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: ##STR00001## 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):	Clarke; Michael O'Neil Hanrahan (Redwood City, CA), Feng; Joy Yang (Hillsborough, CA), Jordan; Robert (Foster City, CA), Mackman; Richard L. (Millbrae, CA), Ray; Adrian S. (Burlingame, CA), Siegel; Dustin (Half Moon Bay, CA)
Assignee:	Gilead Sciences, Inc. (Foster City, CA)
Application Number:	17/222,066
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: ##STR00264## or a pharmaceutically acceptable salt thereof; wherein R.sup.2 and R.sup.3 are each OR.sup.a; R.sup.6 is CN; R.sup.7 is --(C.dbd.O)R.sup.11 or ##STR00265## R.sup.8 is NH.sub.2; R.sup.9 is H; each occurrence of R.sup.a is independently H or --(C.dbd.O)R; R.sup.11 is H or (C.sub.1-C.sub.8)alkyl which is optionally substituted by NH.sub.2; each occurrence of R is independently H or (C.sub.1-C.sub.8)alkyl which is optionally substituted by NH.sub.2; R.sup.f is H or (C.sub.1-C.sub.8)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 R.sup.7 is ##STR00266## 3. The method of claim 2, wherein R.sup.f 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 R.sup.2 and R.sup.3 are each OH. 5. The method of claim 4, wherein R.sup.7 is --(C.dbd.O)R.sup.11 and R.sup.11 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 NH.sub.2. 6. The method of claim 5, wherein R.sup.11 is --CH(CH.sub.3).sub.2. 7. The method of claim 5, wherein R.sup.11 is --CH(NH.sub.2)CH(CH.sub.3).sub.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 R.sup.2 and R.sup.3 are each --O(C.dbd.O)(C.sub.1-C.sub.8)alkyl, wherein the (C.sub.1-C.sub.8)alkyl groups of R.sup.2 and R.sup.3 are each optionally substituted with NH.sub.2. 12. The method of claim 11, wherein the (C.sub.1-C.sub.8)alkyl groups of R.sup.2 and R.sup.3 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 NH.sub.2. 13. The method of claim 12, wherein each of R.sup.2 and R.sup.3 is selected from the group consisting of --O(C.dbd.O)--CH(CH.sub.3).sub.2 and --O(C.dbd.O)--CH(NH.sub.2)CH(CH.sub.3).sub.2. 14. The method of claim 13, wherein R.sup.2 and R.sup.3 are --O(C.dbd.O)--CH(NH.sub.2)CH(CH.sub.3).sub.2 and --O(C.dbd.O)--CH(CH.sub.3).sub.2, respectively; --O(C.dbd.O)--CH(CH.sub.3).sub.2 and --O(C.dbd.O)--CH(NH.sub.2)CH(CH.sub.3).sub.2, respectively; or --O(C.dbd.O)--CH(NH.sub.2)CH(CH.sub.3).sub.2 and --O(C.dbd.O)--CH(NH.sub.2)CH(CH.sub.3).sub.2, respectively. 15. The method of claim 13, wherein R.sup.2 and R.sup.3 are each --O(C.dbd.O)--CH(CH.sub.3).sub.2. 16. The method of claim 11, wherein R.sup.7 is --(C.dbd.O)R.sup.11 and R.sup.11 is --(C.sub.1-C.sub.8)alkyl optionally substituted by NH.sub.2. 17. The method of claim 16, wherein R.sup.11 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 NH.sub.2. 18. The method of claim 17, wherein R.sup.11 is --CH(CH.sub.3).sub.2. 19. The method of claim 17, wherein R.sup.11 is --CH(NH.sub.2)CH(CH.sub.3).sub.2. 20. The method of claim 11, wherein R.sup.2 is --O(C.dbd.O)--CH(CH.sub.3).sub.2, R.sup.3 is --O(C.dbd.O)--CH(CH.sub.3).sub.2, R.sup.7 is --(C.dbd.O)R.sup.11, and R.sup.11 is --CH(CH.sub.3).sub.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 R.sup.2 is OH and R.sup.3 is --O(C.dbd.O)(C.sub.1-C.sub.8)alkyl, wherein the (C.sub.1-C.sub.8)alkyl of R.sup.3 is optionally substituted by NH.sub.2. 26. The method of claim 25, wherein the (C.sub.1-C.sub.8)alkyl of R.sup.3 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 NH.sub.2. 27. The method of claim 26, wherein R.sup.3 is --O(C.dbd.O)--CH(CH.sub.3).sub.2. 28. The method of claim 26, wherein R.sup.3 is --O(C.dbd.O)--CH(NH.sub.2)CH(CH.sub.3).sub.2. 29. The method of claim 25, wherein R.sup.7 is --(C.dbd.O)R.sup.11 and R.sup.11 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 NH.sub.2. 30. The method of claim 29, wherein R.sup.11 is --CH(CH.sub.3).sub.2. 31. The method of claim 29, wherein R.sup.11 is --CH(NH.sub.2)CH(CH.sub.3).sub.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 R.sup.3 is OH and R.sup.2 is --O(C.dbd.O)(C.sub.1-C.sub.8)alkyl, wherein the (C.sub.1-C.sub.8)alkyl of R.sup.2 is optionally substituted by NH.sub.2. 35. The method of claim 34, wherein the (C.sub.1-C.sub.8)alkyl of R.sup.2 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 NH.sub.2. 36. The method of claim 35, wherein R.sup.2 is --O(C.dbd.O)--CH(CH.sub.3).sub.2. 37. The method of claim 35, wherein R.sup.2 is --O(C.dbd.O)--CH(NH.sub.2)CH(CH.sub.3).sub.2. 38. The method of claim 34, wherein R.sup.7 is --(C.dbd.O)R.sup.11 and R.sup.11 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 NH.sub.2. 39. The method of claim 38, wherein R.sup.11is --CH(CH.sub.3).sub.2. 40. The method of claim 38, wherein R.sup.11 is --CH(NH.sub.2)CH(CH.sub.3).sub.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.