Azaheterocyclic compounds as kinase inhibitors

1. A compound of formula I

in which

R 1 denotes phenyl, phenylmethyl, pyridyl, pyridylmethyl, pyridylethyl, pyrimidyl, piperazyl, quinoliny, imidazoyl, imidazyolpropyl, pyrrolyl, pyrrolylethyl, each of which is unsubstituted or mono- or polysubstituted by Hal, cyano, methyl or methoxy, furthermore H, N,N′-dimethylaminopropyl or cyanobutyl or one of the following radicals

where the linking to the remaining part of the structure of the formula I, in each case takes place via the bond to the left side as drawn, which is not a methyl group,

A denotes unbranched, branched or cyclic alkyl having 1-14 C atoms, in which one or two CH 2 groups may be replaced by an O or S atom and/or by an NH, NA, CONH, NHCO or —CH═CH— group and/or, in addition, 1-7 H atoms may be replaced by Hal, and in which one or two CH 3 groups may be replaced by NH 2 , NAH, NA 2 , NHCOOA, NHCONHA, NHCONHAr, or CN,

Ar denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by carbonyl oxygen, Hal, A, OH, OA, NH 2 , NHA, NA 2 , NO 2 , CN, OCN, SCN, COOH, COOA, CONH 2 , CONHA, CONA 2 , NHCOA, NHCONH 2 , NHSO 2 A, CHO, COA, SO 2 NH 2 and/or S(O) g A, or phthalimidoyl,

Ar-A denotes aryl-alkyl

A-Ar denotes alkyl-aryl

Hal denotes F, Cl, Br or I,

X 1 and X 3 denotes CH or N, wherein one of X 1 and X 3 is N and the other of X 1 and X 3 is CH,

X 2 denotes CH,

Y denotes CH 2 or a saturated bond,

Z denotes CH,

R 2′ , R 2″ , R 2′″ each, independently of one another, denote H, methoxy, ethoxy, n-propoxy, i-propoxy, 2-phenylmethoxy, 2-phenylethoxy, 3-phenylpropoxy or 4-phenylbutoxy,

R 2″″ denotes H, Hal, OH, CN, NH 2 , unbranched or branched alkyl having 1-4, 5 or 6 C atoms, in which one CH 2 group may be replaced by an O or S atom and/or by an NH, NA, NHCO or —CH═CH— group and/or, in addition, 1-4 H atoms may be replaced by Hal, and in which one CH 3 group may be replaced by NH 2 , NAH, NA 2 , CN or Ar,

R 3 denotes H, A or Ar-A,

g denotes 0, 1 or 2 and

denotes a single or double bond,

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , which is of formula AII

in which R 1 , R 2′ , R 2″ , R 2′″ , R 3 , Y and Z have the meaning indicated for formula I.

3. A compound according to claim 1 , which is of formula AIII

in which R 1 , R 2′ , R 2″ , and R 2′″ have the meaning indicated for formula I.

4. A compound according to claim 1 , which is of formula BII

in which R 1 , R 2′ , R 2″ , R 2′″ , R 2″″ , R 3 , Y and Z have the meaning indicated for formula I.

5. A compound according to claim 1 , which is of formula BIII

in which R 1 , R 2′ , R 2″ , R 2′″ , R 2″″ , R 3 , Y and Z have the meaning indicated for the formula I.

6. A compound according to claim 1 , in which

I)

R 1 denotes phenyl, phenylmethyl, pyridyl, pyridylmethyl, pyridylethyl, pyrimidyl, piperazyl, quinoliny, imidazoyl, imidazyolpropyl, pyrrolyl, or pyrrolylethyl, each of which is unsubstituted or mono- or polysubstituted by Hal, cyano, methyl or methoxy, or denotes H,

or

II)

R 2′ , R 2″ , R 2′″ each, independently of one another, denote H, methoxy, ethoxy, n-propoxy, or i-propoxy,

R 2″″ denotes H, Hal or NH 2 ,

or

III)

one of the radicals R 2′ , R 2″ , R 2′″ denotes methoxy and the other two denote H,

or

IV)

R 3 denotes 2-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 3-aminomethylcyclobutyl, (isoindole-1,3-dion)-2-yl or 4-(tert-butyl carbamate) but-1-yl,

or

V)

R 2′ , R 2″ , R 2′″ each, independently of one another, denotes H, methoxy, ethoxy, n-propoxy, i-propoxy, 2-phenylmethoxy or 2-phenylethoxy,

