JP2007513872A5

JP2007513872A5 -

Info

Publication number: JP2007513872A5
Application number: JP2006536096A
Authority: JP
Filing date: 2004-10-22
Publication date: 2007-09-13

Claims

A compound of formula (I), (II), (III), (IV) and / or (V) having CB ₁ receptor activity, a prodrug, tautomer or salt thereof use of in the manufacture of a medicament for the treatment and / or prophylaxis of drug induced obesity in patients with adolescent well treatment and / or prophylaxis and / or children CB ₁ receptors related disease in.

The compound having the CB ₁ receptor activity is a) the compound represented by the formula (I)

[Where:
R and R ₁ are independently C _1-3 alkyl or alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C _1-2 ) — amino, mono - or dialkyl _{(C 1-2)} - _{amide, (C 1-3)} - alkylsulfonyl, _{dimethylsulfamide, C 1-3} - alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl And a phenyl, thienyl or pyridyl group optionally substituted by 1, 2, 3 or 4 substituents Y which may be the same or different from the group of acetyl, or R and / or R ₁ is naphthyl Represents
- R ₂ is hydrogen, _{hydroxy, C 1-3} - represents alkoxy, acetyloxy or propionyloxy,
-R ₃ represents a hydrogen atom, or a branched or unbranched C _1-8 alkyl group or C _3-7 -cycloalkyl group, wherein the alkyl group or cycloalkyl group is substituted with a hydroxy group You can,
-R ₄ represents a branched or unbranched C _2-10 heteroalkyl group, a C _3-8 non-aromatic heterocycloalkyl group or a C _4-10 non-aromatic heterocycloalkyl-alkyl group, wherein The group contains one or more heteroatoms of group (O, N, S) or a —SO ₂ — group, wherein said branched or unbranched C _2-10 heteroalkyl group, C _3-8 non-aromatic heterocyclo The alkyl group or C _4-10 non-aromatic heterocycloalkyl-alkyl group is substituted with a keto group, a trifluoromethyl group, a C _1-3 alkyl group, a hydroxy, amino, monoalkylamino or dialkylamino group or a fluoro atom. At best, or _{R 4} is amino, hydroxy, or represents phenoxy or benzyloxy group, or _{R 4} is _{C 1-8} _{alkoxy, C 3-8} alkenyl Represents a C _5-8 cycloalkenyl or C _6-9 cycloalkenylalkyl group, wherein these groups are sulfur, nitrogen or oxygen atom, a keto group or -SO 2 _- may also contain groups, the Alkoxy, alkenyl and cycloalkyl groups may be substituted with hydroxy, trifluoromethyl, amino, monoalkylamino or dialkylamino groups or a fluoro atom, or R ₄ is a C ₂ containing a fluoro atom. _-5 represents an alkyl group, or R ₄ represents an imidazolylalkyl group, benzyl, pyridylmethyl, phenethyl or thienyl group, or R ₄ represents a substituted phenyl, benzyl, pyridyl, thienyl, pyridylmethyl or Represents a phenethyl group, where these aromatic rings are 1, 2 or 3 substituents Substituted with Y (wherein Y has the meaning as indicated above), or when R ₃ is H or methyl, R ₄ may represent the group NR ₆ R ₇ , where
-R ₆ and R ₇ are the same or different and represent C _2-4 alkyl, C _2-4 trifluoroalkyl,
Or R ₆ represents a methyl group provided that R ₇ represents a C _2-4 alkyl group, or R ₆ and R ₇ together with the nitrogen atom to which they are attached Forming a saturated or unsaturated heterocyclic moiety of 4 to 8 atoms, wherein said heterocyclic moiety contains an oxygen or sulfur atom or a keto group or a —SO ₂ — group or an additional nitrogen atom The saturated or unsaturated heterocyclic moiety may be substituted with a C _1-4 alkyl group, or —R ₃ and R ₄ together with the nitrogen atom to which they are attached. To form a saturated or unsaturated monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms, wherein the heterocyclic moiety is an atom of group (O, N, S) 1 Or may contain keto groups or —SO ₂ — groups The moieties are C _1-4 alkyl, hydroxyalkyl, phenyl, thienyl, pyridyl, amino, monoalkylaminoalkyl, dialkylaminoalkyl, monoalkylamino, dialkylamino, aminoalkyl, azetidinyl, pyrrolidinyl, piperidinyl or hexahydro-1H-azepinyl. Optionally substituted with a group
R ₅ is benzyl, phenyl optionally substituted by 1, 2, 3 or 4 substituents Y (where Y has the meaning as given above and may be the same or different) , Thienyl or pyridyl, or R ₅ is branched or unbranched C _1-8 alkyl, C _3-8 alkenyl, C _3-10 cycloalkyl, C _5-10 bicycloalkyl, C _6-10 tri Represents cycloalkyl or C _5-8 cycloalkenyl, or R ₅ represents naphthyl]
And
b) The compound represented by the formula (II) is

