Substituted pyrazoline compounds, their preparation and use as medicaments

Abstract

The present invention relates to substitute pyrazoline 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.

1 . Substituted pyrazoline compounds of general formula I, 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  represents an optionally at least mono-substituted phenyl group; 
 R 2  represents an optionally at least mono-substituted phenyl group; 
 R 3  represents a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; or R 3  represents an optionally at least mono-substituted aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; or R 3  represents an —NR 4 R 5 -moiety, 
 R 4  and R 5 , 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 cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; or an optionally at least mono-substituted aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system and/or bonded via a linear or branched alkylene group; an —SO 2 —R 6 -moiety, or an —NR 7 R 8 -moiety, 
 with the provisos 
 that R 4  and R 5  do not both represent a hydrogen atom; and 
 that if one of the residues R 4  and R 5  represents a hydrogen atom or an alkyl, group, which is optionally at least mono-substituted with an alkoxy group, an alkoxyalkoxy group, a halogen atom or a phenyl group, the other one of these residues R 4  and R 5  does not represent a pyrid-2-yl group, which is optionally mono-substituted in the 5-position; a pyrid-5-yl group, which is optionally mono-substituted in the 2-position; a pyrimid-5-yl group, which is optionally mono-substituted in the 2-position; a pyridaz-3-yl group, which is optionally mono-substituted in the 6-position; a pyrazin-5-yl group, which is optionally mono-substituted in the 2-position; a thien-2-yl group, which is optionally mono-substituted in the 5 position; a thien-2-yl group, which is optionally at least mono-substituted in the 4-position; a benzyl group, which is optionally mono-substituted in the 4-position of the ring; a phenethyl group, which is optionally mono-substituted in the 4-position of the ring; an optionally mono-, di- or tri-substituted phenyl group; a di-substituted phenyl group, wherein the two substituents together form an —OCH 2 O—, —OCH 2 CH 2 O— or —CH 2 CH 2 O— chain, which is optionally substituted with one or more halogen atoms or one or two methyl groups; an —NH-phenyl-moiety, wherein the phenyl group may be mono-substituted in the 4-position, and 
 that if one of the residues R 4  and R 5  represents an alkynyl group, the other one of these residues R 4  and R 5  does not represent a phenyl group, which is optionally substituted in the 4-position, and 
 that if one of the residues R 4  and R 5  represents a hydrogen atom or a linear or branched, saturated or unsaturated, unsubstituted or substituted aliphatic radical, the other one of these residues R 4  and R 5  does not represent an unsubstituted or substituted thiazole group or an unsubstituted or substituted [1,3,4]thiadiazole group; 
 R 6  represents a linear or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloaliphatic group, which may be condensed with a mono- or polycyclic ring-system; or an optionally at least mono-substituted aryl or heteroaryl group, which may be condensed with a mono- or polycyclic ring system and/or bonded via a linear or branched alkylene group; 
 R 7  and R 8 , 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 cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; or an optionally at least mono-substituted aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system and/or bonded via a linear or branched alkylene 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 N-oxide thereof, or a corresponding salt thereof, or a corresponding solvate thereof. 
 
     
     
         2 . Compounds according to  claim 1 , wherein R 1  represents a phenyl group, which is optionally substituted by one or more substituents independently selected from the group consisting of a linear or branched C 1-6 -alkyl group, a linear or branched C 1-6 -alkoxy group, a halogen atom, CH 2 F, CHF 2 , CF 3 , CN, OH, NO 2 , —(C═O)—R′, SH, SR′, SOR′, SO 2 R′, NH 2 , NHR′, NR′R″, —(C═O)—NH 2 , —(C═O)—NHR′ and —(C═O)—NR′R″, whereby R′ and R″ for each substituent independently represent linear or branched C 1-6  alkyl, preferably R 1  represents a phenyl group, which is optionally substituted by one or more substituents selected from the group consisting of methyl, ethyl, F, Cl, Br and CF 3 , more preferably R 1  represents a phenyl group, which is mono-substituted with a chlorine atom in the 4-position. 
     
