HRP20030249A2 - Association of the cb1 receptor antagonist and a sibutramin, pharmaceutical compositions containing same and use thereof for treating obesity - Google Patents

Abstract

The invention concerns the association of the CB1 receptor antagonist and a sibutramin, pharmaceutical compositions containing same and use thereof for treating obesity.

Description

The presented invention relates to the combination of the CB1 receptor antagonist and sibutramine, the pharmaceutical preparation in which they are included, and their use in the treatment of obesity.

CB1 receptor antagonists are known for their effect on food intake, and their use as a weight loss agent (G. COLOMBO et al., Life Sciences, 63 (8), 113-117 (1998); J. SIAMAND et al., Behavioural Pharmacol., 9, 179-181 (1998)).

Sibutramine (BTS 54524; N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N,N-dimethylamine; MeridiaR, ReductilR), its hydrate, and its pharmaceutically acceptable salts, especially its hydrochloride reduces food intake and is useful in the treatment of obesity (WO90/061110; D.H. RYAN et al., Obesity Research, 3(4), 553 (1995); H.C. JACKSON et al., British Journal of Pharmacology, 121, 1758(1997) ; G. FANGHANEL et al., Inter.J.Obes., 24(2), 144(2000); G.A. BRAY et al., Obes.Res., 7 (2) 189(1999)).

A combination of sibutramine, its hydrates and its pharmaceutically acceptable salts with a CB1 receptor antagonist has now been found to have a synergistic effect on reducing food intake, thus being useful in the treatment of obesity.

The combination also refers to multiple CB1 receptor antagonists.

Among CB1 antagonists, the azetidine derivatives described in WO 00/15609, WO 01/64633, WO 01/64634 of the formula can be used in particular:

[image]

where

R represents either chain (A), (B) and

[image]

R1 represents a methyl or ethyl radical,

R2 represents either an aromatic ring selected from phenyl, naphthyl or indenyl, the said aromatic compounds may be substituted or unsubstituted by various halogens, alkyl, alkoxy, -CO-alk, hydroxy, -COOR5, formyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy, nitro, -NR6R7, -CO-NH-NR6R7, -N(alk)COOR8, cyano, -CONHR9, -CO-NR16R17, alkylsulfanyl, hydroxyalkyl, -O-alk-NR12R13 or alkylthioalkyl or a heteroaromatic compound selected from cyclobenzofuryl, 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 , thienyl, said heteroaromatic compounds may be substituted or unsubstituted by halogen, alkyl, alkoxy, -COOR5, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy, nitro, -NR6R7, -CO-NH-NR6R7, cyano, -CONHR9, alkylsulfanyl, hydroxyalkyl or al alkylthioalkyl,

R3 and R4 identical or different, represent either an aromatic compound selected from phenyl, naphthyl or indenyl, said aromatic compounds can be unsubstituted or substituted by one or more halogen, alkyl, alkoxy, formyl, hydroxy, trifluoromethyl, trifluoromethoxy, -CO-alk, cyano, -COOR5, -CONR10R11, -CO-NH-NR6R7, alkylsulfanyl, hydroxyalkyl, -alk-NR6R7 or alkylthioalkyl; or a heteroaromatic compound selected from cyclobenzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, furyl, isochromanyl, isoquinolyl, pyrrolyl, quinolyl, 1,2,3,4-tetrahydroisoquinolyl, thiazolyl, thienyl, said heteroaromatic compounds may be substituted or unsubstituted by halogen, alkyl, alkoxy, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, -COOR5, -CO-NH-NR6R7, -CONR10R11, -alk-NR6R7, alkylsulfanyl, hydroxyalkyl or alkylthioalkyl,

R5 is an alkyl radical or phenyl optionally substituted by one or more halogen atoms,

R6 and R7, identical or different, represent a hydrogen atom or an alkyl radical, -COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk, hydroxyalkyl or also R6 and R7 together with the nitrogen atom to which they are attached form heterocyclic mono or bicyclic, saturated or an unsaturated ring with 3 to 10 atoms, which optionally contains another heteroatom selected from oxygen, sulfur and nitrogen, and which is optionally substituted by one or more alkyl radicals, -COalk, -COOalk, -CO-NHalk, -CS-NHalk , -CO-alk-NR14R15, oxo, hydroxyalkyl, -alk-O-alk, -CO-NH2,

R8 represents an alkyl radical,

R9 represents a hydrogen atom, or an alkyl radical or an alkyl substituted with dialkylamino, phenyl, cycloalkyl (optionally substituted with -COOalk) or a heterocyclic mono or bicyclic compound, saturated or unsaturated with 3 to 10 atoms in the chain, optionally containing one or more heteroatom selected from oxygen, sulfur and nitrogen, and optionally substituted by one or more alkyl radicals,

R10 and R11, identical or different, represent a hydrogen atom or an alkyl radical, and also R10 and R11 together with the nitrogen atom to which they are attached form a heterocyclic mono or bicyclic, saturated or unsaturated ring with 3 to 10 atoms in the chain, which optionally contains a second heteroatom selected from oxygen, sulfur and nitrogen, and optionally substituted with an alkyl radical,

R12 and R13, identical or different, represent a hydrogen atom or an alkyl radical, cycloalkyl or also R12 and R13 together with the nitrogen atom to which they are attached form a heterocyclic mono or bicyclic, saturated or unsaturated ring with 3 to 10 atoms, which optionally contains another heteroatom selected from oxygen, sulfur and nitrogen, and which is optionally substituted by an alkyl radical, -COalk, -COOalk, -CO-NHalk, -CS-NHalk, -CO-alk-NR14R15, or a heterocyclic mono or bicyclic saturated compound having from 3 to 10 atoms, and containing a heteroatom selected from oxygen, sulfur and nitrogen,

R14 and R15, identical or different, represent a hydrogen atom or an alkyl radical or -COOalk,

R16 and R17 form together with the nitrogen atom to which they are attached a heterocyclic mono or bicyclic saturated compound having from 3 to 10 atoms, and optionally containing another heteroatom selected from oxygen, sulfur and nitrogen,

R' represents a hydrogen atom or a -CO-alk radical, or

R represents the radical CHR18, a

R18 represents the radical –NHCOR19 or -N(R20)-Y-R21,

Y is CO or SO2,

R4 and R3, identical or different, represent an aromatic compound selected from phenyl, naphthyl and indenyl, and said aromatic can be unsubstituted or substituted by one or more halogens, alkyl, alkoxy, formyl, hydroxy, trifluoromethyl, trifluoromethoxy, -CO-alk, cyano, -COOH, -COOalk, CONR22R23, -CO-NH-NR24R25, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkyl, or -alk-NR22R23; or a heteroaromatic compound selected from cyclic 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, said heteroatoms can be unsubstituted or substituted by halogen, alkyl, alkoxy, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, -COOH, -COOalk, -CO-NH-NR24R25, -CONR22R23, alk-NR24R25, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl or hydroxyalkyl,

R19 represents the radical -alk-SO2-R26, -alk-SO2-CH=CH-R26, Heti substituted with -SO2-R26 or phenyl substituted with -SO2-R26 or alk-SO2-R26,

R20 represents a hydrogen atom or an alkyl radical, R21 represents a phenylalkyl radical, Het1 or Ar1,

R22 and R23, identical or different, represent a hydrogen atom or an alkyl radical or likewise R22 and R23 form together with the nitrogen atom to which they are attached a heterocyclic mono- or bicyclic saturated compound with 3 to 10 atoms, possibly containing another heteroatom selected from oxygen, of sulfur and nitrogen, and which is optionally substituted by one or more alkyl,

