TREA

SUBSTITUTED 3-AMINO-4 -HYDROXY PYRROLIDINES COMPOUNDS, THEIR PREPARATION AND USE AS MEDICAMENTS

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  • Patent Application
  • 20100168093
  • Publication Number
    20100168093
  • Date Filed
    April 30, 2007
    17 years ago
  • Date Published
    July 01, 2010
    14 years ago
Information
Abstract
The present invention relates to substituted pyrrolidine compounds of general formula (I), methods for their preparation, medicaments comprising these compounds as well as their use for the preparation of a medicament for the treatment of humans and animal.
Description

The present invention relates to substituted pyrrolidine compounds, methods for their preparation, medicaments comprising these compounds as well as their use for the preparation of a medicament for the treatment of humans and animals.


Alzheimer's disease (AD) is a dreaded disease which suffer more and more people. By the year 2010 it is expected that 21 million people will have AD (For review on AD see: Lancet Neurol., 2004, 3:184-90); the herewith associated treatment costs are estimated of being over US$5 billion per year. The disease itself as well as the arising costs associated with the disease are a serious problem to be faced and an adequate treatment for AD is at the moment not existing.


The sigma receptor has been identified almost 20 years ago (reviewed in: Psychopharmacol., 2004, 174(3):301-319). At present two subtypes of sigma receptor are known. They were originally suggested being opioid receptors, however in the 90s they have been reclassified as being non-opioid receptors. From the very beginning, the sigma receptors were associated with various central nervous system disorders and recently the sigma receptor has been suggested of being implicated in neurological diseases such as AD (see e.g. U.S. 2005107432).


Recently it has been found that the sigma-1 receptor may be involved in the pathologenesis of Alzheimer's disease (Uchida et al., Am J Geriatr Psychiatry 2005; 13:1062-1066).


Thus, it was an object of the present invention to provide novel compounds for the use as active substances in medicaments, which are suitable for the prevention/treating Alzheimer's disease or binding to sigma receptor.


Said object was achieved by providing the substituted pyrrolidine compounds of general formula (I) given below, their stereoisomers, corresponding salts and corresponding solvates thereof.


Therefore, in one of its aspects the present invention relates to substituted pyrrolidine compounds of general formula (I),







wherein

    • R1 represents a hydrogen atom, an unbranched or branched, saturated, optionally at least mono-substituted C1-6-aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a hydrogen atom; a substituted or unsubstituted aliphatic group; a (C═O)—R8 group; a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH;
    • R3 and R4, equal or different, represent a hydrogen atom; an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; with the condition (proviso) that R3 and R4 may not at the same time represent a hydrogen atom; or
    • R3 and R4 together with their bridging nitrogen atom form
      • 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
      • 2) an A-X—B group,
        • wherein
        • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—OR11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
        • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
        • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR19 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
      • 3) an A-X—B—Y—C group,
        • wherein
        • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
        • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
        • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
        • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
        • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • R5 and R6 represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;
    • R7 and R7a, identical or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;
    • R8 represents a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;
    • R9, R10 and R11 represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;
    • R12 and R12a, identical or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;
    • optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
    • In an embodiment of the invention none, one, two or more of the following provisos apply:
    • a) with the proviso that
    • if R2 represents a hydrogen atom;
    • and R1 represents a hydrogen atom or a condensed aryl group;
    • R3 and R4 may not form together with their bridging nitrogen atom a triazole group;
    • b) with the proviso that
    • if R2 represents a hydrogen atom;
    • and R1 represents a hydrogen atom; a substituted C1-2 alkyl group; a condensed aryl group; a benzyl group;
    • R3 and R4 may not form together with their bridging nitrogen atom a substituted, unsaturated, condensed ring system containing at least 4 nitrogen atoms as ring members; an unsaturated, (C═O)-substituted, uncondensed, 6-membered ring system in which one additional carbon atom is replaced by nitrogen.
    • c) with the proviso that
    • if R2 represents a hydrogen atom;
    • and R3 and R4 form together with their bridging nitrogen atom a pyrrolidine ring, a piperidine ring, a piperazine ring or a morpholine ring;
    • R1 may not represent a hydrogen atom; a methyl group; an unsaturated tert-butyl group; a (C═O)-substituted alkyl-heteroaryl group;
    • d) with the proviso that
    • if R2 represents a hydrogen atom;
    • and R1 does not represent a benzyl group;
    • and either R3 or R4 represents a hydrogen atom;
    • either R3 or R4 may not represent a substituted alkyl-heteroaryl group; an alkyl-aryl group; a substituted heteroaryl group; an unsubstituted methyl group; a substituted alkyl group; an aryl group; a cyclohexyl group; an alkyl-cycloalkyl group wherein the cycloalkyl group contains at least one heteroatom;
    • e) with the proviso that
    • if R2 represents a hydrogen atom;
    • and R1 represents an alkyl group;
    • and either R3 or R4 represents a hydrogen atom;
    • the other of R3 or R4 may not represent a substituted or unsubstituted C1-2 alkyl group; a branched C1-4 alkyl group; a substituted or unsubstituted C3-6 cycloalkyl group in which optionally at least one carbon atom is optionally replaced by N, S or O; a cycloheptyl group;
    • f) with the proviso that
    • if R2 represents a hydrogen atom;
    • and R1 represents an alkyl group;
    • either R3 or R4 may not represent a cyclohexyl group while the other represents at the same time an alkyl-aryl group; or either R3 or R4 may not represent an alkyl group while the other represents at the same time an alkyl-aryl group;
    • g) with the proviso that
    • if R2 represents a hydrogen atom;
    • and R1 represents a benzhydryl group;
    • and either R3 or R4 represents a hydrogen atom;
    • either R3 or R4 may not represent a a (C═O)-substituted alkyl-aryl group; a (C═O)-substituted aryl group;
    • h) with the proviso that
    • if R2 represents a hydrogen atom;
    • and R1 represents benzyl;
    • and either R3 or R4 represents a hydrogen atom;
    • the other of R3 or R4 may not represent a substituted or unsubstituted C1-2 alkyl group; an unsubstituted benzyl group; a C3-8 substituted alkyl group; a substituted alkyl-aryl group;
    • or
    • R3 or R4, together with their bridging nitrogen atom may not form a a tetrahydropyrimidine ring; a triazolo pyrimidine ring;
    • i) with the proviso that
    • if R2 represents a benzyl group;
    • and either R3 or R4 represents a hydrogen atom
    • either R3 or R4 may not represent a (C═O)-substituted alkyl-aryl group;
    • j) with the proviso that
    • if R2 represents a C1-3 alkyl group;
    • and either R3 or R4 represents a hydrogen atom
    • either R3 or R4 may not represent an unsubstituted C1-2 alkyl group; a substituted alkyl group; a substituted or unsubstituted aryl group; a substituted heteroaryl group; a (C═O)-substituted alkyl-aryl group.


These compounds show binding to the Sigma receptor and/or show promise to be useful for the treatment of Alzheimer's disease.


Any compound that is a prodrug of a compound of formula (I) is within the scope of the invention. The term “prodrug” is used in its broadest sense and encompasses those derivatives that are converted in vivo to the compounds of the invention. Such derivatives would readily occur to those skilled in the art, and include, depending on the functional groups present in the molecule and without limitation, the following derivatives of the present compounds: esters, amino acid esters, phosphate esters, metal salts sulfonate esters, carbamates, and amides. Examples of well known methods of producing a prodrug of a given acting compound are known to those skilled in the art and can be found e.g. in Krogsgaard-Larsen et al. “Textbook of Drug design and Discovery” Taylor & Francis (April 2002).


Unless otherwise stated, the compounds of the invention are also meant to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by 13C- or 14C-enriched carbon or 15N-enriched nitrogen are within the scope of this invention.


The term “pharmacological tool” refers to the property of compounds of the invention through which they are particularly selective ligands for Sigma receptors which implies that compound of formula (I), described in this invention, can be used as a model for testing other compounds as sigma ligands, ex. a radiactive ligands being replaced, and can also be used for modeling physiological actions related to sigma receptors.


The term “condensed” according to the present invention means that a ring or ring-system is attached to another ring or ring-system, whereby the terms “annulated” or “annelated” are also used by those skilled in the art to designate this kind of attachment.


The term “ring system” according to the present invention refers to ring systems comprises saturated, unsaturated or aromatic carbocyclic ring systems which contain optionally at least one heteroatom as ring member and which are optionally at least mono-substituted. Said ring systems may be condensed to other carbocyclic ring systems such as aryl groups, naphtyl groups, heteroaryl groups, cycloalkyl groups, heterocyclyl groups or cyclyl groups, etc. Also, preferably included in the definition of “ring system” are Spiro ring systems. Rings or ring systems as defined above include, but are not limited to aryl, e.g. phenyl or naphtyl; heteroaryl, cycloalkyl, cyclyl, heterocyclyl or spiro groups.


“Optionally at least one heteroatom as ring member” is defined as having no heteroatom as ring member, one heteroatom as ring member or more than one heteroatom as ring member.


,In which optionally at least 1 carbon atom is replaced by” is defined as having no carbonatom (in the ring) being replaced by . . . (e.g. a heteroatom), one carbonatom (in the ring) being replaced by . . . (e.g. one heteroatom), or more than one no carbonatom (in the ring) being replaced by . . . (e.g. a heteroatom each).


“Optionally at least mono-substituted” is defined as no hydrogen radical in the mentioned radical being substituted by another radical, e.g. Cl, F, etc., or one hydrogen radical in the mentioned radical being substituted by another radical, e.g. Cl, F, etc. or more than one hydrogen radical in the mentioned radical being substituted by another radical, e.g. Cl, F, etc. (polysubstituted).


“Optionally mono- or polysubstituted” is defined as no hydrogen radical in the mentioned radical being substituted by another radical, e.g. Cl, F, etc., or one hydrogen radical in the mentioned radical being substituted by another radical, e.g. Cl, F, etc. or more than one hydrogen radical in the mentioned radical being substituted by another radical, e.g. Cl, F, etc. (polysubstituted).


“Optionally substituted” is defined as no hydrogen radical in the mentioned radical being substituted by another radical, e.g. Cl, F, etc., or one hydrogen radical in the mentioned radical being substituted by another radical, e.g. Cl, F, etc. or more than one hydrogen radical in the mentioned radical being substituted by another radical, e.g. Cl, F, etc. (polysubstituted).


Cyclyl groups/radicals, as defined in the present invention, comprise any saturated, unsaturated or aromatic carbocyclic ring systems which contain optionally at least one heteroatom as ring member and which are optionally at least mono-substituted. Cyclyl groups preferably comprise aryl, heteroaryl, cycloalkyl, heterocylcyl and/or Spiro ring systems.


According to the present invention, R3 and R4 together with their bridging nitrogen atom form a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally optionally at least 1 carbon atom is replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group. For a better understanding, some illustrative examples of ring system A, thereby not limiting the scope of said ring system A, is given below:


Ring System A:







According to the present invention, ring system A may be connected via X with another ring system B, which represents a saturated or unsaturated ring system comprising 1 to 2 or 3 optionally condensed rings, in which optionally at least 1 carbon atom is replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group, wherein X preferably represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group.


Some illustrative examples for A-X—B, thereby not limiting the scope of said group, are given below:


A-X—B:







Similarly, an A-X—B—Y—C group, according to the present invention, refers to a ring system A, which is connected via X to a ring system B, with A, X and B as defined above, via Y to a ring system C. Said connector Y may represent a bond, a —NH— group, a —(C═O)— group; a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group. Said ring system C ring system preferably represents a saturated or unsaturated ring system comprising 1 to 2 or 3 optionally condensed rings, in which optionally at least 1 carbon atom is replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR11 group CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;


Some illustrative examples for A-X—B—Y—C, thereby not limiting the scope of said group, are given below:


A-X—B—Y—C:







In an alternative embodiment of the present invention A represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;


Cycloalkyl radicals, as referred to in the present invention, are understood as meaning saturated and unsaturated (but not aromatic), cyclic hydrocarbons, which can optionally be unsubstituted, mono- or polysubstituted. In these radicals, for example C3-4-cycloalkyl represents C3- or C4-cycloalkyl, C3-5-cycloalkyl represents C3-, C4- or C5-cycloalkyl, etc. With respect to cycloalkyl, the term also includes saturated cycloalkyls in which optionally at least one carbon atom may be replaced by a heteroatom, preferably S, N, P or O. However, mono- or polyunsaturated, preferably monounsaturated, cycloalkyls without a heteroatom in the ring also in particular fall under the term cycloalkyl as long as the cycloalkyl is not an aromatic system.


Furthermore, C3-4-cycloalkyl represents C3- or C4-cycloalkyl, C3-5-cycloalkyl represents C3-, C4- or C5-cycloalkyl, C3-6-cycloalkyl represents C3-, C4-, C5- or C6-cycloalkyl, C3-7-cycloalkyl represents C3-, C4-, C5-, C6- or C7-cycloalkyl, C3-8-cycloalkyl represents C3-, C4-, C5-, C6-, C7- or C8-cycloalkyl, C4-5-cycloalkyl represents C4- or C5-cycloalkyl, C4-6-cycloalkyl represents C4-, C5- or C6-cycloalkyl, C44-cycloalkyl represents C4-, C5-, C6- or C7-cycloalkyl, C5-6-cycloalkyl represents C5- or C6-cycloalkyl and C5-7-cycloalkyl represents C5-, C6- or C7-cycloalkyl.


Examples for cycloalkyl radicals preferably include, but are not restricted to cyclopropyl, 2-methylcyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cycloheptyl, cyclooctyl, acetyl, tert-butyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine.


Preferably, cycloalkyl radicals, as defined in the present invention may optionally be mono-or polysubstituted by F, Cl, Br, I, NH2, SH, OH, SO2, CF3, carboxy, amido, cyano, carbamyl, nitro, —SO2NH2, C1-6 alkyl or C1-6-alkoxy.


Aliphatic radicals/groups, as referred to in the present invention, are optionally mono- or polysubstituted and may be branched or unbranched, saturated or unsaturated. Unsaturated aliphatic groups, as defined in the present invention, include alkenyl and alkinyl radicals. Saturated aliphatic groups, as defined in the present invention, include alkyl radicals. Preferred aliphatic radicals according to the present invention include but are not restricted to methyl, ethyl, vinyl(ethenyl), ethinyl, propyl, n-propyl, isopropyl, allyl(2-propenyl), 1-propinyl, methylethyl, butyl, n-butyl, iso-butyl, sec-butyl, tert-butyl butenyl, butinyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, hexyl, 1-methylpentyl, n-heptyl, n-octyl, n-nonyl and n-decyl. Preferred substituents for aliphatic radicals, according to the present invention, are F, Cl, Br, I, NH2, SH, OH, SO2, CF3, carboxy, amido, cyano, carbamyl, nitro, phenyl, benzyl, —SO2NH2, C1-6 alkyl and/or C1-6-alkoxy.


Alkyl radicals, as referred to in the present invention, are saturated aliphatic radicals. They may be linear or branched and are optionally substituted. In these radicals, C1-2-alkyl represents C1- or C2-alkyl, C1-3-alkyl represents C1-, C2- or C3-alkyl, C1-4-alkyl represents C1-, C2-, C3- or C4-alkyl, C1-5-alkyl represents C1-, C2-, C3-, C4-, or C5-alkyl, C1-6-alkyl represents C1-, C2-, C3-, C4-, C5- or C6-alkyl, C1-7-alkyl represents C1-, C2-, C3-, C4-, C5-, C6- or C7-alkyl, C1-8-alkyl represents C1-, C2-, C3-, C4-, C5-, C6-, C7- or C8-alkyl, C1-10-alkyl represents C1-, C2-, C3-, C4-, C5-, C6-, C7-, C8-, C8-, C9- or C10-alkyl and C1-18-alkyl represents Cl-, C2-, C3-, C4-, C5-, C6-, C7-, C8-, C9-, C10-, C11-, C12-, C13-, C14-, C15-, C16-, C17- or C18-alkyl. The alkyl radicals are preferably methyl, ethyl, propyl, methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, hexyl, 1-methylpentyl, if substituted also CHF2, CF3 or CH2OH etc.


Preferably, R3 and R4, according to the present invention, may not represent aliphatic radicals which are substituted by a (C═O) group.


In alternative embodiment of the present invention, R3 and R4 may present at the same moment a hydrogen atom.


Preferably, with respect to the present invention, (C═O)—O groups, if not otherwise defined, do not represent substituents for aliphatic groups, cycloalkyl groups, aryl groups, heteroaryl groups, alky-cycloalkyl groups, alkyl-aryl groups or alkyl-heteroaryl groups.


The term (CH2)3-6 is to be understood as meaning —CH2—CH2—CH2—, —CH2—CH2—CH2—CH2—, —CH2—CH2—CH2—CH2—CH2— and —CH2—CH2—CH2—CH2—CH2—CH2—; (CH2)1-4 is to be understood as meaning —CH2—, —CH2—CH2—, —CH2—CH2—CH2— and —CH2—CH2—CH2—CH2—; (CH2)4-5 is to be understood as meaning —CH2—CH2—CH2—CH2— and —CH2—CH2—CH2—CH2—CH2—, etc.


An aryl radical, as referred to in the present invention, is understood as meaning ring systems with at least one aromatic ring but without heteroatoms even in only one of the rings. These aryl radicals may optionally be mono-or polysubstituted with for example F, Cl, Br, I, NH2, SH, OH, SO2, oxo, carboxy, amido, cyano, carbamyl, nitro, phenyl, benzyl, —SO2NH2, C1-6 alkyl or C1-6-alkoxy. Preferred examples of aryl radicals include but are not restricted to phenyl, naphthyl, fluoranthenyl, fluorenyl, tetralinyl or indanyl or anthracenyl radicals, which may optionally be mono- or polysubstituted.


Heterocyclyl groups/radicals, as defined in the present invention, comprise any saturated, unsaturated or aromatic carbocyclic ring systems which are optionally at least mono-substituted and which contain at least one heteroatom as ring member. Preferred heteroatoms for these heterocyclyl groups are N, S or O.


A heteroaryl radical is understood as meaning heterocyclic ring systems which have at least one aromatic ring and may optionally contain one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur and may optionally be unsubstituted, mono- or polysubstituted by for example F, Cl, Br, I, NH2, SH, OH, SO2, oxo, carboxy, amido, cyano, carbamyl, nitro, henyl, benzyl, —SO2NH2, C1-6 alkyl or C1-6-alkoxy.


Preferred examples of heteroaryls include but are not restricted to furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, pyrimidine, pyridazine, pyrazine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, benzothiazole, indole, benzotriazole, benzodioxolane, benzodioxane, benzimidzole, carbazole and quinazoline.


An alkyl-aryl radical, as defined in the present invention, comprises a linear or branched, optionally at least mono-substituted alkyl chain which is bonded to an aryl group, as defined above. A preferred alkyl-aryl radical is a benzyl group, wherein the alkyl chain is optionally branched or substituted. Preferred substituents for alky-aryl radicals, according to the present invention, are F, Cl, Br, I, NH2, SH, OH, SO2, CF3, carboxy, amido, cyano, carbamyl, nitro, phenyl, benzyl, —SO2NH2, C1-6 alkyl and/or C1-6-alkoxy.


The term “salt” is to be understood as meaning any form of the active compound used according to the invention in which it assumes an ionic form or is charged and is coupled with a counter-ion (a cation or anion) or is in solution. By this are also to be understood complexes of the active compound with other molecules and ions, in particular complexes which are complexed via ionic interactions.


The term “physiologically acceptable salt” means in the context of this invention any salt that is physiologically tolerated (most of the time meaning not being toxic—especially not caused by the counter-ion) if used appropriately for a treatment especially if used on or applied to humans and/or mammals.


These physiologically acceptable salts can be formed with cations or bases and in the context of this invention is understood as meaning salts of at least one of the compounds used according to the invention—usually a (deprotonated) acid—as an anion with at least one, preferably inorganic, cation which is physiologically tolerated—especially if used on humans and/or mammals. The salts of the alkali metals and alkaline earth metals are particularly preferred, and also those with NH4, but in particular (mono)- or (di)sodium, (mono)- or (di)potassium, magnesium or calcium salts.


These physiologically acceptable salts can also be formed with anions or acids and in the context of this invention is understood as meaning salts of at least one of the compounds used according to the invention—usually protonated, for example on the nitrogen—as the cation with at least one anion which are physiologically tolerated—especially if used on humans and/or mammals. By this is understood in particular, in the context of this invention, the salt formed with a physiologically tolerated acid, that is to say salts of the particular active compound with inorganic or organic acids which are physiologically tolerated—especially if used on humans and/or mammals. Examples of physiologically tolerated salts of particular acids are salts of: hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, malic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid or citric acid.


The term “solvate” according to this invention is to be understood as meaning any form of the active compound according to the invention in which this compound has attached to it via non-covalent binding another molecule (most likely a polar solvent) especially including hydrates and alcoholates, e.g. methanolate.


