Antibacterial compounds

1. A compound according to formula (I):

wherein:

R 1 is naphthyl or a nine or ten-membered bicyclic ring, containing one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur; said napthyl is unsubstituted or substituted by methylenedioxy or by one to three substituents selected from the group consisting of C 1-4 alkyl, OR′, SR, C 1-4 alkylsulfonyl, C 1-4 alkylsulfoxyl, arylsulfonyl, arylsulfoxyl, C 1-4 alkyl sulfonamides, aryl sulfonamides, —CN, N(R′) 2 , CH 2 N(R′) 2 ,NO 2 ,CF 3 , CO 2 R′ CON(R′) 2 , COR′, —NR′C(O)R′, F, Cl, Br, I, and CF 3 S(O) r —; said nine or ten-membered bicyclic ring, containing one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur is unsubstituted or substituted by one to three substituents selected from the group consisting of C 1-4 alkyl, OR′, SR′, C 1-4 alkylsulfonyl, C 1-4 alkylsufoxyl, arylsulfonyl, arylsulfoxyl, C 1-4 alkyl sulfonamides, aryl sulfonamides, —CN, (N(R′) 2 , CH 2 N(R′) 2 , —NO 2 , —CF 3 , —CO 2 R′, —NR′C(O)R′, F, Cl, Br, I and CF 3 S(O) r —;

R 2 is C 1-6 alkyl or Ar-C 0-6 alkyl;

X is H, C 1-4 alkyl, OR′, SR′, C 1-4 alkylsulfonyl, C 1-4 alkylsulfoxyl, CN, N(R′) 2 ,

CH 2 N(R′) 2 , NO 2 , CF 3 , CO 2 R′, CON(R′) 2 , COR′, NR′C(O)R′, F, Cl, Br, I, or CF 3 S(O) r —;

R′ is H, C 1-6 alkyl or Ar-C 0-6 alkyl;

r is 0, 1 or 2; and

Ar is unsubstited or substituted by methylenedioxy or by one to three substituents selected from the group consisting of C 1-4 alkyl, OR′, SR′, C 1-4 alkylsulfonyl, C 1-4 alkylsulfoxyl, arylsulfonyl, arylsulfoxyl, C 1-4, alkyl sulfonamides, aryl sulfonamides, —CN, N(R′) 2 , CH 2 N(R′) 2 , NO 2 , CF 3 , CO 2 R′ CON(R′) 2 , COR′, —NR′C(O) R′, F, Cl, Br, I, and CF 3 S(O) r —;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 in which R 1 is selected from benzofuryl, or benzothienyl, unsubstituted or substituted by C 1-4 alkyl, OR′, N(R′) 2 , F, Cl, Br, I, and CF 3 , in which R′ is H or C 1-6 alkyl.

3. A compound according to claim 1 in which R 2 is C 1-6 alkyl or phenyl-C 0-6 alkyl, wherein phenyl is unsubstituted or substituted by methylenedioxy or by one to three substituents selected from the group consisting of C 1-4 alkyl, OR″, CO 2 R′, N(R′) 2 , F, Cl, Br, I, and CF 3 , in which R′ is H or C 1-6 alkyl and R″ is H, C 1-6 alkyl or benzyl.

4. A compound according to claim 1 in which X is H, C 1-4 alkyl, OR′, CN, N(R′) 2 , NO 2 , CF 3 , CO 2 R′, CON(R′) 2 , COR′, F, Cl, Br or I, in which R′ is H or C 1-6 alkyl.

5. A compound which is:

2-benzoyl-9-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4b]indole;

2-benzoyl-9-[(4-benzyloxyphenyl)methyl]-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole;

2-benzoyl-9[(4-hydroxyphenyl)methyl]-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole;

2-(3,4-methylenedioxy)benzoyl-9-[(4-hydroxyphenyl)methyl]-1,3,4,9-tetrahydro-2H-pyrido [3,4b]indole;

2-(2-hydroxy)benzoyl-9-[(4-hydroxyphenyl)methyl]1,3,4,9-tetrahydro-2H-pyrido[3,4b]indole;

2-(3-imidazo)benzoyl-9-[(4-hydroxyphenyl)methyl]-1,3,4,9-tetrahydro-2H-pyrido[3,4b]indole;

2-(6-hydroxy)nicotinoyl-9-[(4-hydroxyphenyl)methyl]-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole;

2-(6-amino)nicotinoyl-9-[(4-hydroxyphenyl)methyl]-1,3,4,9-tetrahydro-2H-pyrido[3,4b]indole;

2-(3-amino)benzoyl-9-methyl]-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole

2-(4-hydroxy)benzoyl-9-[(4-hydroxyphenyl)methyl]-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole;

2-(4-methylamino)benzoyl-9-[(4-hydroxyphenyl)methyl]1,3,4,9-tetrahydro-2H-pyrido [3,4-b]indole;

2-(4-amino)benzoyl-9-[(4-hydroxyphenyl)methyl]1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole;

2-(4-chloro)benzoyl-9-[(4-hydroxyphenyl)methyl]-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole;

2-(4-hydroxy)benzoyl-9-[(4-trifluoromethylphenyl)methyl]-1,3,4,9-tetrahydro-2H-pyrido[3,4b]indole;

2-(3,5-dichloro-4-hydroxy)benzoyl-9-[(4-hydroxyphenyl)methyl]-1,3,4,9-tetrahydro-2H-pyrido [3,4-b]indole;

2-(3-chloro-4-hydroxy)benzoyl-9-[(4-hydroxyphenyl)methyl]-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole;

methyl4-(( 2-[(4-hydroxyphenyl)carbonyl]-1,2,3,4-tetrahydrobeta-carbolin-9-yl) methyl)benzoate;

2-(4-chloro-2-hydroxy)benzoyl-9-[(4-hydroxyphenyl)methyl]1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole;

2-(5-chloro-2-hydroxy)benzoyl-9-[(4-hydroxyphenyl)methyl]1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole;

2-(4-hydroxy)benzoyl-9[(4-fluorophenyl)methyl]1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole;

2-(3-chloro-4-hydroxy)benzoyl-9-[(4-fluorophenyl)methyl]1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole;

2-(3,5-dichloro-4-hydroxy)benzoyl-9-[(4-fluorophenyl)methyl]1,3,4,9-tetrahydro-2H-pyrido [3,4-b]indole;

2-(3-chloro-4-hydroxy)benzoyl-9-[(4-trifluoromethylphenyl)methyl]1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole; or

2-(2-hydroxy-4-methyl)benzoyl-9-[(4-hyrdoxyphenyl)methyl]1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole;

or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition which comprises a compound according to claim 1 and a pharmaceutically acceptable carrier.

7. A method of treating bacterial infections which comprises administering to a subject in need thereof an effective amount of a compound according to claim 1 .

8. A compound according to claim 2 , in which R 2 is C 1-6 alkyl or phenyl-C 0-6 alkyl, wherein phenyl is unsubstituted or substituted by methylenedioxy or by one to three substituents selected from the group consisting of C 1-4 alkyl, OR″, CO 2 R′, N(R′) 2 , F, Cl, Br, I, and CF 3 , in which R′ is H, C 1-6 alkyl and R″ is H, C 1-6 alkyl or benzyl.

9. A compound according to claim 3 in which X is H, C 1-4 alkyl, OR′, CN, N(R′) 2 , NO 2 , CF 3 , CO 2 R′, CON(R′) 2 , COR′, F, Cl, Br or I, in which R′ is H or C 1-6 alkyl.

10. A pharmaceutical composition which comprises a compound according to claim 5 and a pharmaceutically acceptable carrier.

11. A method of treating bacterial infections which comprises administering to a subject in need thereof an effective amount of a compound according to claim 5 .

12. A compound according to formula (II):

wherein:

R′ is selected from the group consisting of benzopyranyl, benzimidazoyl, furyl, morpholinyl, pyridinyl, pyrrolyl, pyrrolidinyl, tetrahydropyridinyl, thiazolyl, and thienyl, unsubstituted or substituted by C 1-4 alkyl, OR′, N(R′) 2 , F, Cl, Br, I, and CF 3 , in which R′ is

H or C 1-6 alkyl;

R 2 is H, C 1-6 alkyl or Ar-C 0-6 alkyl;

X is H, C 1-4 alkyl, OR′, SR′, C 1-4 alkylsulfonyl, C 1-4 alkylsulfoxyl, CN, N(R′) 2 , CH 2 N(R′) 2 ,

NO 2 , CF 3 , CO 2 R′, CON(R′) 2 , COR′, NR′C(O)R′, F, Cl, Br, I, or CF 3 S(O) r —;

R′ is H, C 1-6 alkyl or Ar-C 0-6 alkyl; and

r is 0, 1 or 2;

or a pharmaceutically acceptable salt thereof.