R24 and R25, identical or different, represent a hydrogen atom or an alkyl radical, -COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkyl or also R24 and R25 form together with the nitrogen atom to which they are attached heterocyclic mono or bicyclic saturated or an unsaturated compound with 3 to 10 atoms, which optionally contains another heteroatom selected from oxygen, sulfur and nitrogen, and which is optionally substituted by one or more alkyl, -COalk, -COOalk, -CO-NHalk, -CS-NHalk, oxo, hydroxyalkyl , -alk-O-alk or -CO-NH2,

R26 represents an alkyl radical, Ar1 or Het1,

Ar1 represents a phenyl radical, naphthyl or indenyl, the mentioned radicals can possibly be substituted by one or more halogen, alkyl, alkoxy, cyano, -CO-alk, -COOH, -COOalk, -CONR27R28, -CO-NH-NR29NR28, alkylsulfanyl, alkylsulfinyl , alkylsulfonyl, -alk-NR29R30, -NR29R30, alkylthioalkyl, formyl, hydroxy, hydroxyalkyl, Het, -O-alk-NH-cycloalkyl, OCF3, CF3, -NH-CO-alk, -SO2-NH2, -NH-COCH3 , -NH-COOalk, Het or likewise on two adjacent carbon atoms with dioxymethylene,

Het1 represents a heterocyclic mono or bicyclic unsaturated or saturated compound, with 3 to 10 atoms, and containing one or several heteroatoms selected from oxygen, sulfur and nitrogen optionally substituted by one or more alkyl, alkoxy, vinyl, halogen, alkoxycarbonyl, oxo, hydroxy, OCF3 or CF3, heterocycles with nitrogen may possibly be in their N-oxidized form,

R27 and R28, identical or different, represent a hydrogen atom or an alkyl radical or also R27 and R28 form together with a nitrogen atom to which they are attached a heterocyclic mono- or bicyclic saturated compound with 3 to 10 atoms, possibly containing another heteroatom selected from oxygen, of sulfur and nitrogen, and which is optionally substituted by one or more alkyl,

R29 and R30, identical or different, represent a hydrogen atom or an alkyl radical, -COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkyl or also R29 and R30 form together with the nitrogen atom to which they are attached heterocyclic mono or bicyclic saturated or an unsaturated compound with 3 to 10 atoms, which optionally contains another heteroatom selected from oxygen, sulfur and nitrogen, and which is optionally substituted by one or more alkyl, -COalk, -COOalk, -CO-NHalk, -CS-NHalk, oxo, hydroxyalkyl , -alk-O-alk or -CO-NH2,

or R represents CHR31 and

R31 represents the radical -N(R32)R33, -N (R32) -CO-R33, -N(R32)-SO2R34,

R4 and R3, identical or different, represent an aromatic compound selected from phenyl, naphthyl and indenyl, and said aromatic compounds can be unsubstituted or substituted by one or more halogen, alkyl, alkoxy, formyl, hydroxy, trifluoromethyl, trifluoromethoxy, -CO-alk , cyano, -COOH, -COOalk, -CONR22R23, -CO-NH-NR24R25, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkyl, or -alk-NR7R8; or a heteroaromatic compound selected from cyclic 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, said heteroatoms can be unsubstituted or substituted by halogen, alkyl, alkoxy, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, -COOH, -COOalk, -CO-NH-NR24R25, -CONR22R23, alk-NR24R25, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl or hydroxyalkyl,

R32 represents the radical -C(R35)(R36)-Het2, -Het2, -C(R35)(R36)-Ar2, Ar2, cycloalkyl or norbornyl,

R33 represents a hydrogen atom or a hydroxyalkyl radical, -alk-COOalk, -alk-CONR22R23, -alk-NR22R23, alkoxy, Ar2, Het2, -CH2-Ar2, -CH2Het2 or alkyl optionally substituted by one or more halogens,

R34 represents the radical hydroxyalkyl, -alk-COOalk, -alk-CONR22R23, -alk-NR22R23, alkoxy, Ar2, Het2, -CH2-Ar2, -CH2Het2 or alkyl optionally substituted by one or more halogens,

R35 represents a hydrogen atom or a hydroxyalkyl radical, -alk-COOalk, -alk-CONR22R23, -alk-NR22R23, alkoxyalkyl, Ar2, Het2, -CH2-Ar2, -CH2Het2 or alkyl optionally substituted by one or more halogens,

R36 represents a hydrogen atom or a hydroxyalkyl radical, -alk-COOalk, -alk-CONR22R23, -alk-NR22R23, alkoxyalkyl or alkyl optionally substituted by one or more halogens,

or also R35 and R36 form together with the carbon atom to which they are attached a heterocyclic mono or bicyclic saturated compound having from 3 to 10 atoms, and which contains another heteroatom selected from oxygen, sulfur and nitrogen, and which is optionally substituted by one or more alkyl,

Ar2 represents a phenyl radical, naphthyl or indenyl, the mentioned different radicals can possibly be substituted by one or more halogen, alkyl, alkoxy, -CO-alk, cyano, -COOH, -COOalk, -CONR37R38, -CO-NH-NR39NR40, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, -alk-NR29R30, -NR39R40, alkylthioalkyl, formyl, CF3, OCF3, Het, -O-alk-NH-cycloalkyl, -SO2-NH2, hydroxy, hydroxyalkyl, -NHCOalk, -NHCOOalk, or likewise two adjacent carbon atoms with dioxymethylene,

Het2 represents a heterocyclic mono or bicyclic unsaturated or saturated compound, with 3 to 10 atoms, and which contains one or several heteroatoms selected from oxygen, sulfur and nitrogen optionally substituted by one or more alkyl, alkoxy, halogen, alkoxycarbonyl, oxo, hydroxy, heterocycles with with nitrogen they may possibly be in their N-oxide form,

R37 and R38, identical or different, represent a hydrogen atom or an alkyl radical or also R37 and R38 form together with a nitrogen atom to which they are bound a heterocyclic mono- or bicyclic saturated compound with 3 to 10 atoms, possibly containing another heteroatom selected from oxygen, of sulfur and nitrogen, and which is optionally substituted by one or more alkyl,

R39 and R40, identical or different, represent a hydrogen atom or an alkyl radical, or likewise R39 and R40 form together with a nitrogen atom to which they are attached a heterocyclic mono- or bicyclic saturated compound with 3 to 10 atoms, possibly containing another heteroatom selected from oxygen, of sulfur and nitrogen, and which is optionally substituted by one or more alkyl,

alk represents an alkyl radical or alkylene,

radicals and parts of alkyl and alkylene and radicals and parts of alkoxy come in the form of a straight or branched chain, and contain from 1 to 6 carbon atoms, and cycloalkyl radicals with 3 to 10 carbon atoms, optical isomers of the mentioned compounds and their salts of mineral acids or pharmaceutically acceptable organic substances.

Favorable derivatives of azetidine are the following:

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-[(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)(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)(naphthyl-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-methylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

(R,S)-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]methylsulfonyl methylene} azetidine,

(R,S)-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,

(R,S)-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,

(R,S)-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-{(R,S)-(4-chlorophenyl)[4-(3,3-dimethyl-piperidin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl) methylene]azetidine,

1-{(R)-(4-chlorophenyl)[4-(3,3-dimethyl-piperidin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene] azetidine,

1-{(S)-(4-chlorophenyl)[4-(3,3-dimethyl-piperidin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene] azetidine,

1-{(R,S)-(4-chlorophenyl)[4-(thiomorpholin-4-yl-methyl)phenyl]methyl-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(R)-(4-chlorophenyl)[4-(thiomorpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(S)-(4-chlorophenyl)[4-(thiomorpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(R,S)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexyl-aminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(R)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexyl-aminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(S)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexyl-aminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{{(R,S)-(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-{(R,S)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propyl-aminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(R)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propyl-aminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(S)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propyl-aminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(R,S)-(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-{{(R,S)-(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-{(R,S)-(4-chlorophenyl)[4-(di-n-propylaminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(R)-(4-chlorophenyl)[4-(di-n-propylaminomethyl)phenylmethyl}-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-{(R,S)-(4-chlorophenyl)[4-(piperidin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(R)-(4-chlorophenyl)[4-(piperidin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(S)-(4-chlorophenyl)[4-(piperidin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(R,S)-(4-chlorophenyl)[4-(4-methyl-piperazin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene] azetidine,

