5-(Arylsulfonyl)-Pyrazolopiperidines

Abstract

The invention provides N-cyclic sulfonamido compounds of Formula I wherein A, B, R 1 , R 1a , R 2 , R 2a , R 3 and R 3a are as described in the specification. Compounds of Formula I are useful in treating or preventing cognitive disorders, such as Alzheimer's disease. The invention also encompasses pharmaceutical compositions comprising compounds of Formula I, methods of preparing compounds of formula I, and methods of treating cognitive disorders, such as Alzheimer's disease.

1 . Compounds of the formula: 
       
         
           
           
               
               
           
         
         stereoisomers, tautomers, mixtures of stereoisomers and/or tautomers or pharmaceutically acceptable salts thereof, wherein 
         the A-ring is aryl, cycloalkyl, heteroaryl or heterocycloalkyl, where each ring is optionally substituted at a substitutable position with halogen, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, C 1 -C 6  haloalkoxy, hydroxyl, hydroxyalkyl, CN, aryloxy, arylalkyloxy, —SO 2 —(C 1 -C 6  alkyl), —NR′R″, C 1 -C 6  alkanoyl, C 0 -C 3 alkyl-C(O)OR′, heteroaryl, heterocycloalkyl, aryl, arylalkyl, or —SO 2 —NR′R″, where 
         each R′ and R″ is independently H or C 1 -C 6  alkyl or R′ and R″ with the atom to which they are attached may form a 3-8 membered ring optionally including an additional heteroatom such as N, O or S; 
         the B-ring is a heteroaryl or heterocycloalkyl ring, each of which is optionally substituted at a substitutable position with a group that is independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  alkoxy, amino, C 1 -C 6  alkylamino, C 1 -C 6  dialkylamino, —S(O) 0-2 R′, hydroxyl, hydroxyalkyl, halo, C 1 -C 2  haloalkyl, C 1 -C 2  haloalkoxy, —NR′C(O)R″, —NR′SO 2 R″, —C(O)R′, —CO 2 R′, —C(O)alkylOC(O)R′, —C(O)NR′R″, oxo, CN, or C 0 -C 1 alkylaryl, where the aryl is optionally substituted with 1-5 groups independently selected from halogen, C 1 -C 6  alkyl, —C(O)OR′, C 1 -C 6  alkoxy, haloalkyl, haloalkoxy, hydroxyl, CN, NO 2 , aryloxy, —S(O) 0-2 —(C 1 -C 6  alkyl), —C(O)NR′R″, —NR′R″, C 1 -C 6  alkanoyl, pyridyl, phenyl, and —SO 2 NR′R″; and 
         R 1 , R 1a , R 2 , and R 2a , are independently hydrogen, halogen, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, where the alkenyl group is optionally substituted with one or more halogens; C 2 -C 6  alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylC 1 -C 6  alkyl, aryl, arylC 1 -C 6  alkyl, heteroaryl, —CO 2 R′, CONR′R″, C 1 -C 6  haloalkyl, where the haloalkyl group is optionally substituted with C 1 -C 4  alkoxy; C 1 -C 4  haloalkoxyalkyl, hydroxy C 1 -C 6  alkyl, C 2 -C 6  alkanoyl, aryloxyC 1 -C 6  alkyl, heteroaryloxy C 1 -C 6  alkyl, —C 0 -C 6  alkyl-OC(O)NR′R″, —C 0 -C 6  alkyl-NR′R″, hydroxyl, or —C 0 -C 6  alkyl-OC(O)-heterocycloalkyl, wherein each aryl, heteroaryl, and heterocycloalkyl group is optionally substituted with one or more groups that are independently halogen, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, C 1 -C 6 alkanoyl, halo C 1 -C 4  alkyl, halo C 1 -C 4  alkoxy, —C(O)NR′R″, —NR′R″, hydroxyl, —O—(CH 2 ) 1-2 —O—, —C(O)OR′, phenyl, pyridazinyl, pyrazinyl, pyrimidyl, thiazolyl, pyridyl, N-methylpyrazolyl, N-benzyl pyrazolyl, oxadiazolyl, oxazolyl, or imidazolyl; 
         R 3 , and R 3a  are independently hydrogen, halogen, or C 1 -C 6  alkyl, 
         R 1 , and R 1a , or R 2  and R 2a  or R 3  and R 3a  combined form ═O or ═N—OR, where R is hydrogen, C 1 -C 6  alkyl, aryl (such as phenyl) or arylalkyl (such as benzyl or phenethyl); or 
         R 1 , and R 1a , or R 2  and R 2a  or R 3  and R 3a  together with the carbon to which they are attached form C 3 -C 6  cycloalkyl group wherein one of the carbons is optionally replaced with a heteroatom selected from N, O or S and wherein said ring may be optionally substituted with C 1 -C 6  alkyl; or 
         R 1  and R 3  form a double bond. 
       
