Diaryl-substituted five-membered heterocycle derivative

Abstract

The present invention provides the compounds represented by formula (I): or pharmaceutical salts thereof, wherein: X 1 represents oxygen atoms and the like, X 2 represents nitrogen atoms and the like, X 3 represents nitrogen atoms and the like, X 4 represents nitrogen atoms and the like, R 1 represents formula (II-1): wherein X 5 represents sulfur atoms and the like, A 1 represents carbon atoms and the like, A 2 represents nitrogen atoms and the like and A ring represents phenyl group and the like, having mGluR1 inhibiting effect, and being useful for preventing or treating convulsion, acute pain, inflammatory pain, chronic pain, brain disorder such as cerebral infarction or transient ischemick attack, psychotic disorder such as schizophrenia, anxiety, drug dependence, Parkinson's disease, or gastrointestinal disorder.

1 - 22 . (canceled) 
     
     
         23 . A compound of the formula (I): 
       
         
           
           
               
               
           
         
         wherein:
 X 1  represents an oxygen atom, nitrogen atom or CR 2 ; 
 X 2  represents a nitrogen atom or a carbon atom; 
 X 3  represents a nitrogen atom or a carbon atom; 
 X 4  represents a nitrogen atom or a carbon atom; 
 
         R 1  represents the following formula (II-1): 
       
       
         
           
           
               
               
           
         
         
           wherein: 
           —X 5 — represents —S— or -A 4 =A 3 -, 
           A 1  is a carbon atom or a nitrogen atom, 
           regarding A 2  to A 4 , either all of A 2  to A 4  are CR 4  or any one or two of A 2  to A 4  are nitrogen atoms and the remaining two or one of A 2  to A 4  are CR 4 ; 
              is a double bond when A 1  is a carbon atom, and a single bond when A 1  is a nitrogen atom; 
           R 4  represents a hydrogen atom, lower alkyl group, lower alkyloxy group, halogen atom, mono- or di-lower alkylamino atom, hydroxy group, lower alkyloxycarbonyl group, carbamoyl group or mono- or di-lower alkylcarbamoylamino group; 
           A ring is the following (1) or (2), that may have 1 to 3 substituted groups selected from the group comprising substituted group α; 
           (1) saturated, partially saturated, or unsaturated 5- or 6-membered ring and the ring may be substituted by 1 or 2 oxo groups, wherein all of the constituting atoms of A ring are carbon atoms, or 
           (2) saturated, partially saturated or unsaturated 5- or 6-membered ring that may have 1 to 3 hetero atoms selected from the group comprising N, S and O, besides carbon atoms, as for constituting atoms of A ring and the ring may be substituted by 1 or 2 oxo groups; 
         