     
         3 . Compounds according to  claim 1 , wherein R 2  represents a phenyl group, which is optionally substituted by one or more substituents independently selected from the group consisting of a linear or branched C 1-6 -alkyl group, a linear or branched C 1-6 -alkoxy group, a halogen atom, CH 2 F, CHF 2 , CF 3 , CN, OH, NO 2 , —(C═O)—R′, SH, SR′, SOR′, SO 2 R′, NH 2 , NHR′, NR′R″, —(C═O)—NH 2 , —(C═O)—NHR′ and —(C═O)—NR′R″ whereby R′ and R″ for each substituent independently represent linear or branched C 1-6  alkyl, preferably R 2  represents a phenyl group, which is optionally substituted by one or more substituents selected from the group consisting of methyl, ethyl, F, Cl, Br and CF 3 , more preferably R 2  represents a phenyl group, which is di-substituted with two chlorine atoms in the 2- and 4-position. 
     
     
         4 . Compounds according to  claim 1 , wherein R 3  represents a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing C 3-8  cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system, or R 3  represents an optionally at least mono-substituted, 5- or 6-membered aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system, or R 3  represents an —NR 4 R 5 -moiety, preferably R 3  represents a saturated, optionally at least mono-substituted, optionally one or more nitrogen-atoms as ring member containing C 3-8  cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system, or R 3  represents an —NR 4 R 5 -moiety, more preferably R 3  represents a pyrrolidinyl group, a piperidinyl group or a piperazinyl group, whereby each of these groups may be substituted with one or more C 1-6 -alkyl groups, or R 3  represents an —NR 4 R 5 -moiety. 
     
     
         5 . Compounds according to  claim 1 , wherein R 4  and R 5 , identical or different, represent a hydrogen atom; an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted C 1-6 -aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing C 3-8 -cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; or an optionally at least mono-substituted, 5- or 6-membered aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system and/or bonded via a methylene (—CH 2 —) or ethylene (—CH 2 -CH 2 )-group; an —SO 2 —R 6 -moiety, or an —NR 7 R 8 -moiety, preferably one of these residues R 4  and R 5  represents a hydrogen atom and the other one of these residues R 4  and R 5  represents a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing C 3-8 -cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; or an optionally at least mono-substituted, 5- or 6-membered aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an —SO 2 —R 6 -moiety; or an —NR 7 R 8 -moiety, or R 4  and R 5 , identical or different, each represent a C 1-6  alkyl group, more preferably one of these residues R 4  and R 5  represents a hydrogen atom and the other one of these residues R 4  and R 5  represents an optionally at least mono-substituted pyrrolidinyl group; an optionally at least mono-substituted piperidinyl group; an optionally at least mono-substituted piperazinyl group; an optionally at least mono-substituted triazolyl group; an —SO 2 —R 6 -moiety; or an —NR 7 R 8 -moiety, or R 4  and R 5 , identical or different, represent a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group or a tert-butyl group. 
     
     
         6 . Compounds according to  claim 1 , wherein R 6  represents a linear or branched, saturated or unsaturated, optionally at least mono-substituted C 1-6  aliphatic group, a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing C 3-8  cycloaliphatic group, which may be condensed with a mono- or polycyclic ring-system; or an optionally at least mono-substituted, 5- or 6-membered aryl or heteroaryl group, which may be condensed with a mono- or polycyclic ring system and/or bonded via a methylene (—CH 2 —) or ethylene (—CH 2 —CH 2 )-group, preferably R 6  represents a C 1-6 -alkyl group; a saturated, optionally at least mono-substituted cycloaliphatic group, which may be condensed with a mono- or polycyclic ring-system; or a phenyl group, which is optionally substituted with one or more C 1-6  alkyl groups. 
     
     
         7 . Compounds according to  claim 1 , wherein R 7  and R 8 , identical or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted C 1-6  aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing C 3-8  cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; or an optionally at least mono-substituted, 5- or 6 membered aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system and/or bonded via a methylene (—CH 2 —) or ethylene (—CH 2 —CH 2 )-group, preferably R 7  and R 8 , identical or different, represents a hydrogen atom; or a C 1-6  alkyl radical. 
     
