Claims for Patent: 11,382,926

Summary for Patent: 11,382,926

Title:	Methods for treating Arenaviridae and Coronaviridae virus infections
Abstract:	Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I:wherein the 1′ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.
Inventor(s):	Michael O'Neil Hanrahan Clarke, Joy Yang Feng, Robert Jordan, Richard L. Mackman, Adrian S. Ray, Dustin Siegel
Assignee:	Gilead Sciences Inc
Application Number:	US17/222,066
Patent Claims:	1. A method for treating Coronaviridae infection in a human in need thereof, comprising administering a therapeutically effective amount of a compound of Formula III: or a pharmaceutically acceptable salt thereof; wherein R2 and R3 are each ORa; R6 is CN; R7 is —(C═O)R11 or R8 is NH2; R9 is H; each occurrence of Ra is independently H or —(C═O)R; R11 is H or (C1-C8)alkyl which is optionally substituted by NH2; each occurrence of R is independently H or (C1-C8)alkyl which is optionally substituted by NH2; Rf is H or (C1-C8)alkyl; and one or more hydrogens attached to a carbon of the compound are optionally replaced by deuterium. 2. The method of claim 1, wherein R7 is 3. The method of claim 2, wherein Rf is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl. 4. The method of claim 1, wherein R2 and R3 are each OH. 5. The method of claim 4, wherein R7 is —(C═O)R11 and R11 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted by NH2. 6. The method of claim 5, wherein R11 is —CH(CH3)2. 7. The method of claim 5, wherein R11 is —CH(NH2)CH(CH3)2. 8. The method of claim 5, wherein one or more hydrogens attached to a carbon of the compound are replaced by deuterium. 9. The method of claim 6, wherein one or more hydrogens attached to a carbon of the compound are replaced by deuterium. 10. The method of claim 7, wherein one or more hydrogens attached to a carbon of the compound are replaced by deuterium. 11. The method of claim 1, wherein R2 and R3 are each —O(C═O)(C1-C8)alkyl, wherein the (C1-C8)alkyl groups of R2 and R3 are each optionally substituted with NH2. 12. The method of claim 11, wherein the (C1-C8)alkyl groups of R2 and R3 are each selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted with NH2. 13. The method of claim 12, wherein each of R2 and R3 is selected from the group consisting of —O(C═O)—CH(CH3)2 and —O(C═O)—CH(NH2)CH(CH3)2. 14. The method of claim 13, wherein R2 and R3 are —O(C═O)—CH(NH2)CH(CH3)2 and —O(C═O)—CH(CH3)2, respectively; —O(C═O)—CH(CH3)2 and —O(C═O)—CH(NH2)CH(CH3)2, respectively; or —O(C═O)—CH(NH2)CH(CH3)2 and —O(C═O)—CH(NH2)CH(CH3)2, respectively. 15. The method of claim 13, wherein R2 and R3 are each —O(C═O)—CH(CH3)2. 16. The method of claim 11, wherein R7 is —(C═O)R11 and R11 is —(C1-C8)alkyl optionally substituted by NH2. 17. The method of claim 16, wherein R11 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted by NH2. 18. The method of claim 17, wherein R11 is —CH(CH3)2. 19. The method of claim 17, wherein R11 is —CH(NH2)CH(CH3)2. 20. The method of claim 11, wherein R2 is —O(C═O)—CH(CH3)2, R3 is —O(C═O)—CH(CH3)2, R7 is —(C═O)R11, and R11 is —CH(CH3)2. 21. The method of claim 18, wherein one or more hydrogens attached to a carbon of the compound are replaced by deuterium. 22. The method of claim 19, wherein one or more hydrogens attached to a carbon of the compound are replaced by deuterium. 23. The method of claim 20, wherein one or more hydrogens attached to a carbon of the compound are replaced by deuterium. 24. The method of claim 20, wherein one hydrogen attached to a carbon of the compound is replaced by deuterium. 25. The method of claim 1, wherein R2 is OH and R3 is —O(C═O)(C1-C8)alkyl, wherein the (C1-C8)alkyl of R3 is optionally substituted by NH2. 26. The method of claim 25, wherein the (C1-C8)alkyl of R3 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted by NH2. 27. The method of claim 26, wherein R3 is —O(C═O)—CH(CH3)2. 28. The method of claim 26, wherein R3 is —O(C═O)—CH(NH2)CH(CH3)2. 29. The method of claim 25, wherein R7 is —(C═O)R11 and R11 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted by NH2. 30. The method of claim 29, wherein R11 is —CH(CH3)2. 31. The method of claim 29, wherein R11 is —CH(NH2)CH(CH3)2. 32. The method of claim 30, wherein one or more hydrogens attached to a carbon of the compound are replaced by deuterium. 33. The method of claim 31, wherein one or more hydrogens attached to a carbon of the compound are replaced by deuterium. 34. The method of claim 1, wherein R3 is OH and R2 is —O(C═O)(C1-C8)alkyl, wherein the (C1-C8)alkyl of R2 is optionally substituted by NH2. 35. The method of claim 34, wherein the (C1-C8)alkyl of R2 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, or 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted by NH2. 36. The method of claim 35, wherein R2 is —O(C═O)—CH(CH3)2. 37. The method of claim 35, wherein R2 is —O(C═O)—CH(NH2)CH(CH3)2. 38. The method of claim 34, wherein R7 is —(C═O)R11 and R11 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted by NH2. 39. The method of claim 38, wherein R11is —CH(CH3)2. 40. The method of claim 38, wherein R11 is —CH(NH2)CH(CH3)2. 41. The method of claim 39, wherein one or more hydrogens attached to a carbon of the compound are replaced by deuterium. 42. The method of claim 40, wherein one or more hydrogens attached to a carbon of the compound are replaced by deuterium. 43. The method of claim 1, wherein the Coronaviridae infection is caused by a SARS virus. 44. The method of claim 1, wherein the Coronaviridae infection is caused by a Coronaviridae virus selected from the group consisting of SARS, MERS, 229E, NL63, OC43, and HKU1. 45. The method of claim 1, wherein one or more hydrogens attached to a carbon of the compound are replaced by deuterium.