         R 2  represents a group selected from the group consisting of: hydrogen atom, lower alkyl group, cyano group, lower alkyloxy group, lower alkyloxycarbonyl group and trialkylsilyl group; 
         R 3  is the following group (A) or (B) that may have 1 to 3 substituted groups selected from the group comprising halogen atom, lower alkyl group, cyano group, nitro group, lower alkyloxy group, hydroxy group and amino group, wherein said lower alkyl group may be substituted by a halogen atom; 
         group (A) a phenyl group; 
         group (B) an unsaturated or partially saturated 5- to 6-membered hetero ring group having 1 to 3 hetero atoms selected from the group comprising N, S and O in the ring; 
         wherein substituted group a is selected from: lower alkyl group (the lower alkyl group may be substituted by a hydroxyl group, halogen atom, aryl group di-lower alkylamino group (two di-lower alkyl groups may bound each other and form a 5- to 7-membered aliphatic hetero ring together with nitrogen atom, or 1 of the carbon atom constituting the aliphatic hetero ring may be substituted by an oxygen atom), lower alkoxy group, oxo group, lower alkyloxycarbonyl group, alkanoyloxy group or lower alkylsulfonylamino group; or when the lower alkyl group is a branched-lower alkyl group, the branched alkyls group may bound each other to form a cycloalkyl group or a cycloalkylene group with 3 to 6 carbon atoms, when the lower alkyl group is a branched-lower alkyl group, the branched alkyl groups may be bound each other to form a cycloalkyl group (the cycloalkyl group may be substituted by a lower alkyl group, hydroxy group, aralkyl group, or lower alkoxy group), when the same carbon atom constituting A ring has 2 lower alkyl groups, the lower alkyl group may form together a cycloalkyl group), cycloalkyl group (any 1 of carbon atoms constituting the cycloalkyl group may be substituted by an oxygen atom), lower alkyloxy group, halogen atom, mono- or di-lower alkylamino group, alkanoyl group, alkylsulfonyl group, lower alkyloxycarbonyl group, carbamoyl group, mono- or di-lower alkylcarbamoyl group, mono- or di-lower alkylcarbamoylamino group, amino group and hydroxyl group; 
         with the proviso that the compound of formula (I) excludes: 
         4-[5-(2-naphthalenyl)-1H-[1,2,4]triazole-3-yl]-pyridine, 3-(1-3-benzodioxol-5-yl)-5-(2-ethylphenyl)-1H-1,2,4-triazole, 6-[5-(4-pyridyl)-1H-1,2,4-triazole-4-yl]-quinoline, 3-(5-phenyl-4H-[1,2,4]triazole-3-yl)naphthalene-2-ol, 3-[5-pyridine-4-yl-1H-[1,2,4]triazole-3-yl]-naphthalene-2-ol, 5-(quinoline-2-yl)-2-(3-cyano-phenyl)-tetrazole, 3-[5-(3,5-dichloropyridine-4-yl)-2-methyl-2H-[1,2,4]triazole-3-yl]-quinoline, 3-naphthalene-2-yl-5-phenyl-4H-[1,2,4]triazole, 3-benzo[1,3]dioxol-5-yl-1-methyl-5-o-tolyl-1H-[1,2,4]triazole, 5-(5-phenyl-4H-[1,2,4]triazole-3-yl)isobenzofuran-1,3-dione; 
         and with the further proviso that if the central X ring is [1,2,3]triazole, and R 1  is pyridine, quinoline or isoquinoline, then R3 is other than phenyl; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         24 . The compound of  claim 23  wherein formula (I) is selected from the group consisting of:
 formula (I-1) 
 
       
         
           
           
               
               
           
         
         formula (I-2) 
       
       
         
           
           
               
               
           
         
         formula (I-3) 
       
       
         
           
           
               
               
           
         
       
       and
 formula (I-4) 
 
       
         
           
           
               
               
           
         
       
     
     
         25 . The compound of  claim 23  wherein:
 R 1  is formula (II-A): 
 
       
         
           
           
               
               
           
         
       
     
     
         26 . The compound of  claim 25  wherein:
 the formula (II-A) is formula (II-B) 
 
       
         
           
           
               
               
           
         
         
           in formula (II-A) is a phenyl group. 
         
       
     
     
         27 . The compound of  claim 25  wherein:
 A ring has at least 1 nitrogen atom as a constituting atom of the A ring. 
 
     
     
         28 . The compound of  claim 25  wherein:
 formula (II-A) is a group represented by formula (II-C): 
 
       
         
           
           
               
               
           
         
         or a group represented by formula (II-D): 
       
       
         
           
           
               
               
           
         
         wherein X 6  represents CH 2 , CH═CH or CH—CH, and 
         regarding X 7  to X 10 , one of X 7  to X 10  is a nitrogen atom, and the rest are carbon atoms; 
         and wherein said group may have 1 to 3 substituted groups selected from substituted group α. 
       
     
     
         29 . The compound of  claim 28  wherein formula (II-A) is formula (II-C), or a pharmaceutically acceptable salt thereof. 
     
     
         30 . The compound of  claim 28  wherein formula (II-A) is formula (II-D), or a pharmaceutically acceptable salt thereof. 
     
     
         31 . The compound of  claim 23  wherein formula (I) is
 formula (I-1) 
 
       
         
           
           
               
               
           
         
       
       or
 formula (I-4) 
 
       
         
           
           
               
               
           
         
       
       with the proviso that R 1  is a substituted or non-substituted naphthyl group. 
     
