Heterocyclic compounds, medicaments containing them, use and processes for the preparation thereof

1. A compound of formula (I),

wherein

A and A′ are independently from each other —CH 2 — or —CH 2 —CH 2 —;

R is selected from —NR 1 R 2 , —NR 3 R 4 R 5(+) Z 1 (−) and —OR 13 ;

X is halogen;

Z 1 (−) is a halogen anion or an organic acid anion;

Z 2 (−) is a halogen anion or an organic acid anion;

Z 3 (−) is a halogen anion or an organic acid anion;

Z 4 (−) is a halogen anion or an organic acid anion;

R 1 and R 2 are selected independently from each other from

H, —C(NH 2 )NH, —CN(CH 3 ) 2 N(CH 3 ) 2 + Z 2 − , —C 1-3 -alkyl, —C 2-4 -alkyl-N(CH 3 ) 2 , —C 1-3 -alkyl-phenyl-R 12 , —C 1-3 -alkyl-COOH, —C 1-4 -alkyl-CO—Y 2 —R 11 , —CO-phenyl-CO—O—R 13 , —CO—C 1-4 -alkyl, —CO—C 1-3 -alkyl-NR 6 R 7 , —CO—C 1-3 -alkyl-N(CH 3 ) 3 + Z 3 − , —CO—C 1-4 -alkyl-Y 1 —R 9 , —CO—O—C 1-4 -alkyl-R 8 , —CO—NH—C 3-7 -cycloalkyl, —CO—NH—C 1-4 -alkyl, —CH 2 —CO—O—C 1-3 -alkyl, —CH 2 —CO—O—C 1-3 -alkyl-phenyl and —SO 2 —R 10 ;

R 6 is selected from —C 1-3 -alkyl, H, —C 1-4 -alkyl-OH, —CH 2 —CO—O—C 1-3 -alkyl and —CH 2 COOH;

R 7 is selected from —C 1-3 -alkyl, —CO—O—C 1-3 -alkyl, —C 1-4 -alkyl-OH, H, —CH 2 —CO—O—C 1-3 -alkyl and —CH 2 COOH;

R 8 is H or phenyl;

R 9 is selected from H, —C 1-3 -alkyl, OH, —NR 6 R 7 and ═O;

R 10 is C 1-3 -alkyl or an optionally substituted N-containing nonaromatic heterocycle;

R 11 is selected from H, C 1-3 -alkyl, ═O, —N(CH 3 ) 2 and —N(CH 3 ) 3 + Z 4 − ;

R 12 is selected from H, halogen, —COOH, —PO(OC 1-4 -alkyl)OH optionally substituted at the 2,3 or 4 position of the C 1-4 -alkyl group by —N(C 1-3 -alkyl) 2 or —N(C 1-3 -alkyl) 3 + Z 4 − , and —PO(OC 1-4 -alkyl) 2 , —PO(OH) 2 ;

R 13 is H or C 1-4 -alkyl;

Y 1 is selected from an optionally substituted 5- to 8-membered N-containing nonaromatic heterocycle, —N(C 1-3 -alkyl)-C 2-4 -alkyl-N(C 1-3 -alkyl) 2 and —N(C 1-3 -alkyl)-C 2-4 -alkyl-N + (C 1-3 alkyl) 3 Z 1 (−) ;

Y 2 is an optionally substituted 5- to 8-membered N-containing nonaromatic heterocycle;

or R 1 and R 2 together with the nitrogen atom they are attached to form an optionally substituted 4-7-membered heterocycle selected from the group consisting of piperazino, morpholino, piperidino; thiomorpholino, thiomorpholino-1-oxide, thiomorpholinon-1,1-dioxide, diazepane and pyrrolidino, wherein the nitrogen atoms may be substituted by a group selected from among phenyl, C 1-3 -alkylsulfonyl, C 1-3 -alkyl and —CO—C 1-3 -alkyl;

R 3 , R 4 and R 5 denote independently from each other —C 1-3 -alkyl;

or tautomers or pharmacologically acceptable acid addition salts thereof.

2. The compound of formula (I) according to claim 1 , wherein

A and A′ are both —CH 2 —CH 2 —;

R is —NR 1 R 2 or —NR 3 R 4 R 5(+) X (−) ;

X is halogen;

R 1 and R 2 are selected independently from each other from

H, —C(NH 2 )NH, —CN(CH 3 ) 2 N(CH 3 ) 2 + Z 2 − , —C 1-3 -alkyl, —C 2-4 -alkyl-N(CH 3 ) 2 —C 1-3 -alkyl-phenyl-R 12 , —C 1-3 -alkyl-COOH, —C 1-4 -alkyl-CO—Y 2 —R 11 , —CO-phenyl-CO—O—R 13 , —CO—C 1-4 -alkyl, —CO—C 1-3 -alkyl-NR 6 R 7 , —CO—C 1-3 -alkyl-N(CH 3 ) 3 +

