Neuraminidase inhibitor compounds, compositions and methods for the use thereof in anti-viral treatments

Patent metadata

Field	Value
Publication number	US-9834534-B2
Application number	US-201615162055-A
Country	US
Kind code	B2
Filing date	May 23, 2016
Priority date	Jul 15, 2009
Publication date	Dec 5, 2017
Grant date	Dec 5, 2017

Abstract

Compounds having a structure of Formula I and compositions comprising these compounds are provided. Uses of such compounds and compositions are provided for treatment or prophylaxis of viral infection. In particular, compounds and compositions may be for use in the treatment or prophylaxis of viral influenza.

First claim

What is claimed is:

1. A compound of formula I:

wherein
T is C(O)NH 2 , COOH or COOR 1 ,
wherein R 1 is a C 1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group,
wherein the optional substituent is selected from one or more of the group consisting of:
oxo, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H and NO 2 ;

Z is F, Cl, Br, or OSO 2 R 2 ,
wherein R 2 is a C 1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group,
wherein the optional substituent is selected from one or more of the group consisting of:
oxo, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H and NO 2 ;

A is selected from the group consisting of: H, F, Cl, Br, OH, CN, OR 3 , and NO 2 ,
wherein R 3 is a C 1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group,
wherein the optional substituent is selected from one or more of the group consisting of:
oxo, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H and NO 2 ;

D is selected from the group consisting of: H, F, Cl, Br, OH, CN, OR 4 , and NO 2 , provided A and D are not both H, and
wherein R 4 is a C 1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group,
wherein the optional substituent is selected from one or more of the group consisting of:
oxo, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H and NO 2 ;

X is selected from the group consisting of: NH 2 , NHR 5 , NHC(NH)NH 2 , NHC(NH)NHR 5 , NR 5 R 6 , and NHC(NH)N(R 5 )R 6 ,
wherein R 5 and R 6 are independently C 6 H 5 , CH 2 C 6 H 5 or a C 1-8 alkyl group;

E is selected from the group consisting of: NH 2 , NHC(O)CH 3 , OR 7 , NHR 7 and N(R 7 )(R 8 ),
wherein R 7 and R 8 are independently a C 1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group,
wherein the optional substituent is selected from one or more of the group consisting of:
oxo, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H and NO 2 ;

Q is selected from the group consisting of: CH 2 OH, CH 2 R 9 , CH(R 9 )(R 10 ), C(R 9 )(R 10 )(R 11 ),

wherein
R 9 , R 10 and R 1 are independently CH 3 or CH 2 CH 3 , and
each of J and G is independently selected from the group consisting of: H, OH, OAc, OC(O)CH 3 , F, Cl, Br, NO 2 , CN, OR 12 , SO 2 R 12 , COR 12 and SR 12 ,
wherein R 12 is CH 3 , CH 2 CH 3 or CH 2 CH 2 CH 3 , and
M is H, OH, OAc, OC(O)CH 3 , NH 2 , F or Cl, and
L is H, OH, OAc, OC(O)R 13 or NH 2 ,
wherein R 13 is a C 1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group,
wherein the optional substituent is selected from one or more of the group consisting of: oxo, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H and NO 2 , or a salt thereof.

2. A compound of formula I:

wherein
T is C(O)NH 2 , COOH or COOR 1 ,
wherein R 1 is a C 1-10 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group,
wherein the optional substituent is selected from one or more of the group consisting of:
oxo, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H and NO 2 ;

Z is F or Cl;
A is F or Cl;
D is H;
X is selected from the group consisting of: NH 2 , NHCH 3 , NHCH 2 CH 3 , NHCH 2 CH 2 CH 3 , NHCH 2 CH 2 CH 2 CH 3 , and NHC(NH)NH 2 ;
E is NH 2 or NHC(O)CH 3 ;
Q is selected from the group consisting of:

wherein
each of J and G is independently selected from the group consisting of: H, OH, OAc, OC(O)CH 3 , F, Cl, Br, NO 2 , CN and OCH 3 ,
M is H, OH, or OAc; and
L is H, OH, or OAc, or a salt thereof.