     
         8 . Compounds of general formula I according to  claim 1   
       
         
           
           
               
               
           
         
       
       wherein
 R 1  represents a phenyl ring, which is mono-substituted with a halogen atom, preferably a chlorine atom, in its 4-position, 
 R 2  represents a phenyl ring, which is di-substituted with two halogen atoms, preferably chlorine atoms, in its 2- and 4-position, 
 R 3  represents a pyrrolidinyl group; a piperidinyl group; a piperazinyl group; a homo-piperazinyl group; a morpholinyl group; or an —NR 4 R 5 -moiety, 
 R 4  represents a hydrogen atom or a linear or branched C 1-6 -alkyl group, 
 R 5  represents a linear or branched C 1-6  alkyl group; an SO 2 —R 6 -moiety; a pyrrolidinyl group; a piperidinyl group; a piperazinyl group; a homo-piperazinyl group; a morpholinyl group; a triazolyl group, whereby each of the heterocyclic rings may be substituted with one or more, identical or different, C 1-6 -alkyl groups, and 
 R 6  represents a phenyl group, which is optionally substituted with one or more C 1-6  alkyl groups, which may be identical or different, 
 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 N-oxide thereof, or a corresponding salt thereof, or a corresponding solvate thereof. 
 
     
     
         9 . Compounds according to  claim 1  selected from the group consisting of: 
       N-piperidinyl-5-(4-chloro-phenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide, 
       5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid-[1,2,4]-triazole-4-yl-amide, 
       5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid-(4-methyl-piperazin-1-yl)-amide, 
       5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid diethylamide, 
       [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-piperidine-1-yl-methanone, 
       N-[5-(4-Chloro-phenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carbonyl]-4-methylphenylsufonamide,
 optionally in the form of a corresponding N-oxide, or a corresponding salt, or a corresponding solvate. 
 
     
     
         10 . Process for the manufacture of substituted pyrazoline compounds of general formula I according to  claim 1 , wherein at least one benzaldehyde compound of general formula II 
       
         
           
           
               
               
           
         
       
       wherein R 1  has the meaning according to one or more of  claims 1 - 9 , is reacted with a pyruvate compound of general formula (III) 
       
         
           
           
               
               
           
         
       
       wherein G represents an OR group with R being a branched or unbranched C 1-6  alkyl radical or G represents an O − K group with K being a cation, to yield a compound of general formula (IV) 
       
         
           
           
               
               
           
         
       
       wherein R 1  has the meaning given above, which is optionally isolated and/or optionally purified, and which is reacted with an optionally substituted phenyl hydrazine of general formula (V) 
       
         
           
           
               
               
           
         
       
       or a corresponding salt thereof, wherein R 2  has the meaning according to one or ore of  claims 1 - 9 , under inert atmosphere, to yield a compound of general formula (VI) 
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 2  have the meaning as given above, which is optionally isolated and/or optionally purified, and optionally transferred under inert atmosphere to a compound of general formula (VII) via the reaction with an activating agent 
       
         
           
           
               
               
           
         
       
       wherein the substituents R 1  and R 2  have the meaning given above and A represents a leaving group, said compound being optionally isolated and/or optionally purified, and at least one compound of general formula (VI) is reacted with a compound of general formula R 3 H, wherein R 3  represents an —NR 4 R 5 -moiety, wherein R 4  and R 5  have the meaning to one or more of  claims 1 - 9 , under inert atmosphere to yield a substituted pyrazoline compound of general formula I, wherein R 3  represents an —NR 4 R 5 -moiety,
 and/or at least one compound of general formula (VII) is reacted with a compound of the general formula R 3 H, in which R 3  has the meaning according to one or more of  claims 1 - 9  under inert atmosphere to yield a compound of general formula (I) according to one or ore of  claims 1 - 9 , which is optionally isolated and/or optionally purified. 
 
     
     
         11 . Medicament comprising at least one substituted pyrazoline compound of general formula I, 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  represents an optionally at least mono-substituted phenyl group; 
 R 2  represents an optionally at least mono-substituted phenyl group; 
 R 3  represents a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system, or R 3  represents an optionally at least mono-substituted aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system, or R 3  represents an —NR 4 R 5 -moiety, 
 R 4  and R 5 , 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 cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; or an optionally at least mono-substituted aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system and/or bonded via a linear or branched alkylene group; an —SO 2 —R 6 -moiety; or an —NR 7 R 8 -moiety, with the provsio that R 4  and R 5  do not identically represent hydrogen; 
 R 6  represents a linear or branched, saturated or unsaturated, optionally at least mono-substituted aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing cycloaliphatic group, which may be condensed with a mono- or polycyclic ring-system; or an optionally at least mono-substituted aryl or heteroaryl group, which may be condensed with a mono- or polycyclic ring system and/or bonded via a linear or branched alkylene group; 
   7  and R 8 , 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 cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; or an optionally at least mono-substituted aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system and/or bonded via a linear or branched alkylene 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 N-oxide thereof, or a corresponding salt thereof, or a corresponding solvate thereof, and optionally one or more pharmaceutically acceptable excipients. 
 