     
     
         2 . Compounds or salts according to  claim 1 , where
 the B-ring is pyrazolyl, imidazolyl, pyrrolyl, triazolyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, isoxazolyl, indolyl, pyrimidyl, or pyridyl, each of which is optionally substituted at a substitutable position with a group that is independently C 1 -C 6  alkyl, C 1 -C 6  alkoxy, amino, C 1 -C 6  alkylamino, C 1 -C 6  dialkylamino, C 1 -C 6  alkylthio, halo, C 1 -C 2  haloalkyl, C 1 -C 2  haloalkoxy, or C 0 -C 1 alkyl phenyl, are optionally substituted with 1 to 5 groups that are independently halogen, hydroxyl, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, C 1 -C 6  alkanoyl, NR′R″, —CO 2 R′, —CONR′R″, CN or NO 2 .   
     
     
         3 . Compounds or salts according to  claim 2 , where
 R 1  is C 1 -C 6  alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl C 1 -C 6  alkyl, phenyl, biphenyl, phenylC 1 -C 6  alkyl, pyridyl, benzofuranyl, benzothienyl, benzimidazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, tetrazolyl, oxazolyl, thiazolyl, imidazolyl, oxadiazolyl, thiazolyl, pyrimidyl, —CO 2 R′, —CONR′R′, C 1 -C 6  haloalkyl, hydroxy C 1 -C 6  alkyl, C 1 -C 6  alkoxy, phenyloxyC 1 -C 6  alkyl, naphthyloxyC 1 -C 6  alkyl, pyridyloxy C 1 -C 6  alkyl, benzofuranyloxy C 1 -C 6  alkyl, benzothienyloxy C 1 -C 6  alkyl, quinolinyloxy C 1 -C 6  alkyl, isoquinolinyloxy C 1 -C 6  alkyl, quinoxalinyloxy C 1 -C 6  alkyl, quinazolinyloxy C 1 -C 6  alkyl, —C 0 -C 6  alkyl-OC(O)NR′R″, —C 0 -C 6  alkyl-NR′R″, —C 1 -C 6  alkyl-OC(O)-piperidinyl, —C 1 -C 6  alkyl-OC(O)-pyrrolidinyl, —C 1 -C 6  alkyl-OC(O)-morpholinyl, wherein each aryl, heteroaryl, and heterocycloalkyl group is optionally substituted with one or more groups that are independently halogen, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, halo C 1 -C 4  alkyl, halo C 1 -C 4  alkoxy, C 1 -C 6  alkanoyl, —C(O)NR′R″, NR′R″, —O—(CH 2 ) 1-2 —O—, —CO 2 R′, pyridazinyl, pyrazinyl, pyrimidyl, thiazolyl, pyridyl, N-methylpyrazolyl, N-benzyl pyrazolyl, oxadiazolyl, oxazolyl, or imidazolyl.   
     
     
         4 . Compounds or salts according to  claim 3 , having the following formula: 
       
         
           
           
               
               
           
         
         wherein, 
         R 12  is H, halogen, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, or CN; 
         R 13  is H, halogen, C 1 -C 6  alkyl optionally substituted with —CO 2 —(C 1 -C 6  alkyl), C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, C 1 -C 6  haloalkoxy, CN, aryloxy, isocyanato, —SO 2 —(C 1 -C 6  alkyl), —NR′R″, C 1 -C 6  alkanoyl, pyridyl, or phenyl; or 
         R 14  is H, C 1 -C 4  alkyl, —SO 2 —NR′R″, or halogen;
 where R′ and R″ are independently H or C 1 -C 6  alkyl; or 
 
         R 13  and R 14  and the carbons to which they are attached form a benzo ring; or 
         R 10  and R 11  at each occurrence are independently H, halogen, or C 1 -C 6  alkyl, where the alkyl is optionally substituted with a phenyl, where the phenyl is optionally substituted with 1 to 5 groups that are independently halogen, hydroxyl, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, C 1 -C 4  haloalkyl, C 1 -C 4  haloalkoxy, CN or NO 2 ; or 
         R 10 , R 14 , and the carbons to which they are attached form a benzo ring. 
       
