IP Library › Granted Patent US 7,816,365

Granted Patent B2

US 7,816,365 · App. 10/581,499 · Granted Oct 19, 2010

Amine derivatives

Assignee: Merck Patent GmbH

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Quick Facts

Patent No.: US 7,816,365
App. No.: 10/581,499
Granted: Oct 19, 2010
Kind: B2

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Abstract

Disclosed are compounds of formula (I), which are inhibitors of tyrosine kinases, in particular TIE-2, and Raf kinases and which can be employed, inter alia, for the treatment of tumours.

Claims (355)

1. A compound of formula I

in which

X denotes C,

B denotes N, CH or C—CN,

R 1 denotes, A, —(CH 2 ) m —Ar or —(CH 2 ) m -Het 2 ,

R 2 denotes CN,

R 3 denotes H, A, —S-A, —(CH 2 ) p —Ar, —(CH 2 ) p -Het, NH—(CH 2 ) p —Ar, NH—(CH 2 ) p -Het, NH 2 , NHA, NA 2 , NH-alkylene-NH 2 , NH-alkylene-NHA, NH-alkylene-NA 2 or NA-alkylene-NA 2 ,

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

R 5 denotes H or CH 3 , or

R 4 and R 5 together denote

R 6 denotes Het 4 , —(CH 2 ) r —NH 2 , —(CH 2 ) r —NHA or —(CH 2 ) r —NA 2 ,

Y denotes O, S, (CH 2 ) q or NH,

Ar denotes phenyl, naphthyl or biphenyl, each of which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OH, OA, NH 2 , NO 2 , CN, COOH, COOA, CONH 2 , NHCOA, NHCONH 2 , NHSO 2 A, CHO, COA, SO 2 NH 2 , SO 2 A, —CH 2 —COOH or—OCH 2 —COOH,

Ar 1 denotes phenylene or piperazinediyl,

Het denotes a mono- or bicyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by Hal, A, NHA, NA 2 , OA, COOA, CN, —(CH 2 ) p —Ar, —(CH 2 ) t —OH, —(CH 2 ) p -Het 1 or carbonyl oxygen (═O),

Het 1 denotes a mono- or bicyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono- or disubstituted by A or carbonyl oxygen (═O),

Het 2 denotes a monocyclic aromatic heterocycle having 1 to 3 N, O and/or S atoms, which may be unsubstituted or mono- or disubstituted by A,

Het 3 denotes a monocyclic saturated or aromatic heterocycle having 1 to 3 N, O and/or S atoms, which may be unsubstituted or mono- or disubstituted by A,

Het 4 denotes a mono- or bicyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by Hal, A, CONH 2 , CONHA, CONA 2 or Ar 2 ,

Ar 2 denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OH, OA, NH 2 , NO 2 , CN, COOH, COOA, CONH 2 , NHCOA, NHCONH 2 , NHSO 2 A, CHO, COA, SO 2 NH 2 or SO 2 A,

R 7 , R 8 , R 9 , R 10 each, independently of one another, denote H, A or —(CH 2 ) p —Ar,

A denotes alkyl having 1 to 10 C atoms, where, in addition, 1-7 H atoms may be replaced by F and/or chlorine,

m denotes 0, 1, 2, 3 or 4,

n denotes 0 or 1,

p denotes 0, 1, 2, 3 or 4,

q denotes 0, 1, 2, 3 or 4,

r denotes 0, 1, 2, 3 or 4,

s denotes 0, 1, 2, 3 or 4,

Hal denotes F, Cl, Br or I,

and, if Ar 1 denotes piperazinediyl,

R 6 may also denote H or alkyl having 1-6 C atoms, or a pharmaceutically acceptable tautomer, salt or stereoisomer thereof.

2. A compound according to claim 1 in which

R 1 denotes A, —(CH 2 ) m —Ar or —(CH 2 ) m -Het 2 ,

Ar denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OA, COOH or COOA,

m denotes 0.