     
     
         12 . Medicament according to  claim 11 , wherein R 1  represents a phenyl group, which is optionally substituted by one or more substituents independently selected from the group consisting of a linear or branched C 1-6 -alkyl group, a linear or branched C 1-6 -alkoxy group, a halogen atom, CH 2 F, CHF 2 , CF 3 , CN, OH, NO 2 , —(C═O)—R′, SH, SR′, SOR′, SO 2 R′, NH 2 , NHR′, NR′R″, —(C═O)—NH 2 , —(C═O)—NHR′ and —(C═O)—NR′R″, whereby R′ and R″ for each substituent independently represent linear or branched C 1-6  alkyl, preferably R 1  represents a phenyl group, which is optionally substituted by one or more substituents selected from the group consisting of methyl, ethyl, F, Cl, Br and CF 3 , more preferably R 1  represents a phenyl group, which is mono-substituted with a chlorine atom in the 4-position. 
     
     
         13 . Medicament according to  claim 11 , wherein R 2  represents a phenyl group, which is optionally substituted by one or more substituents independently selected from the group consisting of a linear or branched C 1-6 -alkyl group, a linear or branched C 1-6 -alkoxy group, a halogen atom, CH 2 F, CHF 2 , CF 3 , CN, OH, NO 2 , —(C═O)—R′, SH, SR′, SOR′, SO 2 R′, NH 2 , NHR′, NR′R″, —(C═O)—NH 2 , —(C═O)—NHR′ and —(C═O)—NR′R″, whereby R′ and optionally R″ for each substituent independently represent linear or branched C 1-6  alkyl, preferably R 2  represents a phenyl group, which is optionally substituted by one or more substituents independently selected from the group consisting of methyl, ethyl, F, Cl, Br and CF 3 , more preferably R 2  represents a phenyl group, which is di-substituted with a chlorine atom in its 2- and 4-position. 
     
     
         14 . Medicament according to  claim 11 , wherein R 3  represents a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing C 3-8  cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system, or R 3  represents an optionally at least mono-substituted, 5- or 6-membered aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system, or R 3  represents an —NR 4 R 5 -moiety, preferably R 3  represents a saturated, optionally at least mono-substituted, optionally one or more nitrogen-atoms as ring member containing C 3-8  cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system, or R 3  represents an —NR 4 R 5 -moiety, more preferably R 3  represents a pyrrolidinyl group, a piperidinyl group or a piperazinyl group, whereby each of these groups may be substituted with one or more C 1-6 -alkyl groups, or R 3  represents an —NR 4 R 5 -moiety. 
     
     
         15 . Medicament according to  claim 11 , wherein R 4  and R 5 , identical or different, represent a hydrogen atom; an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted C 1-6 -aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing C 3-8 -cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; or an optionally at least mono-substituted, 5- or 6-membered aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system and/or bonded via a methylene (—CH 2 —) or ethylene (—CH 2 -CH 2 )-group; an —SO 2 —R 6 -moiety; or an —NR 7 R 8 -moiety, preferably one of these residues R 4  and R 5  represents a hydrogen atom and the other one of these residues R 4  and R 5  represents a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing C 3-8 -cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; or an optionally at least mono-substituted, 5- or 6-membered aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; an —SO 2 —R 6 -moiety; or an —NR 7 R 8 -moiety, or R 4  and R 5 , identical or different, each represent a C 1-6  alkyl group, more preferably one of these residues R 4  and R 5  represents a hydrogen atom and the other one of these residues R 4  and R 5  represents an optionally at least mono-substituted pyrrolidinyl group; an optionally at least mono-substituted piperidinyl group; an optionally at least mono-substituted piperazinyl group; an optionally at least mono-substituted triazolyl group; an —SO 2 —R 6 -moiety; or an —NR 7 R 8 -moiety, or R 4  and R 5 , identical or different, represent a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group or a tert-butyl group. 
     