     
     
         5 . Compounds or salts according to  claim 4 , where the B-ring has the following formula: 
       
         
           
           
               
               
           
         
         wherein R 20  is H, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, amino, C 1 -C 6  alkylamino, C 1 -C 6  dialkylamino, C 1 -C 6  alkylhio, halo, CF 3 , or phenyl. 
       
     
     
         6 . Compounds or salts according to  claim 4 , wherein
 R 1  is C 1 -C 6  alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylalkyl, phenyl, biphenyl, phenylC 1 -C 6  alkyl (such as benzyl or phenethyl), phenyloxyC 1 -C 6  alkyl, or naphthyloxyC 1 -C 6  alkyl, wherein each aryl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently halogen, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, halo C 1 -C 4  alkyl, halo C 1 -C 4  alkoxy, —C(O)NR′R″, —NR′R″, hydroxyl, —O—(CH 2 ) 1-2 —O—, —CO 2 R′, phenyl, pyridazinyl, pyrazinyl, pyrimidyl, thiazolyl, pyridyl, N-methylpyrazolyl, N-benzyl pyrazolyl, oxadiazolyl, oxazolyl, or imidazolyl; and R 1a , R 2a , R 3  and R 3a  are H.   
     
     
         7 . Compounds or salts according to  claim 5 , wherein
 R 2  and R 2a  combine to form oxo.   
     
     
         8 . Compounds or salts according to  claim 1 , having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         9 . Compounds or salts according to  claim 8 , where the B-ring has the following formula: 
       
         
           
           
               
               
           
         
         wherein R 30  is H, C 1 -C 4  alkyl, C 1 -C 4  alkoxy, amino, C 1 -C 4  alkylamino, C 1 -C 4  dialkylamino, C 1 -C 4  alkylhio, halo, CF 3 , or phenyl. 
       
     
     
         10 . Compounds or salts according to  claim 9 , wherein
 R 1  is pyridyl, thiazolyl, imidazolyl, benzofuranyl, benzothienyl, benzimidazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, pyridyloxy C 1 -C 6  alkyl, benzofuranyloxy C 1 -C 6  alkyl, benzothienyloxy C 1 -C 6  alkyl, quinolinyloxy C 1 -C 6  alkyl, isoquinolinyloxy C 1 -C 6  alkyl, quinoxalinyloxy C 1 -C 6  alkyl, quinazolinyloxy C 1 -C 6  alkyl, —C 1 -C 6  alkyl-OC(O)NR′R″, —C 1 -C 6  alkyl-OC(O)-piperidinyl, —C 1 -C 6  alkyl-OC(O)-pyrrolidinyl, or —C 1 -C 6  alkyl-OC(O)-morpholinyl, wherein each heteroaryl, and heterocycloalkyl group is optionally substituted with one or more groups that are independently halogen, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, halo C 1 -C 4  alkyl, halo C 1 -C 4  alkoxy, —C(O)NR′R″, —NR′R″, hydroxyl, —O—(CH 2 ) 1-2 —O—, —CO 2 R′, phenyl, pyridazinyl, pyrazinyl, pyrimidyl, thiazolyl, pyridyl, N-methylpyrazolyl, N-benzyl pyrazolyl, oxadiazolyl, oxazolyl, or imidazolyl; and R 1a , R 2a , R 3 , and R 3a  are H.   
     
     
         11 . Compounds of salts of  claim 10 , wherein R 2  is pyridyl, pyrimidyl, —CO 2 —C 1 -C 4  alkyl, C 1 -C 4  alkyl, —C 1 -C 4  alkyl-OC(O)NR′R″, benzimidazolyl, thiazolyl, or imidazolyl, and R 1  is H, methyl, or ethyl; where R′ and R″ are independently H or C 1 -C 4  alkyl. 
     
     
         12 . Compounds of salts of  claim 10 , wherein the heteroaryl group is pyridyl optionally substituted with 1 or 2 groups that are independently halogen, C 1 -C 4  alkyl, C 1 -C 4  alkoxy, CF 3 , OCF 3 , OH, amino, or mono or di(C 1 -C 4  alkyl)amino. 
     