     
         32 . A compound which is selected from the group consisting of:
 5-methyl-4-(1-oxo-indene-5-yl)-1-phenyl-1H-[1,2,3]triazole,   5-methyl-4-(2-methylbenzothiazole-5-yl)-1-phenyl-1H-[1,2,3]triazole,   4-(1H-indole-5-yl)-5-methyl-1-phenyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine3-yl)-5-methyl-4-(quinoline-6-yl)-1H[1,2,3]triazole,   5-methyl-4-(naphthalene-2-yl)-5-methyl-1H-[1,2,3]triazole,   4-(3-cyclohexyl-5-fluoro-6-methyl-4-oxo-4H-chromen-7-yl)-5-methyl-1-phenyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine3-yl)-5-methyl-4-(2-methyl-quinoline-6-yl)-1H-[1,2,3]triazole,   1-(2-fluoropyridine3-yl)-5-methyl-4-quinoxaline-6-yl)-1H-[1,2,3]triazole,   4-(1,3-dioxo-2,3-dihydro-1H-isoindole-5-yl)-5-methyl-1-phenyl-1H-[1,2,3]triazole,   4-(1,3-dioxo-2,3-dihidro-2-methyl-1H-isoindole-5-yl)-5-methyl-1-phenyl-1H-[1,2,3]triazole,   4-(2,2-dimethyl-1-oxo-indene-5-yl)-5-methyl-1-phenyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine3-yl)-5-methyl-4-(2-methyl-imidazo[1,2-a]pyridine-6-yl)-1H-[1,2,3]triazole,   5-methyl-4-(4-oxo-4H-chromen-6-yl)-1-phenyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine3-yl)-5-methyl-4-([1,2,4]triazolo[4,3-a]pyridine-7-yl)-1H-[1,2,3]triazole,   4-(3,4-dihydro-2H-1-oxa-9-aza-anthracene-6-yl)-1-(2-fluoropyridine3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine3-yl)-5-methyl-4-([1,2,4]triazolo[4,3-a]pyridine-6-yl-1H-[1,2,3]triazole,   1-(2-fluoropyridne3-yl)-4-isoquinoline-7-yl-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-isoquinoline-3-yl-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(2,2-dimethyl-1-oxo-indene-5-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-5-yl)-5-methyl-4-(2-methyl-quinoline-6-yl)-1H-[1,2,3]triazole,   1-(6-chloro-[1,5]naphthyridine-2-yl)-4-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methtyl-4-(5,6,7,8-tetrahydro-[1,5]naphthyridine-2-yl)-1H-[1,2,3]triazole,   4-(5-acetyl-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-chloroquinoline-6-yl)-1-(2-fluoropyridine-3-yl)-1-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methyl-4-(2-methyl-1-oxoindene-5-yl)-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methtyl-4-((2R*)-methyl-1-oxoindene-5-yl)-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methyl-4-((2S*)-methyl-1-oxoindene-5-yl)-1H-[1,2,3]triazole,   1-(2-fluoropyridine-5-yl)-4-(2,2-dimethyl-1-oxo-indene-5-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(4-oxo-4H-chromen-7-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(2-methoxyquinoline-6-yl)-5-methyl-[1,2,3]triazole,   4-(2-tert-butyl-imidazo [1,2-a]pyridine-6-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methyl-4-(1-oxo-indene-2-spiro-1′-cyclobutane-5-yl)-1H-[1,2,3]triazole,   4-(2-dimethylamino-quinoline-6-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methyl-4-(1-oxo-indene-2-spiro-1′-cyclopropyl-5-yl)-1H-[1,2,3]triazole,   4-(2-chloro-3-ethyl-quinoline-6-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-isopropyl-1-oxo-is oindoline-5-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(2-methoxy-1-oxo-indene-5-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methyl-4-(2-morpholine-4-yl-quinoline-6-yl)-1H-[1,2,3]triazole,   4-(3-methyl-4-oxo-4H-chromen-7-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]]triazole,   1-(2-fluoropyridine-3-yl)-4-(2-(4-methylpiperazine-1-yl)-quinoline-6-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-isopropyl-imidazo[1,2-a]pyridine-6-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(5-oxo-5,6,7,8-tetrahydro-naphthalene-2-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methyl-4-(2-methyl-1-oxo-isoindoline-5-yl)-1H-[1,2,3]triazole,   4-(2-ethyl-3-methyl-imidazo[1,2-a]pyridine-6-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(1-oxo-2-methylcarbonyloxy-indene-5-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-5-yl)-4-(2-isopropyl-imidazo[1,2-a]pyridine-6-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(1-oxo-4-hydroxy-indene-5-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-cyclopropyl-imidazo[1,2-a]pyridine-6-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-cyclopropyl-1-oxo-isoindoline-5-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-isopropyl-1-oxo-indene-5-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(2-methyl-2-methylcarbonyloxy-1-oxo-indene-5-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(2-hydroxy-2-methyl-1-oxo-indene-5-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(2-methoxy-2-methyl-1-oxo-indene-5-yl)-5-methyl-1H-[1,2,3]triazole,   