Cyclohexane compounds and their use as antibiotics

The compound according to general formula (I) as given as follows and/or racemates, enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts and/or esters thereof:

• wherein:
• R1 is selected from the group comprising H, OH, SH and/or NH2;
• R2 is selected from the group comprising hydrogen, C1-C10-alkyl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4 carbon atoms, C(O)C1-C10-alkyl, OC(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2 and/or S(O)2OH;
• R3 is selected from the group comprising OH, SH and/or NH2;
• R4 is selected from the group comprising OH, SH and/or NH2;
• R5 is selected from the group comprising hydrogen, P(O)(OH)2, S(O)2OH, P(S)(OH)2, P(O)OHSH, S(O)2SH and/or aryloxy phosphoramidates according to general formula (II)
• wherein:
• R6 is selected from the group comprising linear or branched C1-C6-alkyl, benzyl and/or cyclohexyl;
• R7 is a side chain of an amino acid selected from the group comprising hydrogen;
• linear or branched C1-C4-alkyl;
• linear or branched alkyl groups of the type -C1H2n-U-D wherein n is 1, 2, 3 or 4, U is selected from the group comprising O, CO, COO, CONH, S, guanidine and/or NH and D is selected from the group comprising H and/or C1-C3-alkyl;
• —CH2-C6H4-Y wherein Y is selected from the group comprising OH, SH, C1-C3-alkyl and/or NH2;
• —CH2-imidazole;
• —CH2-indole;
• —CH2-(furanyl-3-yl);
• —CH2-(pyridyl-3-yl) and/or —CH2-(imidazolyl-3-yl);
• X is selected from the group comprising Cl, Br, I, C1-C6-alkyl and/or C1-C6-alkoxy;
• A is selected from the group comprising S, NR8, C═CR8R9 and/or CR8R9, wherein
• R8, R9 is selected, the same or each independently of the other, from the group comprising hydrogen, C1-C10-alkyl, C2-C10-alkenyl, C6-C10-aryl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4carbon atoms, C(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2, S(O)2OH and/or a linker,
• for use as a medicament.

The compound according to general formula (I) as given as follows and/or racemates, enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts and/or esters thereof:

• wherein:
• R1 is selected from the group comprising H, OH, SH and/or NH2;
• R2 is selected from the group comprising hydrogen, C1-C10-alkyl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4 carbon atoms, C(O)C1-C10-alkyl, OC(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2 and/or S(O)2OH;
• R3 is selected from the group comprising OH, SH and/or NH2;
• R4 is selected from the group comprising OH, SH and/or NH2;
• R5 is selected from the group comprising hydrogen, P(O)(OH)2, S(O)2OH, P(S)(OH)2, P(O)OHSH, S(O)2SH and/or aryloxy phosphoramidates according to general formula (II)
• wherein:
• R6 is selected from the group comprising linear or branched C1-C6-alkyl, benzyl and/or cyclohexyl;
• R7 is a side chain of an amino acid selected from the group comprising hydrogen;
• linear or branched C1-C4-alkyl;
• linear or branched alkyl groups of the type -CnH2n-U-D wherein n is 1, 2, 3 or 4, U is selected from the group comprising O, CO, COO, CONH, S, guanidine and/or NH and D is selected from the group comprising H and/or C1-C3-alkyl;
• —CH2-C6H4-Y wherein Y is selected from the group comprising OH, SH, C1-C3-alkyl and/or NH2;
• —CH2-imidazole;
• —CH2-indole;
• —CH2-(furanyl-3-yl);
• —CH2-(pyridyl-3-yl) and/or —CH2-(imidazolyl-3-yl);
• X is selected from the group comprising Cl, Br, I, C1-C6-alkyl and/or C1-C6-alkoxy;
• A is selected from the group comprising S, NR8, C═CR8R9 and/or CR8R9, wherein
• R8, R9 is selected, the same or each independently of the other, from the group comprising hydrogen, C1-C10-alkyl, C2-C10-alkenyl, C6-C10-aryl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4carbon atoms, C(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2, S(O)2OH and/or a linker,
• for use in the therapeutic and/or prophylactic treatment of a bacterial infection, particularly for use as an antibiotic.

A pharmaceutical composition comprising as an active ingredient a compound according to general formula (I) as given as follows and/or racemates, enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts and/or esters thereof:

• wherein:
• R1 is selected from the group comprising H, OH, SH and/or NH2;
• R2 is selected from the group comprising hydrogen, C1-C10-alkyl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4 carbon atoms, C(O)C1-C10-alkyl, OC(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2 and/or S(O)2OH;
• R3 is selected from the group comprising OH, SH and/or NH2;
• R4 is selected from the group comprising OH, SH and/or NH2;
• R5 is selected from the group comprising hydrogen, P(O)(OH)2, S(O)2OH, P(S)(OH)2, P(O)OHSH, S(O)2SH and/or aryloxy phosphoramidates according to general formula (II)
• wherein:
• R6 is selected from the group comprising linear or branched C1-C6-alkyl, benzyl and/or cyclohexyl;
• R7 is a side chain of an amino acid selected from the group comprising hydrogen;
• linear or branched C1-C4-alkyl;
• linear or branched alkyl groups of the type -C1H2n-U-D wherein n is 1, 2, 3 or 4, U is selected from the group comprising O, CO, COO, CONH, S, guanidine and/or NH and D is selected from the group comprising H and/or C1-C3-alkyl;
• —CH2-C6H4-Y wherein Y is selected from the group comprising OH, SH, C1-C3-alkyl and/or NH2;
• -CH2-imidazole;
• —CH2-indole;
• —CH2-(furanyl-3-yl);
• -CH2-(pyridyl-3-yl) and/or -CH2-(imidazolyl-3-yl);
• X is selected from the group comprising Cl, Br, I, C1-C6-alkyl and/or C1-C6-alkoxy;
• A is selected from the group comprising S, NR8, C═CR8R9and/or CR8R9, wherein
• R8, R9 is selected, the same or each independently of the other, from the group comprising hydrogen, C1-C10-alkyl, C2-C10-alkenyl, C6-C10-aryl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4carbon atoms, C(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2, S(O)2OH and/or a linker

A pharmaceutical composition comprising as an active ingredient a combination of a compound according to general formula (I) and/or racemates, enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts and/or esters thereof:

• wherein:
• R1 is selected from the group comprising H, OH, SH and/or NH2;
• R2 is selected from the group comprising hydrogen, C1-C10-alkyl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4 carbon atoms, C(O)C1-C10-alkyl, OC(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2 and/or S(O)2OH;
• R3 is selected from the group comprising OH, SH and/or NH2;
• R4 is selected from the group comprising OH, SH and/or NH2;
• R5 is selected from the group comprising hydrogen, P(O)(OH)2, S(O)2OH, P(S)(OH)2, P(O)OHSH, S(O)2SH and/or aryloxy phosphoramidates according to general formula (II)
• wherein:
• R6 is selected from the group comprising linear or branched C1-C6-alkyl, benzyl and/or cyclohexyl;
• R7 is a side chain of an amino acid selected from the group comprising hydrogen;
• linear or branched C1-C4-alkyl;
• linear or branched alkyl groups of the type -CnH12n-U-D wherein n is 1, 2, 3 or 4, U is selected from the group comprising O, CO, COO, CONH, S, guanidine and/or NH and D is selected from the group comprising H and/or C1-C3-alkyl;
• —CH2-C6H4-Y wherein Y is selected from the group comprising OH, SH, C1-C3-alkyl and/or NH2;
• —CH2-imidazole;
• —CH2-indole;
• —CH2-(furanyl-3-yl);
• —CH2-(pyridyl-3-yl) and/or —CH2-(imidazolyl-3-yl);
• X is selected from the group comprising Cl, Br, I, C1-C6-alkyl and/or C1-C6-alkoxy;
• A is selected from the group comprising S, NR8, C=CR8R9 and/or CR8R9, wherein
• R8, R9 is selected, the same or each independently of the other, from the group comprising hydrogen, C1-C10-alkyl, C2-C10-alkenyl, C6-C10-aryl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4carbon atoms, C(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2, S(O)2OH and/or a linker,
• and vancomycin.

Antibiotic comprising as an active ingredient a compound according to general formula (I) as given as follows and/or racemates, enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts and/or esters thereof:

• wherein:
• R1 is selected from the group comprising H, OH, SH and/or NH2;
• R2 is selected from the group comprising hydrogen, C1-C10-alkyl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4 carbon atoms, C(O)C1-C10-alkyl, OC(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2 and/or S(O)2OH;
• R3 is selected from the group comprising OH, SH and/or NH2;
• R4 is selected from the group comprising OH, SH and/or NH2;
• R5 is selected from the group comprising hydrogen, P(O)(OH)2, S(O)2OH, P(S)(OH)2, P(O)OHSH, S(O)2SH and/or aryloxy phosphoramidates according to general formula (II)
• wherein:
• R6 is selected from the group comprising linear or branched C1-C6-alkyl, benzyl and/or cyclohexyl;
• R7 is a side chain of an amino acid selected from the group comprising hydrogen;
• linear or branched C1-C4-alkyl;
• linear or branched alkyl groups of the type —CnH12n-U-D wherein n is 1, 2, 3 or 4, U is selected from the group comprising O, CO, COO, CONH, S, guanidine and/or NH and D is selected from the group comprising H and/or C1-C3-alkyl;
• —CH2-C6H4-Y wherein Y is selected from the group comprising OH, SH, C1-C3-alkyl and/or NH2;
• —CH2-imidazole;
• —CH2-indole;
• —CH2-(furanyl-3-yl);
• -CH2-(pyridyl-3-yl) and/or -CH2-(imidazolyl-3-yl);
• X is selected from the group comprising Cl, Br, I, C1-C6-alkyl and/or C1-C6-alkoxy;
• A is selected from the group comprising S, NR8, C=CR8R9 and/or CR8R9, wherein
• R8, R9 is selected, the same or each independently of the other, from the group comprising hydrogen, C1-C10-alkyl, C2-C10-alkenyl, C6-C10-aryl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4 carbon atoms, C(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2, S(O)2OH and/or a linker.