     
         16 . Medicament according to  claim 11 , wherein R 6  represents a linear or branched, saturated or unsaturated, optionally at least mono-substituted C 1-6  aliphatic group; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing C 3-8  cycloaliphatic group, which may be condensed with a mono- or polycyclic ring-system; or an optionally at least mono-substituted, 5- or 6-membered aryl or heteroaryl group, which may be condensed with a mono- or polycyclic ring system and/or bonded via a methylene (—CH 2 —) or ethylene (—CH 2 —CH 2 )-group, preferably R 6  represents a C 1-6 -alkyl group; a saturated, optionally at least mono-substituted cycloaliphatic group, which may be condensed with a mono- or polycyclic ring-system; or a phenyl group, which is optionally substituted with one or more C 1-6  alkyl groups. 
     
     
         17 . Medicament according to  claim 11 , wherein R 7  and R 8 , identical or different, represent a hydrogen atom, an unbranched or branched, saturated or unsaturated, optionally at least mono-substituted C 1-6  aliphatic radical; a saturated or unsaturated, optionally at least mono-substituted, optionally at least one heteroatom as ring member containing C 3-8  cycloaliphatic group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system; or an optionally at least mono-substituted, 5- or 6 membered aryl or heteroaryl group, which may be condensed with an optionally at least mono-substituted mono- or polycyclic ring system and/or bonded via a methylene (—CH 2 —) or ethylene (—CH 2 —CH 2 )-group, preferably R 7  and R 8 , identical or different, represents a hydrogen atom or a C 1-6  alkyl radical. 
     
     
         18 . Medicament according to  claim 11 , comprising at least one compound of general formula I 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  represents a phenyl group, which is optionally substituted by one or more substituents independently selected from the group consisting of methyl, ethyl, F, Cl, Br and CF 3 , 
 R 2  represents a phenyl group, which is optionally substituted by one or more substituents independently selected from the group consisting of methyl, ethyl, F, Cl, Br and CF 3 , 
 R 3  represents a pyrrolidinyl group, a piperidinyl group or a piperazinyl group, whereby each of these groups may be substituted with one or more C 1-6 -alkyl groups, or R 3  represents an —NR 4 R 5 -moiety, 
 one of the residues R 4  and R 5  represents a hydrogen atom and the other one of these residues R 4  and R 5  represents an optionally at least mono-substituted pyrrolidinyl group; an optionally at least mono-substituted piperidinyl group; an optionally at least mono-substituted piperazinyl group; an optionally at least mono-substituted triazolyl group; an —SO 2 -R 6 -moiety; or an —NR 7 R 8 -moiety, or R 4  and R 5 , identical or different, represents a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group or a tert.-butyl group, 
 R 6  represents a C 1-6 -alkyl group; a saturated, optionally at least mono-substituted cycloaliphatic group, which may be condensed with a mono- or polycyclic ring-system; or a phenyl group, which is optionally substituted with one or more C 1-8  alkyl groups, and 
 R 7  and R 8 , identical or different, represents a hydrogen atom or a C 1-6  alkyl radical 
 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 N-oxide thereof, or a corresponding salt thereof, or a corresponding solvate thereof: 
 
     
     
