abstract

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.

First claim

What is claimed is:

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 .

Assignees

• Gilead Sciences Inc

Inventors

• Brak Katrien
• Carra Ernest A
• Heumann Lars V
• Larson Nate

Classifications

• C07F9/65616 Primary

  containing the ring system [IMAGE cpc-sch-C07F-1006.gif] having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P31/12

  Antivirals · CPC title

• C07F9/6561 Primary

  containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title