     
         13 . Compounds of salts of  claim 10 , wherein the heteroaryl group is thienyl optionally substituted with 1 or 2 groups that are independently halogen, C 1 -C 4  alkyl, C 1 -C 4  alkoxy, CF 3 , OCF 3 , OH, amino, or mono or di(C 1 -C 4  alkyl)amino. 
     
     
         14 . Compounds or salts of  claim 1 , having the formula: 
       
         
           
           
               
               
           
         
         wherein 
         the heterocycloalkyl group is optionally substituted at a substitutable position with halogen, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, haloalkyl, haloalkoxy, hydroxyl, CN, aryloxy, arylalyloxy, —SO 2 —(C 1 -C 6  alkyl), —NR′R″, C 1 -C 6  alkanoyl, pyridyl, phenyl, or —SO 2 —NR′R″, where each R′ and R″ is independently H or C 1 -C 6  alkyl. 
       
     
     
         15 . Compounds of salts of  claim 14 , wherein
 R 1  is —CO 2 R′, —CONR′R″, C 1 -C 4  haloalkyl, or C 1 -C 4  hydroxyalkyl; and R 1a , R 2a , R 3 , and R 3a  are H.   
     
     
         16 . Compounds of salts of  claim 15 , wherein the heterocycloalkyl group is morpholinyl, are piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl S,S-dioxide, tetrahydrofuranyl, or imidazolidinyl, each of which is optionally substituted. 
     
     
         17 . Compounds or salts of  claim 1 , having the formula: 
       
         
           
           
               
               
           
         
         the cycloalkyl group is optionally substituted at a substitutable position with halogen, C 1 -C 6  alkyl, C 1 -C 6 alkoxy, haloalkyl, haloalkoxy, hydroxyl, CN, phenyloxy, benzyloxy, —SO 2 —(C 1 -C 6  alkyl), —NR′R″, C 1 -C 6  alkanoyl, pyridyl, phenyl, or —SO 2 —NR′R″, where each R′ and R″ is independently H or C 1 -C 6  alkyl. 
       
     
     
         18 . A method of treating Alzheimer's disease comprising administering a therapeutically effective amount of a compound or salt of  claim 1  to a patient in need of such treatment. 
     
     
         19 . A composition comprising a compound or salt of  claim 1  and at least one pharmaceutically acceptable solvent, adjuvant, excipient, carrier, binder or disintegrant. 
     