3. A compound according to claim 1 in which

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 0 or 1,

n denotes 1,

Ar 1 denotes phenylene,

R 6 denotes Het 4 ,

Y denotes O,

Het 4 denotes pyridyl which is unsubstituted or monosubstituted by CONHA, or benzo-1,2,5-thiadiazol-5-yl.

4. A compound according to claim 1 in which

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 1,

n denotes 0,

Y denotes (CH 2 ) q ,

q denotes 0,

R 6 denotes Het 4 ,

Het 4 denotes pyridyl, benzo-1,2,5-thiadiazol-5-yl, thiazole, 1,2,3-triazole, thienyl or furyl, each of which is unsubstituted or monosubstituted by CONHA, A and/or Ar 2 ,

Ar 2 denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by A.

5. A compound according to claim 1 in which

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 0,

n denotes 0,

Y denotes (CH 2 ) q ,

q denotes 0,

R 6 denotes —(CH 2 ) r —NH 2 , —(CH 2 ) r NHA or —(CH 2 ) r —NA 2 ,

r denotes 1,2,3 or 4.

6. A compound according to claim 1 in which

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 0,

n denotes 1,

Ar 1 denotes phenylene,

Y denotes O, (CH 2 ) q or NH,

R 6 denotes —(CH 2 ) r —NH 2 , —(CH 2 ) r —NHA or —(CH 2 ) r —NA 2 ,

q denotes 0, 1, 2, 3 or 4,

r denotes 0, 1, 2, 3 or 4.

7. A compound according to claim 1 in which

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 1, 2, 3 or 4,

n denotes 0,

Y denotes (CH 2 ) q ,

q denotes 0,

R 6 denotes Het 4 ,

Het 4 denotes a monocyclic saturated heterocycle having 1 to 2 N and/or O atoms, which may be unsubstituted or mono- or disubstituted by A.

8. A compound according to claim 1 in which

R 1 denotes A, —(CH 2 ) m —Ar,

m denotes 0,

Ar denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OA, COOH or COOA,

R 2 denotes CN,

R 3 denotes H, A, —S-A, phenyl or —(CH 2 ) p -Het.

9. A compound according to claim 1 in which

R 1 denotes A, —(CH 2 ) m —Ar,

m denotes 0,

Ar denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OA, COOH or COOA,

R 2 denotes CN,

R 3 denotes H, A, —S-A, phenyl or —(CH 2 ) p -Het,

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 0,

n denotes 0,

Y denotes (CH 2 ) q ,

q denotes 0,

R 6 denotes —(CH 2 ) r —NH 2 ,—(CH 2 ) r —NHA or —(CH 2 ) r —NA 2 ,

r denotes 1, 2, 3 or 4.

10. A compound according to claim 1 in which

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 0,

n denotes 1,

Y denotes (CH 2 ) q ,

q denotes 0,

R 6 denotes —(CH 2 ) r —NH 2 ,—(CH 2 ) r —NHA or —(CH 2 ) r —NA 2 ,

r denotes 0.

11. A compound according to claim 1 in which

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 0,

n denotes 0 or 1,

Y denotes (CH 2 ) q ,

q denotes 0,

R 6 denotes —(CH 2 ) r —NH 2 ,—(CH 2 ) r —NHA or —(CH 2 ) r —NA 2 ,

r denotes 0, 1, 2, 3 or 4.

12. A compound according to claim 1 in which

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 0,

n denotes 0 or 1,

Y denotes (CH 2 ) q ,

R 6 denotes —(CH 2 ) r —NH 2 ,—(CH 2 ) r —NHA or —(CH 2 ) r —NA 2 ,

Ar 1 denotes phenylene,

Y denotes O, (CH 2 ) q or NH,

q denotes 0, 1, 2, 3 or 4,

r denotes 0, 1, 2, 3 or 4.