1-{(R)-(4-chlorophenyl)[4-(4-methyl-piperazin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(S)-(4-chlorophenyl)[4-(4-methyl-piperazin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(R,S)-(4-chlorophenyl)[4-(morpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(R)-(4-chlorophenyl)[4-(morpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(S)-(4-chlorophenyl)[4-(morpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(R,S)-(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-{(R,S)-(4-chlorophenyl)[4-(piperazin-2-on-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene] azetidine,

1-{(R)-(4-chlorophenyl)[4-(piperazin-2-on-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(S)-(4-chlorophenyl)[4-(piperazin-2-on-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(R,S)-(4-chlorophenyl)[4-(imidazol-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(R)-(4-chlorophenyl)[4-(imidazol-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-{(S)-(4-chlorophenyl)[4-(imidazol-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

(R,S)-1-{(4-chlorophenyl)[4-(N,N-dimethylcarbamoyl)phenylmethyl}-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)phenylethyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

(R,S)-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,

(R,S)-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-difluorophenyl)(methylsulfonyl)methylene]azetidine,

1-benzhydryl-3-[(3-methylsulfanylphenyl)(methylsulfonyl)methylene]azetidine,

1-benzhydryl-3-[(3-methylsulfanylphenyl)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-(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,

(R,S)-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,

(R,S)-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,

(R,S)-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,

1-[bis(4-chlorophenyl)methyl]-3-hydroxy-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methylene]azetidine-(RS),

1-[bis(4-chlorophenyl)methyl]-3-[(2-isobutylaminocarbonylthien-5-yl)(methylsulfonyl)methylene]azetidine,

1-[bis(4-chlorophenyl)methyl]-3-[(3-methoxycarbonylphenyl)(methylsulfonyl)methyl-(RS)]azetidin-3-ol,

1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(pyridin-4-yl)methyl-(RS)]azetidin-3-ol,

1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(pyridin-3-yl)methyl-(RS)]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-dimethylamino-propyl)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-methyl-ethyl)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-isobutyl-benzamide,

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-dimethylamino-ethyl)benzamide,

N'-methyl-hydrazide 3-({1-[bis-(4-chlorophenyl)methyl]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-ethyl-pyrrolidin-2-ylmethyl)benzamide,

3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)N-(2,2-dimethyl-propyl)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-methyl-butyl)benzamide,

3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)N-(2-phenyl-propyl)benzamide,

3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)N-(tetrahydro-furan-2-ylmethyl)benzamide,

3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)N-(2,2-diphenyl-ethyl)benzamide,

3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)N-(2-ethyl-butyl)benzamide,

4-{[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)benzoylamino]methyl}-cyclohexanecarboxylic acid methyl ester,

2-amino-1-{4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazin-1-yl}-ethanone,

tert-butyl ester (2-{4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazin-1-yl}-2-oxo- ethyl) 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 (2-{4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazin-1-yl}-2-oxo- ethyl)-N-methyl-carbamic acid,

N-methylamide 4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine-1-carbothioic acid,

N-methylamide 4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine-1-carboxylic acid,

4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine-1-carboxylic acid methyl ester,

1-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]-4-isobutyl-piperazine,

1-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]-4-ethyl-piperazine,

4-acetyl l-[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-dimethylamino-ethanone,

1-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine,

4-[3- ({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine-1-carboxylic acid tert-butyl ester

acid,

1-[bis-(4-methoxycarbonylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

3-acetoxy-1-[bis-(4-methoxycarbonylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methyl-(RS)]azetidine,

(RS)-4-[4-((4-chlorophenyl)(3-[(3,5-difluorophenyl)methanesulfonyl-methylene]azetidin-1-yl}-methyl)-benzyl]morpholine,

4-(4-{3-[(1-benzhydryl-azetidin-3-ylidene)methanesulfonyl-methyl]phenoxy}butyl)morpholine,

4-(4-{3-[(1-benzhydryl-azetidin-3-ylidene)methanesulfonyl-methyl]phenoxy}propyl)morpholine,

N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-thien-2-yl-sulfonamide,

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-yl-sulfonamide,

N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-naphth-1-yl-sulfonamide,

N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-3,4-difluorophenylsulfonamide,

N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-methyl-1-H-imidazol-4-yl-sulfonamide,

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-yl-sulfonamide,

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-yl-phenyl)sulfonamide,

N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-4-fluorophenylsulfonamide,

N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-quinol-8-ylsulfonamide,

N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-phenylsulfonamide,

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-(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-phenyl-ethylenesulfonyl)-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-vinyl-thiophene-2-carboxy)-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-amide,

(RS)-N-{1-[(4-chloro-phenyl)pyridin-3-yl-methyl]azetidin-3-yl}-3,5-difluoro-benzenesulfonamide,

(RS)-N-{1-[(4-chloro-phenyl)pyrimidin-5-yl-methyl]azetidin-3-yl}-3,5-difluoro-benzenesulfonamide,

N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(6-chloropyrid-2-yl)-methyl-sulfonamide,

N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-quinol-6-yl-methyl-sulfonamide,

N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-quinol-5-yl-methyl-sulfonamide,

N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-isoquinol-5-yl-methyl-sulfonamide,

N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-pyrid-3-yl-methyl-sulfonamide,

N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-(1-oxid-pyrid-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)-methyl sulfonamide,

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,

N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-(methylsulfonyl)-3-aminobenzoate ethyl,

N-(1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-(1-isobutyl-piperid-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-yl-methyl)-methylsulfonamide,

N-{1-[bis-(4-fluoro-phenyl)-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-U-[(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-3-11}-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,

and their optical isomers and their pharmaceutically acceptable salts of mineral or organic acids.

And the following azetidine derivatives are particularly favorable:

{1-[bis-(4-chlorophenyl)-methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methyl-(RS)]azetidin-3-ol,

3-acetoxy-1-[bis-(4-chlorophenyl)-methyl]-3-[(3, 5-difluorophenyl)(methylsulfonyl)methyl)-methyl sulfonylmethyl-(RS)]azetidine,

1-[bis-(4-chlorophenyl)-methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine,

and their optical isomers and their pharmaceutically acceptable salts of mineral or organic acids.

As examples of pharmaceutically acceptable salts of azetidine derivatives, the following salts can be mentioned: benzenesulfonate, hydrobromide, hydrochloride, citrate, ethanesulfonate, fumarate, gluconate, iodate, isethionate, maleate, methanesulfonate, methylene-bis-β-oxonaphthoate, nitrate, oxalate, pamoate, phosphate, salicylate, succinate, sulfate, tartrate, theophylline acetate and p-toluenesulfonate.

Other CB1 antagonists that are used and can be connected with the present invention are, for example, pyrazole derivatives described in EP576357, EP658546, EP656354, WO97/19063 and WO00/46209, benzothiophene and benzofuran derivatives described in WO96/02248, arylsulfonamides described in WO98/ 37061. In particular, the products known under the code SR141716 and LY320135 can be mentioned.

The synergistic effect of sibutiramine and CB1 antagonists on food consumption was determined according to the following protocol:

7-week-old fat Zucker Fa/fa rats from Iffa-Credo, France were used in the above study. The rats were placed in individual cages and weighed every day between 8 and 10 in the morning. The amount of food was equally weighed every morning at the same time. The indicated food (M20, Pietrement, France) was changed every morning and the rats were allowed to eat freely for 24 hours. During one week, all rats were treated with vehicle (miglyol 812N and methylcellulose 0.5%/polysorbate 80 0.2%) in two consecutive applications. From day 8, rats were treated with vehicle, the CB1 antagonist (1-[bis-(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine) or sibutramine orally (see below table).

