Solid forms of a nucleoside analogue and uses thereof
The present disclosure relates to solid forms (e.g. crystalline forms, solvates, and crystalline forms thereof) of a compound which is ((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methyl neopentyl carbonate, which is useful in the treatment of treating viral infections, for example paramyxoviridae, pneumoviridae, picornaviridae, flaviviridae, filoviridae, arenaviridae, orthomyxovirus, and coronaviridae infections.
1 . A solvate of a compound of Formula (I):
wherein the solvate is an organic solvent solvate or hydrate.
2 . The solvate of claim 1 , wherein the solvate is an ethanol solvate or an acetonitrile solvate.
3 . The solvate of claim 1 , wherein the solvate is crystalline.
4 . A pharmaceutical composition comprising:
(i) a solvate of claim 1 ; and
(ii) a pharmaceutically acceptable excipient.
5 . A method of making the solvate of claim 1 wherein the method comprises (i) slurrying the compound of Formula (I) in a solvent and (ii) isolating the solvate or the crystalline form of Formula (I).
6 . A crystalline form of an ethanol solvate of a compound of Formula (I)
wherein the crystalline form is characterized by an XRPD pattern comprising degree 20-reflections (±0.2 degrees 2θ) at 5.4°, 15.2°, and 23.8°.
7 . The crystalline form of claim 6 , wherein the XRPD pattern comprises degree 20-reflections (±0.2 degrees 2θ) at 5.4°, 12.9°, 15.2°, 18.7°, 23.8° and 25.2.
8 . The crystalline form of claim 6 , wherein the XRPD pattern comprises degree 20-reflections (±0.2 degrees 2θ) at 5.4°, 12.9°, 14.0°, 15.2°, 16.8°, 18.7°, 23.8°, 24.0°, and 25.2°.
9 . A pharmaceutical composition comprising:
(i) the crystalline form of claim 6 ; and
(ii) a pharmaceutically acceptable excipient.
10 . A method of making the crystalline form of claim 6 , wherein the method comprises (i) slurrying the compound of Formula (I) in a solvent and (ii) isolating the solvate or the crystalline form of Formula (I).
11 . A crystalline form of an acetonitrile solvate of a compound of Formula (I):
wherein the crystalline form is characterized by an XRPD pattern comprising degree 2θ-reflections (±0.2 degrees 2θ) at 4.6°, 14.6°, and 18.3°.
12 . The crystalline form of claim 11 , wherein the XRPD comprises degree 2θ-reflections (±0.2 degrees 2θ) at 4.6°, 5.0°, 14.6°, 15.7°, 18.3°, and 26.2°.
13 . The crystalline form of claim 11 , wherein the XRPD comprises degree 2θ-reflections (±0.2 degrees 2θ) at 4.6°, 5.0°, 8.3°, 14.6°, 15.7°, 16.6°, 17.5°, 18.3°, and 26.2°.
14 . A pharmaceutical composition comprising:
(i) the crystalline form of claim 11 ; and
(ii) a pharmaceutically acceptable excipient.
15 . A method of making the crystalline form of claim 11 , wherein the method comprises (i) slurrying the compound of Formula (I) in a solvent and (ii) isolating the solvate or the crystalline form of Formula (I).
16 . A crystalline form of a compound of Formula (I)
wherein the crystalline form is characterized by an XRPD pattern comprising degree 2θ-reflections (±0.2 degrees 2θ) at 5.3°, 18.7°, and 20.0°.
17 . The crystalline form of claim 16 , wherein the XRPD pattern comprises degree 2θ-reflections (±0.2 degrees 2θ) at 5.3°, 14.3°, 15.4°, 18.7°, 20.0°, and 25.1°.
18 . The crystalline form of claim 16 , wherein the XRPD pattern comprises degree 2θ-reflections (±0.2 degrees 2θ) at 5.3°, 14.3°, 14.6°, 15.4°, 17.0°, 18.7°, 20.0°, 25.1°, and 25.9°.
19 . The crystalline form of claim 16 , wherein the crystalline form is characterized by a differential scanning calorimetry (DSC) pattern comprising an endothermic transition with an onset at about 162° C.
20 . The crystalline form of claim 16 , wherein the crystalline form is unsolvated.