Z 3 − , —CO—C 1-4 -alkyl-Y 1 —R 9 , —CO—O—C 1-4 -alkyl-R 8 , —CO—NH—C 3-7 -cycloalkyl, —CO—NH—C 1-4 -alkyl, —CH 2 —CO—O—C 1-3 -alkyl, —CH 2 —CO—O—C 1-3 -alkyl-phenyl, —SO 2 —R 10 ;

R 6 is selected from —C 1-3 -alkyl, H, —C 1-4 -alkyl-OH, —CH 2 —CO—O—C 1-3 -alkyl and —CH 2 COOH;

R 7 is selected from —C 1-3 -alkyl, —CO—O—C 1-3 -alkyl, —C 1-4 -alkyl-OH, H, —CH 2 —CO—O—C 1-3 -alkyl and —CH 2 COOH;

R 8 is H or phenyl;

R 9 is selected from H, —C 1-3 -alkyl, —OH, —NR 6 R 7 and ═O;

R 10 is C 1-3 -alkyl or an optionally substituted N-containing nonaromatic heterocycle;

R 11 is selected from H, —C 1-3 -alkyl, ═O, —N(CH 3 ) 2 and —N(CH 3 ) 3 + X − ;

R 12 is H or halogen;

R 13 is H or —C 1-4 -alkyl;

Y 1 is an optionally substituted 5- to 8-membered N-containing nonaromatic heterocycle,

Y 2 is an optionally substituted 5- to 8-membered N-containing nonaromatic heterocycle,

or R 1 and R 2 together with the nitrogen atom they are attached to form an optionally substituted 4-7-membered heterocycle selected from the group consisting of piperazino, morpholino, piperidino; thiomorpholino, thiomorpholino-1-oxide, thiomorpholinon-1,1-dioxide, diazepane and pyrrolidino, wherein the nitrogen atoms may be substituted by a group selected from among phenyl, C 1-3 -alkylsulfonyl, C 1-3 -alkyl and —CO—C 1-3 -alkyl;

R 3 , R 4 and R 5 are selected independently from each other —C 1-3 -alkyl;

or tautomers or pharmacologically acceptable acid addition salts thereof.

3. The compound of formula (I) according to claim 1 , wherein

R is —NR 1 R 2 ;

or tautomers or pharmacologically acceptable acid addition salts thereof.

4. The compound of formula (I) according to claim 1 , wherein

R 1 and R 2 are independently from each other H, —C 1-4 -alkyl-CO—Y 2 —R 11 or —CO—C 1-4 -alkyl-Y 1 —R 9 ;

R 9 is selected from H, —C 1-3 -alkyl, —OH, —NR 6 R 7 and ═O;

R 11 is selected from H, —C 1-3 -alkyl, ═O, —N(CH 3 ) 2 and —N(CH 3 ) 3 + X − ;

Y 1 is selected from a linker of formula (a1) to (j1)

wherein

* denotes the attachment point to the alkyl moiety of —CO—C 1-4 -alkyl-*

** denotes the attachment point to R 9 ;

Y 2 is selected from a linker of formula (a2) to (h2)

wherein

*denotes the attachment point to the carbonyl moiety of —C 1-4 -alkyl-CO—*

**denotes the attachment point to R 11 ;

or tautomers or pharmacologically acceptable acid addition salts thereof.

5. The compound of formula (I) according to claim 1 , wherein

R 1 and R 2 independently from each other denote H, —C(NH 2 )NH or —CN(CH 3 ) 2 N(CH 3 ) 2 + Z 2 − ;

or tautomers or pharmacologically acceptable acid addition salts thereof.

6. The compound of formula (I) according to claim 1 , wherein

R 1 and R 2 independently from each other are selected from —C 1-3 -alkyl, —C 2-4 -alkyl-N(CH 3 ) 2 , —C 1-3 -alkyl-phenyl-R 12 , —C 1-3 -alkyl-COOH, —CH 2 —CO—O—C 1-3 -alkyl and —CH 2 —CO—O—C 1-3 -alkyl-phenyl;

or tautomers or pharmacologically acceptable acid addition salts thereof.

7. The compound of formula (I) according to claim 1 , wherein

R 1 and R 2 independently from each other are selected from CO-phenyl-CO—O—R 13 , —CO—C 1-4 -alkyl and —CO—C 1-3 -alkyl-NR 6 R 7 ;

or tautomers or pharmacologically acceptable acid addition salts thereof.

8. The compound of formula (I) according to claim 1 , wherein

R 1 and R 2 independently from each other are selected from —CO—O—C 1-4 -alkyl-R 8 and —SO 2 —R 10 ;

or tautomers or pharmacologically acceptable acid addition salts thereof.

9. The compound of formula (I) according to claim 1 , wherein

R 1 and R 2 are hydrogen;

or tautomers or pharmacologically acceptable acid addition salts thereof.

10. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.