Substituted nucleosides, nucleotides and analogs thereof

• US 9,073,960 B2
• Filed: 12/20/2012
• Issued: 07/07/2015
• Est. Priority Date: 12/22/2011
• Status: Expired due to Fees

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Alios Biopharma, Inc. (Johnson & Johnson)
• Inventors: Beigelman, Leonid, Wang, Guangyi, Smith, David Bernard, Deval, Jerome, Prhavc, Marija
• Primary Examiner(s): BLAND, LAYLA D
• Application Number:
  US13/721,988
• Publication Number:
  US 20130165400A1
• Time in Patent Office: 929 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 473/18 one oxygen and one nitrogen atom, e.g. guanine
• CPC Class Codes: C07D 473/34 attached in position 6, e.g. adenine
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 493/04 Ortho-condensed systems
• CPC Class Codes: C07H 19/00 Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/12 Triazine radicals
• CPC Class Codes: C07H 19/14 Pyrrolo-pyrimidine radicals
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/207 the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide
• CPC Class Codes: C12N 9/127 RNA-directed RNA polymerase (2.7.7.48), i.e. RNA replicase
• CPC Class Codes: C12Y 207/07048 RNA-directed RNA polymerase (2.7.7.48), i.e. RNA replicase

Abstract

Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof.

Claims

1. A compound selected from Formula (I), or a pharmaceutically acceptable salt thereof:

2. The compound of claim 1, wherein R^1A is

3. The compound of claim 1, wherein R^1A is an optionally substituted acyl.

4. The compound of claim 1, wherein R^1A is H.

5. The compound of claim 1, wherein R^1A is an optionally substituted O-linked amino acid.

6. The compound of claim 1, wherein R^1A is

7. The compound of claim 6, wherein both R^6A and R^7A are independently selected from the group consisting of an optionally substituted C_1-24 alkyl, an optionally substituted C_2-24 alkenyl, an optionally substituted C_2-24 alkynyl, an optionally substituted C_3-6 cycloalkyl, an optionally substituted C_3-6 cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl and an optionally substituted aryl(C_1-6 alkyl).

8. The compound of claim 6, wherein both R^6A and R^7A are independently selected from the group consisting of

9. The compound of claim 6, wherein R^6A and R^7A are both

10. The compound of claim 6, wherein R^8A is selected from the group consisting of absent, hydrogen, an optionally substituted C_1-24 alkyl, an optionally substituted C_2-24 alkenyl, an optionally substituted C_2-24 alkynyl, an optionally substituted C_3-6 cycloalkyl and an optionally substituted C_3-6 cycloalkenyl;

and R^9A is independently selected from the group consisting of an optionally substituted C_1-24 alkyl, an optionally substituted C_2-24 alkenyl, an optionally substituted C_2-24 alkynyl, an optionally substituted C_3-6 cycloalkyl, an optionally substituted C_3-6 cycloalkenyl and NR^30AR^31A.

11. The compound of claim 6, wherein R^8A is an optionally substituted aryl;

and R^9A is an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative.

12. The compound of claim 6, wherein R^1A is

13. The compound of claim 1, wherein B^1A is selected from the group consisting of:

14. The compound of claim 1, wherein R^2A is a halogen substituted C_1-6 alkyl or a sulfenyl substituted C_1-6 alkyl, and R^3A is OH or —

OC(═

O)R″

^A.

15. The compound of claim 1, wherein the compound of Formula (I) is selected from the group consisting of:

16. The compound of claim 1, wherein the compound of Formula (I) is selected from the group consisting of:

17. The compound of claim 1, wherein the compound of Formula (I) is selected from the group consisting of:

18. The compound of claim 1, wherein the compound of Formula (I) is selected from the group consisting of:

19. A pharmaceutical composition comprising an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient, or combination thereof.

20. A method for ameliorating or treating a viral infection comprising contacting a cell infected with the virus in a subject identified as suffering from the viral infection with an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof;

and wherein the viral infection is selected from a paramyxovirus viral infection and an orthomyxovirus viral infection.

21. A method for ameliorating or treating a viral infection in combination with one or more agents comprising administering to or contacting a cell in a subject identified as suffering from the viral infection with an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof;

and wherein the viral infection is selected from a paramyxovirus viral infection and an orthomyxovirus viral infection.

22. The compound of claim 1, wherein the compound of Formula (I) is

23. The compound of claim 1, wherein the compound of Formula (I) is

24. The compound of claim 1, wherein the compound of Formula (I) is

25. The compound of claim 1, wherein the compound of Formula (I) is

26. The compound of claim 1, wherein the compound of Formula (I) is

27. The compound of claim 1, wherein the compound of Formula (I) is

28. The compound of claim 1, wherein the compound of Formula (I) is

29. The compound of claim 1, wherein the compound of Formula (I) is

30. The compound of claim 1, wherein the compound of Formula (I) is

31. The compound of claim 1, wherein the compound of Formula (I) is

32. The compound of claim 1, wherein the compound of Formula (I) is

33. The compound of claim 1, wherein the compound of Formula (I) is

34. The compound of claim 1, wherein the compound of Formula (I) is

35. The compound of claim 1, wherein the compound of Formula (I) is

36. The compound of claim 1, wherein the compound of Formula (I) is

37. The method of claim 20, wherein the viral infection is a paramyxovirus viral infection.

38. The method of claim 37, wherein the paramyxovirus viral infection is human respiratory syncytial virus infection.

39. The method of claim 21, wherein the viral infection is a paramyxovirus viral infection.

40. The method of claim 39, wherein the paramyxovirus viral infection is human respiratory syncytial virus infection.