13. A compound according to claim 12 in which R 2 is H, C 1-6 alkyl or phenyl-C 0-6 alkyl, wherein phenyl is unsubstituted or substituted by methylenedioxy or by one to three substituents selected from the group consisting of C 1-4 alkyl, OR″, CO 2 R′, N(R′) 2 , F, Cl, Br, I, and CF 3 , in which R′ is H, or C 1-6 alkyl and R″ is H, C 1-6 alkyl or benzyl.

14. A compound according to claim 13 in which X is H, C 1-4 alkyl, OR′, CN, N(R′) 2 , NO 2 , CF 3 , CO 2 R′, CON(R′) 2 , COR′, F, Cl, Br or I, in which R′ is H or C 1-6 alkyl.

15. A compound according to claim 12 in which X is H, C 1-4 alkyl, OR′, CN, N(R′) 2 , NO 2 , CF 3 , CO 2 R′, CON(R′) 2 , COR′, F, Cl, Br or I, in which R′ is H or C 1-6 alkyl.

16. A pharmaceutical composition which comprises a compound according to claim 12 and a pharmaceutically acceptable carrier.

17. A method of treating bacterial infections which comprises administering to a subject in need thereof an effective amount of a compound according to claim 12 .

18. A method of treating bacterial infections comprising administering to a subject in need thereof an effective amount of a composition when said composition comprises the compound according to formula (III):

wherein:

R 1 is selected from the group consisting of: phenyl and naphthyl, unsubstituted or substituted by methylenedioxy or by one to three substituents selected from the group consisting of C 1-4 alkyl, OR′, SR′, C 1-4 alkylsulfonyl, C 1-4 alkylsufoxyl, arylsulfonyl, arylsulfoxyl, C 1-4 alkyl sulfonamides, aryl sulfonamides, —CN, (N(R′) 2 , CH 2 N(R′) 2 , —NO 2 , —CF 3 , —CO 2 R′, —NR′C(O)R′, F, Cl, Br, I and CF 3 S(O) r : and an optionally substituted five or six membered monocyclic ring containing one to three heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, unsubstituted or substituted by one to three substituents selected from the group consisting of C 1-4 alkyl, OR′, SR′, C 1-4 alkylsulfonyl, C 1-4 alkylsufoxyl, arylsulfonyl, arylsulfoxyl, C 1-4 alkyl sulfonamides, aryl sulfonamides, —CN, (N(R′) 2 , CH 2 N(R′) 2 , —NO 2 , —CF 3 , —CO 2 R′, —NR′C(O)R′, F, Cl, Br, I and CF 3 S(O) r —; and a nine or ten-membered bicyclic ring containing one to three heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, unsubstituted or substituted by one to three substituents selected from the group consisting of C 1-4 alkyl, OR′, SR′, C 1-4 alkylsulfonyl, C 1-4 alkylsufoxyl, arylsulfonyl, arylsulfoxyl, C 1-4 alkyl sulfonamides, aryl sulfonamides, —CN, (N(R′) 2 , CH 2 N(R′) 2 , —NO 2 , —CF 3 , —CO 2 R′, —NR′C(O)R′, Cl, Br, I and CF 3 S(O) r —;

R 2 is H, C 1-6 alkyl or Ar-C 0-6 alkyl;

X is H, C 1-4 alkyl, OR′, SR′, C 1-4 alkylsulfonyl, C 1-4 alkylsulfoxyl, CN, N(R′) 2 , CH 2 N(R′) 2 ,

NO 2 , CF 3 , CO 2 R′, CON(R′) 2 , COR′, NR′C(O)R′, F, Cl, Br, I, or CF 3 S(O) r —;

R′ is H, C 1-6 alkyl or Ar-C 0-6 alkyl; and

r is 0, 1 or 2; or a pharmaceutically acceptable salt thereof.

19. The method of claim 18 , wherein R 1 is selected from the group consisting of benzimidazolyl and pyridinyl.

20. The method of claims 7 , 11 , 17 , or 18 , wherein said bacterial infection is caused by at least one bacteria selected from the group consisting of Staphylococcus aureus Oxford, Staphylococcus aureus WCUH29, Streptococcus pneumoniae R6, Streptococcus pneumomae ERY2, Streptococcus pneumoniae 1629, Streptococcus pneumoniae N 1387, Streptococcus pyogenes CN10, Enterococcus faecalis I, Enterococcus faecalis 7, Haemophilus influenzae Q1 Haemophilus influenzae NEMC1, Moraxella Catarrhalis 1502, Escherichia coli DC0, Escherichia coli ESS Escherichia coli 7623 AcrAB+, Escherichia coli 120 AcrAB—, Escherichia coli MG1655, Escherichia coli MG 1658, Klebsiella pneumoniae E70, and Pseudomoas aeruginosa K799wt.