         19 . Medicament according to  claim 11 , comprising at least one compound of general formula I 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  represents a phenyl group, which Is optionally substituted with 1, 2, 3, 4 or 5 substituents, independently selected from the group consisting of linear or branched C 1-6 -alkyl, linear or branched C 1-6 -alkoxy, F, Cl, Br, I, CH 2 F, CHF 2 , CF 3 , CN, OH, NO 2 , —(C═O)—R′, SH, SR′, SOR′, SO 2 R′, NH 2 , NHR′, NR′R″, —(C═O)—NH 2 , —(C═O)—NHR′ and —(C═O)—NR′R″, whereby R′ and R″ at each occurrence independently represents a linear or branched C 1-6  alkyl group, 
 R 2  represents a phenyl group, which Is optionally substituted with 1, 2, 3, 4 or 5 substituents, independently selected from the group consisting of linear or branched C 1-6 -alkyl, linear or branched C 1-6 -alkoxy, F, Cl, Br, I, CH 2 F, CHF 2 , CF 3 , CN, OH, NO 2 , —(C═O)—R′, SH, SR′, SOR′, SO 2 R′, NH 2 , NHR′, NR′R″, —(C═O)—NH 2 , —(C═O)—NHR′ and —(C═O)—NR′R″, whereby R′ and R″ at each occurrence independently represents a linear or branched C 1-6  alkyl group, 
 R 3  represents a saturated or unsaturated C 3-8  cycloaliphatic group, whereby said C 3-8  cycloaliphatic group is optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of linear or branched C 1-6  alkyl, linear or branched C 1-8  alkoxy, OH, F, Cl, Br, I, CN, CH 2 F, CHF 2 , CF 3  and oxo (═O) and whereby said C 3-8  cycloaliphatic group may contain 1, 2 or 3 heteroatoms independently selected from the group consisting of N, O and S as ring members, or R 3  represents an —NR 4 R 5 -moiety, 
 R 4  represents a hydrogen atom or a linear or branched C 1-8 -alkyl group, 
 R 5  represents a linear or branched C 1-6  alkyl group; an —SO 2 —R 6 -moiety; a saturated or unsaturated C 3-8  cycloaliphatic group, whereby said C 3-8  cycloaliphatic group is optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of linear or branched C 1-6  alkyl group, a linear or branched C 1-6  alkoxy group, OH, F, Cl, Br, I, CN CH 2 F, CHF 2 , CF 3  and oxo (═O) and whereby said C 3-8  cycloaliphatic group may contain 1, 2 or 3 heteroatoms independently selected from the group consisting of N, O and S as ring members, and 
 R 6  represents a phenyl group, which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of a linear or branched C 1-6 -alkyl group, a linear or branched C 1-6 -alkoxy group, F, Cl, Br, I, CH 2 F, CHF 2 , CF 3 , CN, OH, NO 2 , —(C═O)—R′, SH, SR′, SOR′, SO 2 R′, NH 2 , NHR′, NR′R″, —(C═O)—NH 2 , —(C═O)—NHR′ and —(C═O)—NR′R″, whereby R′ and R″ at each ocurrence independently represent a linear or branched C 1-6  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 N-oxide thereof, or a corresponding salt thereof, or a corresponding solvate thereof. 
 
     
     
         20 . Medicament according to  claim 11 , comprising at least one compound of general formula I 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  represents a phenyl group, which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of methyl, ethyl, F, Cl, Br and CF 3 , 
 R 2  represents a phenyl group, which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of methyl, ethyl, F, Cl, Br and CF 3 , 
 R 3  represents a pyrrolidinyl group, a piperidinyl group or a piperazinyl group, whereby each of these groups may be substituted with one or more C 1-6 -alkyl groups, or R 3  represents an —NR 4 R 5 -moiety, 
 R 4  represents a hydrogen atom or a linear or branched C 1-8 -alkyl group, 
 R 5  represents a linear or branched C 1-6  alkyl group; an —SO 2 - 13  R 6 -moiety; a pyrrolidinyl group; a piperidinyl group; a piperazinyl group; a homo-piperazinyl group; a morpholinyl group; a triazolyl group; whereby each of the heterocyclic rings may be substituted with one or more, identical or different, C 1-6 -alkyl groups, and 
 R 6  represents a phenyl group, which is optionally substituted with one or more C 1-8  alkyl groups, which may be identical or different, 
 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 ration, or a corresponding N-oxide thereof, or a corresponding salt thereof, or a corresponding solvate thereof. 
 
     
     
         21 . Medicament according to  claim 11 , comprising at least one compound of general formula I 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  represents a phenyl ring, which is mono-substituted with a halogen atom, preferably a chlorine atom, in its 4-position, 
 R 2  represents a phenyl ring, which is di-substituted with two halogen atoms, preferably chlorine atoms, in its 2- and 4-position, 
 R 3  represents a pyrrolidinyl group, a piperidinyl group, a piperazinyl group, a homo-piperazinyl group, a morpholinyl group, or an —NR 4 R 5 -moiety, 
 R 4  represents a hydrogen atom or a linear or branched C 1-6 -alkyl group, 
 R 5  represents a linear or branched C 1-6  alkyl group; an —SO 2 —R 6 -moiety, a pyrrolidinyl group; a piperidinyl group; a piperazinyl group; a homo-piperazinyl group; a morpholinyl group; or a triazolyl group whereby each of the heterocyclic rings may be substituted with one or more, identical or different, C 1-6 -alkyl groups, and 
 R 6  represents a phenyl group, which is optionally substituted with one or more C 1-6  alkyl groups, which may be identical or different, 
 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 N-oxide thereof, or a corresponding salt thereof, or a corresponding solvate thereof. 
 