4-((2S*)-methoxy-(2R*)-methyl-1-oxoindene-5-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-((2R*)-methoxy-(2S*)-methyl-1-oxoindene-5-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(2-pyrrolidine-1-yl-quinoline-6-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methyl-4-(2-methyl-4-oxo-4-methyl-chromen-7-yl)-1H-[1,2,3]triazole,   1-(2-fluoropyridine-5-yl)-4-(1-oxo-2-methyl-indene-5-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methyl-4-(1-oxo-1H-indene-5-yl)-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(2-methyl-1-oxo-1H-inden-5-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-5-yl)-4-(3-methyl-4-oxo-4H-chromen-7-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-cyclopropyl-1-oxo-is oindoline-5-yl)-1-(2-fluoropyridine-5-yl)-5-methyl-1H-[1,2,3]triazole,   4-(benzothiazole-6-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(5-fluoro-3-methyl-4-oxo-4H-chromen-7-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   5-methyl-4-(3-methyl-4-oxo-4H-chromen-7-yl)-1-(pyridine-3-yl)-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(2-methanesulfonyl-quinoline-6-yl)-5-methyl-1H-[1,2,3]triazole,   4-[(2-isopropyl-methyl-amino)-quinoline-6-yl]-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(3-benzyl-4-oxo-3,4-dihidroquinazoline-6-yl)1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(5-oxo-6-methyl-5,6,7,8-tetrahydro-naphthalene-2-yl)-5-methyl-1H-[1,2,3]triazole,   4-(3-benzyl-4-oxo-3,4-dihydroquinazoline-6-yl)-1-phenyl-1H-[1,2,3]triazole,   4-(2-isopropyl-1-oxo-isoindoline-5-yl)-1-(2-fluoropyridine-4-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-tert-butyl-1-oxo-isoindoline-5-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-ethyl-1-oxo-isoindoline-5-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(2-methoxy-4-oxo-4H-chromen-7-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(3-methyl-4-oxo-3,4-dihydro-quinazoline-7-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(3-methyl-4-oxo-3,4-dihydro-quinazoline-6-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-[2-(2-hydroxy-1-methyl-ethyl)-1-oxo-isoindoline-5-yl]-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methyl-(2,3-dimethyl-4-oxo-3,4-dihydro-quinazoline-7-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-isopropyl-1-oxo-isoindoline-5-yl)-1-(2-fluoropyridine-3-yl)-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(3-methyl-4-oxo-chroman-7-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-((3R*)-methyl-4-oxo-chroman-7-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-((3S*)-methyl-4-oxo-chroman-7-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-4-(1-oxo-isoindoline-5-yl)-5-methyl-1H-[1,2,3]triazole,   4-(3-benzyl-4-oxo-3,4-dihydroquinazoline-7-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-5-yl)-4-(2-isopropyl-imidazo[1,2-a]pyridine-6-yl)-5-methyl-1H-[1,2,3]triazole,   4-(3-benzyl-2-ethyl-4-oxo-3,4,-dihydroquinazorine-7-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methyl-4-(2-propyl-1-oxo-isoindoline-5-yl)-1H-[1,2,3]triazole,   4-(2-benzyl-1-oxo-isoindoline-5-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-cyclopropyl-1-oxo-isoindoline-5-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-cyclopropylmethyl-1-oxo-isoindoline-5-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-isobutyl1-oxo-isoindoline-5-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methyl-4-(3-methyl-4-oxo-4H-pyrano[2,3-b]pyridine-7-yl)-1H-[1,2,3]triazole,   4-(3,3-dimethyl-4-oxo-chroman-7-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-cyclopropyl-1-oxo-isoindoline-5-yl)-1-phenyl-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methyl-4-(1a-methyl-2-oxo-1,1a,2,7a-tetrahydro-7-oxo-6-cyclopropa[b]naphthalene-5-yl)-1H-[1,2,3]triazole,   4-(2-methyl-1-oxo-isoquinoline-6-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-ethyl-imidazo[1,2-a]pyridine-6-yl]-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-methyl-1-oxo-3,4-dihydroisoquinoline-6-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   ([1,8]naphthyridine-3-yl)-4-phenyl-5-methyl-1H-[1,2,3]triazole,   5-(2-cyclopropyl-1-oxo-isoindoline-5-yl)-1-(2-fluoropyridine-3-yl)-4-carbonitril-1H-[1,2,3]triazole,   4-(2-isopropyl-1-oxo-isoindoline-5-yl)-1-(2,4-difluorophenyl)-5-methyl-1H-[1,2,3]triazole,   4-(2-(2,2-difluoroethyl)-1-oxo-isoindoline-5-yl)-1-(4-fluorophenyl)-5-methyl-1H-[1,2,3]triazole, and   4-(2-(2-hydroxy-2-methyl-propyl)-1-oxo-isoindoline-5-yl)-1-(4-fluorophenyl)-5-methyl-1H-[1,2,3]triazole,   or a pharmaceutically acceptable salt thereof.   
     
