RU2011130833A

RU2011130833A - ANTI-VIRUS COMPOUNDS

Info

Publication number: RU2011130833A
Application number: RU2011130833/04A
Authority: RU
Inventors: Дэвид А. Дегой; Памела Л. Доннер; Уоррен М. Кати; Чарльз В. ХАТЧИНС; Марк А. Матуленко; Тамми К. Джинкерсон; Райан Дж. Кедди
Original assignee: Эбботт Лэборетриз
Priority date: 2008-12-23
Filing date: 2009-12-22
Publication date: 2013-01-27

Claims

1. The compound of formula I or its pharmaceutically acceptable salt,

Where:

A ₁ is C ₃ -C ₁₄ carbocyclyl or 3-14 membered heterocyclyl and is substituted with -X ₁ -R ₇ , wherein said C ₃ -C ₁₄ carbocyclyl and 3-14 membered heterocyclyl are optionally substituted with one or more R _A ;

X ₁ is selected from the bond, —L _S -, —O—, —S— or —N (R _B ) -;

R ₇ is selected from hydrogen, -L _A , C ₅ -C ₁₀ carbocyclyl or 5-10 membered heterocyclyl, where each of these C ₅ -C ₁₀ carbocyclyl and 5-10 membered heterocyclyl in each case is optionally substituted with one or more R _A ;

Z ₁ is selected from the bond, —C (R _C R _{C ′} ) -, —O—, —S— or —N (R _B ) -;

each of W ₁ and W ₂ is independently selected from N or C (R _D );

R ₁ is selected from hydrogen or R _A ;

each of R ₃ and R ₄ is independently selected from hydrogen or R _A ; or R ₃ and R ₄ together with the carbon atoms to which they are attached form a C ₅ -C ₁₀ carbocyclic or 5-10 membered heterocyclic ring, wherein said C ₅ -C ₁₀ carbocyclic and 5-10 membered heterocyclic rings are optionally substituted with one or more R _A ;

A ₂ is C ₃ -C ₁₄ carbocyclyl or a 3-14 membered heterocyclyl and is optionally substituted with one or more R _A ;

R ₂ represents —N (R _B ) C (O) C (R ₅ R ₆ ) N (R ₈ ) —TR _D ,

or -L _K -B;

R ₅ represents R _C ;

R ₆ represents R _{C '} , and R ₈ represents R _B ; or R ₆ and R _8, together with the atoms to which they are attached, form a 3-10 membered heterocyclic ring, which is optionally substituted with one or more R _A ;

L _κ is a bond; C ₁ -C ₆ alkylene, C ₂ -C ₆ alkenylene or C ₂ -C ₆ alkynylene, each independently of which, in each case, is optionally substituted with one or more substituents selected from halogen, R _S (except hydrogen), —OR _S , —SR _S , —N (R _S R _{S ′} ), —OC (O) R _S , —C (O) OR _S , nitro group, phosphate, oxo group, thioxo group, formyl or cyano group; or —N (R _B ) C (O) -, or —C (O) N (R _B ) -;

B is a C ₃ -C ₁₀ carbocycle or a 3-10 membered heterocycle and is optionally substituted with one or more R _A ;

T in each case of its presence is independently selected from the bond, -L _S -, -L _S -ML _{S '} -, -L _S -ML _S' -M'-L _{S ”} -, where each of M and M 'is independently selected from the bond, -O-, -S-, -N (R _B ) -, -C (O) -, -S (O) ₂ -, -S (O) -, -OS (O) -, -OS (O) ₂ -, -S (O) ₂ O-, -S (O) O-, -C (O) O-, -OC (O) -, -OC (O) O-, -C (O) N (R _B ) -, -N (R _B ) C (O) -, -N (R _B ) C (O) O-, -OC (O) N (R _B ) -, -N ( R _B ) S (O) -, -N (R _B ) S (O) ₂ -, -S (O) N (R _B ) -, -S (O) ₂ N (R _B ) -, -C ( O) N (R _B ) C (O) -, -N (R _B ) C (O) N (R _{B '} ) -, -N (R _B ) SO ₂ N (R _B' ) -, -N ( R _B ) S (O) N (R _{B ′} ) -, a C ₅ -C ₁₀ carbocycle or a 5-10 membered heterocycle, and wherein T in each case of its presence is optionally independently substituted with one or more R _A ;

