.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Claims for Patent: 8,501,238

« Back to Dashboard

Claims for Patent: 8,501,238

Title:Anti-infective agents and uses thereof
Abstract: This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.
Inventor(s): Flentge; Charles A. (Salem, WI), Hutchinson; Douglas K. (Antioch, IL), Betebenner; David A. (Libertyville, IL), DeGoey; David A. (Salem, WI), Donner; Pamela L. (Mundelein, IL), Kati; Warren M. (Gurnee, IL), Krueger; Allan C. (Gurnee, IL), Liu; Dachun (Waukegan, IL), Liu; Yaya (Buffalo Grove, IL), Longenecker; Kenton L. (Grayslake, IL), Maring; Clarence J. (Palatine, IL), Motter; Christopher E. (Oak Creek, WI), Pratt; John K. (Kenosha, WI), Randolph; John T. (Libertyville, IL), Rockway; Todd W. (Grayslake, IL), Stewart; Kent D. (Gurnee, IL), Wagner; Rolf (Antioch, IL), Chen; Shuang (Gurnee, IL), Gao; Yi (Vernon Hills, IL), Lou; Xiaochun (Long Grove, IL), Zhang; Geoff G. Z. (Libertyville, IL)
Assignee: AbbVie Inc. (North Chicago, IL)
Application Number:13/451,889
Patent Claims: 1. A crystalline form of N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide and salts thereof.

2. The crystalline form of claim 1, wherein the crystalline form is selected from the group consisting of a solvate, a hydrate and a solvent-free crystalline form.

3. The crystalline form of claim 1, wherein the crystalline form is selected from the group consisting of: crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide ethanol solvate; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide acetonitrile solvate; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide ethyl acetate solvate; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide2-propanol solvate; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide methanol solvate; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide 1-propanol solvate; crystalline solvent free N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl)naphthalen-2-yl)methanesulfonamide; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide hydrate; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-- 2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt; crystalline pattern C N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl)-naphthalen-2-yl)methanesulfonamide disodium salt; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide monopotassium salt; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-- 2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monocholine salt; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monocholine salt; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide dicholine salt.

4. The crystalline form of claim 1, wherein the crystalline form is selected from the group consisting of crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt, crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-- 2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt, and crystalline pattern C N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt.

5. The crystalline form of claim 1, wherein the crystalline form is crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3 ,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesul- fonamide monosodium salt.

6. The crystalline form of claim 5, wherein the crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4.6.+-.0.2, 10.4.+-.0.2, 12.0.+-.0.2, 15.6.+-.0.2, 16.0.+-.0.2, 18.6.+-.0.2, 22.8.+-.0.2, 23.3.+-.0.2, 23.9.+-.0.2, and 28.3.+-.0.2 degrees 2.theta..

7. The crystalline form of claim 1, wherein the crystalline form is crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3 ,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-phenyl)naphthalen-2-yl)methanesul- fonamide monosodium salt.

8. The crystalline form of claim 7, wherein the crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.4.+-.0.2, 10.8.+-.0.2, 14.4.+-.0.2, 16.3.+-.0.2, 17.0.+-.0.2, 18.8.+-.0.2, 19.2.+-.0.2, 19.6.+-.0.2, 21.6.+-.0.2, 22.1.+-.0.2, 23.7.+-.0.2, 28.8.+-.0.2, 29.1.+-.0.2, and 31.8.+-.0.2 degrees 2.theta..

9. The crystalline form of claim 1, wherein the crystalline form is crystalline pattern C N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt.

10. The crystalline form of claim 9, wherein the crystalline pattern C N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.0.+-.0.2, 12.0.+-.0.2, 17.5.+-.0.2, 17.8.+-.0.2, 18.8.+-.0.2, and 22.7.+-.0.2 degrees 2.theta..

11. A pharmaceutical composition comprising one or more crystalline forms recited in claim 1 and one or more excipients.

12. The pharmaceutical composition of claim 11, wherein the composition comprises a crystalline form selected from the group consisting of crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt, crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-- 2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt, and crystalline pattern C N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt.

13. The pharmaceutical composition of claim 11, wherein the composition comprises crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt.

14. The pharmaceutical composition of claim 11, wherein the pharmaceutical composition further comprises one or more additional therapeutic agents.

