Substituted nucleosides, nucleotides and analogs thereof

• US 10,464,965 B2
• Filed: 07/02/2015
• Issued: 11/05/2019
• Est. Priority Date: 12/22/2011
• Status: Expired due to Fees

• Current Assignee: Alios Biopharma, Inc. (Johnson & Johnson)
• Original Assignee: Alios Biopharma, Inc. (Johnson & Johnson)
• Inventors: Beigelman, Leonid, Wang, Guangyi, Smith, David Bernard, Deval, Jerome, Prhavc, Marija
• Primary Examiner(s): Berry, Layla D
• Application Number:
  US14/790,645
• Publication Number:
  US 20150315228A1
• Time in Patent Office: 1,587 Days
• Field of Search: None
• 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 of Formula (I), or a pharmaceutically acceptable salt thereof:

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^1A is

3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^1A is an unsubstituted acyl.

4. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^1A is

5. The compound of claim 4, or a pharmaceutically acceptable salt thereof, wherein both R^6A and R^7A are

6. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein B^1A is

7. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^2A is a halogen-substituted C_1-6 alkyl.

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

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

10. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^1A is

11. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^1A is

12. The compound of claim 3, or a pharmaceutically acceptable salt thereof, wherein the unsubstituted acyl is —

C(═

O)R^39A wherein R^39A is selected from the group consisting of an unsubstituted C_1-12 alkyl, an unsubstituted C_2-12 alkenyl, an unsubstituted C_2-12 alkynyl, an unsubstituted C_3-8 cycloalkyl, an unsubstituted C_5-8 cycloalkenyl, an unsubstituted C_6-10 aryl, an unsubstituted heteroaryl, an unsubstituted heterocyclyl, an unsubstituted aryl(C_1-6 alkyl), an unsubstituted heteroaryl(C_1-6 alkyl) and an unsubstituted heterocyclyl(C_1-6 alkyl).

13. The compound of claim 12, or a pharmaceutically acceptable salt thereof, wherein R^39A is an unsubstituted C_1-12 alkyl.

14. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein B^1A is an optionally substituted purine base.

15. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein B^1A is an optionally substituted pyrimidine base.

16. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein B^1A is

17. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein B^1A is

18. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein B^1A is

19. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^2A is a chloro-substituted C_1-6 alkyl.

20. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^2A is a fluoro-substituted C_1-6 alkyl.

21. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^3A is OH.

22. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^3A is —

OC(═

O)R″

^A.

23. The compound of claim 22, or a pharmaceutically acceptable salt thereof, wherein R″

^A is an unsubstituted C_1-8 alkyl.

24. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^3A is an optionally substituted O-linked amino acid.

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

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

27. A pharmaceutical composition comprising an effective amount of