R _A in each case of its presence is independently selected from halogen, hydroxy group, mercapto group, amino group, carboxy group, nitro group, phosphate, oxo group, thioxo group, formyl, cyano group, -L _A or -L _S -R _E ;

each of R _B and R _{B '} in each case of its presence is independently selected from hydrogen or C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₃ -C ₆ carbocyclyl , C ₃ -C ₆ -carbocyclyl-C ₁ -C ₆ -alkyl, 3-6-membered heterocyclyl or (3- or 6-membered heterocyclyl) -C ₁ -C ₆ -alkyl, each of which is independently in each case the presence is optionally substituted with one or more substituents selected from halogen, hydroxy group, mercapto group, amino group, carboxy group, nitro group, phosphate, oxo group, thioxo group, formyl or cyano group pp;

each of R _C and R _{C '} in each case of its presence is independently selected from hydrogen; halogen; hydroxy groups; mercapto groups; amino groups; carboxy groups; nitro groups; phosphate; oxo groups; thioxo groups; formyl; cyano groups or C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl or C ₃ -C ₆ carbocyclyl, each of which, independently in each case of its presence, is optionally substituted with one or more substituents selected from a halogen, hydroxy group, mercapto group, amino group, carboxy group, nitro group, phosphate, oxo group, thioxo group, formyl or cyano group;

each of R _D , R _{D '} and R _{D ”} in each case of its presence is independently selected from hydrogen or R _A ;

L _A in each case of its presence is independently selected from C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl or C ₂ -C ₆ alkynyl, each of which, independently in each case of its presence, is optionally substituted with one or more substituents selected from halogen, —O — R _S , —SR _S , —N (R _S R _{S ′} ), —OC (O) R _S , —C (O) OR _S , nitro group, phosphate, oxo group, thioxo group, formyl or cyano groups;

each of L _S , L _{S '} and L _{S ”} in each case of its presence is independently selected from the bond; or C ₁ -C ₆ alkylene, C ₂ -C ₆ alkenylene or C ₂ -C ₆ alkynylene, each of which, independently in each case of its presence, is optionally substituted with one or more substituents selected from halogen, -OR _S , —SR _S , —N (R _S R _{S ′} ), —OC (O) R _S , —C (O) OR _S , nitro group, phosphate, oxo group, thioxo group, formyl or cyano group;

R _E in each case of its presence is independently selected from -OR _S , -SR _S , -C (O) R _S , -OC (O) R _S , -C (O) OR _S , -N (R _S R _{S '} ), -S (O) R _S , -SO ₂ R _S , -C (O) N (R _S R _S' ), -N (R _S ) C (O) R _{S '} , -N (R _S ) C (O) N (R _{S '} R _{S ”} ), -N (R _S ) SO ₂ R _S' , -SO ₂ N (R _S R _{S '} ), -N (R _S ) SO ₂ N (R _{S '} R _{S ”} ), N (R _S ) S (O) N (R _S' R _S” ), -OS (O) -R _S , -OS (O) ₂ -R _S , -S (O) ₂ OR _S , -S (O) OR _S , -OC (O) OR _S , -N (R _S ) C (O) OR _{S '} , -OC (O) N (R _S R _S' ), -N (R _S ) S (O) -R _{S '} , -S (O) N (R _S R _S' ), -C (O) N (R _S ) C (O) -R _{S '} , C ₃ -C ₁₀ -carbocyclyl or 3-10 membered heterocyclyl, wherein each of said C ₃ -C ₁₀ -carbocyclyl and 3-10 membered heterocyclyl independently in each occurrence is optionally substituted with one or more substituents selected of C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, R _S (except hydrogen), halogen, _{_{-O-R B, -SR B, -N}} (R B R _{B ′} ), —OC (O) R _B , —C (O) OR _B , nitro group, phosphate, oxo group, thioxo group, formyl or cyano group; and