15. The pharmaceutical composition of claim 14, wherein the one or more additional therapeutic agents are selected from the group consisting of interferon agent, ribavirin, HCV inhibitor, and HIV inhibitor.

16. The pharmaceutical composition of claim 14, wherein the one or more additional therapeutic agents is an HCV inhibitor.

17. A method for inhibiting replication of a ribonucleic acid (RNA) virus, wherein the method comprises exposing the virus to one or more crystalline forms recited in claim 1.

18. The method of claim 17, wherein the RNA virus is hepatitis C virus (HCV).

19. The method of claim 17, wherein the crystalline form is selected from the group consisting of crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt, crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-- 2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt, and crystalline pattern C N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt.

20. The method of claim 17, wherein the crystalline form is crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-- 2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt.

21. A method for treating hepatitis C in a mammal in need of such treatment, wherein the method comprises administering to the mammal one or more crystalline forms recited in claim 1.

22. The method of claim 21, wherein the mammal is human.

23. The method of claim 21, wherein the crystalline form is selected from the group consisting of crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt, crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-- 2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt, and crystalline pattern C N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt.

24. The method of claim 21, wherein the crystalline form is crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-- 2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt.

25. The method of claim 21, wherein the method further comprises administering to the mammal one or more additional therapeutic agents.

26. The method of claim 25, wherein one or more additional therapeutic agents are selected from the group consisting of interferon agent, ribavirin, HCV inhibitor, and HIV inhibitor.