     
     
         22 . Medicament according to  claim 11 , comprising at least one compound selected from the group consisting of: 
       N-piperidinyl-5-(4-chloro-phenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxamide, 
       5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid-[1,2,4]-triazole-4-yl-amide, 
       5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid-(4-methyl-piperazin-1-yl)-amide, 
       5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid diethylamide, 
       [5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4,5-dihydro-1H-pyrazole-3-yl]-piperidine-1-yl-methanone, 
       N-[5-(4-Chloro-phenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carbonyl]-4-methylphenylsufonamide,
 optionally in the form of a corresponding N-oxide, or a corresponding salt, or a corresponding solvate. 
 
     
     
         23 . A method for the modulation of cannabinoid-receptors, the method comprising administering to a patient an effective amount of a medicament according to  claim 11 . 
     
     
         24 . A method for the prophylaxis or treatment of food intake disorders, the method comprising administering to a patient an effective amount of a medicament according to  claim 11 . 
     
     
         25 . A method for the prophylaxis or treatment of psychosis, the method comprising administering to a patient an effective amount of a medicament according to  claim 11 . 
     
     
         26 . A method for the prophylaxis or treatment of drug abuse or drug addiction , the method comprising administering to a patient an effective amount of a medicament according to  claim 11 . 
     
     
         27 . A method for the prophylaxis or treatment of cancer, the method comprising administering to a patient an effective amount of a medicament according to  claim 11 . 
     
     
         28 . A method for the prophylaxis or treatment of one or more disorders selected from the group consisting of bone disorders, schizophrenia, anxiety, depression, epilepsy, neurodegenerative disorders, cerebellar disorders, spinocerebellar disorders, cognitive disorders, cranial trauma, head trauma, stroke panic attacks, peripheric neuropathy, glaucoma, migraine, Morbus Parkinson, Morbus Huntington, Morbus Alzheimer, Raynaud's disease, tremblement disorders, compulsive disorders, senile dementia, thymic disorders, tardive dyskinesia, bipolar disorders, medicament-induced movement disorders, dystonia, endotoxemic shock, hemorrhagic shock, hypotension, insomnia, immunologic disorders, sclerotic plaques, vomiting, diarrhea, asthma, memory disorders, pruritus, pain, or for potentiation of the analgesic effect of narcotic and non-narcotic analgesics, or for influencing intestinal transit, the method comprising administering to a patient an effective amount of a medicament according to  claim 11 . 
     
     
         29 - 34 . (canceled) 
     
     
         35 . The compound 
       
         
           
           
               
               
           
         
         optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two or the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. 
       
     
     
         36 . The method of  claim 23 , wherein the cannabinoid receptors are cannabinoid 1 (CB 1 ) receptors. 
     
     
         37 . A method for the prophylaxis and/or treatment of a disorder selected from the group consisting of disorders of the central nervous system, disorders of the immune system, disorders of the cardiovascular system, disorders of the endocrinous system, disorders of the respiratory system, disorders of the gastrointestinal tract, and reproductive disorders, the method comprising administering to a patient an effective amount of a medicament according to  claim 11 . 
     
     
         38 . The method of  claim 24 , wherein the food intake disorder is selected from the group consisting of bulimia, anorexia, cachexia, obesity, and type II diabetus mellitus (non-insuline dependent diabetes mellitus), the method comprising administering to a patient an effective amount of a medicament according to  claim 11 . 
     
     
         39 . The method of  claim 26 , wherein the drug abuse or drug addiction is alcohol abuse or alcohol addiction, or nicotine abuse or nicotine addiction. 
     
     
         40 . The method of  claim 27 , wherein the cancer is selected from the group consisting of brain cancer, bone cancer, lip cancer, mouth cancer, esophageal cancer, stomach cancer, liver cancer, bladder cancer, pancreas cancer, ovary cancer, cervical cancer, lung cancer, breast cancer, skin cancer, colon cancer, bowel cancer and prostate cancer. 
     
     
         41 . The method of  claim 28 , wherein the bone disorder is osteoporosis, cancer-associated bone disease, or Paget's disease of bone.