21 . A pharmaceutical composition comprising:
(i) the crystalline form of claim 16 ; and
(ii) a pharmaceutically acceptable excipient.
22 . A method of making the crystalline form of claim 16 , wherein the method comprises drying a solvate of a compound of Formula (I), a crystalline form of an ethanol solvate of a compound of Formula (I) wherein the crystalline form of the ethanol solvate is characterized by an XRPD pattern comprising degree 2θ-reflections (±0.2 degrees 2θ) at 5.4°, 15.2°, and 23.8°, or a crystalline form of an acetonitrile solvate of a compound of Formula (I) wherein the crystalline form of the acetonitrile solvate is characterized by an XRPD pattern comprising degree 2θ-reflections (±0.2 degrees 2θ) at about 4.6°, 14.6°, and 18.3°.
23 . A crystalline form of a compound of Formula (I)
wherein the crystalline form is characterized by an XRPD pattern comprising degree 2θ-reflections (±0.2 degrees 2θ) at 5.1°, 10.3°, and 15.2°.
24 . The crystalline form of claim 23 , wherein the XRPD comprises degree 2θ-reflections (±0.2 degrees 2θ) at 5.1°, 10.3°, 14.7°, 15.2°, 17.3°, and 26.2°.
25 . The crystalline form of claim 23 , wherein the XRPD comprises degree 2θ-reflections (±0.2 degrees 2θ) at 5.1°, 10.3°, 11.4°, 13.8°, 14.7°, 15.2°, 17.3°, 25.8°, and 26.2°.
26 . The crystalline form of claim 23 , wherein the crystalline form is characterized by a differential scanning calorimetry pattern comprising a first endothermic transition at about 149° C. followed by an immediate exotherm and a second endotherm is observed with an onset at about 161° C.
27 . The crystalline form of claim 23 , wherein the crystalline form is unsolvated.
28 . A pharmaceutical composition comprising:
(i) the crystalline form of claim 23 ; and
(ii) a pharmaceutically acceptable excipient.
29 . A method of making the crystalline form of claim 23 , wherein the method comprises drying a solvate of a compound of Formula (I), a crystalline form of an ethanol solvate of a compound of Formula (I) wherein the crystalline form of the ethanol solvate is characterized by an XRPD pattern comprising degree 2θ-reflections (±0.2 degrees 2θ) at 5.4°, 15.2°, and 23.8°, or a crystalline form of an acetonitrile solvate of a compound of Formula (I) wherein the crystalline form of the acetonitrile solvate is characterized by an XRPD pattern comprising degree 2θ-reflections (±0.2 degrees 2θ) at about 4.6°, 14.6°, and 18.3°.
30 . A method of treating a viral infection in a human in need thereof, wherein the method comprises administering to the human a solvate of a compound of Formula (I) wherein the solvate is an organic solvent solvate or hydrate, a crystalline form of an ethanol solvate of a compound of Formula (I) wherein the crystalline form of the ethanol solvate is characterized by an XRPD pattern comprising degree 2θ-reflections (±0.2 degrees 2θ) at 5.4°, 15.2°, and 23.8°, a crystalline form of an acetonitrile solvate of a compound of Formula (I) wherein the crystalline form of the acetonitrile solvate is characterized by an XRPD pattern comprising degree 2θ-reflections (±0.2 degrees 2θ) at about 4.6°, 14.6°, and 18.3°, a crystalline form of a compound of Formula (I) characterized by an XRPD pattern comprising degree 2θ-reflections (±0.2 degrees 2θ) at 5.3°, 18.7°, and 20.0°, or a crystalline form of a compound of Formula (I) characterized by an XRPD pattern comprising degree 2θ-reflections (±0.2 degrees 2θ) at 5.1°, 10.3°, and 15.2°;
31 . The method of claim 30 , wherein the method comprises administering to the human at least one additional therapeutic or prophylactic agent.
32 . The method of claim 31 , wherein the additional therapeutic or prophylactic agent is cobicistat, molnupiravir, nirmatrelvir, ritonavir, or a combination thereof.
33 . The method of claim 30 , wherein the viral infection is a coronavirus infection, a pneumoviridae virus infection, a picornaviridae virus infection, an enterovirus infection, a flaviviridae virus infection, a filoviridae virus infection, an orthomyxovirus infection, an influenza virus infection, or a paramyxoviridae virus infection.