27. The method of claim 25, wherein the one or more additional therapeutic agents is an HCV inhibitor.

28. N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-meth- oxyphenyl) naphthalen-2-yl)methanesulfonamide crystalline form selected from the group consisting of: crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide ethanol solvate having an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 8.3.+-.0.2, 9.7.+-.0.2, 10.6.+-.0.2, 13.6.+-.0.2, 17.2.+-.0.2, 19.2.+-.0.2, 22.7.+-.0.2, 26.9.+-.0.2, and 29.4.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide ethanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.3.+-.0.2, 9.7.+-.0.2, 10.0.+-.0.2, 10.6.+-.0.2, 13.6.+-.0.2, 17.2.+-.0.2, 17.5.+-.0.2, 19.2.+-.0.2, 19.4.+-.0.2, 22.7.+-.0.2, 26.9.+-.0.2, and 29.4.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide ethanol solvate having an X-ray powder diffraction pattern as shown in FIG. 1; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide acetonitrile solvate having an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5.3.+-.0.2, 8.3.+-.0.2, 9.7.+-.0.2, 10.5.+-.0.2, 13.8.+-.0.2, 17.2.+-.0.2, 19.1.+-.0.2, and 19.5.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide acetonitrile solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.3.+-.0.2, 8.3.+-.0.2, 9.7.+-.0.2, 10.5.+-.0.2, 13.8.+-.0.2, 17.2.+-.0.2, 17.7.+-.0.2, 19.1.+-.0.2, 19.5.+-.0.2, 22.0.+-.0.2, 22.8.+-.0.2, and 27.2.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide acetonitrile solvate having an X-ray powder diffraction pattern as shown in FIG. 3; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide ethyl acetate solvate having an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 7.9.+-.0.2, 9.3.+-.0.2, 9.7.+-.0.2, 10.6.+-.0.2, 18.7.+-.0.2, 38.5.+-.0.2, and 44.7.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide ethyl acetate solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 7.9.+-.0.2, 9.3.+-.0.2, 9.7.+-.0.2, 10.6.+-.0.2, 13.7.+-.0.2, 17.4.+-.0.2, 18.7.+-.0.2, 21.7.+-.0.2, 22.0.+-.0.2, 28.2.+-.0.2, 38.5.+-.0.2, and 44.7.+-.0.2 degrees 2.theta.. crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide ethyl acetate having an X-ray powder diffraction pattern as shown in FIG. 4; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide 2-propanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.2.+-.0.2, 9.3.+-.0.2, 10.1.+-.0.2, 16.3.+-.0.2, 18.1.+-.0.2, 18.6.+-.0.2, 19.4.+-.0.2, 21.6.+-.0.2, and 22.5.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide 2-propanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.2.+-.0.2, 9.3.+-.0.2, 10.1.+-.0.2, 16.3.+-.0.2, 18.1.+-.0.2, 18.6.+-.0.2, 19.4.+-.0.2, 21.6.+-.0.2, 22.5.+-.0.2, 23.8.+-.0.2, 26.0.+-.0.2, and 28.0.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide 2-propanol solvate having an X-ray powder diffraction pattern as shown in FIG. 5; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide methanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.4.+-.0.2, 9.7.+-.0.2, 10.1.+-.0.2, 13.8.+-.0.2, 17.4.+-.0.2, 19.3.+-.0.2, and 19.6.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide methanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.4.+-.0.2, 9.7.+-.0.2, 10.1.+-.0.2, 13.5.+-.0.2, 13.8.+-.0.2, 17.4.+-.0.2, 19.3.+-.0.2, 19.6.+-.0.2, and 27.1.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide methanol solvate having an X-ray powder diffraction pattern as shown in FIG. 6; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide 1-propanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.2.+-.0.2, 9.3.+-.0.2, 10.1.+-.0.2, 15.7.+-.0.2, 16.2 .+-.0.2, 18.4.+-.0.2, 19.3.+-.0.2, 21.6.+-.0.2, and 22.8.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide 1-propanol solvate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.2.+-.0.2, 9.3.+-.0.2, 10.1.+-.0.2, 10.5.+-.0.2, 15.7.+-.0.2, 16.2 .+-.0.2, 18.4.+-.0.2, 18.6.+-.0.2, 19.3.+-.0.2, 21.0.+-.0.2, 21.6.+-.0.2, and 22.8.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide 1-propanol solvate having an X-ray powder diffraction pattern as shown in FIG. 7. crystalline solvent free N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-met- hoxyphenyl)naphthalen-2-yl)methanesulfonamide having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6.2.+-.0.2, 7.9.+-.0.2, 9.9.+-.0.2, 16.2.+-.0.2, and 18.3.+-.0.2 degrees 2.theta.; crystalline solvent free N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6.2.+-.0.2, 7.9.+-.0.2, 9.9.+-.0.2, 10.1.+-.0.2, 14.9.+-.0.2, 16.2.+-.0.2, 18.3.+-.0.2, 19.8.+-.0.2, and 26.5.+-.0.2 degrees 2.theta.; crystalline solvent free N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide having an X-ray powder diffraction pattern as shown in FIG. 8; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide hydrate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6.4.+-.0.2, 12.9.+-.0.2, 17.9.+-.0.2, and 18.9.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide hydrate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6.4.+-.0.2, 12.9.+-.0.2, 17.5.+-.0.2, 17.9.+-.0.2, 18.9.+-.0.2, and 24.4.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide hydrate having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 6.4.