Nitro-Substituted Phenyl-Piperazine Compounds, Their Preparation and Use in Medicaments

Medicament comprising at least one nitro-substituted phenyl-piperazine compound of general formula Ia,

• wherein
• Xa represents a —NR1aR2a moiety or a —OR3a moiety;
• R1a represents a linear or branched, saturated or unsaturated C1-10 aliphatic radical which is substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5-alkyl, —NH—(C1-5-alkyl) and —N(C1-5-alkyl)2;
• a radical selected from the group consisting of adamantyl, bicyclo[2.2.1]heptyl and bicyclo[3.1.1]heptyl which may be substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of oxo (═O), thioxo (═S), C1-5-alkyl, —O—C1-5-alkyl, —S—C1-5-alkyl, —C(═O)—OH, —C(═O)—C1-5-alkyl, —C(═O)—O—C1-5-alkyl, —O—C(═O)—C1-5-alkyl, F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —NH(C1-5-alkyl), —N(C1-5-alkyl)2, —NO2, —CHO, —CF2H, —CFH2, —C(═O)—NH2, —C(═O)—NH(C1-5-alkyl), —C(═O)—N(C1-5-alkyl)2 and —S(═O)2—C1-5-alkyl and/or which is bonded via a linear or branched C1-6 alkylene group which may contain 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as chain member(s);
• a saturated or unsaturated 3- to 9-membered cycloaliphatic radical, which may be substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of oxo (═O), thioxo (═S), C1-5-alkyl, —O—C1-5-alkyl, —S—C1-5-alkyl, —C(═O)—OH, —C(═O)—C1-5-alkyl, —C(═O)—O—C1-5-alkyl, —O—C(═O)—C1-5-alkyl, F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —NH(C1-5-alkyl), —N(C1-5-alkyl)2, —NO2, —CHO, —CF2H, —CFH2, —C(═O)—NH2, —C(═O)—NH(C1-5-alkyl), —C(═O)—N(C1-5-alkyl)2, —S(═O)2—C1-5-alkyl, —S(═O)2-phenyl, phenyl, phenoxy and benzyl and which is bonded via a linear or branched C1-6 alkylene, C2-6 alkenylene or C2-6 alkinylene group which may be unsubstituted or substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5—alkyl, phenyl, —NH—(C1-5-alkyl) and —N(C1-5-alkyl)2 and/or which may contain 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as ring member(s);
• a 5- to 10-membered aryl or heteroaryl radical which may be substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of C1-5-alkyl, —O—C1-5-alkyl, —S—C1-5-alkyl, —C(═O)—OH, —C(═O)—C1-5-alkyl, —C(═O)—O—C1-5-alkyl, —O—C(═O)—C1-5-alkyl, F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —NH(C1-5-alkyl), —N(C1-5-alkyl)2, —NO2, —CHO, —CF2H, —CFH2, —C(═O)—NH2, —C(═O)—NH(C1-5-alkyl), —C(═O)—N(C1-5-alkyl)2, —S(═O)2—C1-5-alkyl, —S(═O)2-phenyl, phenyl, phenoxy and benzyl and whereby said heteroaryl radical contains 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as ring member(s);
• a 5- to 10-membered aryl radical whereby said aryl radical may be substituted with 1, 2, 3, 4 or 5 substituent(s) independently selected from the group consisting of C1-5-alkyl, —O—C1-5-alkyl, —S—C1-5-alkyl, —C(═O)—O—C1-5-alkyl, —O—C(═O)—C1-5-alkyl, F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —NH(C1-5-alkyl), —N(C1-5-alkyl)2, —NO2, —CHO, —CF2H, —CFH2, —C(═O)—NH2, —C(═O)—NH(C1-5-alkyl), —C(═O)—N(C1-5-alkyl)2, —S(═O)2—C1-5-alkyl, —S(═O)2-phenyl, phenyl, phenoxy and benzyl and said aryl radical is bonded via a linear or branched C1-6 alkylene, C2-6 alkenylene or C2-6 alkinylene group which may be unsubstituted or substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5-alkyl, phenyl, —NH—(C1-5-alkyl) and —N(C1-5-alkyl)2 and which may contain 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as chain member(s);
