Substituted nucleosides, nucleotides and analogs thereof

• US 10,485,815 B2
• Filed: 07/28/2016
• Issued: 11/26/2019
• Est. Priority Date: 03/21/2012
• Status: Expired due to Fees

• Current Assignee: Janssen Biopharma, Inc. (Johnson & Johnson)
• Original Assignee: Alios Biopharma, Inc. (Johnson & Johnson)
• Inventors: Wang, Guangyi, Smith, David Bernard, Beigelman, Leonid, Deval, Jerome, Prhavc, Marija
• Primary Examiner(s): Berry, Layla D
• Application Number:
  US15/221,961
• Publication Number:
  US 20160331770A1
• Time in Patent Office: 1,216 Days
• CPC Class Codes: A61K 31/706 containing six-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 31/708 having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
• 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 19/16 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

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 method of treating a metapneumovirus infection comprising administering to a subject infected with the metapneumovirus an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) has the following structure:

2. The method of claim 1, wherein the metaphenumovirus is human metapneumovirus.

3. The method of claim 1, wherein R^1A is

4. The method of claim 3, wherein R^6A and R^7A are both hydrogen or both absent.

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

6. The method of claim 5, wherein m is 0;

and R^12A and R^13A are independently absent or hydrogen.

7. The method of claim 5, wherein m is 1;

and R^12A, R^13A and R^14A are independently absent or hydrogen.

8. The method of claim 1, wherein R^1A is H.

9. The method of claim 1, wherein R^1A is an unsubstituted acyl.

10. The method of claim 9, wherein the unsubstituted acyl is —

C(═

O)R^39A, wherein R^39A is an unsubstituted C_1-6 alkyl.

11. The method of claim 1, wherein B^1A is an optionally substituted purine-base.

12. The method of claim 1, wherein B^1A is

13. The method of claim 1, wherein B^1A is

14. The method of claim 1, wherein B^1A is

15. The method of claim 1, wherein B^1A is an optionally substituted pyrimidine-base.

16. The method of claim 1, wherein R^2A is a halogen substituted C_1-6 alkyl.

17. The method of claim 16, wherein R^3A is OH.

18. The method of claim 16, wherein R^3A is —

OC(═

O)R<sup>″

A</sup>, wherein R<sup>″

A</sup> is an unsubstituted C_1-6 alkyl.

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

20. The method of claim 19, wherein the compound of Formula (I) is

21. The method of claim 19, wherein the compound of Formula (I) is

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

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

24. The method of claim 1, wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical composition that comprises a pharmaceutically acceptable excipient.

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