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a hydrogen atom, an unbranched or branched, optionally at least mono-substituted C1-6-alkyl radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a (C═O)—R8 group, with R8 representing a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;
    • R3 and R4, equal or different, represent a hydrogen atom; an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted C1-8-aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; with the condition (proviso) that R3 and R4 may not at the same time represent a hydrogen atom;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 2) an A-X-B group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning as defined above;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a hydrogen atom, an unbranched or branched, saturated, optionally at least mono-substituted C1-6-alkyl radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a linear, substituted or unsubstituted C1-6 alkyl group; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R6 group; a (C═O)—OR16 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning as defined above;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted heteroaryl group; a branched or unbranched, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a linear, substituted or unsubstituted C1-6 alkyl group; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH;
    • R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, unsubstituted C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-cycloalkyl group; an unsubstituted alkyl-aryl group; a saturated or unsaturated, optionally at least mono-substtituted alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;
    • R5, R6, R7 and R7a have the meaning as defined above;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents an unbranched or branched, optionally at least mono-substituted C2-6-alkyl radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated unsubstituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a (SO2)—R6 group; a (C═O)—NR7R7a group;
    • R2 represents a hydrogen atom;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a ring system A in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 2) an A-X—B group,
    • wherein
    • A represents a ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R6 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R6 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning as defined above;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a hydrogen atom;
    • R3 represents a hydrogen atom;
    • R4 represents a saturated or unsaturated, unsubstituted, linear C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing 4 or 5-membered cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, unsubstituted alkyl-cycloalkyl group; an unsubstituted C1-6 alkyl-heteroaryl group;
    • R5, R6, R7 and R7a have the meaning as defined above;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a hydrogen atom, an unbranched or branched, saturated C1-6 alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a (C═O)—R8 group, with R8 representing a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;
    • R3 and R4, equal or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted C1-8-aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group; a branched or unbranched, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group; an optionally at least mono-substituted aryl group; an optionally at least mono-substituted heteroaryl group; a branched or unbranched, optionally at least mono-substituted C1-6-alkyl-aryl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted C1-6-alkyl-heteroaryl group; with the condition that R3 and R4 may at the same time not represent a hydrogen atom;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning as defined above;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a hydrogen atom, an unbranched or branched, saturated C1-6 alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, carboxy, amido, cyano, carbamyl, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated, C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the heteroaryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least mono-substituted benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; a group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a C1-6 alkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • R5, R6, R7, R7, R7a, R9, R10, R11, R12 and R12a have the meaning as defined above;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6—alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a C1-6 alkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, unsubstituted C344 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group with substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN, nitro; an unsubstituted heteroaryl group; an optionally at least mono-substituted C14 alkyl-cycloalkyl group; an unsubstituted C1-6 alkyl-aryl group; an unsubstituted C1-6 alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;
    • R5, R6, R7 and R7a have the meaning as defined above;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents an unbranched or branched, optionally at least mono-substituted C1-6-alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6.alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a hydrogen atom;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a 4 to 18 membered ring system A in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 2) an A-X—B group,
    • wherein
    • A represents 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning as defined above;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6—alkyl-heteroaryl group wherein the C1-6—alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a hydrogen atom;
    • R3 represents a hydrogen atom;
    • R4 represents a saturated or unsaturated, unsubstituted, linear C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing 4 or 5-membered cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, unsubstituted alkyl-cycloalkyl group; an unsubstituted C1-6 alkyl-heteroaryl group;
    • R5, R6, R7 and R7a have the meaning as defined above;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a hydrogen atom, an unbranched or branched C1-6 alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group;
    • R2 represents a (C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group;
    • R3 and R4, equal or different, represent a hydrogen atom, an unbranched or branched C,$-alkyl group, which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a saturated or unsaturated, optionally at least one heteroatom as ring member containing cycloalkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, CO—OH, CO—O—CH3, O—CH3, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, CO—OH, CO—O—CH3, O—CH3, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, CO—OH, CO—O—CH3, O—CH3, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; with the condition that R3 and R4 may at the same time not represent a hydrogen atom;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated 4 to 18 membered ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R9, R10 and R11 represent a hydrogen atom, an unbranched or branched C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a hydrogen atom, an unbranched or branched C1-6 alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, carboxy, amido, cyano, carbamyl, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated, C1 alkyl-heteroaryl group wherein the C1-6-alkyl and/or the heteroaryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least mono-substituted benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a group; a (SO2)—R6 group;
    • R2 represents a methyl ,ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated 4 to 18 membered ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cydooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R9, R10 and R11 represent a hydrogen atom, an unbranched or branched C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group;
    • R2 represents a methyl, ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, unsubstituted C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group with substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN, nitro; an unsubstituted heteroaryl group; a C1-6 alkyl-cycloalkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an unsubstituted C1-6 alkyl-aryl group; an unsubstituted C1-6 alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;
    • R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents an unbranched or branched, saturated, optionally at least mono-substituted C1-6-alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6.alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group;
    • R2 represents a hydrogen atom;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a 4 to 18 membered ring system A in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • 2) an A-X—B group,
    • wherein
    • A represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C143-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated 4 to 6membered ring system, in which at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, or CF3;
    • R6 represents a hydrogen atom; a C1.4 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R9, R10 and R11 represent a hydrogen atom, an unbranched or branched C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6—alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group;
    • R2 represents a hydrogen atom;
    • R3 represents a hydrogen atom;
    • R4 represents a saturated or unsaturated, unsubstituted, linear C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing 4 or 5-membered cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, unsubstituted alkyl-cycloalkyl group; an unsubstituted C1-6 alkyl-heteroaryl group;
    • R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2. CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R2 represents a(C═O)—R8group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group;
    • R3 and R4, identical or different, represent a hydrogen atom; a C3-8 alkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; an optionally at least mono-substituted quinoline group; a phenyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated 4 to 18 membered ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R2 represents a methyl ,ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated 4 to 18 membered ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted Ci-raliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R2 represents a methyl ,ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, optionally at least mono-substituted C343aliphatic group with substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN, nitro; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group with substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN, nitro; an unsubstituted heteroaryl group; a saturated or unsaturated, optionally at least mono-substituted C1-6 alkyl-cycloalkyl group; a saturated or unsaturated, unsubstituted C1-6 alkyl-aryl group; a saturated or unsaturated, unsubstituted C1-6 alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R2 represents a hydrogen atom;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a 4 to 18 membered ring system A in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • 2) an A-X—B group,
    • wherein
    • A represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1.43-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R2 represents a hydrogen atom;
    • R3 represents a hydrogen atom;
    • R4 represents a saturated or unsaturated, unsubstituted, linear C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing 4 or 5-membered cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, unsubstituted alkyl-cycloalkyl group; an unsubstituted C1-6 alkyl-heteroaryl group;


A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a benzyl group or a (SO2)—R6 group with R6 being an aryl group;
    • R2 represents a(C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group;
    • R3 and R4, identical or different, represent a C3-8 alkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; an optionally at least mono-substituted quinoline group; a phenyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a ring system A, comprising:









    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • 2) an A-X—B group,

    • wherein

    • A represents a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • X represents a bond, a —NH— group, a —(C═O)— group, a linear optionally substituted C1-2 alkyl chain, —O—, or a —SO2— group;

    • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;

    • 3) an A-X—B—Y—C group,

    • wherein

    • A represents a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • X represents a bond, a —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, or a —SO2— group;

    • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;

    • Y represents a bond, a —NH— group, a linear C1-2-aliphatic group;

    • C represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;





A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a benzyl group or a (SO2)—R6 group with R6 being an aryl group;
    • R2 represents a methyl, ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4 together with their bridging nitrogen atom form
    • a ring system A, comprising:









    • and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • an A-X—B group,

    • wherein

    • A represents a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • X represents a bond, a —NH— group, a —(C═O)— group, a linear Ci-2 alkyl chain, —O—, or a —SO2— group;

    • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;

    • an A-X—B—Y—C group,

    • wherein

    • A represents a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • X represents a bond, a —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, or a —SO2— group;

    • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;

    • Y represents a bond, a —NH— group, a linear C1-2 alkyl group;

    • C represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;





A preferred embodiment of the present invention are compounds of general formula (I) as defined above,


wherein

    • R1 represents a benzyl group or a (SO2)—R6 group with R6 being an aryl group;
    • R2 represents a hydrogen atom;
    • R3 and R4 together with their bridging nitrogen atom form
    • a ring system A, comprising:









    • and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • an A-X—B group,

    • wherein

    • A represents a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • X represents a bond, a —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, or a —SO2— group;

    • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;

    • an A-X—B—Y—C group,

    • wherein

    • A represents a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • X represents a bond, a —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, or a —SO2— group;

    • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6 alkoxy group;

    • Y represents a bond, a —NH— group, a linear C1-2-alkyl group;

    • C represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;





In a highly preferred embodiment of the present invention the substituted pyrrolidine compounds are selected from the group consisting of:

    • [1] (3,4-trans)-1-benzyl-4-(3,4-dihydroisoquinolin-2(1H)yl)pyrrolidine-3-ol,
    • [2] (3,4-trans)-1-benzyl-4-morpholinopyrrolidine-3-ol,
    • [3] (3,4-trans)-1-benzyl-4-(4-(2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)piperidin-1-yl)pyrrolidine-3-ol,
    • [4] (3,4-trans)-1-benzyl-4-(3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propyl amino)pyrrolidine-3-ol,
    • [5] (3,4-trans)-1-benzyl-4-(4-((3,4-dihydroisoquinolin-2(1H)-yl)methyl)piperidin-1-yl)pyrrolidine-3-ol,
    • [6] 1-(4-(6-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-ylamino)phenyl)ethanone,
    • [7] 1-(1-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperidin-4-yl)-1H-benzo[d][1,3]oxazin-2(4H)-one,
    • [8] (3,4-trans)-1-benzyl-4-(2-(4-phenoxyphenylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)pyrrolidine-3-ol,
    • [9] (3,4-trans)-1-benzyl-4-(3-(3,4-dihydroisoquinolin-2(1H)-yl)propylamino)pyrrolidine-3-ol,
    • [10] (3,4-trans)-1-benzyl-4-(4-(4-methoxypyrimidin-2-yl)piperazin-1-yl)pyrrolidine-3-ol,
    • [11] (3,4-trans)-1-benzyl-4-(2,3,8,8a-tetrahydrocyclopenta[ij]isoquinolin-1(7H)-yl)pyrrolidine-3-ol,
    • [12] tert-butyl-4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxylate,
    • [13] tert-butyl 4-((3,4-trans)-4-hydroxy-1-(phenylsulfonyl)pyrrolidine-3-yl)piperazine-1-carboxylate,
    • [14] (3,4-trans)-4-morpholino-1-(phenylsulfonyl)pyrrolidine-3-ol,
    • [15] (3,4-trans)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-1-(phenylsulfonyl)pyrrolidine-3-ol,
    • [16] (3,4-trans)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-1((S)-1-phenylethyl)pyrrolidin-3-ol,
    • [17] (3,4-trans)-1-benzyl-4-(4-benzylpiperazin-1-yl)pyrrolidine-3-ol,
    • [18] (3,4-trans)-1-benzyl-4-(4-phenylpiperazin-1-yl)pyrrolidine-3-ol,
    • [19] Ethyl 2-(4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazin-1-yl)acetate,
    • [20] (4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazin-1-yl)(phenyl)methanone,
    • [21] Ethyl 4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxilate,
    • [22] tert-butyl 4-((3,4-trans)-1-(4-fluorobenzyl)-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxylate,
    • [23] (3,4-trans)-1-benzyl-4-(4-methylpiperazin-1-yl)pyrrolidine-3-ol,
    • [24] tert-butyl-4-(3,4-trans)-4-acetoxy-1-benzylpyrrolidine-3-yl)piperazine-1-carboxylate,
    • [25] (3,4-trans)-1-benzyl-4-(piperazin-1-yl)pyrrolidine-3-yl acetate,
    • [26] tert-butyl 4-((3,4-trans)-4-acetoxypyrrolidine-3-yl)piperazine-1-carboxylate,
    • [27] trans 1-Benzyl-4-(4-(2-phenyl-phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [28] trans 1-Benzyl-4-(4-(2-phenyl-phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [29] (3,4-trans)-1-benzyl-4-(phenylamino)pyrrolidin-3-ol,
    • [30] (3,4-trans)-1-benzyl-4-(benzylamino)pyrrolidin-3-ol,
    • [31] (3R,4R)-1-benzyl-4-(octylamino)pyrrolidin-3-ol,
    • [32] (3,4-trans)-1-benzyl-4-(4-methoxybenzylamino)pyrrolidin-3-ol,
    • [33] (3,4-trans)-1-benzyl-4-(butylamino)pyrrolidin-3-ol,
    • [34] (3R,4R)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [35] (3R,4R)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-yl acetate,
    • [36] (3,4-trans)-1-benzyl-4-(butylamino)pyrrolidin-3-ol,
    • [37] (3R,4R)-1-benzyl-4-(4-methoxyphenylamino)pyrrolidin-3-ol,
    • [38] Methyl 4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidin-3-ylamino)benzoate,
    • [39] (3R,4R)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [40] (3R,4R)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [41] (3R,4R)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [42] (3R,4R)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [43] (3R,4R)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [44] (3R,4R)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [45] (3R,4R)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [46] (3R,4R)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [47] (3R4R)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [48] (3R,4R)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [49] (3R,4R)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol
    • [50] (3R,4R)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [51] (3R,4R)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-ol,
    • [52] (3R,4R)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [53] (3,4-trans)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,
    • [54] (3,4-trans)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [55] (3S,4S)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [56] (3,4-trans)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,
    • [57] (3,4-trans)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [58] (3R, 4R)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [59] (3S, 4S)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [60] (3,4-trans)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,
    • [61] (3,4-trans)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [62] (3S-4S)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [63] (3,4-trans)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,
    • [64] (3,4-trans)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [65] (3S,4S)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [66] (3,4-trans)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,
    • [67] (3,4-trans)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [68] (3S,4S)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [69] (3,4-trans)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,
    • [70] (3,4-trans)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [71] (3S,4S)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [72] (3,4-trans)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [73] (3,4-trans)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [74] (3S,4S)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [75] (3,4-trans)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,
    • [76] (3,4-trans)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [77] (3S,4S)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [78] (3,4-trans)-1-benzyl-4-(4-(2-chloro-6-fluorobenzyl)piperazin-1-yl)pyrrolidine-3-ol
    • [79] (3,4-trans)-1-benzyl-4-(4-(3,4-dichlorobenzyl)piperazin-1-yl)pyrrolidine-3-ol
    • [80] (3,4-trans)-1-benzyl-4-hydroxypyrrolidin-3-yl)piperazin-1-yl)(furan-2-yl)methanone
    • [81] (3,4-trans)-1-benzyl-4-(4-ethylpiperazin-1-yl)pyrrolidin-3-ol,
    • [82] (3,4-trans)-1-benzyl-4-(4-(2-methoxyphenyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [83] (3,4-trans)-1-benzyl-4-(4-(4-fluorophenyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [84] (3,4-trans)-1-benzyl-4-(4-(2-chlorophenyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [85] (3R,4R)-1-benzyl-4-(4-(2-chlorophenyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [86] (3S,4S)-1-benzyl-4-(4-(2-chlorophenyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [87] 1-(4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidin-3-yl)piperazin-1-yl)ethanone,
    • [88] (3,4-trans)-1-benzyl-4-(4-(3,4-dichlorophenyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [89] (3,4-trans)-1-benzyl-4-(4-(3,4-dichlorophenyl)piperazin-1-yl)pyrrolidin-3-ol, or
    • [90] (3,4-trans)-tert-butyl 3-(3,4-dihydroisoquinolin-2(1H)-yl)-4-hydroxypyrrolidine-1-carboxylate;


optionally in form of a corresponding salt, or a corresponding solvate.


Another preferred embodiment of the invention relates to substituted pyrrolidine compounds according to the invention of general formula (IA),









    • wherein

    • Z represents H or CH3;

    • R2 represents a hydrogen atom; a substituted or unsubstituted aliphatic group; a (C═O)—R8group; a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH;

    • R3 and R4, equal or different, represent a hydrogen atom; an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; with the condition (proviso) that R3 and R4 may not at the same time represent a hydrogen atom;

    • or

    • R3 and R4 together with their bridging nitrogen atom form
      • 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
      • 2) an A-X—B group,
        • wherein
        • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
        • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
        • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
      • 3) an A-X—B—Y—C group,
        • wherein
        • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
        • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted Cts-aliphatic chain, —O—, or a —SO2— group;
        • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
        • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
        • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;

    • R8 represents a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;

    • R9, R10 and R11 represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;

    • R12 and R12a, identical or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;

    • W represents F, Cl, Br, I, NH2, SH, OH, SO2, CF3, carboxy, amido, cyano, carbamyl, nitro, phenyl, benzyl, —SO2NH2, C1-6 alkyl and/or C1-6-alkoxy;

    • r represents either 0, 1, 2 or 3;

    • optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.





In one embodiment one or more of the following provisos apply

    • with the provisos that
    • if R2 represents a hydrogen atom;
    • R3 and R4 may not form together with their bridging nitrogen atom a triazole group;
    • if R2 represents a hydrogen atom;
    • R3 and R4 may not form together with their bridging nitrogen atom a substituted, unsaturated, condensed ring system containing at least 4 nitrogen atoms as ring members; an unsaturated, (C═O)-substituted, uncondensed, 6-membered ring system in which one additional carbon atom is replaced by nitrogen.
    • if R2 represents a hydrogen atom;
    • and either R3 or R4 represents a hydrogen atom;
    • the other of R3 or R4 may not represent a substituted or unsubstituted C1-2alkyl group; an unsubstituted benzyl group; a C3-8 substituted alkyl group; a substituted alkyl-aryl group;
    • or
    • R3 or R4, together with their bridging nitrogen atom may not form a a tetrahydropyrimidine ring; a triazolo pyrimidine ring.


A preferred embodiment of the substituted pyrrolidine compounds according to the invention according to general formula (IA) are compounds

    • wherein
    • Z represents H or CH3; preferably Z represents H;
    • R2 represents a hydrogen atom; a methyl, ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a (C=O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; preferably R2 represents a hydrogen atom; a (C═O)—R8group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group
    • R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, unsubstituted C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-cycloalkyl group; an unsubstituted alkyl-aryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
      • 1) a ring system A, comprising:











      • and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

      • 2) an A-X—B group,
        • wherein
        • A represents a ring system comprising:


















        • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

        • X represents a bond, a —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, or a —SO2— group;

        • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:




















        • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;



      • 3) an A-X—B—Y—C group,
        • wherein
        • A represents a ring system comprising:


















        • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

        • X represents a bond, a —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, or a —SO2— group;

        • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:




















        • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6 alkoxy group;

        • Y represents a bond, a —NH— group, a linear C1-2-alkyl group;

        • C represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;





    • R8 represents a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;

    • R9, R10 and R11 represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;

    • R12 and R12a, identical or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;

    • W represents substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, OCF3, unsubstituted and/or unsubstituted C1-6-alkoxy;

    • r represents either 0, 1, 2 or 3;

    • optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.





In one embodiment one or more of the following provisos apply with the provisos that

    • if R2 represents a hydrogen atom;
    • R3 and R4 may not form together with their bridging nitrogen atom a triazole group; a substituted, unsaturated, condensed ring system containing at least 4 nitrogen atoms as ring members; an unsaturated, (C═O)-substituted, uncondensed, 6-membered ring system in which one additional carbon atom is replaced by nitrogen; or may not form a a tetrahydropyrimidine ring; a triazolo pyrimidine ring
    • if R2 represents a hydrogen atom;
    • and either R3 or R4 represents a hydrogen atom;
    • the other of R3 or R4 may not represent a substituted or unsubstituted C1-2 alkyl group; an unsubstituted benzyl group; a C3-8 substituted alkyl group; a substituted alkyl-aryl group.


In a preferred embodiment the substituted pyrrolidine compounds according to the invention are compounds according to either formula (IAa) or (IAb)









    • R2 represents a hydrogen atom; a methyl, ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a (C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; preferably R2 represents hydrogen or (C═O)—CH3;

    • R4,—if present as in case of general formula (IAb)—represents a saturated or unsaturated, unsubstituted C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-cycloalkyl group; an unsubstituted alkyl-aryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group;

    • or

    • Q—if present as in case of general formula (IAa)—represents N or CH, preferably Q represents N; and

    • Rx—if present as in case of general formula (IAa)—represents
      • hydrogen; a —(C═O)R8 group with R8 being either hydrogen or an optionally substituted C1-6 aliphatic group; or a —(C═O)OR10 group with R10 being either hydrogen or an optionally substituted C1-6 aliphatic group;
      • or X—B with
        • X representing a bond, an —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, —S— or an —SO2— group; preferably X represents a bond or SO2; and
        • B representing a phenyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system selected from a heterocyclyl, preferably from:
















        • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;



      • W represents substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, OCF3, unsubstituted C1-6alkyl and/or unsubstituted C1-6-alkoxy; preferably represents H;

      • r represents either 0, 1, 2 or 3; preferably is 0;

      • with the proviso that

      • if in a compound according to general formula (IAb) R2 represents a hydrogen atom;

      • R4 may not represent a substituted or unsubstituted C1-2 alkyl group; an unsubstituted benzyl group; a C3-8 substituted alkyl group; a substituted alkyl-aryl group;

      • optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.







In another preferred embodiment of the substituted pyrrolidine compounds according to the invention the compounds are compounds of general formula (IB),









    • wherein

    • R2 represents a hydrogen atom; a substituted or unsubstituted aliphatic group; a (C═O)—R8 group; a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH;

    • R3 and R4, equal or different, represent a hydrogen atom; an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; with the condition (proviso) that R3 and R4 may not at the same time represent a hydrogen atom;

    • or

    • R3 and R4 together with their bridging nitrogen atom form
      • 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
      • 2) an A-X—B group,
        • wherein
        • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
        • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
        • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
      • 3) an A-X—B—Y—C group,
        • wherein
        • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
        • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
        • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
        • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
        • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;

    • R6 represents a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;

    • R8 represents a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;

    • R9, R10 and R11 represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;

    • R12 and R12a, identical or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.





Another preferred embodiment of the substituted pyrrolidine compounds according to the invention are compounds according to general formula (IB),


wherein

    • R2 represents a hydrogen atom; a methyl, ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a(C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; preferably R2 represents a hydrogen atom; a(C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group
    • R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, unsubstituted C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-cycloalkyl group; an unsubstituted alkyl-aryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
      • 1) a ring system A, comprising:











      • and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

      • 2) an A-X—B group,
        • wherein
        • A represents a ring system comprising:


















        • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

        • X represents a bond, a —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, or a —SO2— group;

        • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:




















        • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;



      • 3) an A-X—B—Y—C group,
        • wherein
        • A represents a ring system comprising:


















        • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

        • X represents a bond, a —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, or a —SO2— group;

        • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:




















        • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6 alkoxy group;

        • Y represents a bond, a —NH— group, a linear C1-2-alkyl group;

        • C represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;





    • R6 represent an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; preferably represents an optionally at least mono-substituted aryl group;

    • R8 represents a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;

    • R9, R10 and R11 represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;

    • R12 and R12a, identical or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;

    • optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.





Another preferred embodiment of the substituted pyrrolidine compounds according to the invention are compounds according to general formula (I),

    • wherein
    • R1 represents H or C(O)OCH3;
    • R2 represents a hydrogen atom; a substituted or unsubstituted aliphatic group; a (C═O)—R8 group; a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH;
    • R3 and R4, equal or different, represent a hydrogen atom; an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; with the condition (proviso) that R3 and R4 may not at the same time represent a hydrogen atom;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
      • 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
      • 2) an A-X—B group,
        • wherein
        • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
        • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
        • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR19 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
      • 3) an A-X—B—Y—C group,
        • wherein
        • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
        • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
        • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR19 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
        • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
        • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • R8 represents a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;
    • R9, R10 and R11 represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;
    • R12 and R12a, identical or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;


In another aspect the present invention also provides a process for the manufacture of substituted pyrrolidine compounds of general formula (I) given above, characterized in that at least one pyrroline compound of general formula (II),







wherein R1 has the meaning given above, is reacted with a per-acid, preferably MCPBA to form a compound of general formula (III),







wherein R1 has the meaning given above, followed by reacting the epoxyo-pyrroline compound of formula III with a compound of formula IV







together with LiClO4, ACN at preferably 90° C. to give a compound of formula I, in which R2 is H; alternatively followed by reacting the pyrrolidine compound of formula (I) with a base to give a compound of formula (I), in which R2 has the meaning as defined above.


The process for obtaining the substituted pyrrolidine compounds of general formula given above is well known for those skilled in the art and is described in detail in e.g. EP 0985664, Synth. Commun, 20(2), 227-230 (1990), Synth. Commun., 34(23), 4421-4430 (2004), JP 11349565, JP-2000-80077, Tetrahedron: Asymmetry 12 (2001), 2989-2997, DE 4309964 and Org. Biomol. Chem. 2004, 2, 2418-2420.


The intermediates of general formula (I)I with R1 being alkyl, cycloalkyl, aryl, alkylaryl, alkyl-heteroaryl are obtained by reacting an amine of general formula VI





R1—NH2   (VI)


with cis-1,4-dichloro-2-butene and dichloromethane at room temperature.


Intermediates of general formula (I)I with R1 being (C═O)—R, (C═O)O—R or (SO2)—R are obtained by reacting an amine of general formula VI





R1—NH2   (VI)


with cis-1,4-dichloro-2-butene, NaH, dimethylformamide (DMF) at room temperature.