R 2″″ denotes H, Cl or NH 2 ,

R 1 denotes phenyl, phenylmethyl, pyridyl, pyridylmethyl, pyridylethyl, pyrimidyl, piperazyl, quinoliny, imidazoyl, imidazyolpropyl, pyrrolyl, or pyrrolylethyl, each of which is unsubstituted or mono- or polysubstituted by Hal, cyano, methyl or methoxy, or denotes H, and

R 3 denotes 2-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 3-aminomethylcyclobutyl, (isoindole-1,3-dion)-2-yl or 4-(tert-butyl carbamate) but-1-yl,

or

VI)

one of the radicals R 2′ , R 2 ″, R 2′″ denotes methoxy and the other two denote H

R 1 denotes H, pyridyl, pyridylmethyl or (4-methoxyphenyl)methyl, and

R 3 denotes 2-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 3-aminomethylcyclobutyl, (isoindole-1,3-dion)-2-yl or 4-(tert-butyl carbamate) but-1-yl,

or

VII)

one of the radicals R 2′ , R 2″ , R 2′″ denotes methoxy or 2-phenylmethoxy and the other two denote H

R 1 denotes H, pyrid-2 or 3-yl, pyrid-2 or 3-ylmethyl or (4-methoxyphenyl)methyl, and

R 3 denotes 2-aminoethyl, 3-amino-n-propyl, 4-amino-n-butyl, 5-amino-n-pentyl, 3-aminomethylcyclobut-1-yl, (isoindole-1,3-dion)-2-yl or 4-(tert-butyl carbamate) but-1-yl.

7. A process for preparing a compound of claim 1 , comprising

reacting a compound of formula (ix)

in which X has the meaning indicated for formula I, with a compound of formula (viii)

in which Z, Y and R 2 have the meanings indicated for formula I, to give a compound of formula (vii)

which is optionally reduced to give a corresponding 2,3-dihydroindole compound, which is, in a next step, converted into a compound of formula (vi)

to which optionally a radical R 1 and/or a radical R 3 is also attached to give a compound of formula (iii)

and optionally a base or acid of the formula (iii) is converted into one of its salts,

or where the linking of the monocyclic aryl moiety to the bicyclic aryl moiety via its 2-position to give a compound of the formula (ii)

optionally, a compound of formula (viii) containing no silyl group is employed in the first reaction step above.

8. A pharmaceutical composition, comprising at least one compound according to claim 1 and one or more pharmaceutically acceptable excipients and/or adjuvants.

9. A pharmaceutically acceptable salt of a compound of claim 1 .

10. A compound according to claim 1 , which is (3-fluoro-phenyl)-[2-(3,4,5-trimethoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]amine.

11. A compound according to claim 1 , wherein

A denotes unbranched, branched or cyclic alkyl having 1-14 C atoms, in which one or two CH 2 groups may be replaced by an O or S atom and/or by an NH, CONH, NHCO or —CH═CH— group and/or, in addition, 1-7 H atoms may be replaced by Hal, and in which one or two CH 3 groups may be replaced by NH 2 or CN.

12. A compound according to claim 1 , wherein

A denotes unbranched, branched or cyclic alkyl having 1-14 C atoms, in which one or two CH 2 groups may be replaced by an S atom and/or by an NH, CONH, NHCO or —CH═CH— group and/or, in addition, 1-7 H atoms may be replaced by Hal, and in which one or two CH 3 groups may be replaced by NH 2 or CN.

13. A compound according to claim 1 , wherein

Y denotes a saturated bond.

14. A compound according to claim 1 , wherein

R 3 denotes H or Ar-A.

15. A compound, which is

16. A compound according to claim 15 , which is

17. A compound according to claim 1 , in which

Ar denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by carbonyl oxygen, Hal, A, OH, OA, NH 2 , NHA, NA 2 , NO 2 , CN, OCN, SCN, COOH, COOA, CONH 2 , CONHA, CONA 2 , NHCOA, NHCONH 2 , NHSO 2 A, CHO, COA, SO 2 NH 2 and/or S(O) g A.

18. A compound according to claim 15 , which is

19. A compound, which is one of the following compounds

or a pharmaceutically acceptable salt thereof.

20. A compound according to claim 19 , which is one of compounds 27-31, 37-41, 43, 44, 46, 47, 49-52, 54-59, 61 or 64-81 or a pharmaceutically acceptable salt thereof.

21. A compound according to claim 19 , which is one of compounds 1-12, 24-26, 32-36, 42, 45, 48, 53, 60, 62, 63 or 82-88 or a pharmaceutically acceptable salt thereof.