13. A compound according to claim 1 in which R 1 denotes A, —(CH 2 ) m —Ar,

m denotes 0,

Ar denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OA, COOH or COOA,

R 2 denotes CN,

R 3 denotes H, A, —S-A, phenyl or —(CH 2 ) p -Het,

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 0,

n denotes 0 or 1,

Y denotes (CH 2 ) q ,

R 6 denotes —(CH 2 ) r —NH 2 ,—(CH 2 ) r —NHA or —(CH 2 ) r —NA 2 ,

Ar 1 denotes phenylene,

Y denotes O, (CH 2 ) q or NH,

q denotes 0, 1, 2, 3 or 4,

r denotes 0, 1, 2, 3 or 4.

14. A compound according to claim 1 in which

R 1 denotes A, —(CH 2 ) m —Ar,

m denotes 0,

Ar denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OA, COOH or COOA,

R 2 denotes CN,

R 3 denotes H, A, —S-A, phenyl or —(CH 2 ) p -Het,

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 0,

n denotes 1,

Ar 1 denotes phenylene,

R 6 denotes Het 4 ,

Y denotes O,

Het 4 denotes pyridyl which is unsubstituted or monosubstituted by CONHA, or benzo-1,2,5-thiadiazol-5-yl.

15. A compound according to claim 1 in which

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 0 or 1,

n denotes 0 or 1,

Y denotes O or (CH 2 ) q ,

q denotes 0,

R 6 denotes Het 4 ,

Het 4 denotes pyridyl, benzo-1,2,5-thiadiazol-5-yl, thiazole, 1,2,3-triazole, thienyl or furyl, each of which is unsubstituted or monosubstituted by CONHA, A and/or Ar 2 ,

Ar 2 denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by A,

Ar 1 denotes phenylene.

16. A compound according to claim 1 in which

Het denotes a monocyclic saturated or aromatic heterocycle having 1 to 3 N and/or O atoms, which may be unsubstituted or mono-, di- or trisubstituted by Hal, A, NHA, NA 2 , COOA, benzyl, —(CH 2 ) t —OH or —(CH 2 ) p -Het 1 ,

Het 1 denotes an unsubstituted monocyclic saturated or aromatic heterocycle having 1 to 3 N and/or O atoms,

17. A compound according to claim 1 in which

Het denotes piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, pyridyl or furyl, which are unsubstituted or may be mono-, di- or trisubstituted by Hal, A, NHA, NA 2 , COOA, benzyl, —(CH 2 ) t —OH or —(CH 2 ) p -Het 1 ,

Het 1 denotes morpholinyl, pyrrolidinyl, pyridyl

18. A compound according to claim 1 in which

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 0 or 1,

n denotes 0 or 1,

Y denotes O, (CH 2 ) q or NH,

Ar 1 denotes phenylene,

q denotes 0,1,2,3 or 4,

R 6 denotes Het 4 , —(CH 2 ) r —NH 2 , —(CH 2 ) r —NHA or —(CH 2 ) r —NA 2 ,

r denotes 0,1,2,3or 4,

Het 4 denotes pyridyl, benzo-1,2,5-thiadiazol-5-yl, thiazole, 1,2,3-triazole, thienyl or furyl, each of which is unsubstituted or monosubstituted by CONHA, A or Ar 2 ,

Ar 2 denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by A.

19. A compound according to claim 1 in which

R 1 denotes A, —(CH 2 ) m —Ar,

m denotes 0,

Ar denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OA, COOH or COOA,

R 2 denotes CN,

R 3 denotes H, A, —S-A, phenyl or —(CH 2 ) p -Het,

Het 1 denotes an unsubstituted monocyclic saturated or aromatic heterocycle having 1 to 2 N and/or O atoms,

20. A compound according to claim 1 in which

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

s denotes 0, 1, 2, 3 or 4,

n denotes 0 or 1,

Y denotes O or (CH 2 ) q ,

Ar 1 denotes phenylene,

q denotes 0,

R 6 denotes Het 4 ,—(CH 2 ) r —NH 2 , —(CH 2 ) r —NHA or —(CH 2 ) r —NA 2 ,

r denotes 0, 1, 2, 3 or 4,

Het 4 denotes a monocyclic saturated or aromatic heterocycle having 1 to 3 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by A, CONH 2 , CONHA, CONA 2 or Ar 2 ,

Ar 2 denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by A.