• a 5- to 10-membered heteroaryl radical, which may be substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of C1-5-alkyl, —O—C1-5-alkyl, —S—C1-5-alkyl, —C(═O)—OH, —C(═O)—C1-5-alkyl, —C(═O)—O—C1-5-alkyl, —O—C(═O)—C1-5-alkyl, F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —NH(C1-5-alkyl), —N(C1-5-alkyl)2, —NO2, —CHO, —CF2H, —CFH2, —C(═O)—NH2, —C(═O)—NH(C1-5-alkyl), —C(═O)—N(C1-5-alkyl)2, —S(═O)2—C1-5-alkyl, —S(═O)2-phenyl, phenyl, phenoxy and benzyl and which is bonded via a linear or branched C1-6 alkylene, C2-6 alkenylene or C2-6 alkinylene group which may be unsubstituted or substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5-alkyl, phenyl, —NH—(C1-5-alkyl) and —N(C1-5-alkyl)2 and which may contain 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as chain member(s) and whereby the heteroaryl radical contains 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as ring member(s);
• or a —C(═O)—R12a moiety;
• R2a represents a hydrogen atom or a linear or branched, saturated or unsaturated C1-10 aliphatic radical which may be unsubstituted or substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5-alkyl, —NH—(C1-5-alkyl) and —N(C1-5-alkyl)2;
• or
• R1a and R2a together with the bridging nitrogen form a saturated, unsaturated or aromatic 3- to 6-membered heterocyclic ring which may be substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of C1-5-alkyl, —O—C1-5-alkyl, —S—C1-5-alkyl, oxo (═O), thioxo (═S), —C(═O)—OH, —C(═O)—C1-5-alkyl, —C(═O)—O—C1-5-alkyl, —O—C(═O)—C1-5-alkyl, F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —NH(C1-5-alkyl), —N(C1-5-alkyl)2, —NO2, —CHO, —CF2H, —CFH2, —C(═O)—NH2, —C(═O)—NH(C1-5-alkyl), —C(═O)—N(C1-5-alkyl)2, —S(═O)2—C1-5-alkyl, —S(═O)2-phenyl, phenyl, phenoxy and benzyl and which may contain 1, 2 or 3 additional heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as ring member(s) and/or which may be condensed with a mono- or bicyclic ring system which may be substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of C1-5-alkyl, —O—C1-5-alkyl, —S—C1-5-alkyl, oxo (═O), thioxo (═S), —C(═O)—OH, —C(═O)—C1-5-alkyl, —C(═O)—O—C1-5-alkyl, —O—C(═O)—C1-5-alkyl, F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —NH(C1-5-alkyl), —N(C1-5-alkyl)2, —NO2, —CHO, —CF2H, —CFH2, —C(═O)—NH2, —C(═O)—NH(C1-5-alkyl), —C(═O)—N(C1-5-alkyl)2, —S(═O)2—C1-5-alkyl, —S(═O)2-phenyl, phenyl, phenoxy and benzyl whereby said cyclic substituent(s) phenyl, phenoxy and benzyl may be unsubstituted or substituted by 1, 2 or 3 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, F, Cl, Br, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2 and NO2;
• whereby the rings of the ring system are 5- 6- or 7-membered and may contain 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur;
• R3a represents a 5- to 10-membered aryl or heteroaryl radical which may be substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of C1-5-alkyl, —O—C1-5-alkyl, —S—C1-5-alkyl, —C(═O)—OH, —C(═O)—C1-5-alkyl, —C(═O)—O—C1-5-alkyl, —O—C(═O)—C1-5-alkyl, F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —NH(C1-5-alkyl), —N(C1-5-alkyl)2, —NO2, —CHO, —CF2H, —CFH2, —C(═O)—NH2, —C(═O)—NH(C1-5-alkyl), —C(═O)—N(C1-5-alkyl)2, —S(═O)2—C1-5-alkyl, —S(═O)2-phenyl, phenyl, phenoxy and benzyl and which may be bonded via a linear or branched C1-6 alkylene, C2-6 alkenylene or C2-6 alkinylene group and which may be unsubstituted or substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5-alkyl, —NH—(C1-5-alkyl) and —N(C1-5-alkyl)2 and whereby the heteroaryl radical contains 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as ring member(s);
• R4a, R5a and R6a, identical or different, each represent a hydrogen atom or a halogen atom;
• or
• R4a and R5a together with the bridging carbon atoms form an unsubstituted 5- or 6-membered heterocyclic ring which contains 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as ring member(s) and which together with the phenyl ring which it is fused with forms a 9- or 10-membered bicyclic aromatic ring system;
• R7a and R8a, identical or different, each represent a hydrogen atom or a linear or branched, saturated or unsaturated C1-10 aliphatic radical which may be unsubstituted or substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5-alkyl, —NH—(C1-5-alkyl) and —N(C1-5-alkyl)2;