[Where:
R is C _1-3 alkyl or alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C _1-2 ) -amino, mono- or dialkyl ( C _1-2 ) -amide, C _1-3 -alkoxycarbonyl, carboxyl, cyano, carbamoyl and acetyl may be substituted with 1, 2, 3 or 4 substituents Y which may be the same or different Represents a good phenyl, thienyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl or triazinyl group, or R represents naphthyl, provided that when R is 4-pyridinyl, R ₄ is halogen. Atom or cyano, carbamoyl, formyl, ace Le, trifluoroacetyl, fluoroacetyl, propionyl, sulfamoyl, methanesulfonyl, methylsulfanyl or branched or unbranched C _1-4 alkyl group (this C _1-4 alkyl group 1-3 fluoro atoms or bromo, Chloro, iodo, cyano or optionally substituted with a hydroxy group)
-R ₁ represents a phenyl or pyridinyl group optionally substituted by 1-4 substituents Y (wherein Y may be the same or different and Y has the meaning described above). Or R ₁ represents a pyrimidinyl, pyrazinyl, pyridazinyl or triazinyl group optionally substituted by 1-2 substituents Y (which may be the same or different), or R ₁ represents a group (N , O, S) represents a 5-membered aromatic heterocyclic ring having 1 or 2 heteroatoms, which may be the same or different, wherein the 5-membered aromatic heterocyclic ring is 1 -May be substituted with two substituents Y (which may be the same or different), or R ₁ represents naphthyl;
R ₂ is H, branched or unbranched C _1-8 alkyl, C _3-8 -cycloalkyl, C _3-8 -alkenyl, C _5-8 -cycloalkenyl (these groups are sulfur, oxygen or Which may contain nitrogen atoms)
-R ₃ is branched or unbranched C _2-8 alkyl, C _1-8 -alkoxy, C _5-8 -cycloalkyloxy, C _3-8 -cycloalkyl, C _5-10 bicycloalkyl, C _{6 Represents -10} tricycloalkyl, C _3-8 alkenyl, C _5-8 cycloalkenyl, wherein these groups optionally contain one or more heteroatoms of the group (O, N, S) Well and these groups may be substituted by hydroxy groups or 1-2 C _1-3 alkyl groups or 1-3 fluoro atoms, or R ₃ represents a benzyl or phenethyl group, wherein These aromatic rings are C _1-3 alkyl or alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- Is properly dialkyl _{(C 1-2)} - amino, mono- - or dialkyl _{(C 1-2)} - _{amide, (C 1-3)} - alkylsulfonyl, _{Dimethylsulfamide, C 1-3} - alkoxycarbonyl, carboxyl, Optionally substituted with 1-5 substituents Z which may be the same or different from the group of trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl, or R ₃ is 1-4 substituents Z (Wherein Z has the meaning as indicated above) represents a phenyl or pyridinyl group substituted, or R ₃ represents a pyridinyl group, or R ₃ represents a phenyl group, However R ₄ is a halogen atom or a cyano, carbamoyl, formyl, acetyl, trifluoroacetyl, fluoroacetyl, propionyl, Sulf Moil, methanesulfonyl, methylsulfanyl or C _1-4 alkyl group (this C _1-4 alkyl group 1-3 fluoro atoms or bromo, chloro, iodo, optionally substituted by cyano or hydroxy groups) of Or R ₃ represents the group NR ₅ R ₆ , provided that R ₂ represents a hydrogen atom or a methyl group, where
R ₅ and R ₆ are the same or different and represent branched or unbranched C _1-4 alkyl, or R ₅ and R ₆ together with the nitrogen atom to which they are attached a ring atom Forming a saturated or unsaturated monocyclic or bicyclic heterocyclic group of 4 to 10, wherein said heterocyclic group is one or two heterocycles of the group (N, O, S) Containing atoms (these heteroatoms may be the same or different), the heterocyclic group may be substituted with a C _1-3 alkyl group or a hydroxy group, or R ₂ and R ₃ may be Together with the nitrogen atom to which is attached forms a saturated or unsaturated heterocyclic group having 4 to 10 ring atoms, wherein said heterocyclic group is a group (N, O, S ) One or two heteroatoms (these heteroatoms may be the same or different Containing also may) it, the heterocyclic group may be substituted by C _1-3 alkyl group or a hydroxy group,
R ₄ is a hydrogen or halogen atom, or a cyano, carbamoyl, formyl, acetyl, trifluoroacetyl, fluoroacetyl, propionyl, sulfamoyl, methanesulfonyl, methylsulfanyl or a branched or unbranched C _1-4 alkyl group (this C _1-4 alkyl group represents 1-3 fluoro atoms or may be substituted with bromo, chloro, iodo, cyano or hydroxy groups]
And
c) The compound represented by the formula (III) is