Methods for obtaining epoxyo-pyrroline compound of formula III as given above, with R1 being alkyl, cycloalkyl, aryl, alkylaryl, alkyl-heteroaryl, are described in EP 0985664.


Methods for obtaining epoxyo-pyrroline compound of formula III as given above, with R1 being (C═O)—R, (C═O)O—R or (SO2)—R, are described in DE 4309964 and Org. Biomol. Chem. 2004, 2, 2418-2420.


The process for obtaining substituted pyrrolidine compounds given above is also illustrated in scheme I given below:







Alternatively, compounds of general formula (I) can be obtained by standard procedures known by those skilled in the art.


The alternative processes is shown in scheme 2 below. A) refers to non-cyclic substituents formed by R3 and R4, B) refers to cyclic substituents formed by R3 and R4, wherein R3 and R4 have the meaning as defined above and Rx represents F, Cl, Br, I, NH2, SH, OH, CF3, a substituted or unsubstituted C1-6-aliphatic group; a substituted or unsubstituted C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a substituted or unsubstituted aryl group; a substituted or unsubstituted heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a (SO2)—R11 group; a NH—R11 group; or (C═O)—NR12R12a group







General Procedure for the Epoxide Opening with Amines.


A mixture of epoxide (1 eq), amine (1.5 eq) and LiClO4 (2 eq) in acetonitrile was heated at 90° C. until starting epoxide is not present (4-48 hours). The reaction mixture was cooled at room temperature and the solvent was evaporated under vacuum. The residue was suspended in dichloromethane and washed with water and saturated solution of NaCl, dried over Na2SO4, filtered and concentrated and the residue was purified by flash chromatography.


During the processes described above the protection of sensitive groups or of reagents may be necessary and/or desirable. The introduction of conventional protective groups as well as their removal may be performed by methods well-known to those skilled in the art.


If the substituted pyrrolidine compounds of general formula (I) themselves are obtained in form of a mixture of stereoisomers, particularly enantiomers or diastereomers, said mixtures may be separated by standard procedures known to those skilled in the art, e.g. chromatographic methods or fractionalized crystallization with chiral reagents. It is also possible to obtain pure stereoisomers via stereoselective synthesis.


Solvates, preferably hydrates, of the substituted pyrrolidine compounds of general formula (I), of corresponding stereoisomers, or of corresponding salts thereof may also be obtained by standard procedures known to those skilled in the art.


The purification and isolation of the inventive substituted pyrrolidine compounds of general formula (I), of a corresponding stereoisomer, or salt, or solvate or any intermediate thereof may, if required, be carried out by conventional methods known to those skilled in the art, e.g. chromatographic methods or recrystallization.


It has been found that the substituted pyrrolidine compounds of general formula (I) and given below, stereoisomers thereof, corresponding salts and corresponding solvates have high affinity to sigma receptors, i.e. they are selective ligands for the sigma receptor and act as modulators, e.g. antagonists, inverse agonists or agonists, on these receptors.


The substituted pyrrolidine compounds of general formula (I) given below, their stereoisomers, corresponding salts thereof and corresponding solvates are toxicologically acceptable and are therefore suitable as pharmaceutical active substances for the preparation of medicaments.


Another aspect of the invention is a medicament comprising at least one combination of compounds according to the invention and optionally one or more pharmaceutically acceptable excipients.


Another aspect of the invention relates to a medicament comprising at least one compound of general formula (I) and optionally one or more pharmaceutically acceptable excipients.


Another (IA) aspect of the invention relates to a medicament comprising at least one compound of general formula (IA), (IAa), (IAb), or (IB) and optionally one or more pharmaceutically acceptable excipients.


Another aspect of the present invention relates to a medicament comprising at least one substituted pyrazoline compound of general formula (I),







wherein

    • R1 represents a hydrogen atom, an unbranched or branched, saturated, optionally at least mono-substituted C1-6-aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a hydrogen atom; a substituted or unsubstituted aliphatic group; a (C═O)—R8group; a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH;
    • R3 and R4, equal or different, represent a hydrogen atom; an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; with the condition (proviso) that R3 and R4 may not at the same time represent a hydrogen atom;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • R5 and R6 represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;
    • R7 and R7a, identical or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;
    • R8 represents a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;
    • R9, R10 and R11 represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;
    • R12 and R12a, identical or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;
    • optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a prodrug thereof, and optionally one or more pharmaceutically acceptable excipients.


In an embodiment of the invention none, one, two or more of the following provisos apply:


a) with the proviso that

    • if R2 represents a hydrogen atom;
    • and R1 represents a hydrogen atom or a condensed aryl group;
    • R3 and R4 may not form together with their bridging nitrogen atom a triazole group;


b) with the proviso that

    • if R2 represents a hydrogen atom;
    • and R1 represents a hydrogen atom; a substituted C1-2 alkyl group; a condensed aryl group; a benzyl group;
    • R3 and R4 may not form together with their bridging nitrogen atom a substituted, unsaturated, condensed ring system containing at least 4 nitrogen atoms as ring members; an unsaturated, (C═O)-substituted, uncondensed, 6-membered ring system in which two carbon atoms are replaced by nitrogen.


c) with the proviso that

    • if R2 represents a hydrogen atom;
    • and R3 and R4 form together with their bridging nitrogen atom a pyrrolidine ring, a piperidine ring, a piperazine ring or a morpholine ring;
    • R1 may not represent a hydrogen atom; a methyl group; an unsaturated tert-butyl group; a (C═O)-substituted alkyl-heteroaryl group;


d) with the proviso that

    • if R2 represents a hydrogen atom;
    • and R1 does not represent a benzyl group;
    • and either R3 or R4 represents a hydrogen atom;
    • either R3 or R4 may not represent a substituted alkyl-heteroaryl group; an alkyl-aryl group; a substituted heteroaryl group; an unsubstituted methyl group; a substituted alkyl group; an aryl group; a cyclohexyl group; an alkyl-cycloalkyl group wherein the cycloalkyl group contains at least one heteroatom;


e) with the proviso that

    • if R2 represents a hydrogen atom;
    • and R1 represents an alkyl group;
    • and either R3 or R4 represents a hydrogen atom;
    • either R3 or R4 may not represent a substituted or unsubstituted C1-2 alkyl group; a branched C1-4 alkyl group; a substituted or unsubstituted C3-6 cycloalkyl group in which optionally at least one carbon atom is optionally replaced by N, S or O; a cycloheptyl group;


f) with the proviso that

    • if R2 represents a hydrogen atom;
    • and R1 represents an alkyl group;
    • either R3 or R4 may not represent a cyclohexyl group while the other represents at the same time an alkyl-aryl group; or either R3 or R4 may not represent an alkyl group while the other represents at the same time an alkyl-aryl group;


g) with the proviso that

    • if R2 represents a hydrogen atom;
    • and R1 represents a benzhydryl group;
    • and either R3 or R4 represents a hydrogen atom;
    • either R3 or R4 may not represent a a (C═O)-substituted alkyl-aryl group; a (C═O)-substituted aryl group;


h) with the proviso that

    • if R2 represents a hydrogen atom;
    • and R1 represents benzyl;
    • and either R3 or R4 represents a hydrogen atom;
    • either R3 or R4 may not represent a substituted or unsubstituted C1-2alkyl group; a substituted C3-8 alkyl group; a substituted aryl group; a substituted alkyl-aryl group;
    • or
    • R3 or R4, together with their bridging nitrogen atom may not form a a tetrahydropyrimidine ring; a triazolo pyrimidine ring;


i) with the proviso that

    • if R2 represents a benzyl group;
    • and either R3 or R4 represents a hydrogen atom;
    • either R3 or R4 may not represent a (C═O)-substituted alkyl-aryl group;


j) with the proviso that

    • if R2 represents a C1-3 alkyl group;
    • and either R3 or R4 represents a hydrogen atom
    • either R3 or R4 may not represent an unsubstituted C1-2 alkyl group; a substituted alkyl group; a substituted or unsubstituted aryl group; a substituted heteroaryl group;
    • a (C═O)-substituted alkyl-aryl group.


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a hydrogen atom, an unbranched or branched, saturated, optionally at least mono-substituted C1-6-alkyl radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a (C═O)—R8 group, with R8 representing a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;
    • R3 and R4, equal or different, represent a hydrogen atom; an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted C1-8-aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; with the condition (proviso) that R3 and R4 may not at the same time represent a hydrogen atom;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning as defined above;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a hydrogen atom, an unbranched or branched, saturated, optionally at least mono-substituted C1-6-alkyl radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a linear, substituted or unsubstituted C1-6 alkyl group; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 2) an A-X—B group.
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a m group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning as defined above;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted heteroaryl group; a branched or unbranched, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a linear, substituted or unsubstituted C1-6 alkyl group; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH;
    • R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, unsubstituted C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-cycloalkyl group; an unsubstituted alkyl-aryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;
    • R5, R6, R7 and R7a have the meaning as defined above;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents an unbranched or branched, optionally at least mono-substituted C2-6-alkyl radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated unsubstituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R6 group; a (SO2)—R6 group; a (C═O)—NR7R7a group;
    • R2 represents a hydrogen atom;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a ring system A in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 2) an A-X—B group,
    • wherein
    • A represents a ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group; R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning as defined above;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R6 group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a hydrogen atom;
    • R3 represents a hydrogen atom;
    • R4 represents a saturated or unsaturated, unsubstituted, linear C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing 4 or 5-membered cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, unsubstituted alkyl-cycloalkyl group; an unsubstituted alkyl-aryl group; an unsubstituted C1-6 alkyl-heteroaryl group;
    • R5, R6, R7 and R7a have the meaning as defined above;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a hydrogen atom, an unbranched or branched, saturated C1-6 alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a (C═O)—R8 group, with R8 representing a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;
    • R3 and R4, equal or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted C1-8-aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group; a branched or unbranched, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group; an optionally at least mono-substituted aryl group; an optionally at least mono-substituted heteroaryl group; a branched or unbranched, optionally at least mono-substituted C1-6-alkyl-aryl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted C1-6-alkyl-heteroaryl group; with the condition that R3 and R4 may at the same time not represent a hydrogen atom;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R8 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning as defined above;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a hydrogen atom, an unbranched or branched, saturated C1-6 alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, carboxy, amido, cyano, carbamyl, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated, C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the heteroaryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least mono-substituted benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; a group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a C1-6 alkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 3) an A-X—B—Y—C group,
    • wherein


A represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;

    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning as defined above;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6 alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a C1-6 alkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, unsubstituted C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group with substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN, nitro; an unsubstituted heteroaryl group; an optionally at least mono-substituted C1-6 alkyl-cycloalkyl group; an unsubstituted C1-6 alkyl-aryl group; an unsubstituted C1-6 alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;
    • R5, R6, R7 and R7a have the meaning as defined above;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents an unbranched or branched, optionally at least mono-substituted C1-6-alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R6 group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a hydrogen atom;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a 4 to 18 membered ring system A in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R3 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 2) an A-X—B group,
    • wherein
    • A represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH-R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH-R11 group; or a (C═O)—NR12R12a group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH-R11 group; or a (C═O)—NR12R12a group;
    • R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning as defined above;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; a (SO2)—R6 group; or a (C═O)—NR7R7a group;
    • R2 represents a hydrogen atom;
    • R3 represents a hydrogen atom;
    • R4 represents a saturated or unsaturated, unsubstituted, linear C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing 4 or 5-membered cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, unsubstituted alkyl-cycloalkyl group; an unsubstituted allkyl-aryl group; an unsubstituted C1-6 alkyl-heteroaryl group;
    • R5, R6, R7 and R7a have the meaning as defined above;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a hydrogen atom, an unbranched or branched C1-6 alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group;
    • R2 represents a (C═O)—R8group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group;
    • R3 and R4, equal or different, represent a hydrogen atom, an unbranched or branched C1-8-alkyl group, which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a saturated or unsaturated, optionally at least one heteroatom as ring member containing cycloalkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, CO—OH, CO—O—CH3, O—CH3, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, CO—OH, CO—O—CH3, O—CH3, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, CO—OH, CO—O—CH3, O—CH3, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; with the condition that R3 and R4 may at the same time not represent a hydrogen atom;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated 4 to 18 membered ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R10 group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R6 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R9, R10 and R11 represent a hydrogen atom, an unbranched or branched C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a hydrogen atom, an unbranched or branched C1-6 alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, carboxy, amido, cyano, carbamyl, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated, C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the heteroaryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least mono-substituted benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a group; a (SO2)—R6 group;
    • R2 represents a methyl ,ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated 4 to 18 membered ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R10 group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R9, R10 and R11 represent a hydrogen atom, an unbranched or branched C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group;
    • R2 represents a methyl, ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, unsubstituted C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group with substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN, nitro; an unsubstituted heteroaryl group; a C1-6 alkyl-cycloalkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an unsubstituted C1-6alkyl-aryl group; an unsubstituted C1-6 alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;
    • R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents an unbranched or branched, saturated, optionally at least mono-substituted C1-6-alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxetane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated Ci-6.alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group;
    • R2 represents a hydrogen atom;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a 4 to 18 membered ring system A in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R6 group; a (C═O)—OR16 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • 2) an A-X—B group,
    • wherein
    • A represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated 4 to 6membered ring system, in which at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, or CF3;
    • R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cydooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R9, R10 and R11 represent a hydrogen atom, an unbranched or branched C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group;
    • R2 represents a hydrogen atom;
    • R3 represents a hydrogen atom;
    • R4 represents a saturated or unsaturated, unsubstituted, linear C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing 4 or 5-membered cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, unsubstituted alkyl-cycloalkyl group; an unsubstituted alkyl-aryl group; an unsubstituted C1-6 alkyl-heteroaryl group;


R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R2 represents a(C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group;
    • R3 and R4, identical or different, represent a hydrogen atom; a C3-8 alkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; an optionally at least mono-substituted quinoline group; a phenyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated 4 to 18 membered ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;


Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;

    • C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R2 represents a methyl ,ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a saturated or unsaturated 4 to 18 membered ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • 2) an A-X—B group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR16 group with R10 being a linear or branched C1-6 alkyl group;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R2 represents a methyl ,ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, optionally at least mono-substituted C3-8 aliphatic group with substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN, nitro; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group with substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN, nitro; an unsubstituted heteroaryl group; a saturated or unsaturated, optionally at least mono-substituted C1-6 alkyl-cycloalkyl group; a saturated or unsaturated, unsubstituted C1-6 alkyl-aryl group; a saturated or unsaturated, unsubstituted C1-6 alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R2 represents a hydrogen atom;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a 4 to 18 membered ring system A in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR16 group with R10 being a linear or branched C1-6 alkyl group;
    • 2) an A-X—B group,
    • wherein
    • A represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • 3) an A-X—B—Y—C group,
    • wherein
    • A represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;
    • Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;
    • C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R2 represents a hydrogen atom;
    • R3 represents a hydrogen atom;
    • R4 represents a saturated or unsaturated, unsubstituted, linear C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing 4 or 5-membered cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, unsubstituted alkyl-cycloalkyl group; an unsubstituted C1-6 alkyl-heteroaryl group;


Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a benzyl group or a (SO2)—R6 group with R6 being an aryl group;
    • R2 represents a(C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group;
    • R3 and R4, identical or different, represent a C3-8 alkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; an optionally at least mono-substituted quinoline group; a phenyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN;
    • or
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a ring system A, comprising:









    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • 2) an A-X—B group,

    • wherein

    • A represents a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • X represents a bond, a —NH— group, a —(C═O)— group, a linear optionally substituted C1-2 alkyl chain, —O—, or a —SO2— group;

    • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;

    • 3) an A-X—B—Y—C group,

    • wherein

    • A represents a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • X represents a bond, a —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, or a —SO2— group;

    • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;

    • Y represents a bond, a —NH— group, a linear C1-2-aliphatic group;

    • C represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;





Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a benzyl group or a (SO2)—R6 group with R6 being an aryl group;
    • R2 represents a methyl ,ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a ring system A, comprising:







and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR11 group with R11 being a linear or branched C1-6 alkyl group;

    • 2) an A-X—B group,
    • wherein
    • A represents a ring system comprising:









    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • X represents a bond, a —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, or a —SO2— group;

    • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;

    • 3) an A-X—B—Y—C group,

    • wherein

    • A represents a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • X represents a bond, a —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, or a —SO2— group;

    • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;

    • Y represents a bond, a —NH— group, a linear C1-2 alkyl group;

    • C represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;





Also preferred is a medicament comprising at least one substituted pyrazoline compound of general formula (I) as defined above,


wherein

    • R1 represents a benzyl group or a (SO2)—R6 group with R6 being an aryl group;
    • R2 represents a hydrogen atom;
    • R3 and R4 together with their bridging nitrogen atom form
    • 1) a ring system A, comprising:









    • and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being or branched C1-6 alkyl group;

    • 2) an A-X—B group,

    • wherein

    • A represents a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • X represents a bond, a —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, or a —SO2— group;

    • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;

    • 3) an A-X—B—Y—C group,

    • wherein

    • A represents a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;

    • X represents a bond, a —NH— group, a —(C═O)— group, a linear C1-2 alkyl chain, —O—, or a —SO2— group;

    • B represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; or a ring system comprising:












    • which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6 alkoxy group;

    • Y represents a bond, a —NH— group, a linear C1-2-alkyl group;

    • C represents an aryl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a naphtyl group which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group;





Most particularly preferred is a medicament comprising at least one substituted pyrrolidine compound selected from the group consisting of:

    • [1] (3,4-trans)-1-benzyl-4-(3,4-dihydroisoquinolin-2(1H)-yl)pyrrolidine-3-ol,
    • [2] (3,4-trans)-1-benzyl-4-morpholinopyrrolidine-3-ol,
    • [3] (3,4-trans)-1-benzyl-4-(4-(2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)piperidin-1-yl)pyrrolidine-3-ol,
    • [4] (3,4-trans)-1-benzyl-4-(3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propylamino)pyrrolidine-3-ol,
    • [5] (3,4-trans)-1-benzyl-4-(4-((3,4-dihydroisoquinolin-2(1H)-yl)methyl)piperidin-1-yl)pyrrolidine-3-ol,
    • [6] 1-(4-(6-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-ylamino)phenyl)ethanone,
    • [7] 1-(1-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperidin-4-yl)-1H-benzo[d][1,3]oxazin-2(4H)-one,
    • [8] (3,4-trans)-1-benzyl-4-(2-(4-phenoxyphenylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)pyrrolidine-3-ol,
    • [9] (3,4-trans)-1-benzyl-4-(3-(3,4-dihydroisoquinolin-2(1H)-yl)propylamino)pyrrolidine-3-ol,
    • [10] (3,4-trans)-1-benzyl-4-(4-(4-methoxypyrimidin-2-yl)piperazin-1-yl)pyrroline-3-ol,
    • [11] (3,4-trans)-1-benzyl-4-(2,3,8,8a-tetrahydrocyclopenta[ij]isoquinolin-1(7H)-yl)pyrrolidine-3-ol,
    • [12] tert-butyl-4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxylate,
    • [13] tert-butyl 4-((3,4-trans)-4-hydroxy-1-(phenylsulfonyl)pyrrolidine-3-yl)piperazine-1-carboxylate,
    • [14] (3,4-trans)-4-morpholino-1-(phenylsulfonyl)pyrrolidine-3-ol,
    • [15] (3,4-trans)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-1-(phenylsulfonyl)pyrrolidine-3-ol,
    • [16] (3,4-trans)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-1((S)-1-phenylethyl)pyrrolidine-3-ol,
    • [17] (3,4-trans)-1-benzyl-4-(4-benzylpiperazin-1-yl)pyrrolidine-3-ol,
    • [18] (3,4-trans)-1-benzyl-4-(4-phenylpiperazin-1-yl)pyrrolidine-3-ol,
    • [19] Ethyl 2-(4-(3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazin-1-yl)acetate,
    • [20] (4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazin-1-yl)(phenyl)methanone,
    • [21] Ethyl 4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxilate,
    • [22] tert-butyl 4-((3,4-trans)-1-(4-fluorobenzyl)-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxylate,
    • [23] (3,4-trans)-1-benzyl-4-(4-methylpiperazin-1-yl)pyrrolidine-3-ol,
    • [24] tert-butyl-4-(3,4-trans)-4-acetoxy-1-benzylpyrrolidine-3-yl)piperazine-1-carboxylate,
    • [25] (3,4-trans)-1-benzyl-4-(piperazin-1-yl)pyrrolidine-3-yl acetate,
    • [26] tert-butyl 4-((3,4-trans)-4-acetoxypyrrolidine-3-yl)piperazine-1-carboxylate,
    • [27] trans 1-Benzyl-4-(4-(2-phenyl-phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [28] trans 1-Benzyl-4-(4-(2-phenyl-phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,
    • [29] (3,4-trans)-1-benzyl-4-(phenylamino)pyrrolidin-3-ol,
    • [30] (3,4-trans)-1-benzyl-4-(benzylamino)pyrrolidin-3-ol,
    • [31] (3R,4R)-1-benzyl-4-(octylamino)pyrrolidin-3-ol,
    • [32] (3,4-trans)-1-benzyl-4-(4-methoxybenzylamino)pyrrolidin-3-ol,
    • [33] (3,4-trans)-1-benzyl-4-(butylamino)pyrrolidin-3-ol,
    • [34] (3R,4R)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [35] (3R,4R)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-yl acetate,
    • [36] (3,4-trans)-1-benzyl-4-(butylamino)pyrrolidin-3-ol,
    • [37] (3R,4R)-1-benzyl-4-(4-methoxyphenylamino)pyrrolidin-3-ol,
    • [38] Methyl 4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidin-3-ylamino)benzoate,
    • [39] (3R,4R)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [40] (3R,4R)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [41] (3R,4R)-1-benzyl-4-(4-(2-bromophenylsuffonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [42] (3R,4R)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [43] (3R,4R)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [44] (3R,4R)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [45] (3R,4R)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ylacetate,
    • [46] (3R,4R)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [47] (3R,4R)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,
    • [48] (3R,4R)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [49] (3R,4R)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [50] (3R,4R)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,
    • [51] (3R,4R)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-ol,
    • [52] (3R,4R)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,


optionally in form of a corresponding salt, or a corresponding solvate.


In an embodiment according to the invention the medicament is for the prophylaxis and/or treatment of a sigma receptor-mediated disease or condition.


In an embodiment according to the invention the medicament is for the prophylaxis and/or treatment of Alzheimer's disease (AD).


In an embodiment according to the invention the medicament is for the prophylaxis and/or treatment of one or more disorders selected from the group consisting of diarrhoea, lipoprotein disorders, migraine, obesity, arthritis, hypertension, arrhythmia, ulcer, learning, memory and attention deficits, cognition disorders, neurodegenerative diseases, demyelinating diseases, addiction to drugs and chemical substances including cocaine, amphetamine, ethanol and nicotine; tardive diskinesia, ischemic stroke, epilepsy, stroke, stress, cancer or psychotic conditions, in particular depression, anxiety, psychosis or schizophrenia; inflammation, or autoimmune diseases.


In an embodiment according to the invention the medicament is for the prophylaxis and/or treatment of one or more disorders selected from the group consisting of elevated trigyceride levels, chylomicronemia, dysbetalipoproteinemia, hyperlipoproteinemia, hyperlipidemia, mixed hyperlipidemia, hypercholesterolemia, lipoprotein disorders, hypertriglyceridemia, sporadic hypertriglyceridemia, inherited hypertriglyceridemia and/or dysbetalipoproteinemia.