• R9a and R10a, identical or different, each represent a hydrogen atom or a linear or branched, saturated or unsaturated C1-10 aliphatic radical which may be unsubstituted or substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5-alkyl, —NH—(C1-5-alkyl) and —N(C1-5-alkyl)2;
• R11a represents a hydrogen atom;
• a linear or branched, saturated or unsaturated C1-10 aliphatic radical which may be unsubstituted or substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5-alkyl, —NH—(C1-5-alkyl) and —N(C1-5-alkyl)2 and which may contain 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as chain member(s);
• a 5- to 10-membered aryl or heteroaryl radical which may be substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of C1-5-alkyl, —O—C1-5-alkyl, —S—C1-5-alkyl, —C(═O)—OH, —C(═O)—C1-5-alkyl, —C(═O)—O—C1-5-alkyl, —O—C(═O)—C1-5-alkyl, F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —NH(C1-5-alkyl), —N(C1-5-alkyl)2, —NO2, —CHO, —CF2H, —CFH2, —C(═O)—NH2, —C(═O)—NH(C1-5-alkyl), —C(═O)—N(C1-5-alkyl)2, —S(═O)2—C1-5-alkyl, —S(═O)2-phenyl, phenyl, phenoxy and benzyl and which may be bonded via a linear or branched, C1-6 alkylene, C2-6 alkenylene or C2-6 alkinylene group which may be unsubstituted or substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5-alkyl, —NH—(C1-5-alkyl) and —N(C1-5-alkyl)2 and whereby the heteroaryl radical contains 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as ring member(s);
• a —C(═O)—R13a moiety or a —S(═O)2—R14a moiety;
• R12a represents a linear or branched, saturated or unsaturated C1-10 aliphatic radical which may be unsubstituted or substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5-alkyl, —NH—(C1-5-alkyl) and —N(C1-5-alkyl)2;
• or a 5- to 10-membered aryl or heteroaryl radical, which may be substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of C1-5-alkyl, —O—C1-15-alkyl, —S—C1-15-alkyl, —C(═O)—OH, —C(═O)—C1-5-alkyl, —C(═O)—O—C1-5-alkyl, —O—C(═O)—C1-15-alkyl, F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —NH(C1-5-alkyl), —N(C1-5-alkyl)2, —NO2, —CHO, —CF2H, —CFH2, —C(═O)—NH2, —C(═O)—NH(C1-5-alkyl), —C(═O)—N(C1-5-alkyl)2, —S(═O)2—C1-5-alkyl, —S(═O)2-phenyl, phenyl, phenoxy and benzyl and which may be bonded via a linear or branched C1-6 alkylene, C2-6 alkenylene or C2-6 alkinylene group which may be unsubstituted or substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5-alkyl, —NH—(C1-5-alkyl) and —N(C1-5-alkyl)2 and whereby the heteroaryl radical contains 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as ring member(s);
• and
• R13a and R14a, identical or different, each represent a linear or branched, saturated or unsaturated C1-10 aliphatic radical which may be unsubstituted or substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5-alkyl, —NH—(C1-5-alkyl) and —N(C1-5-alkyl)2;
• or a 5- to 10-membered aryl or heteroaryl radical, which may be substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of C1-5-alkyl, —O—C1-5-alkyl, —S—C1-5-alkyl, —C(═O)—OH, —C(═O)—C1-5-alkyl, —C(═O)—O—C1-5-alkyl, —O—C(═O)—C1-5-alkyl, F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —NH(C1-5-alkyl), —N(C1-5-alkyl)2, —NO2, —CHO, —CF2H, —CFH2, —C(═O)—NH2, —C(═O)—NH(C1-5-alkyl), —C(═O)—N(C1-5-alkyl)2, —S(═O)2—C1-5-alkyl, —S(═O)2-phenyl, phenyl, phenoxy and benzyl and/or which may be bonded via a linear or branched C1-6 alkylene, C2-6 alkenylene or C2-6 alkinylene group which may be unsubstituted or substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of F, Cl, Br, I, —CN, —CF3, —OCF3, —SCF3, —OH, —SH, —NH2, —O—C1-5-alkyl, —S—C1-5-alkyl, —NH—(C1-15-alkyl) and —N(C1-5-alkyl)2 and whereby the heteroaryl radical contains 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as ring member(s).
• optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof;
• and optionally at least one physiologically compatible auxiliary agent.