Sibutramine comes in the form of a solution in methylcellulose solution 0.5%/polysorbate 80 0.2%, and was administered in a dose of 3 mg/kg; the CB1 antagonist comes in the form of a solution in miglyol 812N (Hüls, Germany) at a dose of 0.6 mg/kg, both products were administered in a volume of 1 ml/kg. Each group consists of 12 to 14 animals. The following groups consist of animals that were fed for five days in the form of two consecutive applications each day.

[image]

Food consumption of each animal was measured every day. The results are expressed as the average amount of food consumed during the 5 days of the procedure. The obtained results are presented in the following table.

[image] * p<0.05 ** p<0.01 *** p<0.0001

The results show that among the animals that received the combination of sibutramine and the CB1 antagonist, the reduction in food intake was significantly less compared to those that received either sibutramine alone or the CB1 antagonist alone.

The combined compounds can be administered orally, parenterally, transdermally or rectally either simultaneously or separately or distributed over time.

The presented invention also relates to pharmaceutical preparations containing a combination of sibutramine, its hydrate or one of its pharmaceutically acceptable salts and a CB1 receptor antagonist in its pure state or with one or more diluents and/or compatible and pharmacologically acceptable adjuvants and/or possibly in in combination with some other pharmacologically compatible and physiologically active product either in simultaneous application, either separately, or distributed over time.

As solid preparations for oral administration, tablets, pills, powders (gelatin capsules, tablets) or granules can be used. In the mentioned preparations, the active components are mixed in one or more inert diluents, such as starch, cellulose, sucrose, lactose or silicon, under a stream of argon. Said preparations may also contain other substances in addition to the diluent, for example one or more lubricants such as magnesium stearate or talc, color, coating agent (dragee) or glaze.

As liquid preparations for oral administration, pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerol, vegetable oils or paraffin oil can be used. Said preparations may contain other substances in addition to diluents, for example wetting agents, sweeteners, thickeners, flavor enhancers or stabilizers.

Sterile preparations for parenteral administration may preferably be aqueous solutions or non-aqueous solutions, suspensions or emulsions. As solvent or vehicle, water, propylene glycol, polyethylene glycol, vegetable oils, especially olive oil, injectable organic esters, for example ethyl oleate or other suitable organic solvents can be used. Said preparations may also contain adjuvants, especially means for wetting, achieving isotonicity, emulsifiers, dispersants and stabilizers. Sterilization can be carried out in several ways, for example by aseptic filtration, incorporation into the preparation of sterile agents, irradiation or heating. They can also be prepared in the form of solid sterile preparations that can be dissolved at the time of application in sterile water or any other sterile means for injection.

Preparations for rectal administration are suppositories or rectal capsules that contain, in addition to the active product, excipients such as cocoa butter, semi-synthetic glycerides or polyethylene glycols.

The pharmaceutical preparations generally contain from 0.5 to 10 mg of sibutramine and from 0.1 to 200 mg of the CB1 antagonist.

The presented invention also relates to the obesity treatment procedure, which consists in the application to the patient of the combination according to the invention, either simultaneously, separately or distributed over time.

The dosage depends on the expected effect, the duration of the treatment and the method of administration; it generally ranges from 1 to 15 mg of sibutramine per day for oral administration in adults, and from 0.10 to 500 mg of CB1 antagonists per day for oral administration in adults.

Generally speaking, the doctor determines the appropriate route of administration depending on the age, weight and other characteristics of the person undergoing treatment.

Claims (12)

