Inclusion complexes of an HCV NS5B inhibitor and uses thereof
The present invention relates to novel Inclusion Complexes of Compound A, compositions comprising an Inclusion Complex of Compound A, and methods of using the Inclusion Complexes of Compound A for preparing compositions useful for treating or preventing HCV infection in a patient, wherein Compound A has the structure:
1. An inclusion complex comprising (a) the compound having the structure:
or a pharmaceutically acceptable salt thereof, and (b) at least one long-chain fatty acid.
2. The inclusion complex of claim 1 , wherein the long-chain fatty acid is palmitic acid.
3. The inclusion complex of claim 1 , wherein long-chain fatty acid is stearic acid.
4. The inclusion complex of claim 1 , wherein long-chain fatty acid is a mixture of palmitic acid and stearic acid.
5. The inclusion complex of claim 2 , having a stoichiometry of (a) to (b) of about 1:1.
6. The inclusion complex of claim 3 , having a stoichiometry of (a) to (b) of about 1:1.
7. The inclusion complex of claim 2 , which is characterized by an X-ray powder diffraction pattern comprising diffraction peaks at 2-theta values, when measured using Cu K α radiation, of about 6.57, 6,87, 17.93, and 21.03 degrees.
8. The inclusion complex of claim 3 , which is characterized by an X-ray powder diffraction pattern comprising diffraction peaks at 2-theta values, when measured using Cu K α radiation, of about 6.57, 6.90, 17.90, and 20.98 degrees.
9. The inclusion complex of claim 4 , which is characterized by an X-ray powder diffraction pattern comprising diffraction peaks at 2-theta values, when measured using Cu K α radiation, of about 6.55, 15.62, 17.94, and 19.17 degrees.
10. The inclusion complex of claim 2 , which is characterized by a DSC thermogram having an endothermic transition at about 132 degrees centrigrade.
11. The inclusion complex of claim 3 , which is characterized by a DSC thermogram having an endothermic transition at about 131 degrees centrigrade.
12. The inclusion complex of claim 4 , which is characterized by a DSC thermogram having an endothermic transition at about 131 degrees centrigrade.
13. The inclusion complex of claim 2 , which is characterized by a solid state carbon-13 NMR spectrum having isotropic chemical shifts at 14.85, 21.74, 22.56, 26.04, 29.14, 30.63, 31.14, 32.43, 33.56, 37.07, 49.41, 49.99, 62.99, 68.62, 69.78, 72.29, 77.00, 78.20, 80.53, 93.56, 102.11, 103.87, 119.96, 120.78, 123.72, 125.13, 129.78, 133.94, 141.64, 150.46, 151.22, 152.12, 167.11, 173.97, 181.75, and 183.24 ppm.
14. The inclusion complex of claim 3 , which is characterized by a solid state carbon-13 NMR spectrum having isotropic chemical shifts at 15.54, 20.31, 21.7023, 22.48, 26.14, 27.20, 29.29, 30.62, 31.16, 34.03, 37.18, 49.36, 50.11, 63.25, 68.68, 69.92, 72.27, 77.27, 78.15, 80.52, 92.65, 93.52, 102.11, 103.90, 120.00, 120.60, 123.83, 125.12, 129.69, 133.82, 141.59, 150.42, 151.15, 152.16, 167.04, 174.15, 181.94, and 183.46 ppm.
15. The inclusion complex of claim 4 , which is characterized by a solid state carbon-13 NMR spectrum having isotropic chemical shifts at 14.98, 20.45, 21.78, 22.49, 26.13, 29.29, 30.65, 31.15, 32.52, 33.58, 37.11, 49.38, 50.05, 63.14, 68.63, 69.85, 72.28, 77.09, 78.20, 80.54, 93.53, 102.12, 103.88, 119.99, 120.76, 123.84, 125.15, 129.75, 133.85, 141.59, 150.46, 151.20, 152.16, 167.08, 174.05, 181.86, and 183.36 ppm.
16. A pharmaceutical composition comprising the inclusion complex of claim 1 , and one or more pharmaceutically acceptable excipients.
17. A method for treating HCV in a patient, said method comprising administering to said patient the inclusion complex of claim 1 .