each of R _S , R _{S '} and R _{S ”} in each case of its presence is independently selected from hydrogen; or C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₃ -C ₆ carbocyclyl, C ₃ -C ₆ carbocyclyl C ₁ -C ₆ alkyl, 3 6-membered heterocyclyl or (3- or 6-membered heterocyclyl) -C ₁ -C ₆ -alkyl, each of which, independently in each case of its presence, is optionally substituted with one or more substituents selected from halogen, -O-R _B , —SR _B , —N (R _B R _{B ′} ), —OC (O) R _B , —C (O) OR _B , nitro group, phosphate, oxo group, thioxo group, formyl or cyano group.

2. The compound or salt according to claim 1, where:

A ₁ is C ₅ -C ₆ carbocyclyl or a 5-6 membered heterocyclyl, which is optionally substituted with one or more R _A , and A ₁ is substituted with —X ₁ -R ₇ ;

R ₇ represents a C ₅ -C ₆ carbocyclyl or a 5-6 membered heterocyclyl and is optionally substituted with one or more R _A ,

each of R ₃ and R ₄ is independently selected from hydrogen or R _A ; or R ₃ and R ₄ together with the carbon atoms to which they are attached form a C ₅ -C ₆ carbocyclic or 5-6 membered heterocyclic ring, wherein said C ₅ -C ₆ carbocyclic and 5-6 membered heterocyclic rings are independently substituted with one or more R _A ; and

A ₂ is C ₅ -C ₁₀ carbocyclyl or 5-10 membered heterocyclyl and is optionally substituted with one or more R _A.

3. The compound or salt according to claim 1 or 2, wherein A ₂ is C ₅ -C ₆ carbocyclyl or 5-6 membered heterocyclyl and is optionally substituted with one or more R _A.

4. The compound or salt according to claim 1, where R ₇ represents phenyl and is optionally substituted with one or more R _A.

5. The compound or salt according to claim 1, where A ₁ represents phenyl and is optionally substituted with one or more R _A.

6. The compound or salt according to claim 1, where A ₂ represents phenyl and is optionally substituted with one or more R _A.

7. The compound or salt according to claim 1, where A ₁ , A ₂ and R ₇ are phenyl and each of them is optionally independently substituted by one or more R _A.

8. The compound or salt according to claim 1, where R ₃ and R ₄ together with the carbon atoms to which they are attached form a C ₅ -C ₆ carbocyclic or 5-6 membered heterocyclic ring, which is optionally substituted with one or more R _A.

9. The compound or salt according to claim 1, where W ₁ and W ₂ represent N, and Z ₁ represents —N (R _B ) -.

10. The compound or salt according to claim 1, where:

W ₁ and W ₂ represent N;

Z ₁ represents —N (R _B ) -;

X ₁ represents —CH ₂ -, —O— or —S—;

R ₃ and R ₄ together with the carbon atoms to which they are attached form

each of R ₉ , R ₁₀ and R ₁₁ is independently selected from hydrogen or R _A.

11. The compound or salt according to claim 1, where

A ₁ represents phenyl and is optionally substituted with one or more R _A ;

R ₇ represents phenyl and is optionally substituted with one or more R _A ;

R ₁ represents hydrogen;

each of R ₉ , R ₁₀ and R ₁₁ is independently selected from hydrogen; halogen; or C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₂ -C ₆ alkynyl, C ₃ -C ₆ carbocyclyl or C ₃ -C ₆ carbocyclyl C ₁ -C ₆ alkyl each of which, independently in each case of its presence, is optionally substituted with one or more substituents selected from halogen, hydroxy group, mercapto group, amino group, carboxy group, nitro group, phosphate, oxo group, thioxo group, formyl or cyano group.

12. The compound or salt according to claim 1, where R ₂ represents -N (R _B ) C (O) C (R ₅ R ₆ ) N (R ₈ ) -TR _D.

13. The compound or salt of claim 12, wherein R ₅ is R _C , and R ₆ and R _8, together with the atoms to which they are attached, form a 5-6 membered heterocyclic ring, which is optionally substituted with one or more than R _A.