1. The presented invention, characterized in that it contains a combination of CB1 antagonist and sibutramine, its hydrate or one of its pharmaceutically acceptable salts. 2. A combination of compounds according to claim 1, characterized in that the CB1 antagonist is a compound represented by the formula: [image] where R represents either chain (A), (B) and [image] R1 represents a methyl or ethyl radical, R2 represents either an aromatic ring selected from phenyl, naphthyl or indenyl, said aromatic compounds may be substituted or unsubstituted by various halogens, alkyl, alkoxy, -CO-alk, hydroxy, -COOR5, formyl, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy, nitro, - NR6R7, -CO-NH-NR6R7, -N (alk) COOR8, cyano, -CONHR9, -CO-NR16R17, alkylsulfanyl, hydroxyalkyl, -O-alk-NR12R13 or alkylthioalkyl or a heteroaromatic compound selected from cyclobenzofuryl, 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, thienyl, said heteroaromatic compounds may be substituted or unsubstituted by halogen, alkyl, alkoxy, -COOR5, trifluoromethyl, trifluoromethylsulfanyl, trifluoromethoxy, nitro, -NR6R7, -CO-NH-NR6R7, cyano, -CONHR9, alkylsulfanyl, hydroxyalkyl or alkylthioalkyl, R3 and R4, identical or different, represent either an aromatic compound selected from phenyl, naphthyl or indenyl, said aromatic compounds may be unsubstituted or substituted by one or more halogen, alkyl, alkoxy, formyl, hydroxy, trifluoromethyl, trifluoromethoxy, -CO-alk , cyano, -COOR5, -CONR10R11, -CO-NH-NR6R7, alkylsulfanyl, hydroxyalkyl, -alk-NR6R7 or alkylthioalkyl; or a heteroaromatic compound selected from cyclo benzofuryl,. benzothiazolyl, benzothienyl, benzoxazolyl, chromanyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, furyl, isochromanyl, isoquinolyl, pyrrolyl, quinolyl, 1,2,3,4-tetrahydroisoquinolyl, thiazolyl, thienyl, the mentioned heteroaromatic compounds can be substituted or unsubstituted by halogen, alkyl, alkoxy, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, -COOR5, -CO-NH-NR6R7, -CONR10R11, -alk-NR6R7, alkylsulfanyl, hydroxyalkyl or alkylthioalkyl, R5 is an alkyl radical or phenyl optionally substituted by one or more halogen atoms, R6 and R7, identical or different, represent a hydrogen atom or an alkyl radical, -COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk, hydroxyalkyl or also R6 and R7 together with the nitrogen atom to which they are attached form heterocyclic mono or bicyclic, saturated or an unsaturated ring with 3 to 10 atoms, which optionally contains another heteroatom selected from oxygen, sulfur and nitrogen, and which is optionally substituted by one or more alkyl radicals, -COalk, -COOalk, -CO-NHalk, -CS-NHalk , -CO-alk-NR14R15, oxo, hydroxyalkyl, -alk-O-alk, -CO-NH2, R8 represents an alkyl radical, R9 represents a hydrogen atom, or an alkyl radical or an alkyl substituted with dialkylamino, phenyl, cycloalkyl (optionally substituted with -COOalk) or a heterocyclic mono or bicyclic compound, saturated or unsaturated with 3 to 10 atoms in the chain, optionally containing one or more heteroatom selected from oxygen, sulfur and nitrogen, and optionally substituted by one or more alkyl radicals, R10 and R11, identical or different, represent a hydrogen atom or an alkyl radical, and also R10 and R11 together with the nitrogen atom to which they are attached form a heterocyclic mono or bicyclic, saturated or unsaturated ring with 3 to 10 atoms in the chain, which optionally contains a second heteroatom selected from oxygen, sulfur and nitrogen, and optionally substituted with an alkyl radical, R12 and R13, identical or different, represent a hydrogen atom or an alkyl radical, cycloalkyl or also R12 and R13 together with the nitrogen atom to which they are attached form a heterocyclic mono or bicyclic, saturated or unsaturated ring with 3 to 10 atoms, which optionally contains another heteroatom selected from oxygen, sulfur and nitrogen, and which is optionally substituted by an alkyl radical, -COalk, -COOalk, -CO-NHalk, -CS-NHalk, -CO-alk-NR14R15, or a heterocyclic mono or bicyclic saturated compound having from 3 to 10 atoms, and containing a heteroatom selected from oxygen, sulfur and nitrogen, R14 and R15, identical or different, represent a hydrogen atom or an alkyl radical or -COOalk, R16 and R17 form together with the nitrogen atom to which they are attached a heterocyclic mono or bicyclic saturated compound having from 3 to 10 atoms, and optionally containing another heteroatom selected from oxygen, sulfur and nitrogen, R' represents a hydrogen atom or a -CO-alk radical, or R represents the radical CHR18, and R18 represents the radical –NHCOR19 or -N(R20)-Y-R21, Y is CO or SO2, R4 and R3, identical or different, represent an aromatic compound selected from phenyl, naphthyl and indenyl, and said aromatic can be unsubstituted or substituted by one or more halogens, alkyl, alkoxy, formyl, hydroxy, trifluoromethyl, trifluoromethoxy, -CO- alk, cyano, -COOH, -COOalk, CONR22R23, -CO-NH-NR24R25, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkyl, or -alk-NR22R23; or a heteroaromatic compound selected from cyclic 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, said heteroatoms can be unsubstituted or substituted by halogen, alkyl, alkoxy, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, -COOH, -COOalk, -CO-NH-NR24R25, -CONR22R23, alk-NR24R25, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl or hydroxyalkyl, R19 represents the radical -alk-SO2-R26, -alk-SO2-CH=CH-R26, Het1 substituted with -SO2-R26 or phenyl substituted with -SO2-R26 or -alk-SO2-R26, R20 represents a hydrogen atom or an alkyl radical, R21 and represents a phenylalkyl radical, Het1 or Ar1, R22 and R23, identical or different, represent a hydrogen atom or an alkyl radical or likewise R22 and R23 form together with the nitrogen atom to which they are attached a heterocyclic mono- or bicyclic saturated compound with 3 to 10 atoms, possibly containing another heteroatom selected from oxygen, of sulfur and nitrogen, and which is optionally substituted by one or more alkyl, R24 and R25, identical or different, represent a hydrogen atom or an alkyl radical, -COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkyl or also R24 and R25 form together with the nitrogen atom to which they are attached heterocyclic mono or bicyclic saturated or an unsaturated compound with 3 to 10 atoms, which optionally contains another heteroatom selected from oxygen, sulfur and nitrogen, and which is optionally substituted by one or more alkyl, -COalk, -COOalk, -CO-NHalk, -CS-NHalk, oxo, hydroxyalkyl , -alk-O-alk or -CO-NH2, R25 represents an alkyl radical, Ar1 or Het1, Ar1 represents a phenyl radical, naphthyl or indenyl, the mentioned radicals can possibly be substituted by one or more halogen, alkyl, alkoxy, cyano, -CO-alk, -COOH, -COOalk, -CONR27R28, -CO-NH-NR29NR28, alkylsulfanyl, alkylsulf inyl, alkylsulfonyl, -alk-NR29R30, -NR29R30, alkylthioalkyl, formyl, hydroxy, hydroxyalkyl, Het, -O-alk-NH-cycloalkyl, OCF3, CF3, -NH-CO-alk, -SO2-NH2, -NH- COCH3, -NH-COOalk, Het or likewise on two adjacent carbon atoms with dioxymethylene, Het1 represents a heterocyclic mono or bicyclic unsaturated or saturated compound, with 3 to 10 atoms, and containing one or several heteroatoms selected from oxygen, sulfur and nitrogen possibly substituted by one or more alkyl, alkoxy, vinyl, halogen, alkoxycarbonyl, oxo, hydroxy, OCF3 or CF3, heterocycles with nitrogen may possibly be in their N-oxidized form, R27 and R28, identical or different, represent a hydrogen atom or an alkyl radical or also R27 and R28 form together with a nitrogen atom to which they are attached a heterocyclic mono- or bicyclic saturated compound with 3 to 10 atoms, possibly containing another heteroatom selected from oxygen, of sulfur and nitrogen, and which is optionally substituted by one or more alkyl, R29 and R30, identical or different, represent a hydrogen atom or an alkyl radical, -COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkyl or also R29 and R30 form together with the nitrogen atom to which they are attached heterocyclic mono or bicyclic saturated or an unsaturated compound with 3 to 10 atoms, which optionally contains another heteroatom selected from oxygen, sulfur and nitrogen, and which is optionally substituted by one or more alkyl, -COalk, -COOalk, -CO-NHalk, -CS-NHalk, oxo, hydroxyalkyl , -alk-O-alk or -CO-NH2, or R represents CHR31 and R31 represents the radical -N(R32)R33, -N(R32)-CO-R33, -N(R32)-SO2R34, R4 and R3, identical or different, represent an aromatic compound selected from phenyl, naphthyl and indenyl, and said aromatic compounds can be unsubstituted or substituted by one or more halogen, alkyl, alkoxy, formyl, hydroxy, trifluoromethyl, trifluoromethoxy, -CO-alk , cyano, -COOH, -COOalk, -CONR22R23, -CO-NH-NR24R25, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkyl, or -alk-NR7R8; or a heteroaromatic compound selected from cyclic 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, said heteroatoms can be unsubstituted or substituted by halogen, alkyl, alkoxy, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, -COOH, -COOalk, -CO-NH-NR24R25, -CONR22R23, alk-NR24R25, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl or hydroxyalkyl, R32 represents the radical -C(R35)(R36)-Het2, -Het2, -C(R35)(R36)-Ar2, Ar2, cycloalkyl or norbornyl, R33 represents a hydrogen atom or a hydroxyalkyl radical, -alk-COOalk, -alk-CONR22R23, -alk-NR22R23, alkoxy, Ar2, Het2, -CH2-Ar2, -CH2Het2 or alkyl optionally substituted