21. A compound according to claim 1 in which

Het 4 denotes pyridyl, benzo-1,2,5-thiadiazol-5-yl, piperazine, thiazole or imidazole, each of which is unsubstituted or monosubstituted by CONHA, A or Ar 2 .

22. A compound according to claim 1 in which

R 4 denotes 4-(pyridin-4-yloxy)phenyl, 4-(pyridin-4-yloxy)-phenylmethyl or 4-(benzo-1,2,5-thiadiazol-5-yloxy)phenyl, where the pyridine radical may be substituted by CONHCH 3 .

23. A compound according to claim 1 in which Het 1 denotes an unsubstituted monocyclic saturated or aromatic heterocycle having 1 to 2 N and/or O atoms,

24. A compound according to claim 1 in which

Het 1 denotes morpholinyl, pyrrolidinyl, piperidinyl, pyridyl

25. A compound according to claim 1 in which

Het 2 denotes an unsubstituted monocyclic aromatic heterocycle having 1-2 N, O and/or S atoms.

26. A compound according to claim 1 in which

R 1 denotes A, —(CH 2 ) m —Ar or —(CH 2 ) m -Het 2 ,

m denotes 0,

Ar denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OA, COOH or COOA,

R 2 denotes CN,

R 3 denotes H, A, —S-A, phenyl, NH-benzyl, —(CH 2 ) p -Het, NH—(CH 2 ) p -Het, NA 2 , NH-alkylene-NA 2 or NA-alkylene-NA 2 .

27. A compound according to claim 1 in which

R 2 denotes CN,

Ar″ denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal or OA,

o denotes 0 or 1.

28. A compound according to claim 1 in which

R 1 denotes A, —(CH 2 ) m —Ar′ or —(CH 2 ) m -Het 2 ,

Ar′ denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, OA, A or COOA,

m denotes 0,

Het 2 denotes thienyl, furyl, imidazolyl, pyrrolyl, thiazolyl or pyridyl.

29. A compound according to claim 1 in which

X denotes C,

B denotes N, CH or C—CN,

R 1 denotes A, —(CH 2 ) m —Ar′ or —(CH 2 ) m -Het 2 ,

Ar′ denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, OA, A or COOA,

m denotes 0,

Het 2 denotes thienyl, furyl, imidazolyl, pyrrolyl, thiazolyl or pyridyl,

R 2 denotes CN,

Ar″ denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal or OA,

o denotes 0 or 1,

R 3 denotes H, A, —S-A, phenyl, NH-benzyl, —(CH 2 ) p -Het, NH—(CH 2 ) p -Het, NA 2 , NH-alkylene-NA 2 or NA-alkylene-NA 2 ,

Het 1 denotes morpholinyl, pyrrolidinyl, pyridyl

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

Y denotes O or (CH 2 ) q ,

R 5 denotes H or CH 3 , or

R 4 and R 5 together denote

R 6 denotes Het 4 , —(CH 2 ) r —NH 2 , —(CH 2 ) r —NHA or —(CH 2 ) r —NA 2 ,

Het 4 denotes pyridyl, benzo-1, 2, 5-thiadiazol-5-yl, piperazine, thiazole or imidazole, each of which is unsubstituted or monosubstituted by CONHA, A and/or Ar 2 ,

Ar 1 denotes phenylene or piperazinediyl,

Ar 2 denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by A,

R 7 , R 8 , R 9 ,R 10 each, independently of one another, denote H, A or —(CH 2 ) p —Ar,

