Combination of a CB1 receptor antagonist and of sibutramine, the pharmaceutical compositions comprising them and their use in the treatment of obesity

Abstract

The present invention relates to the combination of a CB1 receptor antagonist and of sibutramine, to the pharmaceutical compositions comprising them and to their use in the treatment of obesity.

1 . A combination of a CB1 [lacuna] antagonist and of sibutramine, its hydrate or one of its pharmaceutically acceptable salts.  
     
     
         2 . The combination as claimed in  claim 1 , for which the CB1 [lacuna] antagonist is a compound of formula:  
       
         
           
           
               
               
           
         
       
       in which 
 either R represents a chain (A) or (B) and  
                     
 R 1  represents a methyl or ethyl radical,  
 R 2  represents either an aromatic chosen from phenyl, naphthyl or indenyl, these aromatics being unsubstituted or substituted by one or more halogen, alkyl, alkoxy, —CO-alk, hydroxyl, —COOR 5 , formyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy, nitro, —NR 6 R 7 , —CO—NH—NR 6 R 7 , —N(alk)COOR 8 , cyano, —CONHR 9 , —CO—NR 16 R 17 , alkylsulfanyl, hydroxyalkyl, —O-alk-NR 12 R 13  or alkylthioalkyl, or a heteroaromatic chosen from the benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, indolinyl, indolyl, isochromanyl, isoquinolyl, pyridyl, quinolyl, 1,2,3,4-tetrahydroisoquinolyl, 1,2,3,4-tetrahydroquinolyl, thiazolyl or thienyl rings, it being possible for these heteroaromatics to be unsubstituted or substituted by a halogen, alkyl, alkoxy, —COOR 5 , trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy, nitro, —NR 6 R 7 , —CO—NH—NR 6 R), cyano, —CONHR 9 , alkylsulfanyl, hydroxyalkyl or alkylthioalkyl,  
 R 3  and R 4 , which are identical or different, represent either an aromatic chosen from phenyl, naphthyl or indenyl, these aromatics being unsubstituted or substituted by one or more halogen, alkyl, alkoxy, formyl, hydroxyl, trifluoromethyl, trifluoromethoxy, —CO-alk, cyano, —COOR 5 , —CONR 10 R 11 , —CO—NH—NR 6 R 7 , alkylsulfanyl, hydroxyalkyl, -alk-NR 6 R 7  or alkylthioalkyl, or a heteroaromatic chosen from the benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, furyl, isochromanyl, isoquinolyl, pyrrolyl, quinolyl, 1,2,3,4-tetrahydroisoquinolyl, thiazolyl or thienyl rings, it being possible for these heteroaromatics to be unsubstituted or substituted by a halogen, alkyl, alkoxy, hydroxyl, trifluoromethyl, trifluoromethoxy, cyano, —COOR 5 , —CO—NH—NR 6 R 7 , —CONR 10 R 11 , -alk-NR 6 R 7 , alkylsulfanyl, hydroxyalkyl or alkylthioalkyl,  
 R 5  is an alkyl radical or a phenyl radical optionally substituted by one or more halogen atoms,  
 R 6  and R 7 , which are identical or different, represent a hydrogen atom or an alkyl, -COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkyl radical or else R 6  and R 7  form, together with the nitrogen atom to which they are attached, a saturated or unsaturated and mono- or bicyclic heterocycle having 3 to 10 ring members optionally comprising another heteroatom chosen from oxygen, sulfur and nitrogen and optionally being substituted by one or more alkyl, -COalk, -COOalk, -CO-NHalk, -CS-NHalk, -CO-alk-NR 14 R 15 , oxo, hydroxyalkyl, -alk-O-alk or —CO—NH 2  radicals,  
 R 8  represents an alkyl radical,  
 R 9  represents a hydrogen atom or a radical of the type alkyl or alkyl substituted by dialkylamino, phenyl, cycloalkyl (optionally substituted by -COOalk) or a saturated or unsaturated and mono- or bicyclic heterocycle having 3 to 10 ring members optionally comprising one or more heteroatoms chosen from oxygen, sulfur and nitrogen and optionally being substituted by one or more alkyl radicals,  
 R 10  and R 11 , which are identical or different, represent a hydrogen atom or an alkyl radical or else R 10  and R 11  form, together with the nitrogen atom to which they are attached, a saturated mono- or bicyclic heterocycle having 3 to 10 ring members optionally comprising another heteroatom chosen from oxygen, sulfur and nitrogen and optionally being substituted by an alkyl radical,  
 R 12  and R 13 , which are identical or different, represent a hydrogen atom or an alkyl or cycloalkyl radical or else R 12  and R 13  form, together with the nitrogen atom to which they are attached, a saturated mono- or bicyclic heterocycle having 3 to 10 ring members optionally comprising another heteroatom chosen from oxygen, sulfur and nitrogen and optionally being substituted by an alkyl, -COalk, -COOalk, -CO-NHalk, -OS-NHalk or -CO-alk-NR 14 R 15  radical or a saturated mono- or bicyclic heterocycle having 3 to 10 ring members and comprising a heteroatom chosen from oxygen, sulfur and nitrogen,  