14. The compound or salt according to item 12, where:

R ₅ represents H;

R ₆ and R ₈ together with the atoms to which they are attached form

each of which is optionally independently substituted with one or more R _A ;

n is 0, 1 or 2; and

m is 1 or 2.

15. The compound or salt according to 14, where:

—TR _D is —C (O) —L _{S ′} —R ₁₂ or —C (O) —L _{S ′} —M′-L _{S ”} —R ₁₂ ; and

R ₁₂ represents hydrogen; C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl or C ₂ -C ₆ -alkynyl, each of which, independently in each case of its presence, is optionally substituted with one or more substituents selected from halogen, -OR _S , - SR _S , —N (R _S R _{S ′} ), —OC (O) R _S , —C (O) OR _S , nitro group, phosphate, oxo group, thioxo group, formyl or cyano group; or C ₃ -C ₁₀ carbocyclyl, or 3-10 membered heterocyclyl, each of which is independently in each case of its presence optionally substituted with one or more substituents selected from C ₁ -C ₆ alkyl, C ₂ -C ₆ - alkenyl, C ₂ -C ₆ alkynyl, halogen, -OR _B , -SR _B , -N (R _B R _{B '} ), -OC (O) R _B , -C (O) OR _B , nitro group, phosphate, oxo groups, thioxo groups, formyl or cyano groups.

16. The compound or salt according to claim 1, where R ₂ represents

17. The compound or salt according to clause 16, where R ₅ represents R _C and R ₆ and R ₈ together with the atoms to which they are attached form a 5-6 membered heterocyclic ring, which is optionally substituted with one or more R _A.

18. The compound or salt according to clause 16, where:

R ₅ represents H;

R ₆ and R ₈ together with the atoms to which they are attached form

which is optionally substituted with one or more R _A ;

n is 0, 1 or 2; and

m is 1 or 2.

19. The compound or salt according to p, where:

-TR _{D ”} represents —C (O) —L _{S ′} —R ₁₂ or —C (O) —L _{S ′} —M′-L _S” —R ₁₂ ; and

R ₁₂ represents hydrogen; C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl or C ₂ -C ₆ -alkynyl, each of which, independently in each case of its presence, is optionally substituted with one or more substituents selected from halogen, -OR _S , - SR _S , —N (R _S R _{S ′} ), —OC (O) R _S , —C (O) OR _S , nitro group, phosphate, oxo group, thioxo group, formyl or cyano group; or C ₃ -C ₁₀ carbocyclyl or 3-10 membered heterocyclyl, each of which is independently in each occurrence, optionally substituted with one or more substituents selected from C ₁ -C ₆ alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, halogen, -OR _B , -SR _B , -N (R _B R _{B '} ), -OC (O) R _B , -C (O) OR _B , nitro group, phosphate , oxo groups, thioxo groups, formyl or cyano groups.

20. The compound or salt according to claim 1, where R ₂ represents

21. The compound or salt according to claim 1, where R ₂ represents-L _κ -B.

22. The compound or salt according to item 21, where B is a C ₃ -C ₁₀ carbocycle or 3-10 membered heterocycle and, optionally, is substituted by one or more R _A.

23. The compound or salt according to item 21, where B represents

and is optionally substituted with one or more R _A.

24. The compound or salt according to item 21, where:

B is

n is 0, 1, 2, 3 or 4;

m is 0, 1, 2 or 3;

V represents —C (O) - or —S (O) ₂ -;

R ₁₂ represents —R _S , —OR _S or —N (R _S R _{S ′} ).

25. A pharmaceutical composition comprising a compound or salt according to any one of claims 1 to 24.

26. A method of inhibiting replication of HCV virus, comprising contacting cells infected with HCV virus with a compound or salt according to any one of claims 1 to 24.

27. A method of treating HCV infection, comprising administering to a patient with HCV a compound or salt according to any one of claims 1-24.

28. A method of obtaining a compound according to any one of claims 1 to 24, comprising the step described in one of the schemes described herein.