[Where:
R and R ₁ are independently C _1-3 alkyl or alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C _1-2 ) — amino, mono - or dialkyl _{(C 1-2)} - _{amide, (C 1-3)} - alkylsulfonyl, _{dimethylsulfamide, C 1-3} - alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl And a phenyl, thienyl or pyridyl group optionally substituted by 1, 2 or 3 substituents Y which may be the same or different from the group of acetyl, or R and / or R ₁ represents naphthyl ,
- R ₂ is hydrogen, _{hydroxy, C 1-3} - represents alkoxy, acetyloxy or propionyloxy,
-R ₃ represents a hydrogen atom or a branched or unbranched C _1-8 alkyl group or a C _3-7 cycloalkyl group, wherein the alkyl group or cycloalkyl group may be substituted with hydroxy Often,
R ₄ is a hydrogen atom, or branched or unbranched C _1-8 alkyl, C _3-8 cycloalkyl, C _2-10 heteroaryl, C _3-8 non-aromatic heterocycloalkyl or C _4-10 non- Represents an aromatic heterocycloalkyl-alkyl moiety, wherein these moieties may contain one or more heteroatoms of group (O, N, S), said moiety being a keto group, a trifluoromethyl group, C _1-3 alkyl group, hydroxy, amino, monoalkylamino or dialkylamino group or may be substituted with a fluoro atom, or R ₄ represents an amino, hydroxy, phenoxy or benzyloxy group, or R 4 ₄ branched or unbranched _{C 1-8} _{alkoxy, C 3-8} _{alkenyl, C 5-8} cycloalkenyl or _{C 6-9} cycloalkenyl alkyl It represents a group, wherein these groups are sulfur, nitrogen or oxygen atom, a keto group or -SO ₂ - may also contain groups, the _{C 1-8} _{alkoxy, C 3-8} _{alkenyl, C 5- The 8} cycloalkenyl or C _6-9 cycloalkenylalkyl group may be substituted with a hydroxy group, a trifluoromethyl group, an amino group, a monoalkylamino group or a dialkylamino group or a fluoro atom, or R ₄ is phenyl, Represents a benzyl, pyridyl, thienyl, pyridylmethyl or phenethyl group, wherein these aromatic rings are substituted by 1, 2 or 3 substituents Y, where Y has the meaning indicated above Or R ₄ represents the group NR ₈ R ₉ provided that R ₃ represents a hydrogen atom or a methyl group, and R ₈ and R ₉ are the same or different and represent C _1-4 alkyl or C _2-4 trifluoroalkyl, or R ₈ and R ₉ together with the nitrogen atom to which they are attached are ring atoms Forming a saturated or unsaturated heterocyclic moiety of the number 4 to 8, wherein said heterocyclic moiety contains an oxygen or sulfur atom or a keto group or a —SO ₂ — group or an additional nitrogen atom. The saturated or unsaturated heterocyclic moiety may be substituted with a C _1-4 alkyl group, or R ₃ and R ₄ together with the nitrogen atom to which they are attached. Forming a saturated or unsaturated monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms, wherein said heterocyclic moiety contains one or more atoms of the group (O, N, S) Or contains a keto group or a —SO ₂ — group The moiety may be C _1-4 alkyl, hydroxyalkyl, phenyl, thienyl, pyridyl, amino, monoalkylaminoalkyl, dialkylaminoalkyl, monoalkylamino, dialkylamino, aminoalkyl, azetidinyl, pyrrolidinyl, piperidinyl or May be substituted with a hexahydro-1H-azepinyl group,
R ₅ and R ₆ independently of one another represent a hydrogen atom or a branched or unbranched C _1-8 alkyl or alkenyl group, wherein these groups are of the group (O, N, S) It may contain one or more heteroatoms or keto groups or —SO ₂ — groups and these groups may be substituted with hydroxy or amino groups, or R ₅ and R ₆ are independent of each other _Represents a C _3-8 cycloalkyl or C _3-8 cycloalkenyl group, wherein these groups represent one or more ring heteroatoms of the group (O, N, S) or a —SO ₂ — group. And these groups may be a hydroxy group, an alkyl (C _1-3 ), a —SO ₂ — group, a keto group, an amino group, a monoalkylamino group (C _1-3 ) or a dialkylamino group (C be substituted with _1-3) Ku, or R ₅ represents a naphthyl group or a phenyl group, wherein said phenyl group is 1, 2 or 3 substituents Y (wherein, Y has the meaning such as described in the present specification) In which R ₆ is a hydrogen atom, or a branched or unbranched alkyl group (C _1-5 ) (this alkyl group represents one heteroatom of the group (O, N, S)). Or may contain an —SO ₂ — group and the alkyl group may be substituted with a hydroxy, keto or amino group, or R ₅ and R ₆ may be A monocyclic, bicyclic or tricyclic alkyl or alkenyl group which may contain a ring heteroatom of the group (O, N, S), keto or —SO ₂ — group together with the nitrogen atom to which it is attached Where the monocyclic, bicyclic Or tricyclic alkyl or alkenyl group is a hydroxy group, an alkyl _{(C 1-3)} group, SO ₂ group, keto group, amino group, monoalkylamino group _{(C 1-3),} dialkylamino group _{(C 1-3)} , A pyrrolidinyl group or a piperidinyl group, the monocyclic, bicyclic or tricyclic alkyl or alkenyl group may contain a condensed phenyl group, wherein the condensed phenyl group is 1 Or may be substituted with two substituents Y, where Y has the meaning as described herein;
- R ₇ represents a branched or unbranched _{C 1-3} alkyl]
And
d) The compound represented by the formula (IV) is