 R 14  and R 15 , which are identical or different, represent a hydrogen atom or an alkyl or -COOalk radical,  
 R 16  and R 17  form, together with the nitrogen atom to which they are attached, a saturated mono- or bicyclic heterocycle having 3 to 10 ring members optionally comprising another heteroatom chosen from oxygen, sulfur and nitrogen,  
 R′ represents a hydrogen atom or a -CO-alk radical,  
 or R represents a CHR 18  radical and  
 R 18  represents an —NHCOR 19  or —N(R 20 )—Y—R 21  and  
 Y is CO or SO 2 ,  
 R 4  and R 3 , which are identical or different, represent either an aromatic chosen from phenyl, naphthyl and indenyl, these aromatics being unsubstituted or substituted by one or more halogen, alkyl, alkoxy, formyl, hydroxyl, trifluoromethyl, trifluoromethoxy, -CO-alk, cyano, —COOH, -COOalk, —CONR 22 R 23 , —CO—NH—NR 24 R 25 , alkylsulfanyl, alkylsulfonyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkyl or -alk-NH 22 R 21 , or a heteroaromatic chosen from the benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, pyrimidinyl, furyl, imidazolyl, isochromanyl, isoquinolyl, pyrrolyl, pyridyl, quinolyl, 1,2,3,4-tetrahydroisoquinolyl, thiazolyl and thienyl rings, it being possible for these heteroaromatics to be unsubstituted or substituted by a halogen, alkyl, alkoxy, hydroxyl, trifluoromethyl, trifluoromethoxy, cyano, —COOH, -COOalk, —CO—NH—NR 24 R 25 , —CONR 22 R 23 , -alk-NR 24 R 25 , alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl or hydroxyalkyl,  
 R 19  represents an -alk-SO 2 -R 26  radical, an -alk-SO 2 —CH═CH—R 26  radical, a Het 1  radical substituted by —SO 2 —R 25  or a phenyl radical substituted by —SO 2 —R 26  or -alk-SO 2 —R 26 ,  
 R 20  represents a hydrogen atom or an alkyl radical,  
 R 21  represents a phenylalkyl, Het 1  or Ar 1  radical,  
 R 22  and R 23 , which are identical or different, represent a hydrogen atom or an alkyl radical or else R 22  and R 23  form, together with the nitrogen atom to which they are attached, a saturated mono- or bicyclic heterocycle having 3 to 10 ring members optionally comprising another heteroatom chosen from oxygen, sulfur and nitrogen and optionally being substituted by one or more alkyl,  
 R 24  and R 25 , which are identical or different, represent a hydrogen atom or an alkyl, -COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkyl radical or else R 24  and R 25  form, together with the nitrogen atom to which they are attached, a saturated or unsaturated mono- or bicyclic heterocycle having 3 to 10 ring members optionally comprising another heteroatom chosen from oxygen, sulfur and nitrogen and optionally being substituted by one or more alkyl, -COalk, -COOalk, -CO-NHalk, -CS-NHalk, oxo, hydroxyalkyl, -alk-O-alk or —CO—NH 2 ,  
 R 26  represents an alkyl, Ar 1  or Het 1  radical,  
 Ar 1  represents a phenyl, naphthyl or indenyl radical, these radicals optionally being substituted by one or more halogen, alkyl, alkoxy, cyano, -CO-alk, -COOH, -COOalk, —CONR 27 R 28 , —CO—NH—NR 29 R 30 , alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, -alk-NR 29 R 30 , —NR 29 R 30 , alkylthioalkyl, formyl, hydroxyl, hydroxyalkyl, Het, -O-alk-NH-cycloalkyl, OCF 3 , CF 3 , —NH—CO-alk, —SO 2 NH 2 , —NH—COCH 3 , -NH-COOalk or Het or else on 2 adjacent carbon atoms by dioxymethylene,  
 Het 1  represents an unsaturated or saturated mono or bicyclic heterocycle having 3 to 10 ring members and comprising one or more heteroatoms chosen from oxygen, sulfur and nitrogen which is optionally substituted by one or more alkyl, alkoxy, vinyl, halogen, alkoxycarbonyl, oxo, hydroxyl, OCF 3  or CF 3 , the nitrogenous heterocycles optionally being in their N-oxidized form,  
 R 27  and R 28 , which are identical or different, represent a hydrogen atom or an alkyl radical or else R 27  and R 28  form, together with the nitrogen atom to which they are attached, a saturated mono- or bicyclic heterocycle having 3 to 10 ring members optionally comprising another heteroatom chosen from oxygen, sulfur and nitrogen and optionally being substituted by one or more alkyl radicals,  
 R 29  and R 30 , which are identical or different, represent a hydrogen atom or an alkyl, -COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkyl radical or else R 29  and R 30  form, together with the nitrogen atom to which they are attached, a saturated or unsaturated mono- or bicyclic heterocycle having 3 to 10 ring members optionally comprising another heteroatom chosen from oxygen, sulfur and nitrogen and optionally being substituted by one or more alkyl, -COalk, -COOalk, -CO-NHalk, -CS-NHalk, oxo, hydroxyalkyl, -alk-O-alk or -CO-NH 2  radicals,  