In another embodiment according to the invention the medicament is for the prophylaxis and/or treatment of one or more disorders selected from the group consisting of pain, preferably neuropathic pain, inflammatory pain or other pain conditions involving allodynia and/or hyperalgesia.


Said medicaments may also comprise any combination of one or more of the substituted pyrrolidine compounds of general formula (I) given above, stereoisomers thereof, physiologically acceptable salts thereof or physiologically acceptable solvates thereof.


Another aspect of the present invention is the use of at least one substituted pyrazoline compound of general formula (I) given above as suitable active substances, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, and optionally one or more pharmaceutically acceptable excipients, for the preparation of a medicament for the modulation of sigma receptors, preferably for the prophylaxis and/or treatment of Alzheimer's disease (AD).


The medicament according to the present invention may be in any form suitable for the application to humans and/or animals, preferably humans including infants, children and adults and can be produced by standard procedures known to those skilled in the art. The composition of the medicament may vary depending on the route of administration.


The medicament of the present invention may for example be administered parentally in combination with conventional injectable liquid carriers, such as water or suitable alcohols. Conventional pharmaceutical excipients for injection, such as stabilizing agents, solubilizing agents, and buffers, may be included in such injectable compositions. These medicaments may for example be injected intramuscularly, intraperitoneally, or intravenously.


Solid oral compositions (which are preferred as are liquid ones) may be prepared by conventional methods of blending, filling or tabletting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are conventional in the art. The tablets may for example be prepared by wet or dry granulation and optionally coated according to the methods well known in normal pharmaceutical practice., in particular with an enteric coating.


The mentioned formulations will be prepared using standard methods such as those described or referred to in the Spanish and US Pharmacopeias and similar reference texts.


Medicaments according to the present invention may also be formulated into orally administrable compositions containing one or more physiologically compatible carriers or excipients, in solid or liquid form. These compositions may contain conventional ingredients such as binding agents, fillers, lubricants, and acceptable wetting agents. The compositions may take any convenient form, such as tablets, pellets, capsules, lozenges, aqueous or oily solutions, suspensions, emulsions, or dry powdered forms suitable for reconstitution with water or other suitable liquid medium before use, for immediate or retarded release.


The liquid oral forms for administration may also contain certain additives such as sweeteners, flavoring, preservatives, and emulsifying agents. Non-aqueous liquid compositions for oral administration may also be formulated, containing edible oils. Such liquid compositions may be conveniently encapsulated in e.g., gelatin capsules in a unit dosage amount.


The compositions of the present invention may also be administered topically or via a suppository.


The daily dosage for humans and animals may vary depending on factors that have their basis in the respective species or other factors, such as age, sex, weight or degree of illness and so forth. The daily dosage for humans may preferably be in the range from 1 to 2000, preferably 1 to 1500, more preferably 1 to 1000 milligrams of active substance to be administered during one or several intakes per day.


Another aspect of the present invention refers to a method for the prophylaxis and/or treatment of a sigma receptor-mediated disease or condition, the method comprising administering to the subject at least one substituted pyrrolidine compound of general formula (I) as described above and optionally at least one further active substance and/or optionally at least one auxiliary substance to the subject.


Another aspect of the present invention refers to a method for the prophylaxis and/or treatment Alzheimer's disease, the method comprising administering to the subject at least one substituted pyrrolidine compound of general formula (I) as described above and optionally at least one further active substance and/or optionally at least one auxiliary substance to the subject.


Another aspect of the present invention refers to a method for the prophylaxis and/or treatment of diarrhoea, lipoprotein disorders, migraine, obesity, elevated trigyceride levels, chylomicronemia, dysbetalipoproteinemia, hyperlipoproteinemia, hyperlipidemia, mixed hyperlipidemia, hypercholesterolemia, lipoprotein disorders, hypertriglyceridemia, sporadic hypertriglyceridemia, inherited hypertriglyceridemia and dysbetalipoproteinemia, arthritis, hypertension, arrhythmia, ulcer, learning, memory and attention deficits, cognition disorders, neurodegenerative diseases, demyelinating diseases, addiction to drugs and chemical substances including cocaine, amphetamine, ethanol and nicotine; tardive diskinesia, ischemic stroke, epilepsy, stroke, stress, cancer or psychotic conditions, in particular depression, anxiety or schizophrenia; inflammation, or autoimmune diseases, the method comprising administering to the subject at least one compound of general formula (I) as described above and optionally at least one further active substance and/or optionally at least one auxiliary substance to the subject.


A preferred embodiment of the present invention refers to a method for the prophylaxis and/or treatment of elevated trigyceride levels, chylomicronemia, dysbetalipoproteinemia, hyperlipoproteinemia, hyperlipidemia, mixed hyperlipidemia, hypercholesterolemia, lipoprotein disorders, hypertriglyceridemia, sporadic hypertriglyceridemia, inherited hypertriglyceridemia and/or dysbetalipoproteinemia.


The present invention is illustrated below with the aid of examples. These illustrations are given solely by way of example and do not limit the general spirit of the present invention.







EXAMPLES

Obtention of Intermediates


Example 0-A
1-Benzyl-3-pyrroline






Was synthesized according to published methods with slight modifications: a) EP0985664, b) Synthetic Communications 13(13), 1117-1123 (1983).


To a solution of cis-1,4-dichloro-2-butene (0.76 g, 5.77 mmol) in anhydrous dichloromethane (4 ml) cooled at 5° C., benzylamine (3.75 g, 34.66 mol) was added dropwise. The mixture was stirred at 5° C. for 10 min and after at r.t. 24 hours. The white solid was filtered and washed with dichloromethane. The filtrated was cooled at 0° C. and HCl 37% (0.6 ml) was added. The resulting white solid was filtered and washed with dichloromethane. The filtrate was concentrated to give an orange oil that was purified by flash chromatography: silica gel, hexane:ethyl acetate (1:1) to afforded the product (0.76 g, 82%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.38-7.21 (m 5H), 5.78 (s, 2H), 3.80 (s, 3H), 3.81 (s, 2H), 3.48 (s, 4H). 13C NMR (75 MHz, CDCl3) δ (ppm) 139.67, 128.69, 128.34, 127.78, 126.96, 60.40, 59.70.


Example 0-B
1-((S)-1-phenylethyl)-3-pyrroline






Was synthesized according to published methods with slight modifications: a) EP0985664, b) Synthetic Communications 34(23), 4421-4430 (2004).


To a solution of 1,4-dimethylsulphonyl-2-butene (0.52 g, 2.86 mmol) in dichloromethane (10 ml), (S)-alpha-methylbenzylamine (1.31 g, 10.87 mmol) was added and the solution was stirred 20 hours at r.t. The solid obtained was filtrated and the filtrate was washed with water (2×30 ml), dried over Na2SO4, filtered and concentrated. The crude was purified by flash chromatography: silica gel, gradient hexane to hexane:ethyl acetate 1:1 to afforded the product (0.45 g, 90%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.42-7.25 (m, 5H), 5.80 (s, 2H), 3.53 (q, J=6.5 Hz, 1H), 3.44 (m, 2H), 3.36 (m, 2H), 1.44 (d, J=6.5 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ (ppm) 145.90, 128.47, 127.67, 127.28, 127.07, 65.30, 58.55, 23.50.


Example 0-C
1-tert-Butoxycarbonyl-3-pyrroline






Was synthesized according to published methods: a) JP11349565. b) Tetrahedron: Asymmetry 12 (2001) 2989-2997. c) Organic & Biomolecular Chemistry 2004, 2 (17), 2418-2420.


To a solution of tert-butyl carbamate (0.55 g, 4.65 mmol) in DMF (5 ml) cooled at 0° C., NaH (0.41 g, 10.23 mmol) was added in portions. The mixture was stirred at 0° C. for 10 min. Cis-1,4-dichloro-2-butene (0.73 g, 5.58 mmol) was added and the mixture was stirred for 15 min at r.t. and then heated at 65° C. for 20 h. Water was added and the solution was extracted with hexane:ethyl acetate (4:1). The organic phase was washed with water and saturated solution of NaCl, dried over Na2SO4, filtered and concentrated to afford pure product (0.40 g, 51%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 5.70 (m 2H), 4.15 (m, 4H), 1.48 (s, 9H).


Example 0-D
1-Phenylsulfonyl-3-pyrroline






Was synthesized according to published methods: JP2000080077.


To a solution of benzenesulfonamide (0.25 g, 1.55 mmol) in DMF (4 ml), NaH (140 mg, 3.51 mmol) was added in portions and the solution was stirred 10 min at r.t. Cis-1,4-dichloro-2-butene (0.22 g, 1.71 mmol) was added and the mixture was stirred for 20 h. at r.t. Water was added and the solution was extracted with hexane:ethyl acetate (4:1). The organic phase was washed with water and saturated solution of NaCl, dried over Na2SO4, filtered and concentrated to afford pure product (0.32 g, quant. yield) as white solid.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.84 (m, 2H), 7.59 (m, 1H), 7.52 (m, 2H).


Example 0-E
1-(-fluorobenzyl)-3-pyrroline






To a solution of cis-1,4-dichloro-2-butene (0.50 g, 3.8 mmol) in anhydrous dichloromethane (4 ml) cooled at 0° C., 4-fluorobenzylamine (2.94 g, 22.8 mol) was added dropwise. The mixture was stirred at 0° C. for 10 min and then at r.t. 24 hours. The white solid was filtered and washed with dichloromethane. The filtrated was cooled at 0° C. and HCl 10% was added until slightly acid pH. The resulting white solid was filtered and washed with dichloromethane. The filtrate was concentrated and the residue was purified by flash chromatography: silica gel, hexane:ethyl acetate (1:1) to afforded the product (353 m g, 52%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.31 (m, 2H), 6.99 (m, 2H), 5.78 (s, 2H), 3.77 (s, 2H), 3.46 (s, 4H). 13C NMR (75 MHz, CDCl3) δ (ppm) 161.91 (d, JCF=243 Hz), 135.41, 130.14 (d, JCF=8 Hz), 127.78 , 115.05 (d, JCF=21 Hz), 59.59, 59.52. MS (ES+) m/z: 178.1 (M+H+).


Example 0-F
1-Benzyl-3,4-epoxypyrroline






Was synthesized according to published methods: EP0985664.


To a solution of 1-benzyl-3-pyrroline (5.0 g, 31.40 mmol) in methanol (20 ml) cooled at 0° C., water was added (5 ml) and H2SO4 96% (2 ml). The solution was stirred 5 min. and 3-chloroperoxybenzoic acid (10.0 g, 40.56 mmol) was added in portions. The suspension was stirred at r.t. for 18 h. Methanol was evaporated and the aquose solution was neutralized with aq. NaOH 10% until pH=7. The suspension was extracted with dichloromethane and the organic phase was washed with water and saturated solution of NaCl, dried over Na2SO4, filtered and concentrated to afford pure product (4.35 g, 80%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.49-7.23 (m, 5H), 3.81 (s, 2H), 3.66 (s, 2H), 3.23 (d, J=12 Hz, 2H), 2.72 (d, J=12 Hz, 2H).


Example 0-G
1-((S)-1-phenylethyl)-3,4-epoxypyrroline






Was synthesized according to published methods with slight modifications: a) EP0985664, b) Synthetic Communications 34 (23), 4421-4430, 2004.


To a solution of 1-((S)-alpha-methylbenzyl)-3-pyrroline (0.10 g, 0.57 mmol) in methanol (0.35 ml) cooled at 0° C., water was added (0.046 ml) and H2SO4 96% (0.038 ml). The solution was stirred 5 min. and 3-chloroperoxybenzoic acid (0.18 g, 0.75 mmol) was added in portions. The suspension was stirred at r.t. for 18 h. Methanol was evaporated and the aquose solution was neutralized with aq. NaOH 10% until pH=7. The suspension was extracted with dichloromethane and the organic phase was washed with water and saturated solution of NaCl, dried over Na2SO4, filtered and concentrated to afford pure product (0.10 g, 91%) as colourless oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.32-7.20 (m, 5H), 3.63 (dd, J1=1.5, J2=3.5 Hz, 1H), 3.54 (dd, J1=1.5, J2=3.5 Hz, 1H), 3.42 (d, J=11 Hz, 1H), 3.40 (q, J=6.5 Hz, 1H), 3.01 (d, J=11 Hz, 1H), 2.47 (dd, J1=1.5, J2=11 Hz, 1H), 2.27 (dd, J1=1.5, J2=11 Hz, 1H), 1.35 (d, J=6.5 Hz, 3H).


Example 0-H
1-(tert-butoxycarbonyl)-3,4-epoxypyrroline






Was synthesized according to published methods: Organic & Biomolecular Chemistry 2004, 2 (17), 2418-2420.


To a solution of 1-tert-butoxycarbonyl-3-pyrroline (0.16 g, 0.94 mmol) in dichloromethane (3 ml), 3-chloroperoxybenzoic acid (0.46 g, 1.89 mmol) was added in portions. The suspension was stirred at r.t. for 20 h. Dichloromethane was evaporated and the resulting white solid was suspended in diethylether and washed with saturated solution of NaHCO3, saturated solution of NaCl, dried over Na2SO4, filtered and concentrated. The crude was purified by flash chromatography: silica gel, hexane:ethyl acetate (2:1), to give the product (65 mg, 28%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 3.78 (d, J=12.7 Hz, 1H), 3.71 (d, J1=12.7 Hz, 1H), 3.63 (m, 2H), 3.30 (dd, J1=1.5 Hz, J2=6.5 Hz, 1H), 3.27 (dd, J1=1.5 Hz, J2=6.5 Hz, 1H), 1.41 (s, 9H).


Example 0-I
1-(phenylsulfonyl)-3,4-epoxypyrroline






To a solution of 1-phenylsulfonyl-3-pyrroline (4.54 g, 21.69 mmol) in dichloromethane (100 ml), 3-chloroperoxybenzoic acid (10.7 g, 43.46 mmol) was added in portions. The suspension was stirred at r.t. for 16 h. Dichloromethane was added and the solution was washed with saturated solution of NaHCO3, saturated solution of NaCl, dried over Na2SO4, filtered and concentrated. The crude was purified by flash chromatography: silica gel, gradient dichloromethane to dichloromethane:ethyl acetate (9:1), to give the product (3.52 g, 72%) as white solid.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.79 (m, 2H), 7.58 (m, 1H), 7.52 (m, 2H), 3.72 (d, J=12.7 Hz, 1H), 3.58 (s, 2H), 3.38 (d, J1=12.7 Hz, 2H).


Example 0-J
1-(4-fluorobenzyl)-3,4-epoxypyrrolin






To a solution of 1-4-fluorobenzyl-3-pyrroline (105 mg, 0.59 mmol) in methanol (0.5 ml) cooled at 0° C., water was added (0.1 ml) and H2SO4 96% (0.040 ml). The solution was stirred 5 min. and 3-chloroperoxybenzoic acid (173 m g, 0.77 mmol) was added in portions. The suspension was stirred at r.t. for 20 h. Methanol was evaporated and the aquose solution was neutralized with aq. NaOH 10% until pH=7. The suspension was extracted with dichloromethane and the organic phase was washed with water and saturated solution of NaCl, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography: silica gel, gradient dichloromethane to dichloromethane:methanol 8% to afford pure product (71 mg, 62%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.26 (m, 2H), 6.98 (m, 2H), 3.67 (s, 2H), 3.62 (s, 2H), 3.16 (d, J=11 Hz, 2H), 2.53 (d, J=11 Hz, 2H). MS (ES+) m/z: 194.1 (M+H+).


Example 1
(3,4-trans)-1-benzyl-4-(3,4-dihydroisoquinolin-2(1H)-yl)pyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (90 mg, 0.51 mmol), 1,2,3,4-tetrahydroisoquinoline (102 mg, 0.77 mmol), LiClO4 (111 mg, 1.02 mmol) and acetonitrile (4 ml). Reaction time: 4 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 5%, afforded the product (76 mg, 48%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.32 (m, 4H), 7.26 (m, 1H), 7.09 (m, 3H), 6.99 (m, 1H), 4.25 (m, 1H), 3.66 (AB system, 2H), 3.59 (AB system, 2H), 3.13 (t, J=8 Hz, 1H), 2.94-2.81 (m, 4H), 2.79 (d, J=10 Hz, 1H), 2.72-2.61 (m, 2H), 2.60 (bs, 1H), 2.28 (t, J=8 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 137.93, 134.14, 128.86, 128.53, 128.24, 127.11, 126.53, 126.17, 125.58, 74.58, 74.07, 62.21, 60.17, 57.26, 54.56, 48.92, 28.75. MS (El+) m/z: 308.1 (M+).


Example 2
(3,4-trans)-1-benzyl-4-morpholinopyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (90 mg, 0.51 mmol), 1,2,3,4-tetrahydroisoquinoline (67 mg, 0.77 mmol), LiClO4 (111 mg, 1.02 mmol) and acetonitrile (4 ml). Reaction time: 4 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 5%, afforded the product (55 mg, 41%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.28 (m, 5H), 4.15 (m, 1H), 3.71 (m, 4H), 3.57 (AB system, 2H), 3.02 (t, J=8 Hz, 1H), 2.77 (d, J=10 Hz, 1H), 2.65 (m, 2H), 2.57 (m, 3H), 2.43 (m, 2H), 2.19 (t, J=8 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 137.73, 128.85, 128.27, 127.19, 74.79, 74.04, 66.65, 62.21, 60.15, 56.92, 52.14. MS (El+) m/z: 262.1 (M+).


Example 3
(3,4-trans)-1-benzyl-4-(4-(2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)piperidin-1-yl)pyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (60 mg, 0.34 mmol), 2-methyl-3-(piperidin-4-yl)-3H-imidazo[4,5-b]pyridine (128 mg, 0.44 mmol), LiClO4(74 mg, 0.68 mmol) and acetonitrile (3 ml). Reaction time: 18 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:2-propanol 30%, afforded the product (30 mg, 22%) as white solid.



1H NMR (400 MHz, CDCl3): δ (ppm) 8.27 (dd, J1=1.5 Hz, J2=4.5 Hz, 1H), 7.89 (dd, J1=1.5 Hz, J2=8 Hz, 1H), 7.28 (m, 5H), 7.14 (dd, J1=4.5 Hz, J2=8 Hz, 1H), 4.42 (m, 1H), 4.25 (m, 1H), 3.59 (AB system, 2H), 3.35 (d, J=10 Hz, 1H), 2.90-2.76 (m, 4H), 2.70 (m, 1H), 2.67 (s, 3H), 2.38-2.14 (m, 3H), 1.83 (m, 2H). 13C NMR (75 MHz, CDCl3): δ (ppm) 152.40, 148.21, 142.54, 137.85, 134.67, 128.87, 128.31, 127.21, 126.08, 117.73, 74.58, 74.33, 62.25, 60.18, 57.24, 53.93, 52.11, 51.16, 29.99, 15.78. MS (El+) m/z: 392.2 (M+H+).


Example 4
(3,4-trans)-1-benzyl-4-(3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propyl amino)pyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (90 mg, 0.51 mmol), 3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propan-1-amine (153 mg, 0.61 mmol), LiClO4 (111 mg, 1.02 mmol) and acetonitrile (6 ml). Reaction time: 5 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:2-propanol 30%, afforded the product (100 mg, 45%) as colourless oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.28 (m, 5H), 6.58 (s, 1H), 6.50 (s, 1H), 3.95 (m, 1H), 3.83 (s, 3H), 3.82 (s, 3H), 3.56 (AB system, 2H), 3.53 (s, 2H), 3.07 (m, 1H), 3.01 (m, 1H), 2.80 (m, 2H), 2.69 (m, 5H), 2.59 (m, 1H), 2.54 (m, 2H), 2.14 (m, 1H), 1.76 (m, 2H). 13C NMR (75 MHz, CDCl3): δ (ppm) 147.49, 147.14, 138.35, 128.70, 128.18, 126.98, 126.08, 111.36, 109.43, 76.6, 66.91, 61.11, 60.10, 59.31, 56.37, 55.86, 55.69, 50.89, 46.84, 28.53, 27.28. MS (EI+) m/z: 426.2 (M+H+).


Example 5
(3,4-trans)-1-benzyl-4-(4-((3,4-dihydrolsoquinolin-2(1H)-yl)methyl)piperidin-1-yl)pyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (260 mg, 1.48 mmol), 2-(piperidin-4-ylmethyl)-1,2,3,4-tetrahydroisoquinoline (444 mg, 1.92 mmol), LiClO4 (317 mg, 2.92 mmol) and acetonitrile (20 ml). Reaction time: 6 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (430 mg, 71%) as yellow foam.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.30 (m, 5H), 7.12 (m, 3H), 7.02 (m, 1H), 4.25 (m, 1H), 3.61 (s, 2H), 3.58 (AB system, 2H), 3.20 (d, J=10Hz, 1H), 3.02 (t, J=8z, 1H), 2.90 (m, 3H), 2.80-2.65 (m, 5H), 2.36 (d, J=7Hz, 2H), 2.29 (t, J=9 Hz, 1H), 2.09 (m, 2H), 1.85 (m, 2H), 1.67 (m, 1H), 1.35 (m, 2H). 13C NMR (75 MHz, CDCl3): δ (ppm) 137.87, 134.84, 134.32, 128.79, 128.52, 128.19, 127.07, 126.42, 125.94, 125.44, 74.77, 74.01, 64.22, 62.03, 60.06, 56.60, 52.52, 51.41, 51.17, 33.21, 30.29, 28.98. MS (EI+) m/z: 406.2 (M+H+).


Example 6
1-(4-(6-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)-5,6,7,8-tetrahydropyrido [4,3-cl]pyrimidin-2-ylamino)phenyl)ethanone






From 1-benzyl-3,4-epoxypyrroline (125 mg, 0.71 mmol), 1-(4-(5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-ylamino)phenyl)ethanone (140 mg, 0.52 mmol), LiClO4 (151 mg, 1.42 mmol) and acetonitrile (5 ml). Reaction time: 6 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (180 mg, 62%) as yellow solid.



1H NMR (400 MHz, CDCl3): δ (ppm) 8.11 (s, 1H), 7.93 (d, J=8.5Hz, 2H), 7.82 (s, 1H), 7.71 (d, J=8.5 Hz, 2H), 7.30 (m, 5H), 4.27 (m, 1H), 3.87 (bs, 1H), 3.62 (AB system, 2H), 3.85 (AB system, 2H), 3.12 (t, J=8 Hz, 1H), 2.92 (m, 4H), 2.81 (m, 1H), 2.72 (m, 2H), 2.55 (s, 3H), 2.33 (t, J=8 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 196.78, 164.54, 158.04, 155.47, 144.53, 137.63, 130.63, 129.84, 128.95, 128.26, 127.28, 119.88, 117.42, 74.68, 73.68, 62.27, 60.12, 57.21, 50.78, 48.10, 31.71, 26.27. MS (EI+) m/z: 444.2 (M+H+).