[Where:
R is a hydrogen atom or branched or unbranched C _1-3 alkyl or alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl (C _{1- 2} ) -Amino, mono- or dialkyl ( _C1-2 ) -amide, branched or unbranched ( _C1-3 ) -alkoxycarbonyl, trifluoromethylsulfonyl, sulfamoyl, branched or unbranched alkyl (C _1-3 ) of the group of sulfonyl, carboxyl, cyano, carbamoyl, branched or unbranched dialkyl ( _C1-3 ) aminosulfonyl, branched or unbranched monoalkyl ( _C1-3 ) -aminosulfonyl and acetyl Represents the substituent X,
-R ₁ is a hydrogen atom or represents 1-4 substituents X, where X has the meaning described above;
R ₂ represents a phenyl, thienyl, pyridyl or pyrimidinyl group optionally substituted by 1-4 substituents X, where X has the meaning described above, or R ₂ is Represents naphthyl,
R ₃ represents a hydrogen atom, or a branched or unbranched C _1-10 alkyl or cycloalkyl-alkyl group, or a phenyl, benzyl or phenethyl group, wherein these aromatic rings are 1-5 Substituent Z (wherein Z may be the same or different, branched or unbranched C _1-3 alkyl or alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino Mono- or dialkyl ( _C1-2 ) -amino, mono- or dialkyl ( _C1-2 ) -amide, branched or unbranched ( _C1-3 ) -alkylsulfonyl, dimethylsulfamide, branched or unbranched C _{1-3 -} alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano Carbamoyl, is a substituent of the group of sulfamoyl and acetyl) may be substituted with, or R ₃ represents a pyridyl or thienyl group,
R ₄ is a branched or unbranched C _1-10 alkyl or cycloalkyl-alkyl group, branched or unbranched C _1-10 alkoxy, C _3-8 cycloalkyl, C _5-10 bicycloalkyl, C _6-10 tricycloalkyl, branched or unbranched C _3-10 alkenyl, C _5-8 cycloalkenyl, wherein these groups contain one or more heteroatoms of the group (O, N, S) And the group may be substituted with a hydroxy group, 1-3 methyl groups, ethyl groups or 1-3 fluoro atoms, or R ₄ may be a phenyl, benzyl or phenethyl group. Where these aromatic rings may be substituted with 1-5 substituents Z, where Z has the meaning described above, or R ₄ represents a pyridyl or thienyl group. Represent Or R ₄ represents a group NR ₅ R _6, wherein, R ₅ and R ₆ are saturated or unsaturated mono cyclic or together with the nitrogen atom to which they are attached rings atoms from 4 to 10 Forming a bicyclic heterocyclic group, wherein said heterocyclic group contains one or more heteroatoms of group (O, N, S) and said heterocyclic group is branched or unbranched. branched C _1-3 alkyl, hydroxy or may be substituted with a trifluoromethyl group or a fluoro atom, or - R ₃ and R ₄ together with the nitrogen atom to which they are attached the ring atoms is 4 to 10 saturated or unsaturated monocyclic or bicyclic heterocyclic groups, wherein said heterocyclic group contains one or more heteroatoms of group (O, N, S) and the heterocyclic group is a branched or unbranched C _1-3 alkyl, hydroxy Or it may be substituted with a trifluoromethyl group or a fluoro atom,
And
e) The compound represented by the formula (V) is