A method for manufacturing a medicament comprising the steps of preparing a compound, suitable for administration, having a general formula (I) as given as follows and/or racemates, enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts and/or esters thereof:

• wherein:
• R1 is selected from the group comprising H, OH, SH and/or NH2;
• R2 is selected from the group comprising hydrogen, C1-C10-alkyl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4 carbon atoms, C(O)C1-C10-alkyl, OC(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2 and/or S(O)2OH;
• R3 is selected from the group comprising OH, SH and/or NH2;
• R4 is selected from the group comprising OH, SH and/or NH2;
• R5 is selected from the group comprising hydrogen, P(O)(OH)2, S(O)2OH, P(S)(OH)2, P(O)OHSH, S(O)2SH and/or aryloxy phosphoramidates according to general formula (II)
• wherein:
• R6 is selected from the group comprising linear or branched C1-C6-alkyl, benzyl and/or cyclohexyl;
• R7 is a side chain of an amino acid selected from the group comprising hydrogen;
• linear or branched C1-C4-alkyl;
• linear or branched alkyl groups of the type —C1H2n-U-D wherein n is 1, 2, 3 or 4, U is selected from the group comprising O, CO, COO, CONH, S, guanidine and/or NH and D is selected from the group comprising H and/or C1-C3-alkyl;
• —CH2-C6H4-Y wherein Y is selected from the group comprising OH, SH, C1-C3-alkyl and/or NH2;
• —CH2-imidazole;
• —CH2-indole;
• —CH2-(furanyl-3-yl);
• —CH2-(pyridyl-3-yl) and/or —CH2-(imidazolyl-3-yl);
• X is selected from the group comprising Cl, Br, I, C1-C6-alkyl and/or C1-C6-alkoxy;
• A is selected from the group comprising S, NR8, C=CR8R9 and/or CR8R9, wherein
• R8, R9 is selected, the same or each independently of the other, from the group comprising hydrogen, C1-C10-alkyl, C2-C10-alkenyl, C6-C10-aryl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4 carbon atoms, C(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2, S(O)2OH and/or a linker.

A method for treating a bacterial infection comprising the steps of administering to a subject a compound according to general formula (I) as given as follows and/or racemates, enantiomers, diastereomers, solvates, hydrates, and pharmaceutically acceptable salts and/or esters thereof:

• wherein:
• R1 is selected from the group comprising H, OH, SH and/or NH2;
• R2 is selected from the group comprising hydrogen, C1-C10-alkyl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4 carbon atoms, C(O)C1-C10-alkyl, OC(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2 and/or S(O)2OH;
• R3 is selected from the group comprising OH, SH and/or NH2;
• R4 is selected from the group comprising OH, SH and/or NH2;
• R5 is selected from the group comprising hydrogen, P(O)(OH)2, S(O)2OH, P(S)(OH)2, P(O)OHSH, S(O)2SH and/or aryloxy phosphoramidates according to general formula (II)
• wherein:
• R6 is selected from the group comprising linear or branched C1-C6-alkyl, benzyl and/or cyclohexyl;
• R7 is a side chain of an amino acid selected from the group comprising hydrogen;
• linear or branched C1-C4-alkyl;
• linear or branched alkyl groups of the type —CnH12n-U-D wherein n is 1, 2, 3 or 4, U is selected from the group comprising O, CO, COO, CONH, S, guanidine and/or NH and D is selected from the group comprising H and/or C1-C3-alkyl;
• —CH2-C6H4-Y wherein Y is selected from the group comprising OH, SH, C1-C3-alkyl and/or NH2;
• —CH2-imidazole;
• —CH2-indole;
• —CH2-(furanyl-3-yl);
• —CH2-(pyridyl-3-yl) and/or —CH2-(imidazolyl-3-yl);
• X is selected from the group comprising Cl, Br, I, C1-C6-alkyl and/or C1-C6-alkoxy;
• A is selected from the group comprising S, NR8, C=CR8R9 and/or CR8R9, wherein
• R8, R9 is selected, the same or each independently of the other, from the group comprising hydrogen, C1-C10-alkyl, C2-C10-alkenyl, C6-C10-aryl, C7-C14-arylalkyl wherein the aryl group has 6 to 10 carbon atoms and the alkyl group has 1 to 4carbon atoms, C(O)C1-C10-alkyl, C(O)OC1-C10-alkyl, C(O)NH2, NH2, S(O)2OH and/or a linker.