+-.0.2, 12.7.+-.0.2, 12.9.+-.0.2, 14.1.+-.0.2, 15.7.+-.0.2, 17.2.+-.0.2, 17.5.+-.0.2, 17.9.+-.0.2, 18.9.+-.0.2, 21.2.+-.0.2, 24.4.+-.0.2, and 25.0.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide hydrate having an X-ray powder diffraction pattern as shown in FIG. 9; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4.6.+-.0.2, 10.4.+-.0.2, 12.0.+-.0.2, 15.6.+-.0.2, 18.6.+-.0.2, 22.8.+-.0.2, and 23.9.+-.0.2 degrees 2.theta.; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-- 2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4.6.+-.0.2, 10.4.+-.0.2, 12.0.+-.0.2, 15.6.+-.0.2, 18.6.+-.0.2, 22.8.+-.0.2, 23.3.+-.0.2, and 23.9.+-.0.2 degrees 2.theta.; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4.6.+-.0.2, 10.4.+-.0.2, 12.0.+-.0.2, 15. 6.+-.0.2, 16.0.+-.0.2, 18.6.+-.0.2, 22.8.+-.0.2, 23.3.+-.0.2, 23.9.+-.0.2, and 28.3.+-.0.2 degrees 2.theta.; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern as shown in FIG. 10; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.4.+-.0.2, 10.8.+-.0.2, 14.4.+-.0.2, 16.3.+-.0.2, 17.0.+-.0.2, 21.6.+-.0.2, 22.1.+-.0.2, and 23.7.+-.0.2 degrees 2.theta.; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.4.+-.0.2, 10.8.+-.0.2, 14.4.+-.0.2, 16.3.+-.0.2, 17.0.+-.0.2, 18.8.+-.0.2, 19.2.+-.0.2, 19.6.+-.0.2, 21.6.+-.0.2, 22.1.+-.0.2, 23.7.+-.0.2, 28.8.+-.0.2, 29.1.+-.0.2, and 31.8.+-.0.2 degrees 2.theta.; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising three or more peaks selected from the group consisting of 5.4.+-.0.2, 10.8.+-.0.2, 16.3.+-.0.2, 22.1.+-.0.2, and 23.7.+-.0.2 degrees 2.theta.; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising peaks at 5.4.+-.0.2, 10.8.+-.0.2, 16.3.+-.0.2, and 22.1.+-.0.2 degrees 2.theta.; crystalline pattern C N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.0.+-.0.2, 12.0.+-.0.2, 17.5.+-.0.2, 18.8.+-.0.2, and 22.7.+-.0.2 degrees 2.theta.; crystalline pattern C N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.0.+-.0.2, 12.0.+-.0.2, 17.5.+-.0.2, 17.8.+-.0.2, 18.8.+-.0.2, and 22.7.+-.0.2 degrees 2.theta.; crystalline pattern C N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt having pattern C monosodium salt has an X-ray powder diffraction pattern as shown in FIG. 14; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl)-naphthalen-2-yl)methanesulfonamide disodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4.8.+-.0.2, 9.6.+-.0.2, 10.5.+-.0.2, 13.0.+-.0.2, 14.6.+-.0.2, 15.4.+-.0.2, 16.8 .+-.0.2, and 23.0.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide disodium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 4.8.+-.0.2, 9.6.+-.0.2, 10.5.+-.0.2, 13.0.+-.0.2, 14.6.+-.0.2, 15.4.+-.0.2, 16.8 .+-.0.2, 22.7.+-.0.2, 23.0.+-.0.2, and 23.3.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide disodium salt having disodium salt has an X-ray powder diffraction pattern as shown in FIG. 15; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide monopotassium salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.0.+-.0.2, 9.9.+-.0.2, 11.3.+-.0.2, 13.3.+-.0.2, 16.9.+-.0.2, 18.1.+-.0.2, 19.1.+-.0.2, 20.0.+-.0.2, 21.1.+-.0.2, 23.5.+-.0.2, 24.8.+-.0.2, and 25.7.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide monopotassium salt having monopotassium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.0.+-.0.2, 9.9.+-.0.2, 11.3.+-.0.2, 13.3.+-.0.2, 16.9.+-.0.2, 18.1.+-.0.2, 19.1.+-.0.2, 20.0.+-.0.2, 21.1.+-.0.2, 21.5.+-.0.2, 23.5.+-.0.2, 24.8.+-.0.2, and 25.7.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide monopotassium salt having an X-ray powder diffraction pattern as shown in FIG. 17; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methox- y-phenyl)naphthalen-2-yl)methanesulfonamide monocholine salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 10.9.+-.0.2, 12.1.+-.0.2, 13.4.+-.0.2, 15.5.+-.0.2, 17.0.+-.0.2, 17.8.+-.0.2, 18.3.+-.0.2, 19.5.+-.0.2, and 21.9.+-.0.2 degrees 2.theta.; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy phenyl)naphthalen-2-yl)methanesulfonamide monocholine salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 10.9.+-.0.2, 12.1.+-.0.2, 13.0.+-.0.2, 13.4.+-.0.2, 13.6.+-.0.2, 15.5.+-.0.2, 17.0.+-.0.2, 17.8.+-.0.2, 18.3.+-.0.2, 19.5.+-.0.2, 19.7.+-.0.2, and 21.9.+-.0.2 degrees 2.theta.; crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monocholine salt having an X-ray powder diffraction pattern as shown in FIG. 19; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monocholine salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.0.+-.0.2, 9.4.+-.0.2, 11.0.+-.0.2, 13.0.+-.0.2, 13.7.+-.0.2, 15.9.+-.0.2, 17.0.+-.0.2, 18.3.+-.0.2, 18.9.+-.0.2, 19.8.+-.0.2, and 22.1.+-.0.2 degrees 2.theta.; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monocholine salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.0.+-.0.2, 9.4.+-.0.2, 11.0.+-.0.2, 13.0.+-.0.2, 13.3.+-.0.2, 13.7.+-.0.2, 15.9.+-.0.2, 17.0.+-.0.2, 17.4.+-.0.2, 18.3.+-.0.2, 18.9.+-.0.2, 19.8.+-.0.2, 21.8.+-.0.2, and 22.1.+-.0.2 degrees 2.theta.; crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monocholine salt having an X-ray powder diffraction pattern as shown in FIG. 21; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp-