[Where:
R and R ₁ are independently branched or unbranched (C _1-3 ) alkyl or alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or Dialkyl ( _C1-2 ) -amino, mono- or dialkyl ( _C1-2 ) -amide, ( _C1-3 ) -alkoxycarbonyl, trifluoromethylsulfonyl, sulfamoyl, ( _C1-3 ) -alkylsulfonyl, carboxyl, cyano, _{carbamoyl, (C 1-3)} - dialkylamino _{sulfonyl, (C 1-3)} - substituted with mono alkylaminosulfonyl and identical or different substituents may also be 1-4 and X group of acetyl Optionally phenyl, naphthyl, thienyl, pyridyl, pyrimidyl, Represents a pyrazinyl, pyridazinyl or triazinyl group,
-R ₂ represents a hydrogen atom or a branched or unbranched C _1-8 -alkyl or C _1-8 cycloalkyl-alkyl group or a phenyl, benzyl or phenethyl group, wherein these aromatic rings are 1 -4 substituents X, where X has the meaning as indicated above, or R ₂ represents a pyridyl or thienyl group,
R ₃ is branched or unbranched C _1-8 alkyl, C _1-8 alkoxy, C _3-8 cycloalkyl, C _5-10 bicycloalkyl, C _6-10 tricycloalkyl, C _3-8 alkenyl , C _5-8 cycloalkenyl, in which these groups optionally contain one or more heteroatoms of the group (O, N, S), said groups being hydroxy, ethynyl or It may be substituted with 1-3 fluoro atoms, or R ₃ represents a phenyl, benzyl or phenethyl group, wherein these aromatic rings are 1-4 substituents X (where X It may be substituted with a) a means such as shown above, or R ₃ represents pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazinyl or thienyl group, wherein these heteroaromatic rings (Wherein X has the meaning such as shown above) 1-2 substituents X may be substituted with, or R ₃ represents a group NR ₄ R _5, wherein
R ₄ and R ₅ together with the nitrogen atom to which they are attached form a saturated or unsaturated monocyclic or bicyclic heterocyclic moiety having 4 to 10 ring atoms, wherein Heterocyclic groups contain 1 or 2 heteroatoms of group N, O or S, which heteroatoms may be the same or different, wherein said heterocyclic moiety is branched or unbranched C It may be substituted with _1-3 alkyl, hydroxy or trifluoromethyl groups or fluoro atoms, or -R ₂ and R ₃ together with the nitrogen atom to which they are attached together have from 4 ring atoms 10 saturated or unsaturated monocyclic or bicyclic heterocyclic moieties, wherein said heterocyclic group is one or two heteroatoms of group N, O or S (these heteroatoms Are the same or different Containing good), the heterocyclic moiety is a branched or unbranched C _1-3 alkyl, hydroxy, optionally substituted by piperidinyl or trifluoromethyl group or a fluoro atom,
A 4,5-dihydro-1H-pyrazole derivative represented by the formula (I) and / or (III), a 1H-imidazole derivative represented by the formula (II), a formula (IV) A compound having CB ₁ receptor activity according to claim 1 selected from the group of thiazole derivatives represented and / or 1H-1,2,4-triazole-3-carboxamide derivatives represented by formula (V) use.