3. The compound of claim 1 , wherein T is COOH or COOR 1 ,
wherein R 1 is a C 1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group,
wherein the optional substituent is selected from one or more of the group consisting of:
oxo, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H and NO 2 .

4. The compound of claim 1 , wherein T is C(O)OCH 3 , C(O)OCH 2 CH 3 , C(O)OCH 2 CH 2 CH 3 , C(O)OCH 2 CH 2 CH 2 CH 3 , C(O)OCH 2 CH 2 CH 2 CH 2 CH 3 , C(O)OCH 2 CH 2 CH 2 CH 2 CH 2 CH 3 , C(O)OCH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 , C(O)OCH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 , or COOH.

5. The compound of claim 1 , wherein A is selected from the group consisting of: F, Cl, Br, OH, CN, and NO 2 .

6. The compound of claim 1 , wherein A is selected from the group consisting of: F, Cl, and OR 3 ,
wherein R 3 is a C 1-20 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group,
wherein the optional substituent is selected from one or more of the group consisting of:
oxo, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H and NO 2 .

7. The compound of claim 1 , wherein A is F or Cl.

8. The compound of claim 1 , wherein A is F.

9. The compound of claim 1 , wherein D is selected from the group consisting of: H, F, Cl, Br, OH, CN, and NO 2 , provided A and D are not both H.

10. The compound of claim 1 , wherein D is selected from the group consisting of: H, F, and Cl, provided A and D are not both H.

11. The compound of claim 1 , wherein D is F or Cl.

12. The compound of claim 1 , wherein D is H, provided A and D are not both H.

13. The compound of claim 1 , wherein X is selected from the group consisting of: NH 2 , NHR 5 , NHCH 3 , NHCH 2 CH 3 , NHC(NH)NH 2 , NHC(NH)NHR 5 , and NR 5 R 6 , wherein R 5 and R 6 are independently C 6 H 5 , CH 2 C 6 H 5 or a C 1-8 alkyl group.

14. The compound of claim 1 , wherein X is selected from the group consisting of: NH 2 , NHCH 3 , NHCH 2 CH 3 , and NHC(NH)NH 2 .

15. The compound of claim 1 , wherein X is NH 2 or NHC(NH)NH 2 .

16. The compound of claim 1 , wherein E is selected from the group consisting of: NH 2 , NHC(O)CH 3 , OR 7 , and NHR 7 ,
wherein R 7 is independently a C 1-10 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group,
wherein the optional substituent is selected from one or more of the group consisting of:
oxo, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H and NO 2 .

17. The compound of claim 1 , wherein E is NH 2 or NHC(O)CH 3 .

18. The compound of claim 1 , wherein E is NHC(O)CH 3 .

19. The compound of claim 1 , wherein Q is selected from the group consisting of: CH 2 R 9 , CH(R 9 )(R 10 ), C(R 9 )(R 10 )(R 11 ),

wherein
R 9 , R 10 and R 1 are independently CH 3 or CH 2 CH 3 , and
each of J and G is independently selected from the group consisting of: H, OH, OAc, OC(O)CH 3 , F, Cl, Br, NO 2 , CN, OR 12 , SO 2 R 12 , COR 12 and SR 12 ,
wherein R 12 is CH 3 , CH 2 CH 3 or CH 2 CH 2 CH 3 , and
M is H, OH, OAc, OC(O)CH 3 , NH 2 , F or Cl, and
L is H, OH, OAc, OC(O)R 13 or NH 2 ,
wherein R 13 is a C 1-10 linear, branched or cyclic, saturated or unsaturated, optionally substituted alkyl group, and
wherein the optional substituent is selected from one or more of the grou

Assignees

• Univ British Columbia

Inventors

• Withers Stephen
• Watts Andrew Graham
• Kim Jin Hyo
• Wennekes Tom

Classifications

• C07H15/18

  Acyclic radicals, substituted by carbocyclic rings · CPC title

• C07D309/14 Primary

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

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• C07H13/04

  having the esterifying carboxyl radicals attached to acyclic carbon atoms · CPC title

• C07H13/12

  by acids having the group -X-C(=X)-X-, or halides thereof, in which each X means nitrogen, oxygen, sulfur, selenium or tellurium, e.g. carbonic acid, carbamic acid · CPC title