Example 7
1-(1-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperidin-4-yl)-1H-benzo[d][1,3]oxazin-2(4H)-one






From 1-benzyl-3,4-epoxypyrroline (787 mg, 4.49 mmol), 1-(piperidin-4-yl)-1H-benzo[d][1,3]oxazin-2(4H)-one (820 mg, 3.53 mmol), LiClO4 (947 mg, 8.90 mmol) and acetonitrile (20 ml). Reaction time: 6 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 5%, afforded the product (1.2 g, 83%) as white solid.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.31 (m, 5H), 7.27 (m, 1H), 7.14 (d, J=7.5 Hz, 2H), 7.07 (t, J=7.5 Hz, 1H), 5.06 (s, 2H), 4.20 (m, 1H), 3.96 (m, 1H), 3.59 (AB system, 2H), 3.29 (m, 1H), 3.04 (t, J=8 Hz, 1H), 2.95 (m, 1H), 2.80-2.63 (m, 5H), 2.33 (bs, 1H), 2.25 (t, 8 Hz, 1H), 2.16 (m, 2H), 1.82 (m, 2H).



13C NMR (75 MHz, CDCl3): δ (ppm) 152.97, 138.01, 129.00, 128.89, 128.30, 127.19, 124.70, 123.06, 122.62, 114.31, 74.66, 74.40, 67.02, 62.24, 60.20, 57.24, 56.80, 52.35, 51.41, 28.16. MS (El+) m/z: 408.2 (M+H+).


Example 8
(3,4-trans)-1-benzyl-4-(2-(4-phenoxyphenylamino)-7,8-dihydropyrido[4,3-cl]pyrimidin-6(5H)-yl)pyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (41 mg, 0.23 mmol), N-(4-phenoxyphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine (82 mg, 0.25 mmol), LiClO4(50 mg, 0.46 mmol) and acetonitrile (6 ml). Reaction time: 6 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 5%, afforded the product (78 mg, 68%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 8.07 (s, 1H), 7.56 (d, J=9Hz, 2H), 7.31 (m, 7H), 7.18 (s, 1H), 7.06 (t, J=7.5 Hz, 1H), 6.99 (d, J=9 Hz, 4H), 4.26 (m, 1H), 3.62 (AB system, 2H), 3.56 (AB system, 2H), 3.14 (t, J=8 Hz, 1H), 3.07 (bs, 1H), 3.00-2.79 (m, 5H), 2.72 (m, 2H), 2.31 (t, 8 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 164.47, 158.87, 158.05, 155.71, 151.79, 137.68, 135.54, 129.63, 128.92, 128.41, 127.34, 122.75, 120.72, 119.90, 118.58, 118.12, 74.95, 73.95, 62.30, 60.23, 57.51, 50.83, 48.41, 31.86. MS (EI+) m/z: 494.2 (M+H+).


Example 9
(3,4-trans)-1-benzyl-4-(3-(3,4-dihydroisoquinolin-2(1H)-yl)propylamino)pyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (253 mg, 1.44 mmol), 3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-1-amine (302 mg, 1.58 mmol), LiClO4(307 mg, 2.88 mmol) and acetonitrile (12 ml). Reaction time: 6 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 10%, afforded the product (260 mg, 49%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.27 (m, 5H), 7.10 (s, 3H), 7.00 (m, 1H), 3.94 (m, 1H), 3.61 (s, 2H), 3.55 (AB system, 2H), 3.06 (m, 1H), 3.01 (m, 1H), 2.88 (t, J=6 Hz, 2H), 2.70 (m, 5H), 2.56 (m, 3H), 2.37 (bs, 1H), 2.14 (m, 1H), 1.77 (m, 2H). 13C NMR (75 MHz, CDCl3): δ (ppm) 138.46, 134.72, 134.30, 128.90, 128.65, 128.25, 127.06, 126.59, 126.16, 125.63, 76.7, 67.00, 61.18, 60.23, 59.23, 56.63, 56.27, 50.89, 46.99, 29.14, 27.25. MS (EI+) m/z: 366.2 (M+H+).


Example 10
(3,4-trans)-1-benzyl-4-(4-(4-methoxypyrimidin-2-yl)piperazin-1-yl)pyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (284 mg, 1.62 mmol), 4-methoxy-2-(piperazin-1-yl)pyrimidine (346 mg, 1.78 mmol), LiClO4 (345 mg, 3.24 mmol) and acetonitrile (18 ml). Reaction time: 6 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (377 mg, 63%) as white solid.



1H NMR (400 MHz, CDCl3): δ (ppm) 8.04 (d, J=5.5 Hz, 1H), 7.31 (m, 5H), 5.98 (d, J=5.5 Hz, 1H), 4.22 (m, 1H), 3.88 (s, 3H), 3.81 (t, J=4.5 Hz, 4H), 3.59 (AB system, 2H), 3.06 (t, J=8 Hz, 1H), 2.97 (bs, 1H), 2.78 (m, 1H), 2.72 (m, 1H), 2.65 (m, 3H), 2.48 (m, 2H), 2.27 (t, J=8 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 169.87, 161.64, 157.84, 137.93, 128.91, 128.31, 127.28, 96.67, 74.79, 74.55, 62.32, 60.23, 57.34, 52.91, 51.68, 43.51. MS (EI+) m/z: 370.2 (M+H+).


Example 11
(3,4-trans)-1-benzyl-4-(2,3,8,8a-tetrahydrocyclopenta[ij]isoquinolin-1(7H)-yl)pyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (85 mg, 0.48 mmol), 1,2,3,7,8,8a-hexahydrocyclopenta[ij]isoquinoline (85 mg, 0.53 mmol), LiClO4 (103 mg, 0.97 mmol) and acetonitrile (6 ml). Reaction time: 6 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (87 mg, 54%) as brown oil (mixture of two diastereomers).



1H NMR (400 MHz, CDCl3): δ (ppm) 7.31 (m, 10H), 7.08 (m, 2H), 7.00 (m, 2H), 6.91 (m, 2H), 4.42 (m, 1H), 4.36 (m, 1H), 3.78 (m, 1H), 3.61 (AB system, 2H), 3.59 (AB system, 2H), 3.58 (m, 1H), 3.36 (m, 3H), 3.19 (m, 1H), 3.04 (m, 3H), 2.97-2.73 (m, 2.72-2.44 (m, 9H), 1.79 (m, 2H). 13C NMR (75 MHz, CDCl3): δ (ppm) 141.91, 141.76, 141.74, 141.64, 138.38, 137.65, 131.79, 131.62, 128.94, 128.74, 128.36, 128.35, 127.58, 127.38, 127.25, 127.14, 124.68, 124.67, 121.77, 121.65, 73.97, 70.68, 70.11, 69.93, 65.93, 65.48, 62.25, 60.86, 60.35, 60.10, 57.12, 51.17, 48.07, 46.99, 35.40, 34.77, 30.46, 30.39, 27.80, 27.70. MS (EI+) m/z: 335.2 (M+H+).


Example 12
tert-butyl-4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxylate






From 1-benzyl-3,4-epoxypyrroline (90 mg, 0.51 mmol), tert-butyl-1-piperazine carboxylate (124 mg, 0.66 mmol), LiClO4 (109 mg, 1.02 mmol) and acetonitrile (5 ml). Reaction time: 5 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (115 mg, 62%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.30 (m, 5H), 4.14 (m, 1H), 3.56 (AB system, 2H), 3.42 (m, 4H), 3.00 (t, J=8z, 1H), 2.89 (bs, 1H), 2.73 (m, 1H), 2.68 (m, 1H), 2.63 (m, 1H), 2.51 (m, 2H), 2.36 (m, 2H), 2.20 (t, J=8 Hz, 1H), 1.46 (s, 9H). 13C NMR (75 MHz, CDCl3): δ (ppm) 154.54, 137.75, 128.78, 128.17, 127.07, 79.56, 74.24, 74.09, 62.13, 60.11, 56.92, 51.28, 43.25, 28.28. MS (EI+) m/z: 362.2 (M+H+).


Example 13
tert-butyl 4-((3,4-trans)-4-hydroxy-1-(phenylsulfonyl)pyrrolldine-3-yl)piperazine-1-carboxylate






From 1-phenylsulfonyI-3,4-epoxypyrroline (100 mg, 0.44 mmol), tent-butyl-1-piperazine carboxylate (107 mg, 0.57 mmol), LiClO4 (94 mg, 0.88 mmol) and acetonitrile (6 ml). Reaction time: 5 hours. Purification: silica gel, gradient hexane:ethyl acetate 1:1 to 1:3, afforded the product (84 mg, 46%) as colourless oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.77 (m, 2H), 7.60 (m, 1H), 7.52 (m, 2H), 4.18 (m, 1H), 3.45 (m, 2H), 3.31 (t, J=5 Hz, 4H), 3.09 (dd, J1=5 Hz, J2=10 Hz, 1H), 3.00 (dd, J1=7 Hz, J2=10 Hz, 1H), 2.76 (m, 1H), 2.46 (m, 2H), 2.32 (m, 2H), 1.41 (s, 3H), 13C NMR (75 MHz, CDCl3): δ (ppm) 154.66, 135.39, 133.11, 129.23, 127.73, 80.01, 72.09, 71.06, 54.31, 50.63, 48.91, 43.05, 28.41. MS (EI+) m/z: 412.2 (M+H+).


Example 14
(3,4-trans)-4-morpholino-1-(phenylsulfonyl)pyrrolidine-3-ol






From 1-phenylsulfonyl-3,4-epoxypyrroline (40 mg, 0.17 mmol), morpholine (20 mg, 0.23 mmol), LiClO4 (38 mg, 0.35 mmol) and acetonitrile (4 ml). Reaction time: 5 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 5%, afforded the product (26 mg, 47%) as colourless oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.82 (d, J=7.5 Hz, 2H), 7.63 (t, J=7.5 Hz, 1H), 7.55 (t, J=7.5 Hz, 2H), 4.22 (m, 1H), 3.63 (t, J=4 Hz, 4H), 3.50 (m, 2H), 3.16 (dd, J1=4.5 Hz, J2=10 Hz, 1H), 3.06 (dd, J1=7.3 Hz, J2=10 Hz, 1H), 2.76 (m, 1H), 2.54 (m, 2H), 2.41 (m, 2H), 2.25 (bs, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 135.73, 133.08, 129.24, 127.87, 72.24, 71.55, 66.73, 54.35, 51.40, 48.65. MS (EI+) m/z: 313.1 (M+H+).


Example 15
(3,4-trans)-4-(3,4-dihydroisoquinolin-2(1H)-yl-1-(phenylsulfonyl)pyrrolidine-3-ol






From 1-phenylsulfonyl-3,4-epoxypyrroline (100 mg, 0.44 mmol), 1,2,3,4-tetrahydroisoquinoline (77 mg, 0.57 mmol), LiClO4(94 mg, 0.88 mmol) and acetonitrile (6 ml). Reaction time: 5 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (115 mg, 72%) as light brown oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.79 (d, J=7.5 Hz, 2H), 7.58 (t, J=7.5 Hz, 1H), 7.51 (t, J=7.5 Hz, 2H), 7.09 (m, 2H), 7.03 (m, 1H), 6.95 (m, 1H), 4.21 (m, 1H), 3.61 (AB system, 2H), 3.53 (dd, J1=7.5 Hz, J2=10 Hz, 1H), 3.40 (dd, J1=7 Hz, J2=10 Hz, 1H), 3.08 (m, 2H), 2.88 (m, 1H), 2.78 (m, 3H), 2.62 (m, H). 13C NMR (75 MHz, CDCl3): δ (ppm) 135.32, 133.82, 133.08, 129.20, 128.68, 127.78, 126.65, 126.48, 125.84, 72.30, 70.84, 54.32, 53.77, 48.88, 48.22, 28.83. MS (EI+) m/z: 359.1 (M+H+).


Example 16
(3,4-trans)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-1((S)-1-phenylethyl)pyrrolidine-3-ol






From 1-((S)-1-phenylethyl)-3,4-epoxypyrroline (100 mg, 0.52 mmol), 1,2,3,4-tetrahydroisoquinoline (110 mg, 0.79 mmol), LiClO4 (114 mg, 1.05 mmol) and acetonitrile (5 ml). Reaction time: 4 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 5%, afforded the product (90 mg, 53%) as white solid (mixture of two diastereomers).



1H NMR (400 MHz, CDCl3): δ (ppm) 7.33 (m, 8H), 7.26 (m, 2H), 7.10 (m, 6H), 7.01 (m, 1H), 6.97 (m, 1H), 4.26 (m, 1H), 4.22 (m, 1H), 3.70 (AB system, 2H), 3.62 (AB system, 2H), 3.22 (m, 3H), 2.99 (m, 2H), 2.90 (m, 6H), 2.75 (m, 3H), 2.61 (m, 3H), 2.51 (m, 1H), 2.31 (t, J=8 Hz, 1H), 2.18 (t, J=8 Hz, 1H), 1.41 (d, J=6.5 Hz, 3H), 1.37 (d, J=6.5 Hz, 3H), 13C NMR (75 MHz, CDCl3): δ (ppm) 144.04, 143.77, 134.12, 134.11, 134.00, 133.95, 128.57, 128.53, 128.42, 128.39, 127.19, 127.15, 126.57, 126.55, 126.24, 126.20, 125.66, 125.61, 74.63, 74.17, 73.78, 73.65, 65.41, 65.26, 60.97, 60.75, 56.48, 55.64, 54.65, 54.49, 49.08, 48.85, 28.80, 22.22, 22.04. MS (EI+) m/z: 322.2 (M+).


Example 17
(3,4-trans)-1-benzyl-4-(4-benzylpiperazin-1-yl)pyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (103 mg, 0.59 mmol), 1-benzylpiperazine (128 mg, 0.70 mmol), LiClO4 (125 mg, 1.18 mmol) and acetonitrile (5 ml). Reaction time: 3 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (107 mg, 52%) as brown solid. M.p. 102-103° C.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.30 (m, 8H), 7.25 (m, 2H), 4.16 (m, 1H), 3.56 (AB system, 2H), 3.51 (s, 2H), 3.03 (t, J=8z, 1H), 2.76 (d, J=10 Hz, 1H), 2.69 (td, J1=3 Hz, J2=8 Hz, 1H), 2.62 (dd, J,=6 Hz, J2=10 Hz, 2H), 2.48 (bs, 8H), 2.19 (t, J=8 Hz, 1H), 13C NMR (75 MHz, CDCl3): δ (ppm) 137.91, 137.74, 129.11, 128.82, 128.20, 128.10, 127.07, 126.96, 74.55, 74.18, 62.90, 62.27, 60.19, 57.21, 52.66, 51.53. MS (EI+) m/z: 352.2 (M+H+).


Example 18
(3,4-trans)-1-benzyl-4-(4-phenylpiperazin-1-yl)pyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (106 mg, 0.60 mmol), 1-phenylpiperazine (119 mg, 0.72 mmol), LiClO4 (129 mg, 1.21 mmol) and acetonitrile (5 ml). Reaction time: 3 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (74 mg, 36%) as brown solid. M.p. 120-123° C.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.32 (m, 4H), 7.27 (m, 3H), 6.92 (m, 2H), 6.85 (m, 1H), 4.21 (m, 1H), 3.59 (AB system, 2H), 3.20 (t, J=5z, 4H), 3.08 (t, J=8 Hz, 1H), 2.80 (m, 1H), 2.74 (m, 3H), 2.68-2.56 (m, 3H), 2.22 (t, J=8 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 151.38, 138.24, 129.15, 128.84, 128.34, 127.21, 119.82, 116.02, 74.93, 74.79, 62.45, 60.19, 57.54, 51.79, 48.97. MS (EI+) m/z: 338.2 (M+H+).


Example 19
Ethyl 2-(4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazin-1-yl)acetate






From 1-benzyl-3,4-epoxypyrroline (113 mg, 0.64 mmol), 1-ethylpyperazinoacetate (140 mg, 0.77 mmol), LiC104 (140 mg, 1.28 mmol) and acetonitrile (5 ml). Reaction time: 4 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (84 mg, 37%) as brown oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.30 (m, 5H), 4.18 (q, J=7 Hz, 2H), 4.16 (m, 1H), 3.57 (AB system, 2H), 3.19 (s, 2H), 3.02 (t, J=8z, 4H), 2.76 (d, J=10 Hz, 1H), 2.70 (td, J1=3 Hz, J2=7.5 Hz, 1H), 2.62 (m, 6H), 2.51 (m, 4H), 2.19 (t, J=8 Hz, 1H), 1.26 (t, J=7 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ (ppm) 138.06, 128.85, 128.35, 127.19, 74.76, 74.55, 62.32, 60.89, 60.18, 59.45, 57.31, 52.85, 51.40, 14.24. MS (EI+) m/z: 348.2 (M+H+).


Example 20
(4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazin-1-yl)(phenyl)methanone






From 1-benzyl-3,4-epoxypyrroline (253 mg, 1.44 mmol), 1-benzoylpiperazine (330 mg, 1.73 mmol), LiClO4 (308 mg, 2.89 mmol) and acetonitrile (10 ml). Reaction time: 5 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (317 mg, 60%) as brown solid. M.p. 130-134° C.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.38 (m, 5H), 7.30 (m, 5H), 4.14 (m, 1H), 3.84 (bs, 1H), 3.71 (bs, 1H), 3.56 (AB system, 2H), 3.42 (bs, 2H), 3.00 (t, J=8 Hz, 1H), 2.71 (bs, 1H), 2.66-2.54 (m, 4H), 2.33 (m, 1H), 2.19 (t, J=8 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 170.29, 138.00, 135.60, 129.72, 128.82, 128.47, 128.35, 127.24, 127.06, 74.47, 74.45, 62.27, 60.12, 57.16, 47.50, 42.00. MS (EI+) m/z: 366.2 (M+H+).


Example 21
Ethyl 4((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxilate






From 1-benzyl-3,4-epoxypyrroline (122 mg, 0.69 mmol), ethyl-1-piperazinecarboxilate (133 mg, 0.83 mmol), LiC104 (151 mg, 1.39 mmol) and acetonitrile (5 ml). Reaction time: 4 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (90 mg, 39%) as brown oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.30 (m, 5H), 4.14 (m, 1H), 4.12 (q, J=7 Hz, 2H), 3.56 (AB system, 2H), 3.46 (m, 4H), 3.00 (t, J=8 Hz, 1H), 2.75 (m, 1H), 2.67 (td, J1=3 Hz, J2=8 Hz, 1H), 2.62 (m, 1H), 2.52 (m, 2H), 2.36 (m, 2H), 2.18 (t, J=8 Hz, 1H), 1.24 (t, J=7 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ (ppm) 137.99, 128.90, 128.41, 127.28, 74.59, 74.55, 62.35, 61.42, 60.20, 57.35, 51.41, 43.45, 14.65. MS (EI+) m/z: 334.2 (M+H+).


Example 22
tert-butyl 4-((3,4-trans)-1-(4-fluorobenzyl)-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxylate






From 4-fluoro-1-benzyl-3,4-epoxypyrroline (55 mg, 0.28 mmol), tent-butyl-1-piperazinecarboxilate (69 mg, 0.37 mmol), LiClO4 (61 mg, 0.57 mmol) and acetonitrile (3 ml). Reaction time: 8 hours. Purification by crystallization of dichloromethane:hexane afforded the product (58 mg, 53%) as white solid.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.25 (m, 2H), 6.99 (m, 2H), 4.16 (m, 1H), 3.52 (AB system, 2H), 3.42 (m, 4H), 2.99 (t, J=8 Hz, 1H), 2.73 (m, 1H), 2.66 (td, J1=3 Hz, J2=8 Hz, 1H), 2.60 (m, 1H), 2.52 (m, 2H), 2.36 (m, 2H), 2.17 (t, J=8 Hz, 1H), 1.45 (s, 9H). 13C NMR (75 MHz, CDCl3): δ (ppm) 162.40 (d, JCF=244 Hz), 154.66, 133.95, 130.24 (d, JCF=8 Hz), 115.10 (d, JCF=21 Hz), 79.69, 74.69, 74.59, 64.64, 62.19, 59.33, 57.29, 51.48, 44.02, 28.37. MS (EI+) m/z: 380.2 (M+H+).


Example 23
(3,4-trans)-1-benzyl-4-(4-methylpiperazin-1-yl)pyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (116 mg, 0.66 mmol), 1-methylpiperazine (80 mg, 0.79 mmol), LiClO4 (141 mg, 1.33 mmol) and acetonitrile (5 ml). Reaction time: 4 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (103 mg, 56%) as brown oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.30 (m, 5H), 4.16 (m, 1H), 3.57 (AB system, 2H), 3.04 (t, J=8 Hz, 1H), 2.78 (m, 1H), 2.67 (td, J1=3 Hz, J2=8 Hz, 1H), 2.61 (m, 1H), 2.46 (bs, 8H), 2.27 (s, 3H), 2.17 (t, J=8 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 137.74, 128.83, 128.30, 127.13, 74.96, 74.74, 62.45, 60.17, 57.61, 54.95, 51.72, 46.01. MS (EI+) m/z: 276.2


Example 24
tert-butyl-4-(3,4-trans)-4-acetoxy-1-benzylpyrrolidine-3-yl)piperazine-1-carboxylate






To a solution of tert-butyl-4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxylate (5.07 g, 14.02 mmol), 4-dimethylaminopyridine (171 mg, 1.40 mmol) and N,N-diisopropylethylamine (5.43 g, 42 mmol) in dichloromethane (200 ml) cooled at 0° C., was added acetyl chloride (1.68 g, 21.03 mmol). The resulting mixture was stirred for 1.5 hours raising the temperature slowly from 0° C. to r.t. Additional dichloromethane was added and the solution was washed with water and saturated solution of NaCl, dried over NaSO4, filtered and concentrated. Purification by flash chromatography: silica gel, gradient dichloromethane to dichloromethane:methanol 5%, afforded the product (5.4 g, 95%) as light brown oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.31 (m, 5H), 5.12 (m, 1H), 3.57 (AB system, 2H), 3.41 (bs, 4H), 3.05 (t, J=8 Hz, 1H), 2.97 (td, J1=3 Hz, J2=8 Hz, 1H), 2.74 (m, 2H), 2.43 (m, 2H), 2.34 (m, 2H), 2.25 (t, J=8 Hz, 1H), 2.04 (s, 3H), 1.44 (s, 9H). MS (EI+) m/z: 404.2 (M+H+).


Example 25
(3,4-trans)-1-benzyl-4-(piperazin-1-yl)pyrrolidine-3-yl acetate






To a solution of tert-butyl-4-(3,4-trans)-4-acetoxy-1-benzylpyrrolidine-3-yl)piperazine-1-carboxylate (2.5 g, 6.19 mmol) in dioxane (18 ml) was added a solution of HCl 4.0M in dioxane (30 ml, 120 mmol) and the mixture was stirred at r.t. for 5 hours. The suspension obtained was concentrated to dryness and the residue was triturated with dichloromthane. The yellow solid obtained was filtered to afforded the product (2.3 g, 93%) as tri-hydrochloride.



1H NMR (400 MHz, CD3OD): δ (ppm) 7.67 (m, 2H), 7.53 (m, 3H), 5.70 (m, 1H), 4.60 (AB system, 2H), 4.13 (m, 1H), 4.05 (m, 2H), 3.84 (m, 1H), 3.63 (m, 1H), 3.56 (m, 6H), 3.42 (m, 2H), 2.15 (s, 3H). 13C NMR (75 MHz, CD3OD): δ (ppm) 171.40, 132.07, 131.43, 130.84, 130.51, 72.38, 68.34, 60.14, 53.73, 43.28, 20.77. MS (EI+) m/z: 304.1 (M+H+).