Said use is a psychological disorder such as psychosis, anxiety, depression, lack of attention, memory impairment, cognitive impairment, appetite disorder, obesity, addiction, strong desire, drug dependence, etc. and neurological disorders such as neurodegenerative disorders, dementia, Dystonia, muscle spasm, tremor, epilepsy, multiple sclerosis, traumatic brain injury, stroke, Parkinson's disease, Alzheimer's disease, epilepsy, Huntington's disease, Tourette syndrome, cerebral ischemia, cerebral hemorrhage, cranial cerebral trauma, stroke, spinal cord injury, Pain disorders and septic shock, including neuropathic pain disorders as well as pediatric treatment and / or prevention related to neuroinflammatory diseases, plaque sclerosis, viral encephalitis, demyelination related diseases, glaucoma, cancer Other cannabinoids, including pediatric treatment of diabetes, vomiting, nausea, asthma, respiratory disease, gastrointestinal disease, gastric ulcer, diarrhea and cardiovascular disease Compounds having a CB ₁ receptors activity according to any one of claims 1 2, which is used in the preparation of a medicament for pediatric treatment of de neurotransmission-related disease, or its prodrug, tautomer Or the use of salt.

4. The use according to claim 1, wherein the use is in the manufacture of a medicament for the treatment and / or prevention of obesity in child patients and / or drug-induced obesity in adolescent patients as well as children. compound or its prodrug having the CB ₁ receptors activity, tautomer or salt, preferably a CB ₁ receptors antagonistic compound or its prodrug, the use of tautomers or salts.

CB according to claim 2, in combination with at least one lipase inhibitory compound when producing a medicament for the treatment and / or prevention of obesity in adolescents or children and / or drug-induced obesity in adolescents as well as children. _Use of a compound having ₁ receptor activity or a prodrug, tautomer or salt thereof, preferably a CB ₁ receptor antagonist compound or a prodrug, tautomer or salt thereof.

A lipase-inhibiting polymer comprising a compound having CB ₁ receptor activity or a prodrug, tautomer or salt thereof, preferably a CB ₁ receptor antagonist compound or a prodrug, tautomer or salt thereof orlistat, panclicins, use of compounds with ATL-962 and at least one CB ₁ receptors activity according to claim 5, wherein used in combination with a lipase inhibiting compound selected from the group of lipstatin.

At least one compound of formula (I), (II), (III), (IV) and / or (V) having CB ₁ receptor activity or a prodrug, tautomer or salt thereof A pharmaceutical composition comprising as an active ingredient suitable for the treatment and / or prevention of CB ₁ receptor-related diseases in children and / or the treatment and / or prevention of drug-induced obesity in adolescent patients as well as children.

The compound having CB ₁ receptor activity is a 4,5-dihydro-1H-pyrazole derivative represented by the formula (I) and / or (III) according to claim 1 or 2 and represented by the formula (II), respectively. 8. A 1H-imidazole derivative, a thiazole derivative represented by formula (IV) and / or a 1H-1,2,4-triazole-3-carboxamide derivative represented by formula (V). The pharmaceutical composition described.

At least one compound of formula (I), (II), (III), (IV) and / or (V) having CB ₁ receptor activity or a prodrug, tautomer or salt thereof Are mental disorders such as psychosis, anxiety, depression, attention deficit, memory impairment, cognitive impairment, appetite disorder, obesity, addiction, strong desire, drug dependence, and neurological disorders such as neurodegenerative disorders, dementia, dystonia, Muscle spasm, tremor, epilepsy, multiple sclerosis, traumatic brain injury, stroke, Parkinson's disease, Alzheimer's disease, epilepsy, Huntington's disease, Tourette syndrome, cerebral ischemia, cerebral hemorrhage, cranial cerebral trauma, stroke, spinal cord injury, neuroinflammation Pain, including neuropathic pain disorders as well as pediatric treatment and / or prevention related to sexually transmitted diseases, plaque sclerosis, viral encephalitis, demyelination related diseases In need of treatment for other cannabinoid neurotransmission-related diseases including disability and septic shock, glaucoma, cancer, diabetes, vomiting, nausea, asthma, respiratory disease, gastrointestinal disease, gastric ulcer, diarrhea and cardiovascular disease 9. An amount suitable for providing pediatric treatment and / or prophylaxis in a child patient in need of treatment, such as pediatric treatment related thereto in a child patient, according to any one of claims 7-8. Pharmaceutical composition.