A denotes alkyl having 1 to 10 C atoms, where, in addition, 1-7 H atoms may be replaced by F and/or chlorine,

n denotes 0 or 1,

p denotes 0, 1, 2, 3 or 4,

q denotes 0, 1, 2, 3 or 4,

r denotes 0, 1, 2, 3 or 4,

s denotes 0, 1, 2, 3 or 4,

t denotes 1, 2, 3 or 4,

Hal denotes F, Cl, Br or I,

and, if Ar 1 denotes piperazinediyl, R 6 may also denote H or alkyl having 1-6 C atoms.

30. A compound according to claim 1 in which

X denotes C,

B denotes N, CH or C—CN,

R 1 denotes A, —(CH 2 ) m —Ar′ or —(CH 2 ) m -Het 2 ,

Ar′ denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, OA, A or COOA,

m denotes 0,

Het 2 denotes an unsubstituted monocyclic aromatic heterocycle having 1-2 N, O and/or S atoms,

R 2 denotes CN,

Ar″ denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal or OA,

o denotes 0 or 1,

R 3 denotes H, A, —S-A, phenyl, NH-benzyl, —(CH 2 ) p -Het, NH—(CH 2 ) p -Het, NA 2 , NH-alkylene-NA 2 or NA-alkylene-NA 2 ,

Het 1 denotes morpholinyl, pyrrolidinyl, pyridyl

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

Y denotes O or (CH 2 ) q ,

R 5 denotes H or CH 3 , or

R 4 and R 5 together denote

R 6 denotes Het 4 , —(CH 2 ) r —NH 2 , —(CH 2 ) r —NHA or —(CH 2 ) r —NA 2 ,

Het 4 denotes a monocyclic saturated or aromatic heterocycle having 1 to 3 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by A, CONH 2 , CONHA, CONA 2 or Ar 2 ,

Ar 1 denotes phenylene or piperazinediyl,

Ar 2 denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by A,

R 7 , R 8 , R 9 , R 10 each, independently of one another, denote H, A or —(CH 2 ) p —Ar,

A denotes alkyl having 1 to 10 C atoms, where, in addition, 1-7 H atoms may be replaced by F and/or chlorine,

n denotes 0 or 1,

p denotes 0, 1, 2, 3 or 4,

q denotes 0, 1, 2, 3 or 4,

r denotes 0, 1, 2, 3 or 4,

s denotes 0, 1, 2, 3 or 4,

t denotes 1, 2, 3 or 4,

Hal denotes F, Cl, Br or I,

and, if Ar 1 denotes piperazinediyl, R 6 may also denote H or alkyl having 1-6 C atoms.

31. A compound, which is

or a pharmaceutically acceptable tautomer, salt or stereoisomer thereof.

32. A process for preparing a compound according to claim 1 or a pharmaceutically acceptable tautomer, salt or stereoisomer thereof, comprising

a) for the preparation of compounds of the formula I in which X denotes C, reacting a compound of formula II

in which R 4 , R 5 and B have the meanings indicated for the compound of formula I,

i) with a compound of formula IIIa

in which R 1 OA and R 2 and R 3 have the meanings indicated for the compound of formula I,

ii) with a compound of formula IIIb

in which R 1 , R 2 and R 3 have the meanings indicated for the compound of formula I,

and A denotes alkyl having 1, 2, 3 or 4 C atoms,

iii) with a compound of formula IIIc

in which

R 1 , besides the meanings indicated for the compound of formula I, also denotes OA,

R 2 and R 3 have the meanings indicated for the compound of formula I, and A, A′ each, independently of one another, denote alkyl having 1, 2, 3 or 4 C atoms, or A and A′ together form a butylene or pentylene chain,

and/or

a base or acid of a compound of formula I is converted into one of its salts.

33. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.