     
         33 . A compound which is selected from the group consisting of:
 1-(2-fluoropyridine-3-yl)-5-methyl-4-(1-oxoindene-2-spiro-1′-cyclopropyl-5-yl)-1H-[1,2,3]triazole,   4-(2-isopropyl-1-oxo-isoindoline-5-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-isopropyl-1-oxo-isoindoline-5-yl)-1-(2-fluoropyridine-3-yl)-5-methyl-1H-[1,2,3]triazole,   1-(2-fluoropyridine-3-yl)-5-methyl-4-(2-propyl-1-oxo-isoindoline-5-yl)-1H-[1,2,3]triazole,   4-(2-cyclopropyl-1-oxo-isoindoline-5-yl)-1-(2-fluorobenzene-3-yl)-5-methyl-1H-[1,2,3]triazole,   4-(2-isopropyl-1-oxo-isoindoline-5-yl)-1-(2,4-difluorophenyl)-5-methyl-1H-[1,2,3]triazole,   4-(2-(2,2-difluoroethyl)-1-oxo-isoindoline-5-yl)-1-(4-fluorophenyl)-5-methyl-1H-[1,2,3]triazole, and   4-(2-(2-hydroxy-2-methyl-propyl)-1-oxo-isoindoline-5-yl)-1-(4-fluorophenyl)-5-methyl-1H-[1,2,3]triazole,   or a pharmaceutically acceptable salt thereof.   
     
     
         34 . A pharmaceutical composition which comprises an inert carrier and the compound of  claim 23 , or a pharmaceutically acceptable salt thereof. 
     
     
         35 . A method for treating a disease or disorder selected from the group consisting of: convulsion, acute pain, inflammatory pain, chronic pain, brain disorder, cerebral infarction, transient ischemic attack, psychotic disorder, schizophrenia, anxiety, drug dependence, Parkinson's disease or gastrointestinal disorder; in a mammalian patient in need thereof which comprises administering to the patient a therapeutically effective amount of the compound of  claim 23 , or a pharmaceutically acceptable salt thereof.