Example 26
tert-butyl 4-((3,4trans)-4-acetoxypyrrolidine-3-yl)piperazine-1-carboxylate






A solution of tert-butyl-4-(3,4-trans)-4-acetoxy-1-benzylpyrrolidine-3-yl)piperazine-1-carboxylate (2.9 g, 7.18 mmol) in methanol (110 ml) was purgued with argon, and Pd/C 10% was added (1.2 g). The mixture was purgued again with argon and after with hydrogen. The mixture was stirred at r.t. under hydrogen atmosphere for 24 hours. The suspension was purgued with argon, filtered over celite and washed with dichloromethane. The filtrate was concentrated to dryness to afforded the product (2.1 g, 93%) as brown oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 5.18 (m, 1H), 3.42 (m, 4H), 3.30 (m, 1H), 3.24 (m, 1H), 3.00 (m, 1H), 2.85 (m, 2H), 2.64 (bs, 1H), 2.50 (m, 2H), 2.42 (m, 2H), 2.06 (s, 3H), 1.45 (s, 9H). 13C NMR (75 MHz, CDCl3): δ (ppm) 170.35, 154.56, 79.67, 77.55, 72.10, 53.34, 51.43, 50.29, 43.31, 28.37, 21.13.


Synthesis of Piperazine Sulfonamides


A) trans 1-Benzyl-4-(4-(aryl sulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate (dihydrochloride)






trans-1-Benzyl-4-(piperazin-1-yl)pyrrolidin-3-yl acetate trihydrochloride (0.25 mmol, 1 eq.), arylsulfonyl chloride (0.28 mmol, 1.1 eq) and N,N′-diisopropylethylamine (1.5 mmol, 6 eq)) are dissolved in CH2Cl2 (10 mL) and the mixture was stirred overnight at room temperature. The resulting solution was washed with water (3×10 mL), dried over Na2SO4 and evaporated to dryness. The base was crystallized in ethyl acetate (1-2 ml) or was crystallized as a hydrochloride with a mixture of ethyl acetate and a 2.8 M solution of hydrogen chloride in ethanol. Once crystallized, the product was collected by filtration, and vacuum dried to give a white solid (yield: 70-80%).


Example 27
trans 1-Benzyl-4-(4-(2-phenyl-phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate







1H NMR (300 MHz, DMSO-D6) δ ppm 1.98 (s, 3H) 2.13 (m, 6H) 2.57-2.72 (m, 6H) 2.81 (m, 1H) 3.48 (m, 2H) 4.81 (m, 1H) 7.26 (m, 5H) 7.37 (m, 6H) 7.61 (t, J=7.62 Hz, 1H) 7.71 (t, J=7.47 Hz, 1H) 7.99 (d, J=7.76 Hz, 1H).


MS (APCl (M+H)+): 520


B) trans-1-Benzyl-4-(4-(arylsulfonyl)piperazin-1-yl)pyrroliclin-3-ol






trans-1-Benzyl-4-(4-(arylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate (0.24 mmol, 1 eq.) was suspended in 10% aq. NaOH (24 mmol, 100 eq.) and the mixture was heated at reflux overnight. The product was extracted with ethyl acetate (3×10 ml), washed with water and brine and dried over Na2SO4. After the evaporation of the solvent, the oil obtained was treated with 2.8 M of hydrogen chloride in ethanol, crystallized, collected by filtration and vacuum dried to give a white solid identified as the corresponding pyrrolidin-3-ol (yield: 60-80%).


The hydrolysis of the acetate group has been improved by the use of potassium carbonate in a mixture of methanol and water:


trans-1-Benzyl-4-(4-(aryllsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate (6.10 mmol) was dissolved in methanol (130 ml). K2CO3 (8.53 g, 61 mmol) dissolved in water (65 ml) was added and the mixture was heated at 40° C. for 1.5 h. Me0H was concentrated and water (30 ml) was added. The product was extracted with ethyl acetate (3×60 ml), dried over Na2SO4 and filtered. After the evaporation of the solvent, the oil obtained was dissolved in acetone and and treated with 2.8 M of hydrogen chloride in ethanol, crystallized, collected by filtration and vacuum dried to give a white solid identified as the corresponding pyrrolidin-3-ol (80-90% yield). The solid can also be crystallized as a base.


Example 28
trans 1-Benzyl-4-(4-(2-phenyl-phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride







1H NMR (400 MHz, METHANOL-d4) δ ppm 3.08 (m., 2H) 3.21 (m, 2H) 3.54 (m, 2H) 3.54 (m, 4H) 3.65 (m, 2H) 3.86 (m, 1H) 4.46 (d, J=4.30 Hz, 2H) 4.75 (m, 1H), 7.48-7.56 (m, 6H) 7.65 (m, 2H) 8.07 (d, J=7.42 Hz, 1H).


MS (APCl (M+H)+): 478


Example 29
(3,4-trans)-1-benzyl-4-(phenylamino)pyrrolidin-3-ol






From 1-benzyl-3,4-epoxypyrroline (168 mg, 0.95 mmol), aniline (135 mg, 1.43 mmol) and LiC104 (204 mg, 1.91 mmol), no solvent was employed. Reaction time: 24 hours. Purification: silica gel, gradient dichloromethane to dichloromethane:methanol 10%, afforded the product (77 mg, 30%) as yellow solid


1H NMR (400 MHz, CDC13): δ (ppm) 7.31 (m, 5H), 7.18 (t, J=7.5 Hz, 2H), 6.72 (t, J=7.5 Hz, 1H), 6.66 (t, J=7.5 Hz, 2H), 4.06 (m, 1H), 3.79 (m, 2H), 3.67 (AB system, 2H), 3.25 (m, 1H), 2.83 (m, 1H), 2.63 (m, 1H), 2.28 (m, 1H). 13C NMR (75 MHz, CDCl3): 3 (ppm) 147.05, 138.04, 129.37, 128.88, 128.49, 127.32, 117.87, 113.54, 76.65, 61.80, 61.20, 59.88, 59.48. MS (Er) m/z: 269.1 (M+H+).


Example 30
(3,4-trans)-1-benzyl-4-(benzylamino)pyrrolidin-3-ol






From 1-benzyl-3,4-epoxypyrroline (108 mg, 0.61 mmol), benzylamine (100 mg, 0.92 mmol), LiC104 (131 mg, 1.23 mmol) and acetonitrile (5 ml). Reaction time: 6 hours. Purification: silica gel, gradient dichloromethane to dichloromethane:methanol 10%, afforded the product (85 mg, 49%) as yellow solid.


1H NMR (400 MHz, CDC13): δ (ppm) 7.30 (m, 10H), 4.02 (m, 1H), 3.76 (s, 2H), 3.60 (AB system, 2H), 3.15 (td, J1=2.5 Hz, Jz=7 Hz, 11-1), 3.08 (m, 1H), 2.74 (m, 1H), 2.65 (m, 1H), 2.27 (bs, 2H), 2.18 (m, 1H). 13C NMR (75 MHz, CDCl3): S (ppm) 139.76, 138.20, 128.87, 128.52, 128.29, 127.19, 77.06, 66.40, 61.12, 60.12, 59.41, 52.41. MS (EI+) m/z: 283.2 (M+H+).


Example 31
(3R,4R)-1-benzyl-4-(octylamino)pyrrolidin-3-ol






From 1-benzyl-3,4-epoxypyrroline (100 mg, 0.57 mmol), octylamine (112 mg, 0.85 mmol), LiC104 (121 mg, 1.14 mmol) and acetonitrile (5 ml). Reaction time: 7 hours. Purification: silica gel, gradient dichloromethane to dichloromethane:methanol 10%, afforded the product (100 mg, 57%) as yellow solid.


1H NMR (400 MHz, CDC13): δ (ppm) 7.31 (m, 5H), 4.04 (m, 1H), 3.60 (AB system, 2H), 3.11 (td, J,=2.5 Hz, JZ=7 Hz, 1H), 3.03 (m, IH), 2.97 (bs, 2H), 2.76 (m, 1H), 2.60 (m, 3H), 2.22 (m, 1H), 1.48 (m, 2H), 1.26 (m, 12H), 0.87 (t, J=7 Hz, 3H). 3C NMR (75 MHz, CDC13): 8 (ppm) 138.23, 128.82, 128.27, 127.10, 76.61, 67.05, 60.96, 60.11, 58.93, 48.19, 31.82, 29.83, 29.41, 29.20, 27.30, 22.66, 14.10.


Example 32
(3,4-trans)-1-benzyl-4-(4-methoxybenzylamino)pyrrolidin-3-ol






From 1-benzyl-3,4-epoxypyrroline (304 mg, 1.73 mmol), 4-methoxybenzylamine (285 mg, 2.08 mmol), LiC104 (369 mg, 3.47 mmol) and acetonitrile (15 ml). Reaction time: 10 hours. Purifcation: silica gel, gradient dichloromethane to dichloromethane:methanol 111 NMR (400 MHz, CDC13): δ (ppm) 7.30 (m, 5H), 7.21 (d AB, 2H), 6.83 (d AB, 2H), 4.03 (m, 1H), 3.77 (s, 3H), 3.78 (s, 2H), 3.61 (AB system, 2H), 3.16 (td, J1=2.5 Hz, Jz=7 Hz, 1H), 3.07 (m, 1H), 2.76 (m, 3H), 2.66 (m, 1H), 2.22 (m, 1H). 13C NMR (75 MHz, CDC13): 8 (ppm) 158.82, 137.95, 131.48, 129.49, 128.86, 128.29, 127.17, 113.88, 76.77, 66.17, 60.93, 60.03, 59.04, 55.26, 51.63.


Example 33
(3,4-trans)-1-benzyl-4-(butylamino)pyrrolidin-3-ol






From 1-benzyl-3,4-epoxypyrroline (307 mg, 1.75 mmol), butylamine (154 mg, 2.10 mmol), LiC104 (372 mg, 3.50 mmol) and acetonitrile (15 ml). Reaction time: 4 hours. Purification: silica gel, gradient dichloromethane to dichloromethane:methanol 10%, afforded the product (76 mg, 17%) as yellow solid.


1H NMR (400 MHz, CDC13): δ (ppm) 7.31 (m, 5H), 3.98 (m, 1H), 3.59 (AB system, 2H), 3.08 (td, J1=2.5 Hz, Jz=7 Hz, 1H), 3.02 (m, 1H), 2.74 (m, 1H), 2.58 (m, 4H), 2.18 (m, 1H), 1.44 (m, 2H), 1.31 (m, 2H), 0.89 (t, J=7 Hz, 3H). 3C NMR (75 MHz, CDC13): 8 (ppm) 138.36, 128.88, 128.28, 127.11, 76.88, 67.11, 61.09, 60.11, 59.29, 48.05, 32.20, 20.45, 13.93.


Example 34
(3R,4R)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate






1H NMR (400 MHz, METHANOL-d4) δ ppm 2.08 (s, 3H) 2.41 (s, 3H) 2.55 (s, 3H) 2.89-2.98 (m, 2H) 3.03 (br. s., 2H) 3.33 (m, 4H) 3.53 (d, J=13.29 Hz, 2H) 3.64-3.70 (m, 1H) 3.82-3.90 (m, 2H) 4.46 (d, J=5.47 Hz, 2H) 5.51-5.55 (m, 1H) 7.46 (s, 1H), 7.48-7.56 (m, 5H) 7.79 (s, 1H)


MS (APCl (M+H)+): 506


Example 35
(3R,4R)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-yl acetate






1H NMR (400 MHz, METHANOL-d4) δ ppm 2.09 (s, 3H) 2.46 (s, 3H) 3.13 (d, J=7.03 Hz, 2H) 3.22 (br. s., 6H) 3.54 (d, J=12.90 Hz, 1H) 3.67 (br. s., 1H) 3.90 (dd, J=12.90, 7.03 Hz, 3H) 4.47 (d, J=4.30 Hz, 2H) 5.58 (m, 1H) 7.44-7.51 (m, 5H) 7.54 (m, 2H), 7.68 (d, J=7.42 Hz, 2H)


MS (APCl (M+H)+): 458


Example 36
(3,4-trans)-1-benzyl-4-(butylamino)pyrrolidin-3-ol






From 1-benzyl-3,4-epoxypyrroline (90 mg, 0.51 mmol), piperidine (65 mg, 0.77 mmol), LiC104 (111 mg, 1.02 mmol) and acetonitrile (4 ml). Reaction time: 4 hours. Purification: silica gel, gradient dichloromethane to dichloromethane:methanol 5%, afforded the product (64 mg, 48%) as yellow oil.


1H NMR (400 MHz, CDC13): δ (ppm) 7.30 (m, 5H), 4.17 (m, 1H), 3.56 (AB system, 2H), 3.03 (t, J=8 Hz, 1H), 2.76 (m, 1H), 2.62 (m, 2H), 2.53 (m, 3H), 2.37 (m, 2H), 2.18 (t, J=8 Hz, 1H), 1.59 (m, 4H), 1.45 (m, 2H). 13C NMR (75 MHz, CDC13): 8 (ppm) 138.02, 128.86, 128.21, 127.04, 75.31, 74.34, 62.23, 60.21, 57.20, 52.83, 25.60, 24.22. MS (EI+) m/z: 260.1 (M+).


Example 37
(3R,4R)-1-benzyl-4-(4-methoxyphenylamino)pyrrolidin-3-ol






From 1-benzyl-3,4-epoxypyrroline (121 mg, 0.69 mmol), p-anisidine (129 mg, 1.04 mmol) and LiC104 (148 mg, 1.39 mmol), no solvent was employed. Reaction time: 24 hours. Purification: silica gel, gradient dichloromethane to dichloromethanc:methanol 10%, afforded the product (106 mg, 51%) as yellow solid.


1H NMR (400 MHz, CDC13): δ (ppm) 7.31 (m, 5H), 6.78 (d AB, 2H), 6.62 (d AB, 2H), 4.03 (m, 1H), 3.73 (s, 3H), 3.72 (m, 1H), 3.64 (AB system, 2H), 3.22 (m, 1H), 2.80 (m, 1H), 2.62 (m, 1H), 2.25 (m, 1H). 13C NMR (75 MHz, CDC13): S (ppm) 141.18, 137.99, 128.77, 128.41, 127.26, 114.95, 114.82, 76.55, 62.62, 61.14, 59.82, 59.50, 55.75. MS (EI+) m/z: 299.2 (M+H+).


Example 38
Methyl 4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidin-3-ylamino)benzoate






From 1-benzyl-3,4-epoxypyrroline (126 mg, 0.72 mmol), methyl 4-aminobenzoate (163 mg, 1.07 mmol), LiC104 (153 mg, 1.43 mmol) and acetonitrile (5 ml). Reaction time: 48 hours. Purification: silica gel, gradient dichloromethane to dichloromethane:methanol 10%, afforded the product (80 mg, 34%) as yellow solid.


1H NMR (400 MHz, CDC13): δ (ppm) 7.85 (d AB, 2H), 7.31 (m, 5H), 6.61 (d AB, 2H), 4.28 (d, J=7.5 Hz, 1H), 4.06 (m, 1H), 3.84 (s, 3H), 3.82 (m, 1H), 3.67 (AB system, 2H), 3.21 (m, 1H), 2.89 (m, 1H), 2.59 (m, 1H), 2.34 (m, 1H). 13C NMR (75 MHz, CDC13): S (ppm) 167.33, 137.93, 131.66, 128.84, 128.46, 127.39, 118, 99, 112.26, 76.59, 61.30, 61.26, 59.77, 59.11, 51.58. MS (EI+) m/z: 327.2 (M+H+).


Resolution of Example 12 with mandelic acid. Obtention of enantiopure compounds.







To a solution of tert-butyl-4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxylate (49 g) in acetone (710 ml) (for complete solution was necessary heating at 50° C., then cooled at r.t.) was dropped a solution of R-mandelic acid (41,6 g) in acetone (390 ml). Scratched with spatule until a precipitate begins to appear and let at r.t. for 18 hours.


The precipitate (R,R enantiomer) was filtered and the filtrate (S,S enantiomer as main product) was reserved for the next precipitation.


The precipitate (R,R enantiomer) was recrystalized from acetone (250 ml), heating at reflux until complete solution, and hexane (50 ml) was added. The mixture cooled at r.t. and let to precipitate. The white solid (R,R enantiomer, as di-mandelate salt) was filtered. The disalt was suspended in DCM and washed with sat solution of NaHCO3, water and sat solution of NaCl, dried over Na2SO4, filtered and concentrated to afford the R,R enantiomer as free base (15.0 g , 30% yield, white solid). HPLC: Chiralcel OD-H (0.46 cm×25 cm), hexane:2-propanol, 215 nm, 0.5 ml, min: R.T. 19.0 min (>99% ee).


The filtrate reserved in the first cristalization (S,S enantiomer as main product) was concentrated to dryness, suspended in DCM and washed with sat solution of NaHCO3 and water, dried over Na2SO4, filtered and concentrated. The residue was solved in acetone (300 ml, heating at 50° C. was necesary) and S-mandelic acid (29 g) in acetone (200 ml) was added. The flask was scrathed with spatule until precipitate begins to appear and let at r.t. for 18 hours. The white solid obtained was filtered and recrystalized from acetone (300 ml), heating at reflux until solution, and hexane (100 ml) was added. The mixture was cooled at r.t. and let to precipitate for 18 h. The white solid was filtered to afford the S,S enantiomer as di mandelate salt. The disalt was suspended in DCM (500 ml) and washed with sat solution of NaHCO3 sat , water and sat solution of NaCl, dried over Na2SO4, filtered and concentrated, to afford the S,S enantiomer (free base) as white solid (18,3 g, 37%) yield. HPLC: Chiralcel OD-H (0.46 cm×25 cm), hexane:2-propanol, 215 nm, 0.5 ml, min: R.T. 21.4 min (>99% ee).


Example 39
(3R,4R)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate






1H NMR (400 MHz, METHANOL-d4) δ ppm 2.07 (s, 3H) 3.08 (m, 2H) 3.17 (m, 2H) 3.43 (br. s., 4H) 3.52 (d, J=13.29 Hz, 1H) 3.66 (m, 1H) 3.88 (dd, J=12.90, 6.64 Hz, 2H) 4.46 (d, J=5.08 Hz, 2H) 5.56 (m, 1H) 7.45-7.54 (m, 5H) 7.63-7.73 (m, 3H), 8.05 (d, J=7.82 Hz, 1H) 8.24 (d, J=7.82 Hz, 2H) 8.70 (d, J=8.60 Hz, 1H)


MS (APCl (M+H)+): 494


Example 40
(3R,4R)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol






MS (APCl (M+H)+): 436


Example 41
(3R,4R)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate






MS (APCl (M+H)+): 522


Example 42
(3R,4R)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol






1H NMR (300 MHz, DMSO-d6) δ ppm 3.12 (br. s., 4H) 3.30-4.01 (br. s., 9H) 4.36 (br. s., 2H) 4.57 (br. s., 1H) 7.43 (m, 3H) 7.50-7.67 (m, 4H) 7.85-7.95 (m, 1H) 8.00 (dd, J=7.32, 2.20 Hz, 1H)


MS (APCl (M+H)+): 480


Example 43
(3R,4R)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate






Example 44
(3R,4R)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol






1H NMR (300 MHz, DMSO-d6) δ ppm 2.52 (s, 3H) 3.28 (br. s., 6H) 3.47 (br. s., 2H) 3.67 (br. s., 2H) 4.01 (d, J=7.18 Hz, 3H) 4.36 (br. s., 2H) 4.61 (br. s., 1H) 7.41-7.45 (m, 3H) 7.50-7.63 (m, 5H)


MS (APCl (M+H)+): 434


Example 45
(3R,4R)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate






MS (APCl (M+H)+): 444


Example 46
(3R,4R)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol






1H NMR (300 MHz, DMSO-d6) δ ppm 2.07 (dd, J=8.72, 7.40 Hz, 1H) 2.28-2.46 (m, 5H) 2.53 (br. s., 2H) 2.70 (t, J=8.06 Hz, 1H) 2.82 (br. s., 4H) 3.38 (d, J=13.04 Hz, 1H), 3.48 (d, J=13.04 Hz, 1H) 3.87 (m, 1H) 4.85 (d, J=5.42 Hz, 1H) 7.17-7.32 (m, 5H) 7.60-7.76 (m, 5H)


MS (APCl (M+H)+): 402


Example 47
(3R,4R)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate







1H NMR (400 MHz, DMSO-d6) δ ppm 2.00 (s, 3H) 2.75 (br. s., 2H) 2.81 (br. s., 2H) 3.10 (m, 4H) 3.25 (br. s., 2H) 3.55 (m, 3H) 4.29 (br. s., 2H) 5.24 (br. s., 1H) 7.39-7.56 (m, 7H) 7.77 (m, 2H) 11.49 (br. s., 1H).


MS (APCl (M+H)+): 462


Example 48
(3R,4R)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol







IH NMR (300 MHz, DMSO-d6) δ ppm 3.23 (br. s., 7H) 3.44 (m, 6H) 4.35 (br. s., 2H) 4.60 (br. s., 1H) 7.37-7.60 (m, 7H) 7.78 (m, 2H) 11.36 (br. s., 1H).


