HCV polymerase inhibitors

Patent metadata

Field	Value
Publication number	US-9540411-B2
Application number	US-201615210500-A
Country	US
Kind code	B2
Filing date	Jul 14, 2016
Priority date	Sep 4, 2013
Publication date	Jan 10, 2017
Grant date	Jan 10, 2017

Abstract

The invention provides compounds of the formula:

wherein B is a nucleobase selected from the groups (a) to (d):

and the other variables are as defined in the claims,

which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.

First claim

The invention claimed is:

1. A compound represented by formula:

wherein:
B is a nucleobase selected from the groups (a) to (d):

wherein Y is N or —C(R 19 )—;

R 3 is OH, C 1 -C 6 alkoxy, C 3 -C 7 cycloalkoxy, C 3 -C 7 cycloalkylC 1 -C 3 alkoxy, benzyloxy, O—(C 1 -C 6 alkylene)-T-R 21 or NHC(R 15 )(R 15′ )C(═O)R 16 ;
R 4 , R 5 , R 7 and R 8 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, halo, —OR 18 , —SR 18 or —N(R 18 ) 2 ;
R 6 , R 9 , R 10 , R 11 are each independently selected from H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, halo, OR 18 , SR 18 , N(R 18 ) 2 , —NHC(O)OR 18 , —NHC(O)N(R 18 ) 2 , —CN, —NO 2 , —C(O)R 18 , —C(O)OR 18 , —C(O)N(R 18 ) 2 and —NHC(O)R 18 , wherein said C 2 -C 6 alkenyl group and said C 2 -C 6 alkynyl group can be optionally substituted with halo or C 3 -C 5 cycloalkyl;
R 16 is H, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkylC 1 -C 3 alkyl, benzyl, phenyl or adamantyl, any of which is optionally substituted with 1, 2 or 3 groups, each independently selected from halo, OR 18 and N(R 18 ) 2 ;
each R 18 is independently H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 3 -C 7 cycloalkyl;
each R 21 is independently H, C 1 -C 24 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl or C 3 -C 7 cycloalkenyl;
U is O or S;
each T is independently —S—, —O—, —SC(O)—, —C(O)S—, —SC(S)—, —C(S)S—, —OC(O)—, —C(O)O— and —OC(O)O—;
or a pharmaceutically acceptable salt and/or solvate thereof.

2. The compound according to claim 1 , wherein B is the group (a′):

wherein
R 5 is H or F, and R 6 is N(R 18 ) 2 or NHCOC 1 -C 6 alkyl.

3. The compound according to claim 2 , wherein R 6 is NH 2 .

4. The compound according to claim 1 , wherein B is the group (b′):

wherein R 8 is H or F.

5. The compound according to claim 4 , wherein R 8 is H.

6. The compound according to claim 1 , wherein U is O.

7. The compound according to claim 1 wherein R 3 is C 1 -C 6 alkoxy or NHC(R 15 )(R 15′ )C(═O)R 16 .

8. The compound according to claim 1 , wherein R 2 is H.

9. A pharmaceutical composition comprising a compound according to claim 1 in association with a pharmaceutically acceptable adjuvant, diluent or carrier.

10. A pharmaceutical composition comprising a compound according to claim 1 , further comprising one or more additional other antiviral agent(s).

11. A method for the treatment of hepatitis C virus infection comprising the administration of a compound according to claim 1 to a patient in need thereof.

12. The compound according to claim 7 , wherein R 3 is C 1 -C 3 alkoxy.

13. The compound according to claim 12 wherein R 3 is isopropoxy or methoxy.

14. The compound according to claim 7 , wherein one of R 15 and R 15′ is H and the other is methyl, isopropyl, isobutyl or 1-methylprop-1-yl.

15. The compound according to claim 14 , wherein one of R 15 and R 15′ is H and the other is methyl.

16. The compound according to claim 7 , wherein R 16 is straight or branched C 1 -C 6 alkyl or C 3 -C 7 alkyl.

17. The compound according to claim 16 , wherein R 16 is isopropyl.

Assignees

• Medivir Ab

Inventors

• Kalayanov Genadiy
• Torssell Staffan
• Wahling Horst

Classifications

• C07H19/16

  Purine radicals · CPC title

• C07H19/20

  with the saccharide radical esterified by phosphoric or polyphosphoric acids · CPC title

• C07H19/06 Primary

  Pyrimidine radicals · CPC title

• A61K31/7072

  having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine · CPC title

• C07H19/11

  containing cyclic phosphate · CPC title