     
         20 . Compounds according to  claim 1  that are
 5-(4-chlorophenylsulfonyl)-4,6-dicyclopropyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   cis-(5-(4-chlorophenylsulfonyl)-4-ethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-6-yl)methanol;   5-(4-chlorophenylsulfonyl)-6-(pyrimidin-5-yl)-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one;   5-(4-chlorophenylsulfonyl)-4-(pyrimidin-5-yl)-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one;   5-(4-chlorophenylsulfonyl)-6-cyclopropyl-6,7-dihydro-1H-pyrazolo[4,3-c]pyridin-4(5H)-one;   4-(pyrimidin-5-yl)-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   6-methyl-4-(pyrimidin-5-yl)-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   4,6-dimethyl-5-(4-(trifluoromethyl)phenylsulfonyl)-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one;   (4-(pyrimidin-5-yl)-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-6-yl)methanol;   5-(4-chlorophenylsulfonyl)-6-methyl-4-(pyrimidin-5-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-6-cyclopropyl-4-(pyrimidin-5-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-fluorophenylsulfonyl)-4,6-dimethyl-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one;   4,6-dimethyl-5-(pyridin-2-ylsulfonyl)-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one;   5-(4-chlorophenylsulfonyl)-4,6-bis(1,1-difluoroethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-4,6-bis(difluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   1,1′-(5-(4-chlorophenylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-4,6-diyl)diethanone;   5-(4-chlorophenylsulfonyl)-4,6-bis(2,2-difluorovinyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-4,6-bis(2,2-difluoroethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-4,6-bis(fluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-4,6-bis(difluoro(methoxy)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-4,6-bis((trifluoromethoxy)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-4,6-bis(2,2,2-trifluoroethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-4,6-diisopropyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5′-(4-chlorophenylsulfonyl)-1′,5′,6′,7′-tetrahydrospiro[cyclopropane-1,4′-pyrazolo[4,3-c]pyridine];   6-methyl-4-(pyrimidin-5-yl)-5-(4-(trifluoromethyl)phenylsulfonyl)-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one;   6-methyl-4-(pyridin-3-yl)-5-(4-(trifluoromethyl)phenylsulfonyl)-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one;   6-methyl-4-(pyridin-4-yl)-5-(4-(trifluoromethyl)phenylsulfonyl)-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one;   5-(4-chlorophenylsulfonyl)-4,6-diethyl-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one O-methyl oxime;   5-(4-chlorophenylsulfonyl)-4,6-diethyl-N,N-dimethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-7-amine;   5-(4-chlorophenylsulfonyl)-4,6-diethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-7-amine;   5-(4-chlorophenylsulfonyl)-4,6-diethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-7-ol;   5-(4-chlorophenylsulfonyl)-4,6-diethyl-7-fluoro-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-4,6-diethyl-7,7-difluoro-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   6-methyl-4-(thiazol-2-yl)-5-(4-(trifluoromethyl)phenylsulfonyl)-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one;   4-(1H-imidazol-5-yl)-6-methyl-5-(4-(trifluoromethyl)phenylsulfonyl)-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one;   4-(1H-imidazol-2-yl)-6-methyl-5-(4-(trifluoromethyl)phenylsulfonyl)-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one,   5-(4-chlorophenylsulfonyl)-4,6-bis(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-4-isopropyl-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one;   5-(4-chlorophenylsulfonyl)-6-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   6-benzyl-5-(4-chlorophenylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-6-isopropyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-6-(4-fluorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   6-(4-chlorophenyl)-5-(4-chlorophenylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-6-(3,5-difluorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   4-(4-chlorophenyl)-5-(4-chlorophenylsulfonyl)-6-ethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   6-(4-chlorophenyl)-5-(4-chlorophenylsulfonyl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   6-(4-chlorophenyl)-5-(4-chlorophenylsulfonyl)-4-ethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-4,6-dimethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-6-(pyridin-3-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-6-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-4,6-diethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-6-(pyrimidin-5-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-Chloro-benzenesulfonyl)-4-pyrimidin-5-yl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   ethyl 5-(4-chlorophenylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-4-carboxylate;   ethyl 5-(4-chlorophenylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-6-carboxylate;   5-(4-chlorophenylsulfonyl)-6-ethyl-6,7-dihydro-1H-pyrazolo[4,3-c]pyridin-4(5H)-one;   (5-(4-chlorophenylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-6-yl)methanol;   5-(4-chlorophenylsulfonyl)-4,6-diethyl-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one;   diethyl 5-(4-chlorophenylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-4,6-dicarboxylate;   5-(4-chlorophenylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-4,6-diyl)dimethanol;   (5-(4-chlorophenylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-4-yl)methyl dimethylcarbamate,   5-(4-chlorophenylsulfonyl)-4,6-diethyl-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one;   (5-(4-chlorophenylsulfonyl)-1-(dimethylcarbamoyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-4-yl)methyl dimethylcarbamate;   4,6-diethyl-5-(pyridin-2-ylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   4-(1H-benzoimidazol-2-yl)-5-(4-chloro-benzenesulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-4,6-diethyl-5,6-dihydro-1H-pyrazolo[4,3-c]pyridin-7(4H)-one oxime;   ethyl 5-(4-chlorophenylsulfonyl)-6-ethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-4-carboxylate;   4,6-diethyl-5-(4-fluorophenylsulfonyl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine;   5-(4-chlorophenylsulfonyl)-6-ethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-4-yl)methyl dimethylcarbamate;   5-(4-chlorophenylsulfonyl)-4-ethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-6-yl)methyl dimethylcarbamate;   2-(5-(4-chlorophenylsulfonyl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-6-yl)thiazole;   2-(5-(4-chlorophenylsulfonyl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-4-yl)thiazole;   5-(4-chlorophenylsulfonyl)-4-ethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-6-yl)methanol;   4,6-diethyl-5-(pyridin-2-ylsulfonyl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine;   4,6-diethyl-5-(pyridin-2-ylsulfonyl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine;   4,6-dimethyl-5-(4-(trifluoromethyl)phenylsulfonyl)-5,6-dihydro-2H-pyrazolo[4,3-c]pyridin-7(4H)-one;   and stereoisomers, tautomers, mixtures of stereoisomers and/or tautomers or pharmaceutically acceptable salts thereof.