MS (APCl (M+H)+): 420


[α]20D−4.0° (c=1, H2O)


Example 49
(3R,4R)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol






MS (APCl (M+H)+): 452


Example 50
(3R,4R)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol






MS (APCl (M+H)+): 464


Example 51
(3R,4R)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-ol






MS (APCl (M+H)+): 416


Example 52
(3R,4R)-1-benzyl-4(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate






MS (APCl (M+H)+): 478


Example 53
(3,4-trans)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochioride






1H NMR (400 MHz, METHANOL-d4) δ ppm 2.08 (s, 3H) 2.41 (s, 3H) 2.55 (s, 3H) 2.89-2.98 (m, 2H) 3.03 (br. s., 2H) 3.33 (m, 4H) 3.53 (d, J=13.29 Hz, 2H) 3.64-3.70 (m, 1H) 3.82-3.90 (m, 2H) 4.46 (d, J=5.47 Hz, 2H) 5.51-5.55 (m, 1H) 7.46 (s, 1H) 7.48-7.56 (m, 5H) 7.79 (s, 1H)


MS (APCl (M+H)+): 506


Example 54
(3,4-trans)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochioride






MS (APCl (M+H)+): 464


Example 55
(3S,4S)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride






MS (APCl (M+H)+): 464


Example 56
(3,4-trans)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride






1H NMR (400 MHz, METHANOL-d4) Δ ppm 2.09 (s, 3H) 2.46 (s, 3H) 3.13 (d, J=7.03 Hz, 2H) 3.22 (br. s., 6H) 3.54 (d, J=12.90 Hz, 1H) 3.67 (br. s., 1H) 3.90 (dd, J=12.90, 7.03 Hz, 3H) 4.47 (d, J=4.30 Hz, 2H) 5.58 (m, 1H) 7.44-7.51 (m, 5H) 7.54 (m, 2H) 7.68 (d, J=7.42 Hz, 2H)


MS (APCl (M+H)+): 458


Example 57
(3,4-trans)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-ol dihydrochloride






MS (APCl (M+H)+): 416


Example 58
(3R, 4R)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-ol dihydorchloride






MS (APCl (M+H)+): 416


Example 59
(3S, 45)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-ol dihydrochloride






MS (APCl (M+H)+): 416


Example 60
(3,4-trans)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride






1H NMR (400 MHz, METHANOL-d4) δ ppm 2.07 (s, 3H) 3.08 (m, 2H) 3.17 (m, 2H) 3.43 (br. s., 4H) 3.52 (d, J=13.29 Hz, 1H) 3.66 (m, 1H) 3.88 (dd, J=12.90, 6.64 Hz, 2H) 4.46 (d, J=5.08 Hz, 2H) 5.56 (m, 1H) 7.45-7.54 (m, 5H) 7.63-7.73 (m, 3H), 8.05 (d, J=7.82 Hz, 1H) 8.24 (d, J=7.82 Hz, 2H) 8.70 (d, J=8.60 Hz, 1H)


MS (APCl (M+H)+): 494


Example 61
(3,4-trans)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride






MS (APCl (M+H)+): 452


Example 62
(3S-4S)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochioride






MS (APCl (M+H)+): 452


Example 63
(3,4-trans)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride






MS (APCl (M+H)+): 478


Example 64
(3,4-trans)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride






MS (APCl (M+H)+): 436


Example 65
(3S,4S)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride






MS (APCl (M+H)+): 436


Example 66
(3,4-trans)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride






MS (APCl (M+H)+): 522


Example 67
(3,4-trans)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride






1H NMR (300 MHz, DMSO-d6) δ ppm 3.12 (br. s., 4H) 3.30-4.01 (br. s.,9H) 4.36 (br. s., 2H) 4.57 (br. s., 1H) 7.43 (m, 3H) 7.50-7.67 (m, 4H) 7.85-7.95 (m, 1H) 8.00 (dd, J=7.32, 2.20 Hz, 1H)


MS (APCl (M+H)+): 480


Example 68
(3S,4S)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochioride






MS (APCl (M+H)+): 480


Example 69
(3,4-trans)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride






MS (APCl (M+H)+): 476


Example 70
(3,4-trans)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochioride






1H NMR (300 MHz, DMSO-d6) δ ppm 2.52 (s, 3H) 3.28 (br. s., 6H) 3.47 (br. s., 2H) 3.67 (br. s., 2H) 4.01 (d, J=7.18 Hz, 3H) 4.36 (br. s., 2H) 4.61 (br. s., 1H) 7.41-7.45 (m, 3H) 7.50-7.63 (m, 5H)


MS (APCl (M+H)+): 434


Example 71
(3S,4S)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochioride






MS (APCl (M+H)+): 434


Example 72
(3,4-trans)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate






MS (APCl (M+H)+): 444


Example 73
(3,4-trans)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol






1H NMR (300 MHz, DMSO-d6) δ ppm 2.07 (dd, J=8.72, 7.40 Hz, 1H) 2.28-2.46 (m, 5H) 2.53 (br. s., 2H) 2.70 (t, J=8.06 Hz, 1H) 2.82 (br. s., 4H) 3.38 (d, J=13.04 Hz, 1H) 3.48 (d, J=13.04 Hz, 1H) 3.87 (m, 1H) 4.85 (d, J=5.42 Hz, 1H) 7.17-7.32 (m, 5H) 7.60-7.76 (m, 5H)


MS (APCl (M+H)+): 402


Example 74
(3S,4S)-1-benzyl-4-(4-(nhanvisuifenvilninerazin-1-yl)pyrrolidin-3-ol






MS (APCl (M+H)+): 402


Example 75
(3,4-trans)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride







1H NMR (400 MHz, DMSO-d6) δ ppm 2.00 (s, 3H) 2.75 (br. s., 2H) 2.81 (br. s., 2H) 3.10 (m, 4H) 3.25 (br. s., 2H) 3.55 (m, 3H) 4.29 (br. s., 2H) 5.24 (br. s., 1H) 7.39-7.56 (m, 7H) 7.77 (m, 2H) 11.49 (br. s., 1H).


MS (APCl (M+H)+): 462


Example 76
(3,4-trans)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride







1H NMR (300 MHz, DMSO-d6) δ ppm 3.23 (br. s., 7H) 3.44 (m, 6H) 4.35 (br. s., 2H) 4.60 (br. s., 1H) 7.37-7.60 (m, 7H) 7.78 (m, 2H) 11.36 (br. s., 1H).


MS (APCl (M+H)+): 420


Example 77
(3S,4S)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride







1H NMR (300 MHz, DMSO-d6) δ ppm 3.23 (br. s., 7H) 3.44 (m, 6H) 4.35 (br. s., 2H) 4.60 (br. s., 1H) 7.37-7.60 (m, 7H) 7.78 (m, 2H) 11.36 (br. s., 1H).


MS (APCl (M+H)+): 420


[α]20D+4.1° (c=1, DMF)


Example 78
(3,4-trans)-1-benzyl-4-(4-(2-chloro-6-fluorobenzyl)piperazin-1-yl)pyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (100 mg, 0.57 mmol), 1-(2-chloro-6-fluorobenzyl)piperazine (98 mg, 0.42 mmol), LiClO4(121 mg, 1.14 mmol) and acetonitrile (6 ml). Reaction time: 16 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (80 mg, 49%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.28 (m, 5H), 7.18 (m, 2H), 6.97 (m, 1H), 4.12 (m, 1H), 3.75 (AB system, 2H), 3.54 (AB system, 2H), 3.17 (bs, 1H), 2.99 (t, J=8 z, 1H), 2.75-2.51 (m, 8H), 2.43 (bs, 2H), 2.18 (t, J=8 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 161.97 (d, JCF=248 Hz), 137.97, 136.60 (d, JCF=6 Hz), 129.0.3 (d, JCF=10 Hz), 128.85, 128.21, 127.08, 125.32 (d, JCF=3 Hz), 123.46 (d, JCF=18 Hz), 125.32 (d, JCF=24 Hz), 74.57, 74.27, 62.19, 60.12, 57.24, 52.22, 52.09, 51.53. HR-MS calc for M+H: 404.1905, obs: 404.1891.


Example 79
(3,4-trans)-1-benzyl-4-(4-(3,4-dichlorobenzyl)piperazin-1-yl)pyrrolidine-3-ol






From 1-benzyl-3,4-epoxypyrroline (100 mg, 0.57 mmol), 1-(3,4-dichlorobenzyl)piperazine (105 mg, 0.42 mmol), LiClO4 (121 mg, 1.14 mmol) and acetonitrile (6 ml). Reaction time: 16 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (86 mg, 49%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.42 (d, J=2 Hz, 1H), 7.37 (d, J=8 Hz, 1H), 7.29 (m, 5H), 7.14 (dd, J1=2 Hz, J2=8 Hz, 1H), 4.15 (m, 1H), 3.56 (AB system, 2H), 3.44 (s, 2H), 3.15 (bs, 1H), 3.01 (t, J=8z, 1H), 2.77-2.58 (m, 5H), 2.46 (bs, 6H), 2.19 (t, J=8 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 138.52, 137.92, 132.23, 130.85, 130.69, 130.11, 128.85, 128.25, 127.12, 74.63, 74.32, 62.23, 61.56, 60.18, 57.25, 52.67, 51.52. HR-MS calc for M+H: 420.1609, obs: 420.1609.


Example 80
(3,4-trans)-1-benzyl-4-hydroxypyrrolidin-3-yl)piperazin-1-yl)(furan-2-yl)methanone






From 1-benzyl-3,4-epoxypyrroline (100 mg, 0.57 mmol), 1-(2-furoyl)piperazine (87 mg, 0.47 mmol), LiClO4 (121 mg, 1.14 mmol) and acetonitrile (6 ml). Reaction time: 6 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (64 mg, 38%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.45 (s, 1H), 7.28 (m, 5H), 6.97 (d, J=3 Hz, 1H), 6.45 (m, 1H), 4.16 (m, 1H), 3.79 (m, 4H), 3.55 (AB system, 2H), 3.16 (bs, 1H), 2.98 (t, J=8z, 1H), 2.71 (m, 2H), 2.62 (m, 2H), 2.46 (m, 2H), 2.23 (t, J=8 Hz, 1H), 13C NMR (75 MHz, CDCl3): δ (ppm) 158.92, 147.82, 143.62, 137.83, 128.84, 128.29, 127.17, 116.40, 111.21, 74.19, 74.17, 62.19, 60.16, 57.02, 51.56. HR-MS calc for M+H: 356.1974, obs: 356.1987.


Example 81
(3,4-trans)-1-benzyl-4-(4-ethylpiperazin-1-yl)pyrrolidin-3-ol






From 1-benzyl-3,4-epoxypyrroline (100 mg, 0.57 mmol), 1-ethylpiperazine (55 mg, 0.47 mmol), LiClO4 (121 mg, 1.14 mmol) and acetonitrile (6 ml). Reaction time: 12 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (32 mg, 23%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.28 (m, 5H), 4.16 (m, 1H), 3.56 (AB system, 2H), 3.15 (bs, 1H), 3.00 (t, J=8z, 1H), 2.78-2.58 (m, 5H), 2.48 (m, 6H), 2.40 (q, J=7 Hz, 2H), 2.20 (t, J=8 Hz, 1H), 1.07 (t. J=7 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ (ppm) 138.06, 128.82, 128.22, 127.08, 74.72, 74.30, 62.31, 60.14, 57.27, 52.50, 52.15, 51.59, 11.77. HR-MS calc for M+H: 290.2232, obs: 290.2228.


Example 82
(3,4-trans)-1-benzyl-4-(4-(2-methoxyphenyl)piperazin-1-yl)pyrrolidin-3-ol






From 1-benzyl-3,4-epoxypyrroline (100 mg, 0.57 mmol), 1-(2-methoxyphenyl)piperazine (93 mg, 0.47 mmol), LiClO4(121 mg, 1.14 mmol) and acetonitrile (6 ml). Reaction time: 6 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (100 mg, 39%) as colourless oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.29 (m, 5H), 7.01 (m, 1H), 6.93 (m, 2H), 6.87 (m, 1H), 4.23 (m, 1H), 3.86 (s, 3H), 3.59 (AB system, 2H), 3.09 (m, 5H), 3.02 (bs, 1H), 2.79 (m, 4H), 2.67 (m, 3H), 2.27 (t, J=8z, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 152.18, 141.11, 137.98, 128.85, 128.23, 127.10, 122.89, 120.95, 118.06, 111.10, 74.81, 74.42, 62.26, 60.18, 57.26, 55.25, 51.88, 50.35. HR-MS calc for M+H: 368.2338, obs: 368.2348.


Example 83
(3,4-trans)-1-benzyl-4-(4-(4-fluorophenyl)piperazin-1-yl)pyrrolidin-3-ol






From 1-benzyl-3,4-epoxypyrroline (100 mg, 0.57 mmol), 1-(4-fluorophenyl)piperazine (94 mg, 0.51 mmol), LiClO4 (121 mg, 1.14 mmol) and acetonitrile (5 ml). Reaction time: 12 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (80 mg, 44%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.29 (m, 5H), 6.94 (m, 2H), 6.84 (m, 2H), 4.17 (m, 1H), 3.56 (AB system, 2H), 3.25 (bs, 1H), 3.10 (m, 4H), 3.04 (t, J=8 Hz, 1H), 2.72 (m, 4H), 2.64 (m, 1H), 2.57 (m, 2H), 2.25 (t, J=8z, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 157.19 (d, JCF=238 Hz), 147.77, 137.89, 128.90, 128.30, 127.21, 117.66 (d, JCF=8 Hz), 115.44 (d, JCF=22 Hz), 74.53, 74.40, 62.29, 60.16, 57.20, 51.60, 49.83. HR-MS calc for M+H: 356.2138, obs: 356.2137.


Example 84
(3,4-trans)-1-benzyl-4-(4-(2-chlorophenyl)piperazin-1-yl)pyrrolidin-3-ol






From 1-benzyl-3,4-epoxypyrroline (100 mg, 0.57 mmol), 1-(2-chlorophenyl)piperazine (102 mg, 0.43 mmol), LiClO4(121 mg, 1.14 mmol) and acetonitrile (6 ml). Reaction time: 16 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (51 mg, 32%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.36 (dd, J1=7.8 Hz, J2=1.5 Hz, 1H), 7.29 (m, 5H), 7.21 (dt, J1=8 Hz, J2=1.5 Hz, 1H), 7.04 (dd, J1=8 Hz, J2=1.5 Hz, 1H), 6.97 (dt, J1=7.8 Hz, J2=1.5 Hz, 1H), 4.22 (m, 1H), 3.59 (AB system, 2H), 3.09 (m, 5H), 2.99 (bs, 1H), 2.79 (m, 4H), 2.65 (m, 3H), 2.26 (t, J=8z, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 149.07, 137.89, 130.55, 128.86, 128.72, 128.22, 127.52, 127.15, 123.66, 120.25, 74.76, 74.46, 62.31, 60.19, 57.32, 51.86, 50.93. HR-MS calc for M+H: 372.1844, obs: 372.1843.


Example 85
(3R,4R)-1-benzyl-4-(4-(4-(2-chlorophenyl)piperazin-1-yl)pyrrolidin-3-ol






Example 86
(3S,4S)-1-benzyl-4-(4-(2-chlorophenyl)piperazin-1-yl)pyrrolidin-3-ol






Example 87
1-(4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidin-3-yl)piperazin-1-yl)ethanone






From 1-benzyl-3,4-epoxypyrroline (148 mg, 0.84 mmol), 1-acetylpiperazine (131 mg, 1.01 mmol), LiClO4 (183 mg, 1.69 mmol) and acetonitrile (7 ml). Reaction time: 6 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (42 mg, 17%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.29 (m, 5H), 4.15 (m, 1H), 3.67 (m, 1H), 3.56 (AB system, 2H), 3.52 (m, 1H), 3.44 (m, 2H), 2.99 (t, J=8 Hz, 1H), 2.78-2.58 (m, 5H), 2.48 (m, 1H), 2.39 (m, 2H), 2.20 (t, J=8 Hz, 1H), 2.06 (s, 3H). 13C NMR (75 MHz, CDCl3): δ (ppm) 168.92, 137.82, 128.82, 128.30, 127.21, 74.28, 74.26, 62.22, 60.12, 57.12, 51.76, 51.15, 46.04, 41.16, 21.21. MS(ES+) 304.2 (M+H).


Example 88
(3,4-trans)-1-benzyl-4-(4-(3,4-dichlorophenyl)piperazin-1-yl)pyrrolidin-3-ol






From 1-benzyl-3,4-epoxypyrroline (100 mg, 0.57 mmol), 1-(3,4-dichlorophenyl)piperazine (112 mg, 0.47 mmol), LiClO4 (121 mg, 1.14 mmol) and acetonitrile (6 ml). Reaction time: 6 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 8%, afforded the product (127 mg, 55%) as brown oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.31 (m, 5H), 7.26 (d, J1=9 Hz, 1H), 6.93 (d, J1=2.8 Hz, 1H), 6.72 (dd, J1=9 Hz, J2=2.8 Hz, 1H), 4.18 (m, 1H), 3,58 (AB system, 2H), 3.15 (m, 4H), 3.05 (t, J=8 Hz, 1H), 2.79-2.62 (m, 5H), 2.56 (m, 2H), 2.23 (t, J=8z, 1H). 13C NMR (75 MHz, CDCl3): δ (ppm) 150.48, 137.83, 132.70, 130.35, 128.88, 128.28, 127.21, 122.12, 116.98, 115.11, 74.41, 62.27, 60.16, 57.17, 51.27, 48.37. HR-MS calc for M+H: 406.1453, obs: 406.1443.


Example 89
(3,4-trans)-1-benzyl-4-(4-(3,4-dichlorophenyl)piperazin-1-yl)pyrrolidin-3-ol






tert-butyl-4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxylate (115 mg, 0.31 mmol) was treated with a solution of HCl 4.0 M in dioxane (3 ml) and the resulting solution was stirred at r.t. for 4 hours. Dichloromethane was added and the organic solution was washed with sat. solution of NaHCO3, and water, dried over Na2SO4, filtered and concentrated to give the product (80 mg, 96%) as yellow oil.



1H NMR (400 MHz, CD3OD): δ (ppm) 7.30 (m, 5H), 4.16 (m, 1H), 3.59 (AB system, 2H), 3.02 (t, J=8 Hz, 1H), 2.86 (m, 4H), 2.75-2.55 (m, 5H), 2.46 (m, 2H), 2.29 (t, J=8 Hz, 1H). 13C NMR (75 MHz, CD3OD): δ (ppm) 139.00, 129.94, 129.13, 128.09, 74.92, 74.19, 62.90, 61.08, 58.04, 53.14, 45.74. HR-MS calc for M+H: 262


Example 90
(3,4-trans)-tert-butyl 3-(3,4-dihydroisoquinolin-2(1H)-yl-4-hydroxypyrrolidine-1-carboxylate






From 1-tert-butoxycarbonyl-3,4-epoxypyrroline (62 mg, 0.33 mmol), 1,2,3,4-tetrahydroisoquinoline (69 mg, 0.50 mmol), LiClO4 (72 mg, 0.66 mmol) and acetonitrile (3 ml). Reaction time: 5 hours. Purification: silica gel, gradient dichloromethane to dichlorometane:methanol 5%, afforded the product (57 mg, 53%) as yellow oil.



1H NMR (400 MHz, CDCl3): δ (ppm) 7.11 (m, 3H), 7.00 (m, 1H), 4.34 (m, 1H), 3.79 (AB system, 2H), 3.70 (bs, 2H), 3.33 (bs, 1H), 3.17 (bs, 1H), 3.01 (bs, 1H), 2.88 (m, 4H), 1.46 (s, 9H). 13C NMR (75 MHz, CDCl3): δ (ppm) 154.41, 134.17, 133.98, 128.64, 126.59, 126.30, 125.73, 79.67, 72.19, 69.90, 53.62, 52.00, 48.19, 46.78, 28.93, 28.44. MS (EI+) m/z: 318.2 (M+).


Biological Activity

Some representative compounds of the invention were tested for their activity as sigma (sigma-1) inhibitors. The following protocol was followed:


Sigma-1

Brain membrane preparation and binding assays for the σ1-receptor were performed as described (DeHaven-Hudkins et al., 1992, Eur. J. Pharmacol. 227, 371-378.) with some modifications. In brief, guinea pig brains were homogenized in 10 vols. (w/v) of Tris-HCl 50 mM 0.32 M sucrose, pH 7.4, with a Kinematica Polytron PT 3000 at 15000 r.p.m. for 30 s. The homogenate was centrifuged at 1000g for 10 min at 4° C. and the supematants collected and centrifuged again at 48000 g for 15 min at 4° C. The pellet was resuspended in 10 volumes of Tris-HCl buffer (50 mM, pH 7.4), incubated at 37° C. for 30 min, and centrifuged at 48000 g for 20 min at 4° C. Following this, the pellet was resuspended in fresh Tris-HCl buffer (50 mM, pH 7.4) and stored on ice until use.


Each assay tube contained 10 μL of [3H](+)-pentazocine (final concentration of 0.5 nM), 900 μL of the tissue suspension to a final assay volume of 1 mL and a final tissue concentration of approximately 30 mg tissue net weight/mL. Non-specific binding was defined by addition of a final concentration of 1 μM haloperidol. All tubes were incubated at 37° C. for 150 min before termination of the reaction by rapid filtration over Schleicher & Schuell GF 3362 glass fibre filters [previously soaked in a solution of 0.5% polyethylenimine for at least 1 h]. Filters were then washed with four times with 4 mL of cold Tris-HCl buffer (50 mM, pH 7.4). Following addition of scintillation cocktail, the samples were allowed to equilibrate overnight. The amount of bound radioactivity was determined by liquid scintillation spectrometry using a Wallac Winspectral 1414 liquid scintillation counter. Protein concentrations were determined by the method of Lowry et al. (1951; J. Biol. Chem, 193, 265.).


Some of the results with respect to sigma-1 receptor binding are shown in table I.












TABLE I








Percent Replacement Sigma-1



Example
receptor [10−7 M]



