by one or more halogens, R34 represents the radical hydroxyalkyl, -alk-COOalk, -alk-CONR22R23, -alk-NR22R23, alkoxy, Ar2, Het2, -CH2-Ar2, -CH2Het2 or alkyl optionally substituted by one or more halogens, R35 represents a hydrogen atom or a hydroxyalkyl radical, -alk-COOalk, -alk-CONR22R23, -alk-NR22R23, alkoxyalkyl, Ar2, Het2, -CH2-Ar2, -CH2Het2 or alkyl optionally substituted by one or more halogens, R36 represents a hydrogen atom or a hydroxyalkyl radical, -alk-COOalk, -alk-CONR22R23, -alk-NR22R23, alkoxyalkyl or alkyl optionally substituted by one or more halogens, or also R35 and R36 form together with the carbon atom to which they are attached a heterocyclic mono or bicyclic saturated compound having from 3 to 10 atoms, and which contains another heteroatom selected from oxygen, sulfur and nitrogen, and which is optionally substituted by one or more alkyl, Ar2 represents a phenyl radical, naphthyl or indenyl, the mentioned different radicals can possibly be substituted by one or more halogen, alkyl, alkoxy, -CO-alk, cyano, -COOH, -COOalk, -CONR37R38, -CO-NH-NR39NR40, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, -alk-NR29R30, -NR39R40, alkylthioalkyl, formyl, CF3, OCF3, Het, -O-alk-NH-cycloalkyl, -SO2-NH2, hydroxy, hydroxyalkyl, -NHCOalk, -NHCOOalk, or likewise two adjacent carbon atoms with dioxymethylene, Het2 represents a heterocyclic mono or bicyclic unsaturated or saturated compound, with 3 to 10 atoms, and which contains one or several heteroatoms selected from oxygen, sulfur and nitrogen optionally substituted by one or more alkyl, alkoxy, halogen, alkoxycarbonyl, oxo, hydroxy, heterocyclic with with nitrogen they may possibly be in their N-oxide form, R37 and R38, identical or different, represent a hydrogen atom or an alkyl radical or also R37 and R38 form together with a nitrogen atom to which they are bound a heterocyclic mono- or bicyclic saturated compound with 3 to 10 atoms, possibly containing another heteroatom selected from oxygen, of sulfur and nitrogen, and which is optionally substituted by one or more alkyl, R39 and R40, identical or different, represent a hydrogen atom or an alkyl radical, or likewise R39 and R40 form together with a nitrogen atom to which they are attached a heterocyclic mono- or bicyclic saturated compound with 3 to 10 atoms, possibly containing another heteroatom selected from oxygen, sulfur and nitrogen, and which is possibly substituted by one or more alkyl, alk represents an alkyl radical or alkylene, radicals and parts of alkyl and alkylene, and radicals and parts of alkoxy come in the form of a straight or branched chain, and contain from 1 to 6 carbon atoms, and cycloalkyl radicals with 3 to 10 carbon atoms, optical isomers of the mentioned compounds and their salts of mineral acids or pharmaceutically acceptable organic substances. 3. A combination of compounds according to claim 2, characterized in that it contains a compound of formula (I) selected from the group of 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-[(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)(3-trifluoromethoxyphenyl)methylene]azetidine, 3-trifluoromethylphenyl)methylene]azetidine, 1-benzhydryl-3-{[3,5-bis(trifluoromethyl)phenyl](methylsulfonyl)methylene}azetidine, 1-benzy dryl-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)(naphthyl-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-methylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, (R,S)-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]methylsulfonyl methylene}azetidine, (R,S)-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, (R,S)-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, (R,S)-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-{(R,S)-(4- chlorophenyl)[4-(3,3-dimethyl-piperidin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-( 4-chlorophenyl)[4-(3,3-dimethyl-piperidin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(S) -(4-chlorophenyl)[4-(3,3-dimethyl-piperidin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{( R,S)-(4-chlorophenyl)[4-(thiomorpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R) -(4-chlorophenyl)[4-(thiomorpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(S)-(4- chlorophenyl)[4-(thiomorpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R,S)-(4-chlorophenyl) [4-(N-ethyl-N-cyclohexyl-aminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-(4-chlorophenyl)[4 -(N-ethyl-N-cycl lohexyl-aminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(S)-(4-chlorophenyl)[4-(N-ethyl-N-cyclohexyl- aminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{{(R,S)-(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-{(R,S)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propyl-aminomethyl)phenyl]methyl}- 3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propyl-aminomethyl)phenyl]methyl}-3- [(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(S)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propyl-aminomethyl)phenyl]methyl}-3-[( 3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R,S)-(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-{{(R,S)-(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-{(R,S)-(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]me tyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R,S)-(4-chlorophenyl)[4-(piperidin-1-yl-methyl)phenyl]methyl} -3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-(4-chlorophenyl)[4-(piperidin-1-yl-methyl)phenyl]methyl}-3-[ (3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, l-{(S)-(4-chlorophenyl)[4-(piperidin-1-yl-methyl)phenyl]methyl}-3-[(3, 5 -difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R,S)-(4-chlorophenyl)[4-(4-methyl-piperazin-1-yl-methyl)phenyl]methyl}-3-[(3 ,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-(4-chlorophenyl)[4-(4-methyl-piperazin-1-yl-methyl)phenyljmethyl}-3-[(3,5 -difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(S)-(4-chlorophenyl)[4-(4-methyl-piperazin-1-yl-methyl)phenyl]methyl}-3-[(3,5 -difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R,S)-(4-chlorophenyl)[4-(morpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl )(methylsulfonyl)methylene]azetidine, 1-{(R)-(4-chlorophenyl)[4-(morpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl) methylene]azetidine, 1-{(S)-(4-chlorophenyl)[4-(morpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{( R,S)-(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-{(R,S)-(4-chlorophenyl)[4-(piperazin-2-on-4-yl-methyl)phenyl] methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-(4-chlorophenyl)[4-(piperazin-2-on-4-yl-methyl)phenyl] methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(S)-(4-chlorophenyl)[4-(piperazin-2-on-4-yl-methyl)phenyl] methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R,S)-(4-chlorophenyl)[4-(imidazol-1-yl-methyl)phenyl]methyl} -3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-(4-chlorophenyl)[4-(imidazol-1-yl-methyl)phenyl]methyl}-3-[ (3,5-difluorophenyl) (methylsulfonyl)methylene]azetidine, 1-{(S)-(4-chlorophenyl)[4-(imidazol-1-yl-methyl)phenyljmethyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine , (R,S)-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, (R,S)-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, (R,S)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene] azetidine, (R)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulf onyl)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 -methylsulfanylphenyl)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-(N-piperidylcarba moyl)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, (R,S)-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, (R,S)-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-[(methylsulfonii)(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, (R,S)-1-[(4 -chlorophenyl)(thiazol-2-yl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, (R)-1-t(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, 1-[bis(4-chlorophenyl)methyl] -3-hydroxy-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methylene]azetidine-(RS), 1-[bis(4-chlorophenyl)methyl]-3-[(2-isobutylaminocarbonylthien-5- yl)(methylsulfonyl)methylene]azetidine, 1-[bis(4-chlorophenyl)methyl]-3-[(3-methoxycarbonylphenyl)(methylsulfonyl)methyl-(RS)]azetidin-3-ol, 1-[bis(4 -chlorophenyl)methyl]-3-[(methylsulfonyl)(pyridine- 4-yl)methyl-(RS)]azetidin-3-ol, 1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(pyridin-3-yl)methyl-(RS)]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-dimethylamino-propyl)benzamide, 3-({1-[bis(4-chlorophenyl)methyl]azetidine-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-methyl-ethyl)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-isobutyl-benzamide, 3-({1-[bis(4-chlorophenyl)methyl]azetidine-3- ylidene}-methanesulfonyl-methyl)N-(3-imidazol-1-yl-propyl)benzamide, 3-({1- [bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)N- (2-dimethylamino-ethyl)benzamide, N'-methyl-hydrazide 3-({1-[bis-(4-chlorophenyl)methyl]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-ethyl-pyrrolidin-2-ylmethyl)benzamide, 3-({1-[bis( 4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)N-(2,2-dimethyl-propyl)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-methyl-butyl)benzamide, 3-({1-[bis(4-chlorophenyl)methyl]azetidine-3- ylidene}-methanesulfonyl-methyl)N-(2-phenyl-propyl)benzamide, 3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)N-(tetrahydro-furan -2-ylmethyl)benzamide, 3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)N-(2,2-diphenyl-ethyl)benzamide, 3-({ 