 or R represents CHR 31  and  
 R 31  represents an —N(R 32 )R 33 , —N(R 32 )—CO—R 33  or —N(R 32 )—SO 2 R 34  radical,  
 R 4  and R 3 , which are identical or different, represent either an aromatic chosen from phenyl, naphthyl and indenyl, these aromatics being unsubstituted or substituted by one or more halogen, alkyl, alkoxy, formyl, hydroxyl, trifluoromethyl, trifluoromethoxy, -CO-alk, cyano, —COOH, COOalk, —CONR 22 R 25 , —CO—NH—NR 24 R 25 , alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkyl or -alk-NR 7 R 8 , or a heteroaromatic chosen from the benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, furyl, imidazolyl, isochromanyl, isoquinolyl, pyrrolyl, pyridyl, pyrimidyl, quinolyl, 1,2,3,4-tetra-hydroisoquinolyl, thiazolyl and thienyl rings, it being possible for these heteroaromatics to be unsubstituted or substituted by a halogen, alkyl, alkoxy, hydroxyl, trifluoromethyl, trifluoromethoxy, cyano, —COOH, -COOalk, —CO—NH—NR 24 R 25 , —CONR 22 R 23 , -alk-NR 24 R 25 , alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkyl sulfonylalkyl or hydroxyalkyl,  
 R 32  represents a C(R 35 ) (R 36 )-Het 2 , -Het 2 , —C(R 35 )(R 36 )—Ar 2 , Ar 2 , cycloalkyl or norbornyl radical,  
 R 33  represents a hydrogen atom or a hydroxyalkyl, -alk-COOalk, -alk-CONR 22 R 23 , -alk-NR 22 R 23 , alkoxy, Ar 2 , Het 2 , —CH 2 Ar 2 , —CH 2 Het 2  or alkyl radical, the latter optionally substituted by one or more halogen,  
 R 34  represents a hydroxyalkyl, -alk-COOalk, -alk-CONR 22 R 23 , -alk-NR 22 R 23 , alkoxy, Ar 2 , Het 2 , —CH 2 Ar 2 , -CH 2 Het 2  or alkyl radical, the latter optionally substituted by one or more halogen,  
 R 36  represents a hydrogen atom or a hydroxyalkyl, alk-COOalk, -alk-CONR 22 R 23 , -alk-NR 22 R 23 , alkoxyalkyl, Ar 2 , Het 2 , —CH 2 Ar 2 , —CH 2 Het 2  or alkyl radical, the latter optionally substituted by one or more halogen,  
 R 36  represents a hydrogen atom or a hydroxyalkyl, -alk-COOalk, -alk-CONR 22 R 23 , -alk-NR 22 R 23 , alkoxyalkyl or alkyl radical, the latter optionally substituted by one or more halogen,  
 or else R 35  and R 35  form, together with the carbon atom to which they are attached, a saturated mono- or bicyclic ring having 3 to 10 ring members optionally comprising another heteroatom chosen from oxygen, sulfur and nitrogen and optionally being substituted by one or more alkyl,  
 Ar 2  represents a phenyl, naphthyl or indenyl radical, these various radicals optionally being substituted by one or more halogen, alkyl, alkoxy, -CO-alk, cyano, —COOH, -COalk, —CONR 37 R 38 , —CO—NH—R 39 R 40 , alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, -alk-NR 39 R 40 , —NR 39 R 40 , alkylthioalkyl, formyl, CF 3 , OCF 3 , Het, -O-alkNH-cycloalkyl, SO 2 NH 2 , hydroxyl, hydroxyalkyl, -NHCOalk or NHOOalk or on 2 adjacent carbon atoms by dioxymethylene,  
 Het 2  represents an unsaturated or saturated mono- or bicyclic heterocycle having S to 10 ring members and comprising one or more heteroatoms chosen from oxygen, sulfur and nitrogen which is optionally substituted by one or more alkyl, alkoxy, halogen, alkoxycarbonyl, oxo or hydroxyl, the nitrogenous heterocycles optionally being in their N-oxidized form,  
 R 37  and R 38 , which are identical or different, represent a hydrogen atom or an alkyl radical or else R 37  and R 38  form, together with the nitrogen atom to which they are attached, a saturated mono- or bicyclic heterocycle having 3 to 10 ring members optionally comprising another heteroatom chosen from oxygen, sulfur and nitrogen and optionally being substituted by one or more alkyl,  
 R 39  and R 40 , which are identical or different, represent a hydrogen atom or an alkyl radical or else R 39  and R 40  form, together with the nitrogen atom to which they are attached, a saturated mono- or bicyclic heterocycle having 3 to 10 ring members optionally comprising another heteroatom chosen from oxygen, sulfur and nitrogen and optionally being substituted by one or more alkyl,  
 alk represents an alkyl or alkylene radical,  
 the alkyl and alkylene radicals and portions and the alkoxy radicals and portions have straight or branched chains and comprise 1 to 6 carbon atoms and the cycloalkyl radicals comprise 3 to 10 carbon atoms,  
 the optical isomers of these compounds and their pharmaceutically acceptable salts with an inorganic or organic acid.  
 