1
84.9



5
63.5



9
38.6



10
77.8



11
81.1



12
96.5



16
49.9



17
82.1



18
90.9



24
73.0



29
39.3



31
89.9



32
59.1



56
38.0



37
65.4



38
55.9



60
40.8



52
92.4



27
24.7



61
30.1



57
16.8



67
86.7



70
81.4



73
84



75
95.5



76
85



48
96.5



77
46.1



85
107



86
86.2



78
81.9



79
88.4



83
69.7



84
94.6



88
93.1









Claims
  • 1. Substituted pyrrolidine compounds of general formula (I),
  • 2. Compound according to claim 1, characterized in that R1 represents a hydrogen atom, an unbranched or branched, optionally at least mono-substituted C1-6-alkyl radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a group; a (SO2)—R8 group; or a (C═O)—NR7R7a group; R2 represents a (C═O)—R8 group, with R8 representing a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;R3 and R4, equal or different, represent a hydrogen atom; an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted C1-8-aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; with the condition (proviso) that R3 and R4 may not at the same time represent a hydrogen atom;orR3 and R4 together with their bridging nitrogen atom form 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;2) an A-X—B group, whereinA represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF2, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N1 S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—N R12R12a group;3) an A-X—B—Y—C group, whereinA represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR11 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;R5, R6, R7a, R9, R10, R11, R12 and R12a have the meaning according to claim 1; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 3. Compounds according to claim 1, characterized in that R1 represents a hydrogen atom, an unbranched or branched, saturated, optionally at least mono-substituted C1-6-alkyl radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a group; a (SO2)—R6 group; or a (C═O)—NR7R7a group; R2 represents a linear, substituted or unsubstituted C C1-6 alkyl group; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH;R3 and R4 together with their bridging nitrogen atom form 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;2) an A-X—B group, whereinA represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;3) an A-X—B—Y—C group, whereinA represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;Y represents a bond, a —NH— group, a — (C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning according to claim 1;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 4. Compounds according to claim 1, characterized in that R1 represents a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted heteroaryl group; a branched or unbranched, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a group; a (SO2)—R6 group; or a (C═O)—NR7R7a group; R2 represents a linear, substituted or unsubstituted C1-6 alkyl group; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH;R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, unsubstituted C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-cycloalkyl group; an unsubstituted alkyl-aryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;R5, R6, R7 and R7a have the meaning according to claim 1;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 5. Compounds according to claim 1, characterized in that R1 represents an unbranched or branched, optionally at least mono-substituted C2-6-alkyl radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated unsubstituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a (SO2)—R6 group; a (C═O)—NR7R7a group; R2 represents a hydrogen atom;R3 and R4 together with their bridging nitrogen atom form 1) a ring system A in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;2) an A-X—B group, whereinA represents a ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF2, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF2, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group; 3) an A-X—B—Y—C group, whereinA represents a ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF2, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning according to claim 1;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 6. Compounds according to claim 1, characterized in that R1 represents a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; an optionally at least mono-substituted benzhydryl group; a (C═O)—R5 group; a (SO2)—R6 group; or a (C═O)—NR7R7a group; R2 represents a hydrogen atom;R3 represents a hydrogen atom;R4 represents a saturated or unsaturated, unsubstituted, linear C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing 4 or 5-membered cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, unsubstituted alkyl-cycloalkyl group; an unsubstituted C1-6alkyl-heteroaryl group;R5, R6, R7 and R7a have the meaning according to claim 1;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 7. Compounds according to claim 1, characterized in that R1 represents a hydrogen atom, an unbranched or branched, saturated C1-6 alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C3-6-alkyl-aryl group wherein the C3-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C3-6-alkyl-heteroaryl group wherein the C3-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; a (SO2)—R6 group; or a (C═O)— NR7R7a group; R2 represents a (C═O)—R8 group, with R8 representing a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;R3 and R4, equal or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted C1-8-aliphatic radical; a saturated or unsaturated, optionally at least mono- substituted, optionally at least one heteroatom as ring member containing cycloalkyl group; a branched or unbranched, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group; an optionally at least mono-substituted aryl group; an optionally at least mono-substituted heteroaryl group; a branched or unbranched, optionally at least mono-substituted C1-6-alkyl-aryl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted C1-6-alkyl-heteroaryl group; with the condition that R3 and R4 may at the same time not represent a hydrogen atom;orR3 and R4 together with their bridging nitrogen atom form 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;2) an A-X—B group, whereinA represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;3) an A-X—B—Y—C group, whereinA represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF2, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF2, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning according to claim 1;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 8. Compounds according to claim 1, characterized in that R1 represents a hydrogen atom, an unbranched or branched, saturated C1-6 alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, carboxy, amido, cyano, carbamyl, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF2, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF2, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated, C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the heteroaryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH1 OH, SO2, CF2, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least mono-substituted benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF2, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; a group; a (SO2)—R6 group; or a (C═O)—NR7R7a group; R2 represents a C1-6 alkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF2; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF2;R3 and R4 together with their bridging nitrogen atom form 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12 group;2) an A-X—B group, whereinA represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12 group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;3) an A-X—B—Y—C group, whereinA represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;R5, R6, R7, R7a, R9, R10, R11, R12 and R12a have the meaning according to claim 1;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 9. Compounds according to claim 1, characterized in that R1 represents an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; a (SO2)—R6 group; or a (C═O)—NR7R7a group; R2 represents a C1-6 alkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH1 CF3;R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, unsubstituted C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group with substituents independently selected from the group consisting of F1 Cl, Br, I, NH2, SH, OH, CF3, CN1 nitro; an unsubstituted heteroaryl group; an optionally at least mono-substituted C1-6 alkyl-cycloalkyl group; an unsubstituted C1-6 alkyl-aryl group; an unsubstituted C1-6 alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;R5, R6, R7 and R7a have the meaning according to claim 1;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 10. Compounds according to claim 1, characterized in that R1 represents an unbranched or branched, optionally at least mono-substituted C1-6-alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C3-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; a (SO2)—R6 group; or a (C═O)—NR7R7a group; R2 represents a hydrogen atom;R3 and R4 together with their bridging nitrogen atom form 1) a 4 to 18 membered ring system A in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;2) an A-X—B group, whereinA represents 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12 group;3) an A-X—B—Y—C group, whereinA represents 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF2, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a —O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;R5, R5, R7, R7a, R9, R10, R11, R12 and R12a have the meaning according to claim 1;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 11. Compounds according to any of claims 1, characterized in that R1 represents an optionally at least one heteroatom as ring member containing cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optional: substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optional: substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN1 nitro, —SO2NH2 or C1-6-alkoxy; a (C═O)—R5 group; a (SO2)—R6 group; or a (C═O)—NR7R7a group; R2 represents a hydrogen atom;R3 represents a hydrogen atom;R4 represents a saturated or unsaturated, unsubstituted, linear C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing 4 or 5-membered cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, unsubstituted alkyl-cycloalkyl group; an unsubstituted C1-6 alkyl-heteroaryl group;R5, R6, R7 and R7a have the meaning according to claim 1;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 12. Compound according to claim 1, characterized in that R1 represents a hydrogen atom, an unbranched or branched C1-6 alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH; OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN1 nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN1 nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group; R2 represents a (C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group;R3 and R4, equal or different, represent a hydrogen atom, an unbranched or branched C1-8-alkyl group, which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a saturated or unsaturated, optionally at least one heteroatom as ring member containing cycloalkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, CO—OH, CO—O—CH3, O—CH3, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, CO—OH, CO—O—CH3, O—CH3, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, CO—OH, CO—O—CH3, O—CH3, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; with the condition that R3 and R4 may at the same time not represent a hydrogen atom;orR3 and R4 together with their bridging nitrogen atom form 1) a saturated or unsaturated 4 to 18 membered ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a OH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;2) an A-X—B group, whereinA represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted 01-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group;a NH—R11 group;3) an A-X—B—Y—C group, whereinA represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11n group; a NH—R11 group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH1 OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono- substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;R9, R10 and R11 represent a hydrogen atom, an unbranched or branched C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 13. Compounds according to claim 1, characterized in that R1 represents a hydrogen atom, an unbranched or branched C1-6 alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, carboxy, amido, cyano, carbamyl, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated, C16-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the heteroaryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least mono-substituted benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a group; a (SO2)—R6 group; R2 represents a methyl , ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;R3 and R4 together with their bridging nitrogen atom form 1) a saturated or unsaturated 4 to 18 membered ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C3-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;2) an A-X—B group, whereinA represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;3) an A-X—B—Y—C group, whereinA represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;R9, R10 and R11 represent a hydrogen atom, an unbranched or branched C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 14. Compounds according to claim 1, characterized in that re represents an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I1 NH2, SH1 OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group; R2 represents a methyl, ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, unsubstituted C3-6 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group with substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN, nitro;an unsubstituted heteroaryl group; a C1-6 alkyl-cycloalkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an unsubstituted C1-6 alkyl-aryl group; an unsubstituted C1-6 alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 15. Compounds according to claim 1, characterized in that R1 represents an unbranched or branched, saturated, optionally at least mono-substituted C1-6-alkyl radical which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; an aryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group; R2 represents a hydrogen atom;R3 and R4 together with their bridging nitrogen atom form 1) a 4 to 18 membered ring system A in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;2) an A-X—B group, whereinA represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;X group; a —NH— group; a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;3) an A-X—B—Y—C group, whereinA represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2—(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group;Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;C represents a saturated or unsaturated 4 to β membered ring system, in which at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, or CF3;R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;R9, R10 and R11 represent a hydrogen atom, an unbranched or branched alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 16. Compounds according to claim 1, characterized in that R1 represents an optionally at least one heteroatom as ring member containing C1-6-alkyl-cycloalkyl group wherein the C1-6-alkyl and/or the cycloalkyl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN1 nitro, —SO2NH2 or C1-6-alkoxy; a heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched, saturated C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group; R2 represents a hydrogen atom;R3 represents a hydrogen atom;R4 represents a saturated or unsaturated, unsubstituted, linear C3-13 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing 4 or 5-membered cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, unsubstituted alkyl-cycloalkyl group; an unsubstituted C1-6 alkyl-heteroaryl group;R6 represents a hydrogen atom; a C1-6 alkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a cycloalkyl group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, pyrroline, pyrrolidine, pyrrolidineone, pyrazoline, pyrazolinone, oxopyrazolinone, aziridine, acetidine, tetrahydropyrrole, oxirane, oxetane, dioxetane, tetrahydrofurane, dioxane, dioxolane, oxathiolane, oxazolidine, thiirane, thietane, thiolane, thiane, thiazolidine, piperidine, piperazine or morpholine which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, or CN; an alkyl-cycloalkyl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a branched or unbranched alkyl-aryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; an alkyl-heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 17. Compounds according to claim 1, characterized in that R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; R2 represents a (C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group;R3 and R4, identical or different, represent a hydrogen atom; a C3-8 alkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; an optionally at least mono-substituted quinoline group; a phenyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;orR3 and R4 together with their bridging nitrogen atom form 1) a saturated or unsaturated 4 to 18 membered ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;2) an A-X—B group, whereinA represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with Rn being a linear or branched C1-6 alkyl group;3) an A-X—B—Y—C group, whereinA represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF2, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 18. Compounds according to claim 1, characterized in that R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; R2 represents a methyl, ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;R3 and R4 together with their bridging nitrogen atom form 1) a saturated or unsaturated 4 to 18 membered ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR16 group with R10 being a linear or branched C1-6 alkyl group;2) an A-X—B group, whereinA represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;3) an A-X—B—Y—C group, whereinA represents a saturated or unsaturated 4 to 18 membered ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 19. Compounds according to any of claim 1, characterized in that R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; R2 represents a methyl, ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;R3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, optionally at least mono-substituted C3-8 aliphatic group with substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN, nitro; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group with substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN, nitro; an unsubstituted heteroaryl group; a saturated or unsaturated, optionally at least mono-substituted C1-6 alkyl-cycloalkyl group; a saturated or unsaturated, unsubstituted C1-6 alkyl-aryl group; a saturated or unsaturated, unsubstituted C1-6 alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 20. Compounds according to claim 1, characterized in that R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; R2 represents a hydrogen atom;R3 and R4 together with their bridging nitrogen atom form 1) a 4 to 18 membered ring system A in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;2) an A-X—B group, whereinA represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;3) an A-X—B—Y—C group, whereinA represents a 4 to 18 membered ring system in which the ring containing the nitrogen atom is saturated, but may be condensed with an unsaturated ring, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;C represents a saturated or unsaturated 4 to 12 membered ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3; a C1-6-aliphatic group; a C1-6-alkoxy group; a (C═O)—OR10 group with R10 being a linear or branched C1-6 alkyl group;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 21. Compounds according to claim 1, characterized in that R1 represents a branched or unbranched C1-6-alkyl-aryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a branched or unbranched C1-6-alkyl-heteroaryl group wherein the C1-6-alkyl and/or the aryl group is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a benzhydryl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, SO2, CF3, CN, nitro, —SO2NH2 or C1-6-alkoxy; a (SO2)—R6 group with R6 being an aryl group, preferably a phenyl or a naphtyl group, which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a heteroaryl group which is optionally at least mono-substituted by substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; R2 represents a hydrogen atom;R3 represents a hydrogen atom;R4 represents a saturated or unsaturated, unsubstituted, linear C3-6 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing 4 or 5-membered cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, unsubstituted alkyl-cycloalkyl group; an unsubstituted C1-6 alkyl-heteroaryl group;optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • 22. Compounds according to claim 1, characterized in that R1 represents a benzyl group or a (SO2)—R6 group with R6 being an aryl group; R2 represents a (C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group;R3 and R4, identical or different, represent a C3-8 alkyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; an optionally at least mono-substituted quinoline group; a phenyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN; a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3, CN;orR3 and R4 together with their bridging nitrogen atom form 1) a ring system A, comprising:
  • 23. Compounds according to claim 1, characterized in that R1 represents a benzyl group or a (SO2)—R6 group with R6 being an aryl group; R2 represents a methyl, ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3;R3 and R4 together with their bridging nitrogen atom form 1) a ring system A, comprising:
  • 24. Compounds according to claim 1, characterized in that R1 represents a benzyl group or a (SO2)—R6 group with R6 being an aryl group; R2 represents a hydrogen atom;R3 and R4 together with their bridging nitrogen atom form 1) a ring system A, comprising:
  • 25. Compounds according to claim 1 selected from the group consisting of [1] (3,4-trans)-1-benzyl-4-(3,4-dihydroisoquinolin-2(1H)-yl)pyrrolidine-3-ol,[2] (3,4-trans)-1-benzyl-4-morpholinopyrrolidine-3-ol,[3] (3,4-trans)-1-benzyl-4-(4-(2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)piperidin-1-yl)pyrrolidine-3-ol,[4] (3,4-trans)-1-benzyl-4-(3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propyl amino)pyrrolidine-3-ol,[5] (3,4-trans)-1-benzyl-4-(4-((3,4-dihydroisoquinolin-2(1H)-yl)methyl)piperidin-1-yl)pyrrolidine-3-ol,[6] 1-(4-(6-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)-5,6,7,8-tetrahydropyrido [4,3-d]pyrimidin-2-ylamino)phenyl)ethanone,[7] 1-(1-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperidin-4-yl)-1H-benzo[d] [1,3] oxazin-2(4H)-one,[8] (3,4-trans)-1-benzyl-4-(2-(4-phenoxyphenylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)pyrrolidine-3-ol,[9] (3,4-trans)-1-benzyl-4-(3-(3,4-dihydroisoquinolin-2(1H)-yl)propylamino)pyrrolidine -3-ol,[10] (3,4-trans)-1-benzyl-4-(4-(4-methoxypyrimidin-2-yl)piperazin-1-yl)pyrrolidine-3-ol,[11] (3,4-trans)-1-benzyl-4-(2,3,8,8a-tetrahydrocyclopenta[ij]isoquinolin-1(7H)-yl)pyrrolidine-3-ol,[12] tert-butyl-4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxylate,[13] tert-butyl 4-((3,4-trans)-4-hydroxy-1-(phenylsulfonyl)pyrrolidine-3-yl)piperazine-1-carboxylate,[14] (3,4-trans)-4-morpholino-1-(phenylsulfonyl)pyrrolidine-3-ol,[15] (3,4-trans)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-1-(phenylsulfonyl)pyrrolidine-3-ol,[16] (3,4-trans)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-1((S)-I-phenylethyl)pyrrolidine-3-ol,[17] (3,4-trans)-1-benzyl-4-(4-benzylpiperazin-1-yl)pyrrolidine-3-ol,[18] (3,4-trans)-1-benzyl-4-(4-phenylpiperazin-1-yl)pyrrolidine-3-ol,[19] Ethyl 2-(4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazin-1-yl)acetate,[20] (4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazin-1-yl)(phenyl)methanone,[21] Ethyl 4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxilate,[22] tert-butyl 4-((3,4-trans)-1-(4-fluorobenzyl)-4-hydroxypyrrolidine-3-yl)piperazine-1-carboxylate,[23] (3,4-trans)-1-benzyl-4-(4-methylpiperazin-1-yl)pyrrolidine-3-ol,[24] tert-butyl-4-(3,4-trans)-4-acetoxy-1-benzylpyrrolidine-3-yl)piperazine-1-carboxylate,[25] (3,4-trans)-1-benzyl-4-(piperazin-1-yl)pyrrolidine-3-yl acetate,[26] tert-butyl 4-((3,4-trans)-4-acetoxypyrrolidine-3-yl)piperazine-1-carboxylate,[27] trans 1-Benzyl-4-(4-(2-phenyl-phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,[28] trans 1-Benzyl-4-(4-(2-phenyl-phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[29] (3,4-trans)-1-benzyl-4-(phenylamino)pyrrolidin-3-ol,[30] (3,4-trans)-1-benzyl-4-(benzylamino)pyrrolidin-3-ol,[31] (3R,4R)-1-benzyl-4-(octylamino)pyrrolidin-3-ol,[32] (3,4-trans)-1-benzyl-4-(4-methoxybenzylamino)pyrrolidin-3-ol,[33] (3,4-trans)-1-benzyl-4-(butylamino)pyrrolidin-3-ol,[34] (3R,4R)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,[35] (3R,4R)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-yl acetate,[36] (3,4-trans)-1-benzyl-4-(butylamino)pyrrolidin-3-ol,[37] (3R,4R)-1-benzyl-4-(4-methoxyphenylamino)pyrrolidin-3-ol,[38] Methyl 4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidin-3-ylamino)benzoate,[39] (3R,4R)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,[40] (3R,4R)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,[41] (3R,4R)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,[42] (3R,4R)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,[43] (3R,4R)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,[44] (3R,4R)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,[45] (3R,4R)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,[46] (3R,4R)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,[47] (3R,4R)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,[48] (3R,4R)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,[49] (3R,4R)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,[50] (3R,4R)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,[51] (3R,4R)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-ol,[52] (3R,4R)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,[53] (3,4-trans)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,[54] (3,4-trans)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[55] (3S,4S)-1-benzyl-4-(4-(4-chloro-2,5-dimethylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[56] (3,4-trans)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,[57] (3,4-trans)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[58] (3R,4R)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-ol dihydorchloride,[59] (3S,4S)-1-benzyl-4-(4-tosylpiperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[60] (3,4-trans)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,[61] (3,4-trans)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[62] (3S-4S)-1-benzyl-4-(4-(naphthalen-1-ylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[63] (3,4-trans)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,[64] (3,4-trans)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[65] (3S,4S)-1-benzyl-4-(4-(2-chlorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[66] (3,4-trans)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,[67] (3,4-trans)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[68] (3S,4S)-1-benzyl-4-(4-(2-bromophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[69] (3,4-trans)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,[70] (3,4-trans)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[71] (3S,4S)-1-benzyl-4-(4-(5-fluoro-2-methylphenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[72] (3,4-trans)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate,[73] (3,4-trans)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,[74] (3S,4S)-1-benzyl-4-(4-(phenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol,[75] (3,4-trans)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-yl acetate dihydrochloride,[76] (3,4-trans)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[77] (3S,4S)-1-benzyl-4-(4-(2-fluorophenylsulfonyl)piperazin-1-yl)pyrrolidin-3-ol dihydrochloride,[78] (3,4-trans)-1-benzyl-4-(4-(2-chloro-6-fluorobenzyl)piperazin-1-yl)pyrrolidine-3-ol[79] (3,4-trans)-1-benzyl-4-(4-(3,4-dichlorobenzyl)piperazin-1-yl)pyrrolidine-3-ol[80] (3,4-trans)-1-benzyl-4-hydroxypyrrolidin-3-yl)piperazin-1-yl)(furan-2-yl)methanone[81] (3,4-trans)-1-benzyl-4-(4-ethylpiperazin-1-yl)pyrrolidin-3-ol,[82] (3,4-trans)-1-benzyl-4-(4-(2-methoxyphenyl)piperazin-1-yl)pyrrolidin-3-ol,[83] (3,4-trans)-1-benzyl-4-(4-(4-fluorophenyl)piperazin-1-yl)pyrrolidin-3-ol,[84] (3,4-trans)-1-benzyl-4-(4-(2-chlorophenyl)piperazin-1-yl)pyrrolidin-3-ol,[85] (3R,4R)-1-benzyl-4-(4-(2-chlorophenyl)piperazin-1-yl)pyrrolidin-3-ol,[86] (35,45)-1-benzyl-4-(4-(2-chlorophenyl)piperazin-1-yl)pyrrolidin-3-ol,[87] 1-(4-((3,4-trans)-1-benzyl-4-hydroxypyrrolidin-3-yl)piperazin-1-yl)ethanone,[88] (3,4-trans)-1-benzyl-4-(4-(3,4-dichlorophenyl)piperazin-1-yl)pyrrolidin-3-ol,[89] (3,4-trans)-1-benzyl-4-(4-(3,4-dichlorophenyl)piperazin-1-yl)pyrrolidin-3-ol, or[90] (3,4-trans)-cert-butyl 3-(3,4-dihydroisoquinolin-2(1H)-yl)-4-hydroxypyrrolidine-1-carboxylate;optionally in form of a corresponding salt, or a corresponding solvate.
  • 26. Substituted pyrrolidine compounds according to claim 1 of general formula (IA),
  • 27. Substituted pyrrolidine compounds according to claim 26whereinZ represents H or CH3; preferably Z represents H;R2 represents a hydrogen atom; a methyl, ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a (C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; preferably R2 represents a hydrogen atom; a (C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl groupR3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, unsubstituted C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-cycloalkyl group; an unsubstituted alkyl-aryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;orR3 and R4 together with their bridging nitrogen atom form 1) a ring system A, comprising:
  • 28. Substituted pyrrolidine compounds according to claim 27, according to either formula (IAa) or (IAb)
  • 29. Substituted pyrrolidine compounds according to claim 1 of general formula (IB),
  • 30. Substituted pyrrolidine compounds according to claim 29, whereinR2 represents a hydrogen atom; a methyl, ethyl, propyl or butyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; a (C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl group; or a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH, CF3; preferably R2 represents a hydrogen atom; a (C═O)—R8 group, with R8 representing a hydrogen atom; a methyl group; an ethyl group; a propyl group; a butyl group; a pentyl group; a hexyl groupR3 and R4, identical or different, represent a hydrogen atom; a saturated or unsaturated, unsubstituted C3-8 aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group; an unsubstituted heteroaryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-cycloalkyl group; an unsubstituted alkyl-aryl group; a saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group; with the condition that R3 and R4 may not at the same time represent a hydrogen atom;orR3 and R4 together with their bridging nitrogen atom form 1) a ring system A, comprising:
  • 31. Substituted pyrrolidine compounds according to claim 1 according to general formula (I), whereinR1 represents H or C(O)OCH3;R2 represents a hydrogen atom; a substituted or unsubstituted aliphatic group; a (C═O)—R8 group; a benzyl group which is optionally substituted by one or more substituents independently selected from the group consisting of F, Cl, Br, I, NH2, SH, OH;R3 and R4, equal or different, represent a hydrogen atom;an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloalkyl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group in which the cycloalkyl group may be optionally at least mono-substituted; an optionally at least mono-substituted aryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an optionally at least mono-substituted heteroaryl group which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be optionally at least mono-substituted and/or condensed with a mono- or polycyclic ring system; with the condition (proviso) that R3 and R4 may not at the same time represent a hydrogen atom;orR3 and R4 together with their bridging nitrogen atom form 1) a saturated or unsaturated ring system A, comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;2) an A-X—B group, whereinA represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;3) an A-X—B—Y—C group, whereinA represents a saturated or unsaturated ring system comprising 1 to 3 optionally condensed rings, in which additionally at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R10 group; or a (C═O)—NR12R12a group;X represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;B represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;Y represents a bond, a —NH— group, a —(C═O)— group, a branched or linear, optionally substituted C1-6-aliphatic chain, —O—, or a —SO2— group;C represents a saturated or unsaturated ring system comprising 1 to 2 optionally condensed rings, in which at least 1 carbon atom is optionally replaced by N, S or O and which is optionally at least mono-substituted by F, Cl, Br, I, NH2, SH, OH, oxo, CF3, a C1-6-aliphatic group; a C1-6-alkyl-aryl group; a C1-6-alkyl-heteroaryl group; a C1-6-alkoxy group; a (C═O)—R9 group; a (C═O)—OR10 group; a CH2-(C═O)—O—R11 group; a (SO2)—R11 group; a NH—R11 group; or a (C═O)—NR12R12a group;R8 represents a hydrogen atom; a branched or unbranched, saturated or unsaturated, unsubstituted aliphatic group;R9, R10 and R11 represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;R12 and R12a, identical or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic radical; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing alkyl-cycloalkyl group; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-aryl group in which the aryl group may be condensed with a mono- or polycyclic ring system; a branched or unbranched, saturated or unsaturated, optionally at least mono-substituted alkyl-heteroaryl group in which the heteroaryl group may be condensed with a mono- or polycyclic ring system;
  • 32. A process for the manufacture of substituted pyrrolidine compounds of general formula (I) according to claim 1, characterized in that at least one pyrroline compound of general formula (II),
  • 33. A medicament comprising at least one substituted pyrrolidine compound of general formula (I) according to claim 1,
  • 34-57. (canceled)
  • 58. A method for the prophylaxis and/or treatment of a sigma receptor-mediated disease or condition, which comprises administering to a subject in need thereof at least one substituted pyrrolidine compound according to claim 1.
  • 59-63. (canceled)
Priority Claims (1)
Number Date Country Kind
06384009.4 Apr 2006 EP regional
PCT Information
Filing Document Filing Date Country Kind 371c Date
PCT/EP2007/003828 4/30/2007 WO 00 3/20/2009