1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene} -methanesulfonyl-methyl)N-(2-ethyl-butyl)benzamide, methyl ester 4-{[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl )benzoylamino]methyl}-cyclohexanecarboxylic acids, 2-amino-1-{4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine- 1-yl}-ethanone, tert-butyl ester (2-{4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine-1- yl}-2-oxo-ethyl)carbamic acid, 1-{4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine-1 -yl}-2-methylamino-ethanone, tert-butyl ester (2-{4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine -1-yl}-2-oxo-ethyl)-N-methyl-carbamic acid, N-methylamide 4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl -methyl)phenyl]piperazine-1-carbothioic acid, N-methylamide 4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine-1 -carboxylic acids, methyl ester 4-[3 -({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine-1-carboxylic acids, 1-[3-({1-[bis-(4- chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]-4-isobutyl-piperazine, 1-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene} methanesulfonyl-methyl)phenyl]-4-ethyl-piperazine, 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-dimethylamino-ethanone, 1 -[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine, tert-butyl ester 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-[(3,5-difluorophenyl)(methylsulfonyl)methyl-(RS)]azetidine, (RS)-4- [4-((4-chlorophenyl){3-[(3,5-difluorophenyl) m ethanesulfonyl-methylene]azetidin-1-yl}-methyl)-benzyl]morpholine, 4-(4-{3-[(1-benzhydryl-azetidin-3-ylidene)methanesulfonyl-methyl]phenoxy}butyl)morpholine, 4- (4-{3-[(1-Benzhydryl-azetidin-3-ylidene)methanesulfonyl-methyl]phenoxy}propyl)morpholine, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-thiene -2-yl-sulfonamide, 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-yl-s sulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-naphth-1-yl-sulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl }-3, 4-difluorophenylsulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-methyl-1-H-imidazol-4-yl-sulfonamide, 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-yl-sulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-fluorophenylsulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidine-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-yl-phenyl)sulfonamide, N- {1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-4-fluorophenylsulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N- targets l-quinol-8-ylsulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-phenylsulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidine -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-(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-phenyl-ethylenesulfonyl)-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]azetidine -3-yl}-amide, (5-methylsulfonyl-3-methyl-4-vinyl-thiophene-2-carboxy)-{1- [bis (4-chlorophenyl) methyl]azetidin-3-yl}-amide, ( RS)-N-{1-[(4-chloro-phenyl)pyridin-3-yl-methyl]azetidin-3-yl}-3,5-difluoro-benzenesulfonamide, (RS)-N-{1-[( 4-k chloro-phenyl)-pyrimidin-5-yl-methyl]azetidin-3-yl}-3,5-difluoro-benzenesulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N -(6-chloropyrid-2-yl)-methyl-sulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(6-ethylpyrid-2-yl)-methyl- sulfonamide, N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-quinol-6-yl-methyl-sulfonamide, N-{1-[bis-(4-chlorophenyl)methyl ]azetidin-3-yl}-N-quinol-5-yl-methyl-sulfonamide, ]N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-isoquinol-5-yl -methyl-sulfonamide, N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-pyrid-3-yl-methyl-sulfonamide, N-{1-[bis-(4- chlorophenyl)methyl]azetidin-3-yl}-N-(1-oxide-pyrid-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)-methyl sulfonamide , 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, N -{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-(methylsulfonyl)-3-aminobenzoate ethyl, N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3 -yl}-N-(1-isobutyl-piperid-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-di-fluorobenzyl)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-yl-methyl)-methylsulfonamide, N-{1-[bis-(4-fluoro-phenyl)-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)-methyl sulfonamide, (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]-azetidine-3-11}-N-(3,5-difluorophenyl)-methylsulfonamide, (R)-N-{1-[(4-chlorophenyl)-pyrimidin-5-yl-methyl]-azetidine-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, and their optical isomers and their pharmaceutical acceptable salts. 4. A combination of compounds according to claim 2, characterized in that it contains a compound of formula (I) selected from the group of the following compounds: {1-[bis-(4-chlorophenyl)-methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methyl-(RS)]azetidin-3-ol, 3-acetoxy-1-[bis-(4-chlorophenyl)-methyl]-3-[(3, 5-difluorophenyl)(methylsulfonyl)methyl)-methyl sulfonylmethyl-(RS)]azetidine, 1-[bis-(4-chlorophenyl)-methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, and their optical isomers and their pharmaceutically acceptable salts. 5. The combination of compounds according to claim 1, characterized in that it contains the CB1 antagonist representing SR141716, its hydrates, and its pharmaceutically acceptable salts or LY320135 and its pharmaceutically acceptable salts. 6. Pharmaceutical preparation, characterized in that it contains CB1 antagonist and sibutramine, its hydrate or one of its pharmaceutically acceptable salts in pure form or in combination with one or more diluents and/or compatible and pharmaceutically acceptable adjuvants and/or optionally in combination with another pharmaceutically acceptable and physiologically active product. 7. Pharmaceutical preparation in accordance with claim 6, characterized in that it contains a CB1 antagonist of formula I in accordance with the definition in claim 2. 8. Pharmaceutical preparation according to claim 7, characterized in that it contains a compound of formula (I) selected from the group of 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-[(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)(3-trifluoromethoxyphenyl)methylene]azetidine, 3-trifluoromethylphenyl)methylene]azetidine, 1-benzhydryl-3-{[3,5-bis(trifluoromethyl)phenyl](methylsulfonyl)methylene}azetidine, 1-benz hydryl-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)(naphthyl-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-methylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, (R, S)-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)me ethyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-[bis-(4-chlorophenyl)methyl]-3-[(3,5-bis(trifluoromethyl)phenyl]methylsulfonyl methylene} azetidine, (R,S)-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, (R,S)-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, (R,S)-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]azetide in, (S)-1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R,S) -(4-chlorophenyl)[4-(3,3-dimethyl-piperidin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{( R)-(4-chlorophenyl)[4-(3,3-dimethyl-piperidin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1- {(S)-(4-chlorophenyl)[4-(3,3-dimethyl-piperidin-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R,S)-(4-chlorophenyl)[4-(thiomorpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1- { (R)-(4-chlorophenyl)[4-(thiomorpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{ (S) -(4-chlorophenyl)[4-(thiomorpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R,S)-( 4-chlorophenyl)[4-(N-ethyl-N-cyclohexyl-aminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-(4- chlorophenyl)[4-(N-eth yl-N-cyclohexyl-aminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(S)-(4-chlorophenyl)[4-(N-ethyl- N-cyclohexyl-aminomethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{{(R,S)-(4-chlorophenyl){4-[(4- ethoxycarbonylpiperazinyl)methyl]phenyl}methyl}}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{{(R)-(4-chlorophenyl){4-[(4-ethoxycarbonylpiperazinyl)methyl ]phenyljmethyl}}-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-{(R,S)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propyl-aminomethyl)phenyl]methyl }-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propyl-aminomethyl)phenyl]methyl}- 3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(S)-(4-chlorophenyl)[4-(N-cyclopropyl-N-propyl-aminomethyl)phenyl]methyl}-3- [(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{( R,S)-(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-{{(R,S)-(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-{(R,S)-(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-{(R,S)-(4-chlorophenyl)[4-(piperidin-1-yl-methyl)phenyl] methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-(4-chlorophenyl)[4-(piperidin-1-yl-methyl)phenyl]methyl}-3 -[(3, 5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(S)-(4-chlorophenyl)[4-(piperidin-1-yl-methyl)phenyl]methyl}-3-[(3 , 5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R,S)-(4-chlorophenyl)[4-(4-methyl-piperazin-1-yl-methyl)phenyl]methyl}-3-[ (3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-(4-chlorophenyl)[4-(4-methyl-piperazin-1-yl-methyl)phenyl]methyl}-3-[ (3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(S)-(4-chlorophenyl)[4-(4-methyl-piperazin-1-yl-methyl)phenyl]methyl}-3-[ (3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R,S)-(4-chlorophenyl)[4-(morpholin-4-yl-methyl)phenyl]methyl}-3-[(3 ,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-(4-chlorophenyl)[4-(morpholin-4-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl )(methylsulfonyl)methylene] azetidine, 1-{(S)-(4-chlorophenyl)[4-(morpholin-4-yl-methyl)phenyl]methyl} -3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1- {(R,S)-(4-chlorophenyl)[4-(diethylaminomethyl)phenyljmethyl}-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-{(R,S)-(4-chlorophenyl)[4-(piperazin-2-on-4-yl-methyl)phenyl] methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-(4-chlorophenyl)[4-(piperazin-2-on-4-yl-methyl)phenyl] methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(S)-(4-chlorophenyl)[4-(piperazin-2-on-4-yl-methyl)phenyl] methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R,S)-(4-chlorophenyl)[4-(imidazol-1-yl-methyl)phenyl]methyl} -3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(R)-(4-chlorophenyl)[4-(imidazol-1-yl-methyl)phenyl]methyl}-3-[ (3,5-difl uorophenyl)(methylsulfonyl)methylene]azetidine, 1-{(S)-(4-chlorophenyl)[4-(imidazol-1-yl-methyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl) )methylene]azetidine, (R,S)-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, (R,S)-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, (R,S)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl)( methylsulfonyl)methylene]azetidine, (R)-1-[(4-carbamoylphenyl)(4-chlorophenyl)methyl]-3-[(3,5-difluorophenyl l)(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-methylsulfanylphenyl)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-(N-pi peridylcarbamoyl)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, (R,S)-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, (R,S)-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, (R,S)-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, 1-[bis(4-chlorophenyl)methyl]-3-hydroxy-3-[ (methylsulfonyl)(2-methoxycarbonylthien-5-yl)methylene]ase thydine-(RS) , 1-[bis(4-chlorophenyl)methyl]-3-[(2-isobutylaminocarbonylthien-5-yl)(methylsulfonyl)methylene]azetidine, 1-[bis(4-chlorophenyl)methyl]-3 -[(3-methoxycarbonylphenyl)(methylsulfonyl)methyl-(RS)]azetidin-3-ol, 1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(pyridin-4-yl)methyl-( RS)]azetidin-3-ol, 1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(pyridin-3-yl)methyl-(RS)]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-dimethylamino-propyl)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- methyl-ethyl)benzamide, 3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-1-methyl)N-piperidin-1-yl-benzamide, 3-({1-[bis (4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)N-isobutyl-benzamide, 3-({1-[bis( 4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-1-methyl)N-(3-imidazol-1-yl-propyl)benzamide, 3-({1-[bis(4-chlorophenyl)methyl]azetidine-3 -ylidene}-methanesulfonyl-methyl)N-(2-dimethylamino-ethyl)benzamide, N'-methyl-hydrazide 3-({1-[bis-(4-chlorophenyl)methyl]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-ethyl-pyrrolidin-2-ylmethyl)benzamide, 3-({1-[bis(4- chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)N-(2,2-dimethyl-propyl)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-methyl-butyl)benzamide, 3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene} -methanesulfonyl-methyl)N-(2-phenyl-propyl)b enzamide, 3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)N-(tetrahydro-furan-2-ylmethyl)benzamide, 3-({1-[bis( 4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)N-(2,2-diphenyl-ethyl)benzamide, 3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene }-methanesulfonyl-methyl)N-(2-ethyl-butyl)benzamide, methyl ester 4-{[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl- methyl)benzoylamino]methyl}-cyclohexanecarboxylic acids, 2-amino-1-{4- [3- ({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine -1-yl}-ethanone, tert-butyl ester (2-{4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine-1 -yl}-2-oxo-ethyl)carbamic acid, 1-{4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine- 1-yl}-2-methylamino-ethanone, tert-butyl ester (2-{4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl] Piperazin-1-yl}-2-oxo-ethyl)-N-methyl-carbamic acid, N -methylamide 4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine-1-carbothioic acid, N-methylamide 4-[3-( {1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine-1-carboxylic acid, methyl ester 4-[3-({1-[bis-(4- chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine-1-carboxylic acid, 1-13-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl -methyl)phenyl]-4-isobutyl-piperazine, l-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]-4-ethyl-piperazine , 4-acetyl l-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine, l-{4-[3-({1- [bis-(4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]-piperazin-1-yl}-2-dimethylamino-ethanone, l-[3-({1-[bis-( 4-chlorophenyl)methyl]azetidin-3-ylidene}-methanesulfonyl-methyl)phenyl]piperazine, tert-butyl ester 4-[3-({1-[bis-(4-chlorophenyl)methyl]azetidin-3-ylidene} -methanesulfonyl-methyl)phenyl]piperazine-1-carb oxylic acids, 1-[bis-(4-methoxycarbonylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, 3-acetoxy-1-[bis-(4-methoxycarbonylphenyl)methyl]- 3-[(3,5-difluorophenyl)(methylsulfonyl)methyl-(RS)]azetidine, (RS)-4-[4-((4-chlorophenyl){3-[(3,5-difluorophenyl)methanesulfonyl-methylene) ]azetidin-1-yl}-methyl)-benzyl]morpholine, 4-(4-{3-[(1-benzhydryl-azetidin-3-ylidene)methanesulfonyl-methyl]phenoxy}butyl)morpholine, 4-(4- {3-[(1-Benzhydryl-azetidin-3-ylidene)methanesulfonyl-methyl]phenoxy}propyl)morpholine, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-thien-2- yl-sulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-4-methoxyphenylsulfonamide, N-[4-(N-{1-[bis(4-chlorophenyl)methyl]azetidine -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-yl-sulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-naphth-1-yl-sulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}- 3,4-difluorophenylsulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-1-methyl-1-H-imidazol-4-yl-sulfonamide, 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-yl-sulfonamide, 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-cl orophenyl)methyl]azetidin-3-yl}pyrid-2-ylsulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}(3-fluoro-5-pyrrolidin-1-yl- phenyl)sulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-4-fluorophenylsulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidine-3 -yl}-N-methyl-quinol-8-ylsulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-methyl-phenylsulfonamide, 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-(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-phenyl-ethylenesulfonyl)-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-vinyl-thiophene-2-carboxy)-{1-[bis (4-chlorophenyl)methyl]azetidin-3-yl}-amide, (RS)-N-{1-[(4-chloro-phenyl)pyridin-3-yl-methyl]azetidin-3-yl}-3, 5-difluoro-benzenesulfonamide, (RS)-N-{1-[(4-chloro-phenyl)-pyrimidin-5-yl-methyl]azetidin-3-yl}-3,5-difluoro-benzenesulfonamide, N-{ 1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-N-(6-chloropyrid-2-yl)-methyl-sulfonamide, N-{1-[bis(4-chlorophenyl)methyl]azetidin- 3-yl}-N-(6-ethylpyrid-2-yl)-methyl-sulfonamide, N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-quinol-6-yl -methyl-sulfonamide, N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-quinol-5-yl-methyl-sulfonamide, N-{1-[bis-(4- chlorophenyl)methyl]azetidin-3-yl}-N-isoquinol-5-yl-methyl-sulfonamide, N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-pyrid-3 -yl-methyl-sulfonamide, N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-(1-oxid-pyrid-3-yl)-methylsulfonamide, N-(1R, 2S,4S)-bicyclo[2,2,1]hept-2-yl-N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-methylsulfonami d, 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)-methyl sulfonamide, 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, N-{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-(methylsulfonyl)-3-aminobenzoate ethyl, N -{1-[bis-(4-chlorophenyl)methyl]azetidin-3-yl}-N-(1-isobutyl-piperid-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-yl-methyl)-methylsulfonamide, N-{1-[bis-(4 -fluoro-phenyl)-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)m ethyl]azetidin-3-yl}-N-(3,5-difluorophenyl)-benzylsulfonamide, and their optical isomers and their pharmaceutically acceptable salts. 9. Pharmaceutical preparation according to claim 7, characterized in that it contains a compound of formula (I) selected from the group of the following compounds: (1-[bis-(4-chlorophenyl)-methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methyl-(RS)]azetidin-3-ol, 3-acetoxy-1-[bis-(4-chlorophenyl)-methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methyl)-methyl sulfonylmethyl-(RS)]azetidine, 1-[bis-(4-chlorophenyl)-methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine, and their optical isomers and their pharmaceutically acceptable salts. 10. Pharmaceutical preparation according to claim 6, characterized in that it contains the CB1 antagonist represented by SR141716, its hydrate and its pharmaceutically acceptable salts or LY320135 and its pharmaceutically acceptable salts. 11. Pharmaceutical preparation according to one of claims 6 to 10, characterized in that it is applied in combination, individually or distributed over a certain period of time. 12. Pharmaceutical preparation according to one of claims 6 to 11, characterized in that it contains from 0.5 to 10 mg of sibutramine and 0.1 to 200 mg of CB1 antagonist.