At least one compound represented by formula (I), (II), (III), (IV) and / or (V) having the CB ₁ receptor activity, or a prodrug, tautomer thereof, or salts, preferably the CB ₁ receptors antagonistic compound or its prodrug, the treatment and / or prophylaxis of drug induced obesity in patients with adolescent not tautomer or salt only obesity and / or children in the patient's children 10. A pharmaceutical composition according to any one of claims 7 to 9 present in an amount that is effectively suitable for.

3. At least one compound having CB ₁ receptor activity according to claim 2 or a prodrug, tautomer or salt thereof, preferably a CB ₁ receptor antagonist compound or a prodrug or tautomer thereof Or a pharmaceutical composition comprising salt and at least one lipase-inhibiting compound as active ingredients for the treatment and / or prevention of obesity in adolescents or children and / or drug-induced obesity in adolescents as well as children.

Lipase of at least one compound having CB ₁ receptor activity or a prodrug, tautomer or salt thereof, preferably CB ₁ receptor antagonist compound or a prodrug, tautomer or salt thereof 12. The pharmaceutical composition according to claim 11, comprising in combination with at least one lipase inhibitory compound selected from the group of inhibitory polymers, orlistat, panclicin, ATL-962 and lipstatin.

Formula according to claim 2, further comprising a CB ₁ receptors activity (I), (II), (III), (IV) or at least one compound or its prodrug represented by (V), tautomeric A body or salt, preferably a CB ₁ receptor antagonist compound or a prodrug, tautomer or salt thereof and at least one lipase inhibitory compound each in a patient in need of treatment for obesity 13. A pharmaceutical composition according to any one of claims 10 to 12 which is present in an amount which is effectively suitable for preventing and / or preventing.

Formula according to claim 2, further comprising a CB ₁ receptors activity (I), (II), (III), (IV) or at least one compound or its prodrug represented by (V), tautomeric Each of the body or salt, preferably a CB ₁ receptor antagonist compound or a prodrug thereof, a tautomer or salt and at least one lipase inhibitory compound of drug-induced obesity in adolescent patients as well as children. 13. A pharmaceutical composition according to any one of claims 10 to 12 present in an amount effectively suitable for treating and / or preventing it in a patient in need of treatment.

At the same time when treating obesity and / or prophylaxis, wherein according to claim 2, further comprising a CB ₁ receptors activity as a formulation in combination with at least one lipase inhibiting compound for administration separately or stepwise (I ), (II), (III), (IV) or (V) or a prodrug, tautomer or salt thereof, preferably a CB ₁ receptor antagonist compound or A drug containing a prodrug, tautomer or salt thereof as a drug.

Formula according to claim 2, further comprising a CB ₁ receptors activity (I), (II), (III), (IV) or at least one compound or its prodrug represented by (V), tautomeric Or a salt, preferably a CB ₁ receptor antagonist compound or a prodrug, tautomer or salt thereof as a drug, and a compound having the CB ₁ receptor activity when treating and / or preventing obesity , Preferably a pharmaceutical comprising instructions indicating that the CB ₁ antagonistic compound may be administered in combination with the lipase inhibitory compound at the same time, separately or in stages.

At least one compound of formula according to claim 2, further comprising a CB ₁ receptors activity in combination with lipase inhibiting compounds (I), (II), (III), 1 Tsude in (IV) or (V) Or a prodrug, tautomer or salt thereof, preferably a CB ₁ receptor antagonist compound or a prodrug, tautomer or salt thereof.

A lipase-inhibiting polymer comprising a compound having CB ₁ receptor activity or a prodrug, tautomer or salt thereof, preferably a CB ₁ receptor antagonist compound or a prodrug, tautomer or salt thereof orlistat, panclicins, ATL-962 and lipstatin least one compound of formula according to claim 2, further comprising a CB ₁ receptors activity according to claim 17, wherein combining the lipase inhibiting compound selected from the group of (I), (II ), (III), (IV) or a combination of compounds represented by one of (V).