3′ Equatorial-fluorine-substituted neuraminidase inhibitor compounds, compositions and methods for the use thereof as anti-virals

Patent metadata

Field	Value
Publication number	US-9637465-B2
Application number	US-201314372820-A
Country	US
Kind code	B2
Filing date	Jan 17, 2013
Priority date	Jan 19, 2012
Publication date	May 2, 2017
Grant date	May 2, 2017

Abstract

Equatorial 2,3-fluorinated glycosides compounds of formula (I) useful for the treatment or prophylaxis of viral infection, particularly viral influenza, the methods for their preparation, and their pharmaceutical compositions. The therapeutic effect is achieved via inhibition of viral neuraminidases.

First claim

What is claimed is:

1. A method of treating a viral infection comprising administering to a subject in need thereof an effective amount of a compound of formula I:

or an effective amount of a pharmaceutically acceptable salt thereof
wherein
T is COOH or COOR 1 ,
wherein R 1 is a C 1-20 linear, branched or cyclic, saturated or unsaturated, unsubstituted alkyl group,
Z is F, or Cl;
D is F, or Cl;
X is NH 2 , NHC(NH)NH 2 , NHCH 3 , NHCH 2 CH 3 , NHCH 2 CH 2 CH 3 , NHCH 2 CH 2 CH 2 CH 3 , or NHCH(CH 3 )CH 3 ;
Q is OH, OMe, or OAc;
E is OH, or OAc; and
A is OH, or OAc,

and wherein the viral infection is caused, at least in part, by an influenza virus that is resistant to zanamivir, oseltamivir, or peramivir, or a combination thereof.

2. The method of claim 1 , wherein the influenza virus is an H1N1, H3N2 or H1N9 subtype.

3. The method of claim 1 , wherein the influenza virus is resistant to zanamivir.

4. The method of claim 1 , wherein the influenza virus is resistant to oseltamivir.

5. The method of claim 1 , wherein the influenza virus is resistant to peramivir.

6. The method of claim 1 , wherein the influenza virus is an influenza B virus.

7. The method of claim 1 , wherein R 1 is a C 1-10 .

8. The method of claim 1 , wherein
T is COOEt;
Z is F;
D is F;
X is NH 2 or NHC(NH)NH 2 ;
Q is OH;
E is OH; and
A is OH.

9. The method of claim 1 , wherein
T is COOH;
Z is F;
D is F;
X is NH 2 or NHC(NH)NH 2 ;
Q is OH;
E is OH; and
A is OH.

10. The method of claim 1 , wherein
T is COOH;
Z is F;
D is F;
X is NH 2 ;
Q is OH;
E is OH; and
A is OH.

11. The method of claim 1 , wherein
T is COOH;
Z is F;
D is F;
X is NHC(NH)NH 2 ;
Q is OH;
E is OH; and
A is OH.

12. A method of treating a viral infection comprising administering to a subject in need thereof an effective amount of a compound having the formula:

or an effective amount of a pharmaceutically acceptable salt thereof, wherein the viral infection is caused, at least in part, by an influenza virus that is resistant to zanamivir, oseltamivir, or peramivir, or a combination thereof.

13. The method of claim 12 , wherein the influenza virus is resistant to zanamivir.

14. The method of claim 12 , wherein the influenza virus is resistant to oseltamivir.

15. The method of claim 12 , wherein the influenza virus is resistant to peramivir.

16. The method of claim 12 , wherein the influenza virus is an H1N1, H3N2 or H1N9 subtype.

17. The method of claim 12 , wherein the influenza virus is an influenza B virus.

18. The method of claim 12 , wherein the method comprises administering to a subject in need thereof an effective amount of a compound having the formula:

or an effective amount of a pharmaceutically acceptable salt thereof.

19. The method of claim 18 , wherein the influenza virus is an H1N1 subtype that is resistant to zanamivir.

20. The method of claim 18 , wherein the influenza virus is an H1N1 subtype that is resistant to oseltamivir.

21. The method of claim 18 , wherein the influenza virus is an H1N1 subtype that is resistant to peramivir.

22. The method of claim 18 , wherein the influenza virus is an H3N2 subtype that is resistant to zanamivir.

23. The method of claim 18 , wherein the influenza virus is an H3N2 subtype that is resistant to oseltamivir.

24. The method of claim 18 , wherein the influenza virus is an H3N2 subtype that is resistant to peramivir.

25. The method of claim 18 , wherein the influenza virus is an H1N9 subtype that is resistant to zanamivir.

26. The method of claim 18 , wherein the influenza virus is an H1N9 subtype that is resistant to oseltamivir.

27. The method of claim 18 , wherein the influenza virus is an H1N9 subtype that is resistant to peramivir.

28. The method of claim 18 , wherein the influenza virus is an influenza B virus that is resistant to zanamivir.

29. The method of claim 18 , wherein the influenza virus is an influenza B virus that is resistant to oseltamivir.

30. The method of claim 18 , wherein the influenza virus is an influenza B virus that is resistant to peramivir.

31. A method of treating a viral infection comprising administering to a subject in need thereof an effective amount of a compound of formula I:

or an effective amount of a pharmaceutically acceptable salt thereof,
wherein
T is COOH or COOR 1 ,
wherein R 1 is a C 1-20 linear, branched or cyclic, saturated or unsaturated, unsubstituted alkyl group,
Z is F, or Cl;
D is F, or Cl;
X is NH 2 , NHC(NH)NH 2 , NHCH 3 , NHCH 2 CH 3 , NHCH 2 CH 2 CH 3 , NHCH 2 CH 2 CH 2 CH 3 , or NHCH(CH 3 )CH 3 ;
Q is OH, OMe, or OAc;
E is OH, or OAc; and
A is OH, or OAc,

and wherein the viral infection is caused, at least in part, by an influenza B virus.

32. The method of claim 31 , wherein R 1 is a C 1-10 .

33. The method of claim 31 , wherein
T is COOEt;
Z is F;
D is F;
X is NH 2 or NHC(NH)NH 2 ;
Q is OH;
E is OH; and
A is OH.

34. The method of claim 31 , wherein
T is COOH;
Z is F;
D is F;
X is NH 2 or NHC(NH)NH 2 ;
Q is OH;
E is OH; and
A is OH.

35. The method of claim 31 , wherein
T is COOH;
Z is F;
D is F;
X is NH 2 ;
Q is OH;
E is OH; and
A is OH.

36. The method of claim 31 , wherein
T is COOH;
Z is F;
D is F;
X is NHC(NH)NH 2 ;
Q is OH;
E is OH; and
A is OH.

37. A method of treating a viral infection comprising administering to a subject in need thereof an effective amount of a compound having the formula:

or an effective amount of a pharmaceutically acceptable salt thereof, wherein the viral infection is caused, at least in part, by an influenza B virus.

38. A method of treating a viral infection comprising administering to a subject in need thereof an effective amount of a compound having the formula:

or an effective amount of a pharmaceutically acceptable salt thereof, wherein the viral infection is caused, at least in part, by an influenza B virus.

Assignees

• Univ British Columbia

Inventors

• Withers Stephen
• Chen Hongming
• Resende Ricardo
• Breschkin Jennifer Lois

Classifications

• C07D309/14 Primary

  Nitrogen atoms not forming part of a nitro radical · CPC title

• A61K31/351 Primary

  not condensed with another ring · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title