34. A process according to claim 32 , wherein one or more radical(s) R 1 ,R 2 and/or R 3 in a compound of formula I is (are) converted into one or more other radical(s) R 1 ,R 2 and/or R 3 , by

i) converting an alkylsulfanyl group into an amine,

ii) hydrolysing an ester to the acid, reducing it to the aldehyde or alcohol, or

iii) reducing a nitrite to the aldehyde or amine.

35. A pharmaceutical composition comprising a compound according to claim 31 and a pharmaceutically acceptable carrier.

36. A compound of formula I according to claim 1 ,

in which

X denotes C,

B denotes N, CH or C—CN,

R 1 denotes A, —(CH 2 ) m —Ar or —(CH 2 ) m -Het 2 ,

R 2 denotes CN,

R 4 denotes —(CH 2 ) s —(Ar 1 ) n —Y—R 6 ,

R 5 denotes H or CH 3 , or

R 4 and R 5 together denote

R 6 denotes Het 4 , —(CH 2 ) r —NH 2 , —(CH 2 ) r —NHA or —(CH 2 ) r —NA 2 ,

Y denotes O, S, (CH 2 ) q or NH,

Ar 1 denotes phenylene or piperazinediyl,

Het 2 denotes a monocyclic aromatic heterocycle having 1 to 3 N, O and/or S atoms, which may be unsubstituted or mono- or disubstituted by A,

Het 3 denotes a monocyclic saturated or aromatic heterocycle having 1 to 3 N, O and/or S atoms, which may be unsubstituted or mono- or disubstituted by A,

Ar 2 denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OH, OA, NH 2 , NO 2 , CN, COOH, COOA, CONH 2 , NHCOA, NHCONH 2 , NHSO 2 A, CHO, COA, SO 2 NH 2 or SO 2 A,

R 7 , R 8 , R 9 , R 10 each, independently of one another, denote H, A or —(CH 2 ) p —Ar,

A denotes alkyl having 1 to 10 C atoms, where, in addition, 1-7 H atoms may be replaced by F and/or chlorine,

m denotes 0, 1, 2, 3 or 4,

n denotes 0 or 1,

p denotes 0, 1, 2, 3 or 4,

q denotes 0, 1, 2, 3 or 4,

r denotes 0, 1, 2, 3 or 4,

s denotes 0, 1, 2, 3 or 4,

Hal denotes F, Cl, Br or I,

and, if Ar 1 denotes piperazinediyl,

R 6 may also denote H or alkyl having 1-6 C atoms, or a pharmaceutically acceptable salt thereof.

37. A pharmaceutical composition comprising a compound according to claim 36 and a pharmaceutically acceptable carrier.

38. A compound according to claim 31 , which is

or a pharmaceutically acceptable salt thereof.

39. A pharmaceutical composition comprising a compound according to claim 38 and a pharmaceutically acceptable carrier.

40. A pharmaceutical composition comprising a compound according to claim 2 and a pharmaceutically acceptable carrier.

41. A pharmaceutical composition comprising a compound according to claim 29 and a pharmaceutically acceptable carrier.

42. A pharmaceutical composition comprising a compound according to claim 30 and a pharmaceutically acceptable carrier.

43. A compound according to claim 1 , in which R 1 denotes A.

44. A compound according to claim 1 , in which R 1 denotes —(CH 2 ) m —Ar.

45. A compound according to claim 1 , in which R 1 denotes —(CH 2 ) m -Het 2 .

46. A compound according to claim 1 , in which B denotes N.

47. A compound according to claim 1 , in which B denotes C—CN.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 2, 2006

From: SCHIEMANN, KAI; HOELZEMANN, GUENTER; RAUTENBERG, WILFRIED

To: MERCK PATENT GMBH

Reel/Frame 017986/0982 →

Priority Claims (1)

DE 103 56 579 · Dec 4, 2003 · national

Continuity (1)

Related Publication 20070112006A1 · May 17, 2007