     
     
         3 . The combination as claimed in  claim 2 , for which the compound of formula (I) is chosen from the following compounds: 
 1-benzhydryl-3-[(methylsulfonyl)(phenyl)methylene]azetidine,    1-benzhydryl-3-[(3-methylphenyl)(methylsulfonyl)-methylene]azetidine,    1benzhydryl-3-[(3-chlorophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3,5-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(2,5-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(2,3-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3-fluorophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-1(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3-bromophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3-iodophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(methylsulfonyl)(3-trifluoromethoxyphenyl)methylene]azetidine,    1-benzhydryl-3-[(methylsulfonyl)(3trifluoromethylphenyl)methylene]azetidine,    1-benzhydryl-3-{[3,5-bis(trifluoromethyl)phenyl]-(methylsulfonyl)methylene}azetidine,    1-benzhydryl-3-[(3,5-dibromophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3-methoxycarbonylphenyl)-(methylsulfonyl)methylene]azetidine,    1-benzhydryl-3-[(3-cyanophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3-carbamoylphenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(methylsulfonyl)(naphth-1-yl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)miethylene]azetidine,    1-[bis(4-methoxyphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-methylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (RS)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-1-[(4-methoxyphenyl)(phenyl)methyl)]azetidine,    (R)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-1-[(4-methoxyphenyl)(phenyl)methyl]azetidine,    (S)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-1-[(4-methoxyphenyl)(phenyl)methyl]azetidine,    1-[bis(4-trifluoromethoxyphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-trifluoromethylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-{[3,5-bis(trifluoromethyl)phenyl]methylsulfonylmethylene}azetidine,    (RS)-1-[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,    (R)-1-[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,    (S)-1-[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl) methylene]azetidine,    (RS)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (S)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (RS)-1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (S)-1{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS) -(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmethyl)phenyl]methyl}-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmthyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{{(RS)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{{(R)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl)}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{{(S)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS) -(4-chlorophenyl)[4-(diisopropylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)-(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(diisopropylaminomethyl)-phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(diisopropylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)-methylene)azetidine,    1-{{(RS)-(4-chlorophenyl){4-[bis(2methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{{(R)-(4-chlorophenyl){4-[bis(2-methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{{(S)-(4-chlorophenyl){4-[his(2-methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-[di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(di-n-propylaminomethyl)phenyl]methyl}-3-1(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl) phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)(4-(diethylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(diethylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(diethylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)pphenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1{(R)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (RS)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (S)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (RS)-1-{(4-chlorophenyl)[4-(N-ethylcarbarmoyl)phenyl]methyl)}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)-1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (S)1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (RS)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-azetidine,    (R)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-azetidine,    (S)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3,5-dichlorophenyl)(methylsulfonyl)methylene]azetidine,    1-benzhydryl-3-[(3-methylsulfanylphenyl)(methylsulfonyl)methylene]azetidine,    1-benzhydryl-3-[(3-methylsulfanylmethyl)phenyl)]-(methylsulfonyl)methylene)azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3-cyanophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3-carbamoylphenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3-methoxyphenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3-hydroxyphenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(3-pyrrolidinylphenyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3-hydroxymethylphenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-{(methylsulfonyl)[3-(N-piperidylcarbamoyl)phenyl]methylene}azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(3-trifluoromethylsulfanylphenyl)(methylsulfonyl)-methylene]azetidine,    1-[bis(4-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(2-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(3-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (RS)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenylmethylene]azetidine,    (R)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,    (S)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,    (RS)-1-[(4-chlorophenyl)(thien-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)-1-[(4-chlorophenyl)(thien-2-yl)methyl]-3-[(3,5difluorophenyl)(methylsulfonyl)methylene]azetidine,    (S)-1-[(4-chlorophenyl)(thien-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-benzhydryl-3-[(ethylsulfonyl)(phenyl)methylene]-azetidine,    1-[bis(4-chlorophenyl)methyl]3-{{3-[N-(4-methylpiperazinyl)carbamoyl]phenyl}(methylsulfonyl)methylene}azetidine,    1-[bis(4-chlorophenyl)methyl]3-{[3-(2,2-dimethylcarbohydrazido)phenyl](methylsulfonyl)methylene}azetidine,    1-[bis(thien-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(p-tolyl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,    1-[(4-chlorophenyl)(4-hydroxymethylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3-methylaminophenyl)(methylsulfonyl)methylene]azetidine,    (RS)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (S)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methylene]azetidine,    (RS)-1-[bis(4-chlorophenyl)methyl]-3-hydroxy-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methyl]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(2isobutylamino-carbonylthien-5-yl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(3-methoxycarbonylphenyl)(methylsulfonyl)methyl]azetidin-3-ol,    1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(methylsulfonyl)(pyridin-4-yl)methyl]azetidin-3-ol,    1-[bis(4-chlorophenyl)methyl)-3-[(RS)-(methylsulfonyl)(pyridin-3-yl)methyl]azetidin-3-ol,    3-({1-[bis(4-chlorophenyl)methyl)azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-(morpholin-4-yl)propyl)benzamide,    3-({1[his(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-dimethylaminopropyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-(pyrrolidin-1-yl)ethyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl)azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-dimethylamino-1-methylethyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(piperidin-1-yl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-isobutylbenzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-(imidazol-1-yl)propyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-dimethylaminoethyl)benzamide,    N′-methylhydrazide of 3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)-methyl)benzoic acid,    3-({1-[bis(4-chlorophenyl)methylazetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-(morpholin-4-yl) ethyl)benzamide,    3-({1-bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(1-ethylpyrrolidin-2-ylmethyl)benzamide,    3-({1-(bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2,2-dimethylpropyl) benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(cyclohexylmethyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(cyclopropylmethyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-methylbutyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-phenylpropyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(tetrahydrofuran-2-ylmethyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2,2-diphenylethyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-ethylbutyl)benzamide,    methyl ester of 4-{[3-({1-[bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}(methanesulfonyl)methyl)benzoylamino]methyl}cyclohexanecarboxylic acid,    2-amino-1-{4-(3-({1-(bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]-piperazin-1-yl}ethanone,    tert-butyl ester of (2-{4-[3-({1-[bis(4-chlorophenyl)-methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-oxoethyl)carbamic acid,    1-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-(methylamino)ethanone,    tert-butyl ester of (2-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-oxoethyl)-N-methylcarbamic acid,    N-methylamide of 4-[3-({[1-bis(4-chlorophenyl)methylgazetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carbothioic acid,    N-methylamide of 4-[3-({1-[bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylic acid,    methyl ester of 4-[3-({1-[bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylic acid,    1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]-4-isobutylpiperazine,    1-[3-({1-[bis(4chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]-4-ethylpiperazine,    4-acetyl-1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine,    1-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-dimethylaminoethanone,    1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine,    tert-butyl ester of 4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylic acid,    1-[bis(4-methoxycarbonylphenyl)methyl]3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    3-acetoxy-1-[bis(4-methoxycarbonylphenyl)methyl]-3-[(RS)-(3,5-difluorophenyl)(methylsulfonyl)methyl]-azetidine,    (RS)-4-[4-((4-chlorophenyl){3-[(3,5-difluorophenyl)(methanesulfonyl)methylene]azetidin-1-yl}methyl)benzyl]morpholine,    4-(4-{3-[(1-benzhydrylazetidin-3-ylidene)(methanesulfonyl)methyl]phenoxy}butyl)morpholine,    4-(4-{3-[(1-benzhydrylazetidin-3-ylidene)(methanesulfonyl)methyl]phenoxy}propyl)morpholine,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}thien-2-ylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-methoxyphenylsulfonamide,    N-[4-(N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}sulfamoyl)phenyl]acetamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-methylphenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-dimethoxyphenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-fluorophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-dichlorophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-cyanophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2,5-dimethoxyphenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-trifluoromethylphenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}naphth-2-ylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}naphth-1-ylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-difluorophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-methyl-1H-imidazol-4-ylsulfonamide,    N-[4-(N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}sulfamoyl)-2-chlorophenyl]acetamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}pyrid-3-ylsulfonamide,    N-{1-[bis(4-chlorophenylmethyl]azetidin-3-yl}-4-fluorophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}quinol-8-ylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}phenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}(phenylmethyl)sulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,5-difluorophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}pyrid-2-ylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-(3-fluoro-5-pyrrolidin-1-ylphenyl)sulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-4-fluorophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methylquinol-8-ylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methylphenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl(phenylmethyl)sulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-sulfamoylphenylsulfonamide,    2-benzenesulfonyl-N-{1-[bis(4-chlorophenyl)methyl]-azetidin-3-yl}acetamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(4-toluene-4-sulfonyl)acetamide,    (3-chloro-4-(methylsulfonyl)thiophene-2-carboxy)-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl]amide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-(2-phenylethylenesulfonyl)propionamide,    N-[1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-(methylsulfonyl)benzamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-(methanesulfonyl)benzamide,    (5-(methylsulfonyl)thiophene-2-carboxy)-{1-[bis(4-chlorophenyl)methylazetidin-3-yl}amide,    (5-methylsulfonyl-3-methyl-4-vinylthiophene-2-carboxy){1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}amide,    (RS)-N-{1-[(4-chlorophenyl)(pyridin-3-yl)methyl]-azetidin-3-yl}-3,5-difluorobenzenesulfonamide,    (RS)-N-{1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl}-3,5-difluorobenzenesulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(6-chloropyrid-2-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(6-ethylpyrid-2-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(quinol-6-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(quinol-5-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(isoquinol-5-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-3-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-1-oxide-3-yl)methylsulfonamide,    N-(1R,2S,4S)-(bicyclo[2.2.1]hept-2-yl)-N-(1-[bis-(4-chlorophenyl)methylazetidin-3-yl)methylsulfonamide,    N-(1R,2R,4S)-(bicyclo[2.2.1]hept-2-yl)-N-{1-(bis-(4-chlorophenyl)methyl]azetidin-3-yl}methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(thiazol-2-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3-methoxyphenyl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3-hydroxyphenyl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3-(hydroxymethyl)phenyl)methylsulfonamide,    ethyl N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(methylsulfonyl)-3-aminobenzoate,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(isobutylpiperid-4-yl)methyl sulfonamide,    N-benzyl-N-{1-[bis(4-chlorophenyl)methyl)azetidin-3-yl}amine,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorobenzyl)amine,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorobenzyl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-3-ylmethyl)methylsulfonamide,    N-{1-[bis(4-fluorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    (RS)-N-{1-[(4-chlorophenyl)(pyrid-3-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    (R)-N-{1-[(4-chlorophenyl)(pyrid-3-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    (S)-N-{1-[(4-chlorophenyl)(pyrid-3-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    (RS)-N-{1-[(4-chlorophenyl)(pyrid-4-yl)methyl]azetidin-3-yl)-N-(3,5-difluorophenyl)methylsulfonamide,    (R)-N-{1-[(4-chlorophenyl)(pyrid-4-yl)methyl}azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    (S)-N-{1-[(4-chlorophenyl)(pyrid-4-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    (RS)-N-{1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    (R)-N-(1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl)-N-(3,5-difluorophenyl)methylsulfonamide,    (S)-N-{1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)benzylsulfonamide,    their optical isomers and their pharmaceutically acceptable salts.    
     
     
         4 . The combination as claimed in  claim 2 , for which the compound of formula (I) is chosen from 1.5 the following compounds: 
 1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(3,5-difluorophenyl)(methylsulfonyl)methyl]azetidin-3-ol,    3-acetoxy-1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(3,5-difluorophenyl)(methylulphonyl)methyl)methylsulfonyl-methylazetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    their optical isomers and their pharmaceutically acceptable salts.    
     
     
         5 . The combination as claimed in  claim 1 , in which the CB1 [lacuna] antagonist is SR141716, its hydrates and its pharmaceutically acceptable salts or LY320135 and its pharmaceutically acceptable salts.  
     
     
         6 . A pharmaceutical composition comprising a CE1 [lacuna] antagonist and sibutramine, its hydrate or one of its pharmaceutically acceptable salts in the pure state ox with one or more compatible and pharmacologically acceptable diluents and/or adjuvants and/or optionally in combination with another pharmaceutically compatible and physiologically active product.  
     
     
         7 . The pharmaceutical composition as claimed in  claim 6 , for which the CB1 [lacuna] antagonist [lacuna] of formula I as defined in  claim 2 .  
     
     
         8 . The pharmaceutical composition as claimed in  claim 7 , for which the compound of formula (1) is chosen from the following compounds: 
 1-benzhydryl-3-[(methylsulfonyl)(phenyl)methylene]azetidine,    1-benzhydryl-3-[(3-methylphenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3-chlorophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3,5-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(2,5-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(2,3-dichlorophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3-fluorophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3,5-difluorophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3bromophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3-iodophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-2-[(methylsulfonyl)(3-trifluoromethoxyphenyl)methylene]azetidine,    1-benzhydryl-3-[(methylsulfonyl)(3-trifluoromethylphenyl)methylene]azetidine,    1-benzhydryl-3-{[3,5-bis(trifluoromethyl)phenyl]-(methylsulfonyl)methylene}azetidine,    1-benzhydryl-3-[(3,5-dibromophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3-methoxycarbonylphenyl)(methylsulfonyl)methylene]azetidine,    1-benzhydryl-3-[(3-cyanophenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(3-carbamoylphenyl)(methylsulfonyl)-methylene]azetidine,    1-benzhydryl-3-[(methylsulfonyl)(naphth-1-yl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-methoxyphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-methylphenylmethyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (RS)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-1-[(4-methoxyphenyl)(phenyl)methyl)]azetidine,    (R)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-3-1-1(4-methoxyphenyl)(phenyl)methyl]azetidine,    (S)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]-1-[(4-methoxyphenyl)(phenyl)methyl]azetidine,    1-[bis(4-trifluoromethoxyphenyl)methyl-1-3-[(3,5-di-fluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-trifluoromethylphenyl)methyl]-3-[(3,5-di-fluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-{[3,5-bis(trifluoromethyl)phenyl]methylsulfonylmethylene}azetidine,    (RS)-1-[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)-1-[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)ethylene]azetidine,    (S)-1[(4-chlorophenyl)(2,4-dichlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)ethylene]azetidine,    (RS)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (S)-1{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methymene]azetidine,    (RS)-1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)-1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (S)-1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(3,3-dimethylpiperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(thiomorpholin-4-ylmthyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{{(RS)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{{(R)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{{(S)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-((4-chlorophenyl)[4-(diisopropylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(diisopropylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)14-(diisopropylaminomethyl)phenyl]methyl}-3-1(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{{(RS)-(4-chlorophenyl){4-[bis(2-methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{{(R)-(4-chlorophenyl){4-[bis(2-methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{{(S)-(4-chlorophenyl){4-[bis(2-methoxyethyl)aminomethyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-[di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1{(S)-(4-chlorophenyl)[4-(piperidin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(4-methylpiperazin-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-1(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-3-((3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(diethylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(diethylaminomethyl)phenyl]methyl}-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(diethylaminomethyl)phenyl]methyl}-3[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)phenyl]methyl}-3-1(3,5difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(piperazin-2-one-4-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(RS)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(R)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-{(S)-(4-chlorophenyl)[4-(imidazol-1-ylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (RS)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (S)-1-{(4chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (RS)-1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl)}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)-1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (S)-1-{(4-chlorophenyl)[4-(N-ethylcarbamoyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (RS)-1-[4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl -3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (S)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3,5-dichlorophenyl)(methylsulfonyl)methylene]azetidine,    1-benzhydryl-3-[(3-methylsulfanylphenyl)(methylsulfonyl)methylene]azetidine,    1-benzhydryl-3-[(3-methylsulfanylmethyl)phenyl)](methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-3-[(3-cyanophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3-carbamoylphenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3-methoxyphenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3-hydroxyphenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(3-pyrrolidinylphenyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3-hydroxymethylphenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-((methylsulfonyl)[3-(N-piperidylcarbamoyl)phenyl]methylene}azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(3-trifluoromethylsulfanylphenyl)(methylsulfonyl)-methylene]azetidine,    1-[bis(4-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(2-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(3-fluorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (RS)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,    (R)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,    (S)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,    (RS)-1-[(4-chlorophenyl)(thien-2-yl)methyl)-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)-1-[(4-chlorophenyl)(thien-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (S)-1-[(4-chlorophenyl)(thien-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-benzhydryl-3-[(ethylsulfonyl)(phenyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-{{3-[N-(4-methylpiperazinyl)carbamoyl]phenyl}(methylsulfonyl)methylene)azetidine,    1-[bis(4-chlorophenyl)methyl]-3-{[3-(2,2-dimethylcarbohydrazido)phenyl](methylsulfonyl)methylene}azetidine,    1-[bis(thien-2-yl)methyl]-3[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(p-tolyl)methyl]-3-[(methylsulfonyl)(phenyl)methylene]azetidine,    1-[(4-chlorophenyl)(4-hydroxymethylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3-methylaminophenyl)(methylsulfonyl)methylene]azetidine,    (RS)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (R)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    (S)-1-[(4-chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methylene]azetidine,    (RS)-1-[bis(4-chlorophenyl)methyl]3-hydroxy-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methyl]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(2-isobutylaminocarbonylthien-5-yl)(methylsulfonyl)methylene]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(3-methoxycarbonylphenyl)(methylsulfonyl)methyl]azetidin-3-ol,    1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(methylsulfonyl)(pyridin-4-yl)methyl]azetidin-3-ol,    1-[bis(4-chlorophenyl)methyl]-3-((RS)-(methylsulfonyl)(pyridin-3-yl)methyl]azetidin-3-ol,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-(morpholin-4-yl)propyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-dimethylaminopropyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-(pyrrolidin-1-yl)ethyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-dimethylamino-1-methylethyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(piperidin-1-yl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-isobutylbenzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(3-(imidazol-1-yl)propyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-dimethylaminoethyl)benzamide,    N′-methylhydrazide of 3-({1-[bis(4-chlorophenyl)methyl-3-azetidin-3-ylidene}(methanesulfonyl)methyl)benzoic acid,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-(morpholin-4-yl)ethyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(1-ethylpyrrolidin-2-ylmethyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2,2-dimethylpropyl)benzamide,    3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(cyclohexylmethyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(cyclopropylmethyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-methylbutyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-phenylpropyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(tetrahydrofuran-2-ylmethyl)benzamide,    3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2,2-diphenylethyl)benzamide,    3-({1-[bis(4-chlorophenylbmethyl]azetidin-3-ylidene}(methanesulfonyl)methyl)-N-(2-ethylbutyl)benzamide,    methyl ester of 4-{[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)benzoylamino]methyl}cyclohexanecarboxylic acid,    2-amino-1-{4-[3-({1-[bis(4-chlorophenyl)methyl]-azetidin-3ylidene}(methanesulfonyl)methyl)phenyl]-piperazin-1-yl}ethanone,    tert-butyl ester of (2-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-oxoethyl)carbamic acid,    1-(4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methylphenyl]piperazin-1-yl]-2-(methylamino)ethanone,    tert-butyl ester of (2-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-oxoethyl)-N-methylcarbamic acid,    N-methylamide of 4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carbothioic acid,    N-methylamide of 4-[3-({1-[bis(4-chlorophenyl)methyl]-azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylic acid,    methyl ester of 4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylic acid,    1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]-4-isobutylpiperazine,    1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]-4-ethylpiperazine,    4-acetyl-1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine,    1-{4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazin-1-yl}-2-dimethylaminoethanone,    1-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine,    tert-butyl ester of 4-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}(methanesulfonyl)methyl)phenyl]piperazine-1-carboxylic acid,    1-[bis(4-methoxycarbonylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,    3-acetoxy-1-[bis(4-methoxycarbonylphenyl)methyl]-3-[(RS)-(3,5-difluorophenyl)(methylsulfonyl)methyl]-azetidine,    (RS)-4-[4-((4-chlorophenyl){3-[(3,5 difluorophenyl)(methanesulfonyl)methylene]azetidin-1-yl}methyl)benzyl]morpholine,    4-(4-{3-[(1-benzhydrylazetidin-3-ylidene)(methanesulfonyl)methyl]phenoxy}butyl)morpholine,    4-(4-{3-[(1-benzhydrylazetidin-3-ylidene)(methanesulfonyl)methyl]phenoxy}propyl)morpholine,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}thien-2-ylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-methoxyphenylsulfonamide,    N-[4-(N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-sulfamoyl)phenyl]acetamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-methylphenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-dimethoxyphenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-fluorophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-dichlorophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-cyanophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2,5-dimethoxyphenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-trifluoromethylphenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}naphth-2-ylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}naphth-1-ylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-difluorophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-methyl-1H-imidazol-4-ylsulfonamide,    N-[4-(N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}sulfamoyl)-2-chlorophenyl]acetamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}pyrid-3-ylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-fluorophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}quinol-8-ylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}phenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}(phenylmethyl)sulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,5-difluorophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}pyrid-2-ylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-(3-fluoro-5-pyrrolidin-1-ylphenyl)sulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-4-fluorophenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methylquinol-8-ylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methylphenylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl(phenylmethyl)sulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-sulfamoylphenylsulfonamide,    2-benzenesulfonyl-N-{1-[bis(4-chlorophenyl)methyl]-azetidin-3-yl}acetamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(4-toluene-4-sulfonyl)acetamide,    (3-chloro-4-(methylsulfonyl)thiophene-2-carboxy)-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl]amide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3-(2-phenylethylenesulfonyl)propionamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-(methylsulfonyl)benzamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-(methanesulfonyl)benzamide,    (5-(methylsulfonyl)thiophene-2-carboxy)-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}amide,    (5-methylsulfonyl-3-methyl-4-vinylthiophene-2-carboxy){-[bis(4-chlorophenyl)methyl]azetidin-3-yl}amide,    (RS)-N-{1-[(4-chlorophenyl)(pyridin-3-yl)methyl]-azetidin-3-yl}-3,5-difluorobenzenesulfonamide,    (RS)-N-{1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]azetidin-3-yl}-3,5-difluorobenzenesulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N(6-chloropyrid-2-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(6-ethylpyrid-2-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(quinol-6-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(quinol-5-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(isoquinol-5-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-3-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-1-oxide-3-yl)methylsulfonamide,    N-(1R,2S,4S)-(bicyclo[2.2.1]hept-2-yl)-N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}methylsulfonamide,    N-(1R,2R,4S)-(bicyclo[2.2.1]hept-2-yl)-N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(thiazol-2-yl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3-methoxyphenyl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3-(hydroxymethyl)phenyl)methylsulfonamide,    ethyl N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(methylsulfonyl)-3-aminobenzoate,    N-1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(isobutylpiperid-4-yl)methylsulfonamide,    N-benzyl-N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}amine,    N-1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorobenzyl)amine,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorobenzyl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(pyrid-3-ylmethyl)methylsulfonamide,    N-{1-[bis(4-fluorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    (RS)-N-{1-[(4-chlorophenyl)(pyrid-3-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    (R)-N-1-[(4chlorophenyl)(pyrid-3-yl)methyl]azetidin-3-yl)-N-(3,5-difluorophenyl)methylsulfonamide,    (S)-N-{1-[(4-chlorophenyl)(pyrid-5-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    (RS)-N-{1-[(4-chlorophenyl)(pyrid-4-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    (R)-N-{1-[(4-chlorophenyl)(pyrid 4-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    (S)-N-{1-[(4-chlorophenyl)(pyrid-4-yl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    (RS)-N-1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]azetidin-yl)-N-(3,5-difluorophenyl)methylsulfonamide,    (R)-N-{1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl)-N-(3,5-difluorophenyl)methylsulfonamide,    (S)-N-1-[(4-chlorophenyl)(pyrimidin-5-yl)methyl]-azetidin-3-yl}-N-(3,5-difluorophenyl)methylsulfonamide,    N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(3,5-difluorophenyl)benzylsulfonamide,    their optical isomers and their pharmaceutically acceptable salts.    
     
     
         9 . The pharmaceutical composition as. claimed in  claim 7 , for which the compound of formula (I) is chosen from the following compounds: 
 1-[bis(4-chlorophenyl)methyl]3-3-[(RS)-(3,5-difluorophenyl)(methylsulfonyl)methyl]azetidin-3-ol,    3-acetoxy-1-[bis(4-chlorophenyl)methyl]-3-[(RS)-(3,5-difluorophenyl)(methylulphonyl)methyl)methylsulfonylmethyl]azetidine,    1-[bis(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, their optical isomers and their pharmaceutically acceptable salts.    
     
     
         10 . The pharmaceutical composition as claimed in  claim 6 , in which the CB1 [lacuna] antagonist is SR141716, its hydrates and its pharmaceutically acceptable salts or LY320135 and its pharmaceutically acceptable salts.  
     
     
         11 . The pharmaceutical composition as claimed in one of  claims 6  to  10  for a use which is simultaneous, separate or spread out over time.  
     
     
         12 . The pharmaceutical composition as claimed in one of  claim 6  to  11 , comprising 0.5 to mg of sibutramine and 0.1 to 200 mg of the CB1 [lacuna] antagonist.