henyl) naphthalen-2-yl)methanesulfonamide dicholine salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.6.+-.0.2, 11.0.+-.0.2, 12.9.+-.0.2, 17.0.+-.0.2, 17.5.+-.0.2, 18.9.+-.0.2, 19.8.+-.0.2, and 21.9.+-.0.2 degrees 2.theta.; crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl) naphthalen-2-yl)methanesulfonamide dicholine salt having an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 8.6.+-.0.2, 11.0.+-.0.2, 12.9.+-.0.2, 17.0.+-.0.2, 17.5.+-.0.2, 18.9.+-.0.2, 19.8.+-.0.2, 21.9.+-.0.2, and 22.1.+-.0.2 degrees 2.theta.; and crystalline N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide dicholine salt having an X-ray powder diffraction pattern as shown in FIG. 23.

29. A pharmaceutical composition comprising one or more crystalline forms recited in claim 28 and one or more excipients.

30. The pharmaceutical composition of claim 29, wherein the pharmaceutical composition further comprises one or more additional therapeutic agents.

31. The pharmaceutical composition of claim 30, wherein the one or more additional therapeutic agents are selected from the group consisting of interferon agent, ribavirin, HCV inhibitor, and HIV inhibitor.

32. The pharmaceutical composition of claim 30, wherein the one or more additional therapeutic agents is an HCV inhibitor.

33. A method for inhibiting replication of a ribonucleic acid (RNA) virus, wherein the method comprises exposing the virus to one or more crystalline forms recited in claim 27.

34. The method of claim 33, wherein the RNA virus is hepatitis C virus (HCV).

35. A method for treating hepatitis C in a mammal in need of such treatment, wherein the method comprises administering to the mammal one or more crystalline forms recited in claim 28.

36. The method of claim 35, wherein the mammal is human.

37. The method of claim 35, wherein the method further comprises administering to the mammal one or more additional therapeutic agents.

38. The method of claim 37, wherein one or more additional therapeutic agents are selected from the group consisting of interferon agent, ribavirin, HCV inhibitor, and HIV inhibitor.

39. The method of claim 37, wherein the one or more additional therapeutic agents is an HCV inhibitor.

40. A process for preparing a crystalline form of N-(6-(3-tert-butyl-5-(2,4-dioxo-3 ,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulf- onamide, sodium salt comprising contacting a sodium base and N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl)naphthalen-2-yl)methanesulfonamide to form a mixture.

41. The process of claim 40, wherein the crystalline form is selected from the group consisting of crystalline pattern A N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt, crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-- 2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt, and crystalline pattern C N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt.

42. The process of claim 40, wherein the crystalline form is crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-- 2-methoxy-phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt.

43. The process of claim 42, wherein the crystalline pattern B N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxy-- phenyl)naphthalen-2-yl)methanesulfonamide monosodium salt has an X-ray powder diffraction pattern comprising one or more peaks selected from the group consisting of 5.4.+-.0.2, 10.8.+-.0.2, 14.4.+-.0.2, 16.3.+-.0.2, 17.0.+-.0.2, 18.8.+-.0.2, 19.2.+-.0.2, 19.6.+-.0.2, 21.6.+-.0.2, 22.1.+-.0.2, 23.7.+-.0.2, 28.8.+-.0.2, 29.1.+-.0.2, and 31.8.+-.0.2 degrees 2.theta..

44. The process of claim 40, wherein the sodium base is sodium hydroxide.

45. The process of claim 40, further comprising contacting a solvent and N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl)naphthalen-2-yl)methanesulfonamide.

46. The process of claim 45, wherein the solvent is selected from the group consisting of acetonitrile, dimethyl sulfoxide, ethanol, 1-propanol, 2-propanol, water and combinations thereof.

47. The process of claim 45, wherein the sodium base is dissolved in the solvent.

48. The process of claim 40, further comprising seeding the mixture with a seeding crystalline form of N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyp- henyl)naphthalen-2-yl)methanesulfonamide sodium salt.

49. The process of claim 48, wherein the seeding crystalline form is a disodium salt.

50. The process of claim 48, wherein the seeding crystalline form is a crystalline pattern B monosodium salt.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc