Aryl sulfamide derivatives and methods of their use

Abstract

The present invention is directed to aryl sulfamide derivatives of formula I: or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof, which are monoamine reuptake inhibitors, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions, including, inter alia, vasomotor symptoms, sexual dysfunction, gastrointestinal disorders and genitourinary disorder, depression disorders, endogenous behavioral disorders, cognitive disorders, diabetic neuropathy, pain, and other diseases or disorders.

1 . A compound of formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof; 
         wherein: 
         n is an integer from 0 to 4; 
         m is an integer from 0 to 6; 
         X is, independently at each occurrence, C(R 7 ) 2 , N(R 3 ), O, S, S(═O), or S(═O) 2 ; 
         Y is C; or 
         Y and an adjacent X together form —CR 7 ═CR 7 —, —C≡C—, or arylenyl substituted with 0-3 R 10 ; 
         R 1  is, independently at each occurrence, H, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R 11 , heteroaryl substituted with 0-3 R 11 , alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide substituted with 0-3 R 5 , alkylamido, or arylamido substituted with 0-3 R 5 ; 
         R 2  is aryl substituted with 0-3 R 9  or heteroaryl substituted with 0-3 R 9 ; 
         R 3  is, independently at each occurrence, H, halo, hydroxy, alkyl substituted with 0-3 R 13 , a heterocyclic ring, aryl substituted with 0-3 R 12 , or heteroaryl substituted with 0-3 R 12 ; 
         R 4  is, independently at each occurrence, H, alkyl substituted with 0-3 R 13 , arylalkyl substituted with 0-3 R 13  or heteroarylmethyl substituted with 0-3 R 13 ; 
         R 5  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido; 
         R 6  is, independently at each occurrence, H, hydroxy, C 1 -C 4  alkyl, C 1 -C 6  alkoxy, halo, aryl substituted with 0-3 R 1 , heteroaryl substituted with 0-3 R 1 , —N(R 3 ) 2 , —S(R 3 ), or —R 8 —O—R 3 ; or both R 6  groups form a cycloalkyl, a heterocyclic ring, ═O or ═N—OH; 
         provided that if each R 3  is H, each X is CH 2 , and either each R 6  is H or one R 6  is hydroxy; then, both of said R 4 , together with the nitrogen through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, hydroxyalkyl, aminoalkyl, or a heterocyclic ring, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl; 
         R 7  is, independently at each occurrence, H, hydroxy, alkoxy, or C 1 -C 4  alkyl; 
         R 8  is, independently at each occurrence, straight or branched alkylenyl; 
         or 
         one of said R 3  and one of said R 4 , together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with alkyl; 
         or 
         both of said R 4 , together with the nitrogen through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, hydroxyalkyl, aminoalkyl, a heterocyclic ring, F, or CF 3 ; and where any additional N atom may be optionally substituted with alkyl; 
         or 
         one of said R 6  or one of said R 7  and one of said R 4 , together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two C 1 -C 4  alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl; provided that R 4  and R 7 , taken together, do not form a piperidinyl ring; 
         R 9  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R 11 , heteroaryl substituted with 0-3 R 11 , alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide, alkylamido, or arylamido; 
         R 10  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; 
         R 11  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; 
         R 12  and R 13  are each, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, hydroxyalkyl, aminoalkyl, a heterocyclic ring, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; and 
         wherein 1-3 carbon atoms in ring A may optionally be replaced with N. 
       
     
     
         2 . The compound of  claim 1 , wherein:
 R 4  and R 6 , taken together, form a morpholinyl group optionally substituted with C 1 -C 4  alkyl, F, or CF 3 .   
     
     
         3 . The compound of  claim 2 , wherein:
 R 4  and R 6 , taken together, form morpholin-2-yl.   
     
     
         4 . The compound of  claim 3 , wherein:
 R 4  and R 6 , taken together, form (R)-morpholin-2-yl.   
     
     
         5 . The compound of  claim 3 , wherein:
 R 4  and R 6 , taken together, form (S)-morpholin-2-yl.   
     
     
         6 . The compound of  claim 1 , wherein:
 n is an integer from 0 to 2.   
     
     
         7 . The compound of  claim 1 , wherein:
 m is an integer from 1 to 6.   
     
     
         8 . The compound of  claim 1 , wherein:
 X is, independently at each occurrence, C(R 7 ) 2 , N(R 3 ), or O.   
     
     
         9 . The compound of  claim 1 , wherein:
 X is, independently at each occurrence, C(R 7 ) 2 .   
     
     
         10 . The compound of  claim 1 , wherein:
 R 1  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3  or nitrile.   
     
     
         11 . The compound of  claim 1 , wherein:
 R 2  is aryl substituted with 0-3 R 9 .   
     
     
         12 . The compound of  claim 1 , wherein:
 R 2  is phenyl, fluoro-phenyl, difluoro-phenyl, trifluoro-phenyl, chloro-phenyl, fluoro-chloro-phenyl, bromo-phenyl, trifluoromethyl-phenyl trifluoromethoxy-phenyl, methyl-fluoro-phenyl, methoxy-fluoro-phenyl, or naphthyl.   
     
     
         13 . The compound of  claim 1 , wherein:
 R 2  is heteroaryl substituted with 0-3 R 9 .   
     
     
         14 . The compound of  claim 1 , wherein:
 R 2  is pyridinyl, methyl-pyridinyl, ethyl-pyridinyl, methoxy-pyridinyl, or quinolinyl.   
     
     
         15 . The compound of  claim 1 , wherein:
 R 3  is, independently at each occurrence, H, methyl, or phenyl.   
     
     
         16 . The compound of  claim 1 , wherein:
 R 4  is, independently at each occurrence, hydrogen, methyl, ethyl, cyclopropyl, or n-butyl.   
     
     
         17 . The compound of  claim 1 , wherein:
 both of said R 4 , together with the nitrogen through which they are attached, form a heterocyclic ring of 4 to 7 atoms, where one carbon may be optionally replaced with N or O; where any carbon ring atom may be optionally substituted with one or two C 1 -C 4  alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl.   
     
     
         18 . The compound of  claim 1 , wherein:
 R 5  is, independently at each occurrence, alkyl, alkoxy, halo, or OCF 3 .   
     
     
         19 . The compound of  claim 1 , wherein:
 R 6  is, independently at each occurrence, H methyl, or fluoro.   
     
     
         20 . The compound of  claim 1 , wherein:
 R 7  is, independently at each occurrence, H, methyl, or phenyl.   
     
     
         21 . The compound of  claim 1 , wherein:
 Y and an adjacent X together form —CH═CH—, —C≡C—, or phenylenyl.   
     
     
         22 . The compound of  claim 1 , wherein:
 m is an integer from 1 to 3;   X is, independently at each occurrence, C(R 7 ) 2 , N(R 3 ), or O;   Y is C;   R 1  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , or OCF 3 ;   R 2  is aryl substituted with 0-3 R 9  or heteroaryl substituted with 0-3 R 9 ;   R 3  is, independently at each occurrence, H or C 1 -C 4  alkyl;   R 4  is, independently at each occurrence, H or C 1 -C 6  alkyl;   R 6  is, independently at each occurrence, H, C 1 -C 4  alkyl, or halo; and   R 7  is, independently at each occurrence, H or C 1 -C 4  alkyl.   
     
     
         23 . The compound of  claim 1 , wherein:
 m is an integer from 0 to 1;   X is, independently at each occurrence, C(R 7 ) 2 ;   Y is C;   R 1  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , or OCF 3 ;   R 2  is aryl substituted with 0-3 R 9  or heteroaryl substituted with 0-3 R 9 ;   R 3  is, independently at each occurrence, H or C 1 -C 4  alkyl;   R 6  is, independently at each occurrence, H, C 1 -C 4  alkyl, or halo; and   R 7  is, independently at each occurrence, H or C 1 -C 4  alkyl; or   both of said R 4 , together with the nitrogen through which they are attached, form a heterocyclic ring of 4 to 7 atoms, where one carbon may be optionally replaced with N or O, where any carbon ring atom may be optionally substituted with one or two C 1 -C 4  alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl.   
     
     
         24 . The compound of  claim 1 , wherein:
 m is an integer from 0-1;   X is, independently at each occurrence, C(R 7 ) 2      Y is C   R 1  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , or OCF 3 ;   R 2  is aryl substituted with 0-3 R 9  or heteroaryl substituted with 0-3 R 9 ;   R 3  is, independently at each occurrence, H or C 1 -C 4  alkyl;   R 6  is, independently at each occurrence, H, C 1 -C 4  alkyl, or halo; and   R 7  is, independently at each occurrence, H or C 1 -C 4  alkyl, or   one of said R 6  or one of said R 7  and one of said R 4 , together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two C 1 -C 4  alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl.   
     
     
         25 . The compound of  claim 1 , wherein the pharmaceutically acceptable salt is a hydrochloride (HCl) salt. 
     
     
         26 . A compound of formula II: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof; 
         wherein: 
         n is an integer from 0 to 4; 
         m is an integer from 1 to 6; 
         X is, independently at each occurrence, C(R 7 ) 2 , N(R 3 ), O, S, S(═O), or S(═O) 2 ; 
         Z is O, N(R 3 ), S, or C(R 7 ) 2 ; 
         R 1  is, independently at each occurrence, H, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R 11 , heteroaryl substituted with 0-3 R 11 , alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide substituted with 0-3 R 5 , alkylamido, or arylamido substituted with 0-3 R 5 ; 
         R 2  is aryl substituted with 0-3 R 9  or heteroaryl substituted with 0-3 R 9 ; 
         R 3  is, independently at each occurrence, H, C 1 -C 4  alkyl, aryl substituted with 0-3 R 12 , or heteroaryl substituted with 0-3 R 12 ; 
         R 4  is H, C 1 -C 6  alkyl, arylalkyl substituted with 0-3 R 13  or heteroarylmethyl substituted with 0-3 R 13 ; 
         R 5  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido; 
         R 6a  is H, C 1 -C 4  alkyl, C 1 -C 6  alkoxy, halo, aryl substituted with 0-3 R 1 , heteroaryl substituted with 0-3 R 1 , —N(R 3 ) 2 , —S(R 3 ), or —R 8 —O—R 3 ; 
         R 7  is, independently at each occurrence, H, hydroxy, C 1 -C 6  alkoxy, or C 1 -C 4  alkyl; 
         R 8  is, independently at each occurrence, straight or branched C 1 -C 6  alkylenyl; 
         or 
         one of said R 3  and one of said R 4 , together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two C 1 -C 4  alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl; 
         R 9  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R 11 , heteroaryl substituted with 0-3 R 11 , alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide, alkylamido, or arylamido; 
         R 10  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; 
         R 11  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; 
         R 12  and R 13  are each, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, hydroxyalkyl, aminoalkyl, a heterocyclic ring, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; and 
         wherein 1-3 carbon atoms in ring A may optionally be replaced with N. 
       
     
     
         27 . The compound of  claim 26 , wherein Z is O. 
     
     
         28 . The compound of  claim 26 , wherein Z is N(R 3 ). 
     
     
         29 . The compound of  claim 26 , wherein X is CH 2  and m is 2 to 4. 
     
     
         30 . The compound of  claim 26 , wherein:
 ring A is composed of all carbon atoms;   R 1  is H;   R 2  is phenyl substituted with one to three fluoro (F) atoms;   each R 3  is H;   R 4  is H; and   R 6a  is H.   
     
     
         31 . The compound of  claim 26 , wherein the compound is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         32 . The compound of  claim 1 , selected from the group consisting of:
 1-(morpholin-2-ylmethyl)-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-[(2R)-morpholin-2-ylmethyl]-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-[(2S)-morpholin-2-ylmethyl]-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-[(4-methylmorpholin-2-yl)methyl]-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-chloro-4-fluorophenyl)-3-{2-[(3R,5S)-3,5-dimethylpiperazin-1-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(2-chloro-4-fluorophenyl)-3-{2-piperazin-1-ylethyl}-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(4-fluoro-2-methylphenyl)-3-{2-piperazin-1-ylethyl}-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(4-fluoro-2-methylphenyl)-3-{2-[(3R,5S)-3,5-dimethylpiperazin-1-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(4-fluoro-2-methoxyphenyl)-3-{2-piperazin-1-ylethyl}-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-[2-(2,5-diazabicyclo[2.2.1]hept-2-yl)ethyl]-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   2-{2-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}ethanamine;   2-{2-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}-N-methylethanamine;   2-{2-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}-N,N-dimethylethanamine;   1-{2-[2-(3,5-dimethylpiperazin-1-yl)ethoxy]ethyl}-3-(2-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-[5-(3,5-dimethylpiperazin-1-yl)pentyl]-3-(2-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   (2R)-3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-2-methylpropan-1-amine;   (2S)-3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-2-methylpropan-1-amine;   4-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]butan-2-amine;   3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amine;   4-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-2-amine;   (2R)-3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,2-dimethylpropan-1-amine;   (2S)-3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,2-dimethylpropan-1-amine;   3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]butan-1-amine;   1-Phenyl-3-(piperidin-4-ylmethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,6-Difluorophenyl)-3-(morpholin-2-ylmethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,6-Difluorophenyl)-3-[(2R)-morpholin-2-ylmethyl]-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,6-Difluorophenyl)-3-[(2S)-morpholin-2-ylmethyl]-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,3-Difluorophenyl)-3-(morpholin-2-ylmethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(Morpholin-2-ylmethyl)-3-[2-(trifluoromethoxy)phenyl]-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-Phenyl-3-(2-piperidin-4-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide   1-Phenyl-3-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   4-Fluoro-3-phenyl-1-(piperidin-4-ylmethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   4-Fluoro-3-phenyl-1-(2-piperidin-4-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   4-Fluoro-3-phenyl-1-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   4-Fluoro-3-(morpholin-2-ylmethyl)-1-phenyl-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-Phenyl-3-(3-piperidin-4-ylpropyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-Phenyl-3-(2-piperidin-2-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide   1-(2,6-Difluorophenyl)-3-(2-piperidin-4-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(2,6-Difluorophenyl)-3-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-Phenyl-3-(piperidin-3-ylmethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-Phenyl-3-[(3R)-piperidin-3-ylmethyl]-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-Phenyl-3-[(3S)-piperidin-3-ylmethyl]-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-Phenyl-3-(2-piperidin-3-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-Phenyl-3-{2-[(3S)-piperidin-3-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-Phenyl-3-{2-[(3R)-piperidin-3-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(2,3-Difluorophenyl)-3-(2-piperidin-4-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(2,5-Difluorophenyl)-3-(2-piperidin-4-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(2,3-Difluorophenyl)-3-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(2,5-Difluorophenyl)-3-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-[2-(cis-3,5-Dimethylpiperazin-1-yl)ethyl]-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(2-Fluorophenyl)-3-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-[2-(cis-3,5-Dimethylpiperazin-1-yl)ethyl]-3-(2-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-[3-(cis-3,5-Dimethylpiperazin-1-yl)propyl]-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,6-Difluorophenyl)-3-[2-(cis-3,5-dimethylpiperazin-1-yl)ethyl]-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(2-piperazin-1-ylethyl)-3-(2,4,6-trifluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-[2-(cis-3,5-Dimethylpiperazin-1-yl)ethyl]-3-(2,4,6-trifluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-Phenyl-3-(3-piperazin-1-ylpropyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(4-Fluorophenyl)-3-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-[2-(cis-3,5-Dimethylpiperazin-1-yl)ethyl]-3-(4-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(2,4-difluorophenyl)-3-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,4-difluorophenyl)-3-[2-(3,5-dimethylpiperazin-1-yl)ethyl]-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-[2-(3,5-dimethylpiperazin-1-yl)ethyl]-4-fluoro-3-(2-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-{[3-(2,3-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]methyl}phenyl)-N-methylmethanamine;   3-[3-(2,3-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methyl-1-phenylpropan-1-amine;   3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methyl-1-phenylpropan-1-amine;   4-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbut-2-yn-1-amine;   4-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,N-dimethylbut-2-yn-1-amine;   (2E)-4-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbut-2-en-1-amine;   (2E)-4-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,N-dimethylbut-2-en-1-amine;   3-{2-[(3R,5S)-3,5-dimethylpiperazin-1-yl]ethyl}-4-fluoro-1-(2-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   2,2-difluoro-3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;   1-(2-Fluorophenyl)-3-(2-piperidin-4-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-[2-(1,4-Diazepan-1-yl)ethyl]-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(2,4-Difluorophenyl)-4-fluoro-3-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   3-(2,4-Difluorophenyl)-4-fluoro-1-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide   1-[2-(1,4-Diazepan-1-yl)ethyl]-3-(2,4,6-trifluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide   1-{2-[(1S,4S)-2,5-Diazabicyclo[2.2.1]hept-2-yl]ethyl}-3-(2,4,6-trifluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   3-[2-(1,4-Diazepan-1-yl)ethyl]-1-(2,4-difluorophenyl)-4-fluoro-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-[2-(1,4-Diazepan-1-yl)ethyl]-3-(2-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-{2-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]ethyl}-3-(2-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-Phenyl-3-(2-piperidin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(2,4-Difluorophenyl)-3-[2-(cis-3,5-dimethylpiperazin-1-yl)ethyl]-4-fluoro-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-[3-(1,4-Diazepan-1-yl)propyl]-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-[2-(1,4-Diazepan-1-yl)ethyl]-3-(2,6-difluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-[2-(1,4-Diazepan-1-yl)ethyl]-3-(2,4-difluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-{2-[(1S,4S)-2,5-Diazabicyclo[2.2.1]hept-2-yl]ethyl}-3-(2,4-difluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(2,4-Difluorophenyl)-3-(2-piperidin-4-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole-2,2-dioxide;   1-(2,4-Difluorophenyl)-3-[2-(4-methylpiperazin-1-yl)ethyl]-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,4-Difluorophenyl)-4-fluoro-3-[2-(4-methylpiperazin-1-yl)ethyl]-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,4-Difluorophenyl)-3-[2-(4-methyl-1,4-diazepan-1-yl)ethyl]-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-[2-(4-Methyl-1,4-diazepan-1-yl)ethyl]-3-(2,4,6-trifluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   N-{2-[3-(2-Fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethyl}-N,N′-dimethylethane-1,2-diamine;   N-{2-[3-(2,4-Difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethyl}-N,N′-dimethylethane-1,2-diamine;   N-{2-[2,2-Dioxido-3-(2,4,6-trifluorophenyl)-2,1,3-benzothiadiazol-1(3H)-yl]ethyl}-N,N′-dimethylethane-1,2-diamine;   1-{3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propyl}piperidin-4-amine;   1-[3-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)propyl]piperidin-4-amine;   1-{2-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethyl}piperidin-4-amine;   1-{2-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethyl}-N-methylpiperidin-4-amine;   1-{2-[3-phenyl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethyl}piperidin-4-amine;   1-{2-[3-phenyl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethyl}-N-methylpiperidin-4-amine;   1-{1-[2-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)ethyl]pyrrolidin-3-yl}methanamine;   1-phenyl-3-[2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   2-{2-[3-(2-chloro-4-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}-N-methylethanamine;   2-{2-[3-(2-chloro-4-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}-N,N-dimethylethanamine;   1-(4-chloro-2-fluorophenyl)-3-(2-piperazin-1-yl-ethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(4-chloro-2-fluorophenyl)-3-{2-[(3R,5S)-3,5-dimethylpiperazin-1-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(4-chloro-2-fluorophenyl)-3-(2-piperidin-4-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(4-chloro-2-methylphenyl)-3-{2-[(3R,5S)-3,5-dimethylpiperazin-1-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(4-chloro-2-methylphenyl)-3-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(tert-butylamino)-4-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)butan-2-one;   4-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-1-(isopropylamino)butan-2-one;   1-(cyclopropylamino)-4-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)butan-2-one;   4-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-1-(methylamino)butan-2-one;   4-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-one;   (2Z)-4-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-1-(methylamino)butan-2-one oxime;   (2S)-4-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-2-methoxy-N-methylbutan-1-amine;   (2S)-2-methoxy-N-methyl-4-[3-(2-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]butan-1-amine;   (2S)-2-methoxy-4-[3-(3-methoxyphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amine;   4-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-2-methoxy-N-methylbutan-1-amine;   (2R)-4-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-2-methoxy-N-methylbutan-1-amine;   (2S)-4-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-2-methoxy-N-methylbutan-1-amine;   N-{(2S)-4-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-2-methoxybutyl}cyclopropanamine;   N-{(2S)-2-methoxy-4-[3-(2-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]butyl}cyclopropanamine;   N-{(2S)-2-methoxy-4-[3-(3-methoxyphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]butyl}cyclopropanamine;   N-{(2S)-4-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-2-methoxybutyl}cyclopropanamine;   N-{(2S)-4-[3-(2,5-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-2-methoxybutyl}cyclopropanamine;   N-{(2S)-4-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-2-methoxybutyl}cyclopropanamine;   2S)-4-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-2-methoxy-N-methylbutan-1-amine;   (2S)-4-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-2-methoxy-N-methylbutan-1-amine;   1-(2-morpholin-2-ylethyl)-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-{2-[(2S)-morpholin-2-yl]ethyl}-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-{2-[(2R)-morpholin-2-yl]ethyl}-3-phenyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(4-fluorophenyl)-3-(2-morpholin-2-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(4-fluorophenyl)-3-{2-[(2S)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(4-fluorophenyl)-3-{2-[(2R)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,4-difluorophenyl)-3-(2-morpholin-2-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,4-difluorophenyl)-3-{2-[(2S)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,4-difluorophenyl)-3-{2-[(2R)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-morpholin-2-ylethyl)-3-(2,4,6-trifluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-{2-[(2S)-morpholin-2-yl]ethyl}-3-(2,4,6-trifluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-{2-[(2R)-morpholin-2-yl]ethyl}-3-(2,4,6-trifluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(3-methoxyphenyl)-3-{2-[(2S)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(3-methoxyphenyl)-3-{2-[(2R)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-fluorophenyl)-3-{2-[(2S)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-fluorophenyl)-3-{2-[(2R)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,6-difluorophenyl)-3-{2-[(2S)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(3-{[3-(2-fluorophenyl)-2,2-dioxido-2,1,3 benzothiadiazol-1(3H)-yl]methyl}phenyl)-N-methylmethanamine;   1-(3-{[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]methyl}phenyl)methanamine;   1-(3-{[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]methyl}phenyl)-N,N-dimethylmethanamine;   1-(4-{[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]methyl}phenyl)-N,N-dimethylmethanamine;   1-(4-{[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]methyl}phenyl)methanamine;   1-(4-{[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]methyl}phenyl)-N-methylmethanamine;   (2Z)-4-[3-(2-fluoro-4-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbut-2-en-1-amine;   (2Z)-4-[3-(2-fluoro-4-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]but-2-en-1-amine;   (2Z)-4-[3-(2-fluoro-4-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,N-dimethylbut-2-en-1-amine;   (2Z)-N-ethyl-4-[3-(2-fluoro-4-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]but-2-en-1-amine;   1-(3,4-difluorophenyl)-3-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(3,4-difluorophenyl)-3-(3-piperazin-1-ylpropyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(3,4-difluorophenyl)-3-[3-(3,5-dimethylpiperazin-1-yl)propyl]-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   2-{2-[3-(3,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}-N-methylethanamine;   1-(2-piperazin-1-ylethyl)-3-(2,3,4-trifluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-methylphenyl)-3-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-chlorophenyl)-3-(2-piperazin-1-ylethyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   2-{2-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}-N-methylethanamine;   2-{2-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}ethanamine;   2-{2-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}-N,N-dimethylethanamine;   (2E)-4-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbut-2-en-1-amine;   (2E)-4-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,N-dimethylbut-2-en-1-amine;   (2E)-4-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]but-2-en-1-amine;   N-(2-{2-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}ethyl)cyclopropanamine;   N-(2-{2-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}ethyl)cyclobutanamine;   N-(2-{2-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}ethyl)cyclopentanamine;   2-{2-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}-N-methylethanamine;   2-{2-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}-N-ethylethanamine;   N-(2-{2-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethoxy}ethyl)propan-2-amine;   1-(4-chlorophenyl)-3-(4-morpholin-4-ylbutyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-Fluorophenyl)-4-fluoro-3-{2-[(2R)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-Fluorophenyl)-4-fluoro-3-{2-[(2S)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-Fluorophenyl)-5-fluoro-3-{2-[(2R)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-Fluorophenyl)-5-fluoro-3-{2-[(2S)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-Fluorophenyl)-6-fluoro-3-{2-[(2R)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-Fluorophenyl)-6-fluoro-3-{2-[(2S)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-Fluorophenyl)-7-fluoro-3-{2-[(2R)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2-Fluorophenyl)-7-fluoro-3-{2-[(2S)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,6-Difluorophenyl)-4-fluoro-3-{2-[(2R)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,6-Difluorophenyl)-4-fluoro-3-{2-[(2S)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,6-Difluorophenyl)-5-fluoro-3-{2-[(2R)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,6-Difluorophenyl)-5-fluoro-3-{2-[(2S)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,6-Difluorophenyl)-6-fluoro-3-{2-[(2R)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,6-Difluorophenyl)-6-fluoro-3-{2-[(2S)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,6-Difluorophenyl)-7-fluoro-3-{2-[(2R)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide;   1-(2,6-Difluorophenyl)-7-fluoro-3-{2-[(2S)-morpholin-2-yl]ethyl}-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide; and   pharmaceutically acceptable salts thereof.   
     
     
         33 . A composition, comprising:
 a. at least one compound of formula I:   
       
         
           
           
               
               
           
         
         
           or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof; 
           wherein: 
           n is an integer from 0 to 4; 
           m is an integer from 0 to 6; 
           X is, independently at each occurrence, C(R 7 ) 2 , N(R 3 ), O, S, S(═O), or S(═O) 2 ; 
           Y is C; or 
           Y and an adjacent X together form —CR 7 ═CR 7 —, —C≡C—, or arylenyl substituted with 0-3 R 10 ; 
           R 1  is, independently at each occurrence, H, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R 11 , heteroaryl substituted with 0-3 R 11 , alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide substituted with 0-3 R 5 , alkylamido, or arylamido substituted with 0-3 R 5 ; 
           R 2  is aryl substituted with 0-3 R 9  or heteroaryl substituted with 0-3 R 9 ; 
           R 3  is, independently at each occurrence, H, halo, hydroxy, alkyl substituted with 0-3 R 13 , a heterocyclic ring, aryl substituted with 0-3 R 12 , or heteroaryl substituted with 0-3 R 12 ; 
           R 4  is, independently at each occurrence, H, alkyl substituted with 0-3 R 13 , arylalkyl substituted with 0-3 R 13  or heteroarylmethyl substituted with 0-3 R 13 ; 
           R 5  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido; 
           R 6  is, independently at each occurrence, H, hydroxy, C 1 -C 4  alkyl, C 1 -C 6  alkoxy, halo, aryl substituted with 0-3 R 1 , heteroaryl substituted with 0-3 R 1 , —N(R 3 ) 2 , —S(R 3 ), or —R 8 —O—R 3 ; or both R 6  groups form a cycloalkyl, a heterocyclic ring, ═O or ═N—OH; 
           provided that if each R 3  is H, each X is CH 2 , and either each R 6  is H or one R 6  is hydroxy; then, both of said R 4 , together with the nitrogen through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, hydroxyalkyl, aminoalkyl, or a heterocyclic ring, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl; 
           R 7  is, independently at each occurrence, H, hydroxy, alkoxy, or C 1 -C 4  alkyl; 
           R 8  is, independently at each occurrence, straight or branched alkylenyl; 
           or 
           one of said R 3  and one of said R 4 , together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with alkyl; 
           or 
           both of said R 4 , together with the nitrogen through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, hydroxyalkyl, aminoalkyl, a heterocyclic ring, F, or CF 3 ; and where any additional N atom may be optionally substituted with alkyl; 
           or 
           one of said R 6  or one of said R 7  and one of said R 4 , together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two C 1 -C 4  alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl; provided that R 4  and R 7 , taken together, do not form a piperidinyl ring; 
           R 9  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R 11 , heteroaryl substituted with 0-3 R 11 , alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide, alkylamido, or arylamido; 
           R 10  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; 
           R 11  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; 
           R 12  and R 13  are each, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, hydroxyalkyl, aminoalkyl, a heterocyclic ring, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; and 
         
         wherein 1-3 carbon atoms in ring A may optionally be replaced with N; and 
         b. at least one pharmaceutically acceptable carrier. 
       
     
     
         34 . A method for treating or preventing a condition selected from the group consisting of a vasomotor symptom, sexual dysfunction, gastrointestinal disorder, genitourinary disorder, chronic fatigue syndrome, fibromyalgia syndrome, depression disorder, diabetic neuropathy, endogenous behavioral disorder, cognitive disorder, pain, and combinations thereof in a subject in need thereof, comprising the step of:
 administering to said subject an effective amount of a compound of formula I:   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof; 
         wherein: 
         n is an integer from 0 to 4; 
         m is an integer from 0 to 6; 
         X is, independently at each occurrence, C(R 7 ) 2 , N(R 3 ), O, S, S(═O), or S(═O) 2 ; 
         Y is C; or 
         Y and an adjacent X together form —CR 7 ═CR 7 —, —C≡C—, or arylenyl substituted with 0-3 R 10 ; 
         R 1  is, independently at each occurrence, H, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R 11 , heteroaryl substituted with 0-3 R 11 , alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide substituted with 0-3 R 5 , alkylamido, or arylamido substituted with 0-3 R 5 ; 
         R 2  is aryl substituted with 0-3 R 9  or heteroaryl substituted with 0-3 R 9 ; 
         R 3  is, independently at each occurrence, H, halo, hydroxy, alkyl substituted with 0-3 R 13 , a heterocyclic ring, aryl substituted with 0-3 R 12 , or heteroaryl substituted with 0-3 R 12 ; 
         R 4  is, independently at each occurrence, H, alkyl substituted with 0-3 R 13 , arylalkyl substituted with 0-3 R 13  or heteroarylmethyl substituted with 0-3 R 13 ; 
         R 5  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido; 
         R 6  is, independently at each occurrence, H, hydroxy, C 1 -C 4  alkyl, C 1 -C 6  alkoxy, halo, aryl substituted with 0-3 R 1 , heteroaryl substituted with 0-3 R 1 , —N(R 3 ) 2 , —S(R 3 ), or —R 3 —O—R 3 ; or both R 6  groups form a cycloalkyl, a heterocyclic ring, ═O or ═N—OH; 
         provided that if each R 3  is H, each X is CH 2 , and either each R 6  is H or one R 6  is hydroxy; then, both of said R 4 , together with the nitrogen through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, hydroxyalkyl, aminoalkyl, or a heterocyclic ring, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl; 
         R 7  is, independently at each occurrence, H, hydroxy, alkoxy, or C 1 -C 4  alkyl; 
         R 8  is, independently at each occurrence, straight or branched alkylenyl; 
         or 
         one of said R 3  and one of said R 4 , together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with alkyl; 
         or 
         both of said R 4 , together with the nitrogen through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, hydroxyalkyl, aminoalkyl, a heterocyclic ring, F, or CF 3 ; and where any additional N atom may be optionally substituted with alkyl; 
         or 
         one of said R 6  or one of said R 7  and one of said R 4 , together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two C 1 -C 4  alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl; provided that R 4  and R 7 , taken together, do not form a piperidinyl ring; 
         R 9  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R 11 , heteroaryl substituted with 0-3 R 11 , alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide, alkylamido, or arylamido; 
         R 10  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; 
         R 11  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; 
         R 12  and R 13  are each, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, hydroxyalkyl, aminoalkyl, a heterocyclic ring, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; and 
         wherein 1-3 carbon atoms in ring A may optionally be replaced with N. 
       
     
     
         35 . The method of  claim 34 , wherein said vasomotor symptom is hot flush. 
     
     
         36 . The method of  claim 34 , wherein said sexual dysfunction is desire-related or arousal-related. 
     
     
         37 . The method of  claim 34 , wherein said gastrointestinal disorder or said genitourinary disorder is stress incontinence or urge incontinence. 
     
     
         38 . The method of  claim 34 , wherein said condition is chronic fatigue syndrome or fibromyalgia syndrome. 
     
     
         39 . The method of  claim 34 , wherein said condition is a depression disorder selected from the group consisting of major depressive disorder, generalized anxiety disorder, panic disorder, attention deficit disorder with or without hyperactivity, sleep disturbance, social phobia, and combinations thereof. 
     
     
         40 . The method of  claim 34 , wherein said condition is diabetic neuropathy. 
     
     
         41 . The method of  claim 34 , wherein said condition is pain. 
     
     
         42 . The method of  claim 41 , wherein said pain is acute centralized pain, acute peripheral pain, or a combination thereof. 
     
     
         43 . The method of  claim 41 , wherein said pain is chronic centralized pain, chronic peripheral pain, or a combination thereof. 
     
     
         44 . The method of  claim 41 , wherein said pain is neuropathic pain, visceral pain, musculoskeletal pain, bony pain, cancer pain, inflammatory pain, or a combination thereof. 
     
     
         45 . The method of  claim 44 , wherein said neuropathic pain is associated with diabetes, post traumatic pain of amputation, lower back pain, cancer, chemical injury, toxins, major surgery, peripheral nerve damage due to traumatic injury compression, post-herpetic neuralgia, trigeminal neuralgia, lumbar or cervical radiculopathies, fibromyalgia, glossopharyngeal neuralgia, reflex sympathetic dystrophy, casualgia, thalamic syndrome, nerve root avulsion, reflex sympathetic dystrophy or post thoracotomy pain, nutritional deficiencies, viral infection, bacterial infection, metastatic infiltration, adiposis dolorosa, burns, central pain conditions related to thalamic conditions, or a combination thereof. 
     
     
         46 . The method of  claim 44 , wherein said neuropathic pain is post-herpetic neuralgia. 
     
     
         47 . The method of  claim 44 , wherein said visceral pain is associated with ulcerative colitis, irritable bowel syndrome, irritable bladder, Crohn's disease, rheumatologic (arthralgias), tumors, gastritis, pancreatitis, infections of the organs, biliary tract disorders, or a combination thereof. 
     
     
         48 . The method of  claim 41 , wherein said subject is female. 
     
     
         49 . The method of  claim 48 , wherein said pain is female-specific pain. 
     
     
         50 . A process for the preparation of a compound of formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof; 
         wherein: 
         n is an integer from 0 to 4; 
         m is an integer from 0 to 6; 
         X is, independently at each occurrence, C(R 7 ) 2 , N(R 3 ), O, S, S(═O), or S(═O) 2 ; 
         Y is C; or 
         Y and an adjacent X together form —CR 7 ═CR 7 —, —C≡C—, or arylenyl substituted with 0-3 R 10 ; 
         R 1  is, independently at each occurrence, H, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R 11 , heteroaryl substituted with 0-3 R 11 , alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide substituted with 0-3 R 5 , alkylamido, or arylamido substituted with 0-3 R 5 ; 
         R 2  is aryl substituted with 0-3 R 9  or heteroaryl substituted with 0-3 R 9 ; 
         R 3  is, independently at each occurrence, H, halo, hydroxy, alkyl substituted with 0-3 R 13 , a heterocyclic ring, aryl substituted with 0-3 R 12 , or heteroaryl substituted with 0-3 R 12 ; 
         R 4  is, independently at each occurrence, H, alkyl substituted with 0-3 R 13 , arylalkyl substituted with 0-3 R 13  or heteroarylmethyl substituted with 0-3 R 13 ; 
         R 5  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido; 
         R 6  is, independently at each occurrence, H, hydroxy, C 1 -C 4  alkyl, C 1 -C 6  alkoxy, halo, aryl substituted with 0-3 R 1 , heteroaryl substituted with 0-3 R 1 , —N(R 3 ) 2 , —S(R 3 ), or —R 8 —O—R 3 ; or both R 6  groups form a cycloalkyl, a heterocyclic ring, ═O or ═N—OH; 
         provided that if each R 3  is H, each X is CH 2 , and either each R 6  is H or one R 6  is hydroxy; then, both of said R 4 , together with the nitrogen through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, hydroxyalkyl, aminoalkyl, or a heterocyclic ring, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl; 
         R 7  is, independently at each occurrence, H, hydroxy, alkoxy, or C 1 -C 4  alkyl; 
         R 8  is, independently at each occurrence, straight or branched alkylenyl; 
         or 
         one of said R 3  and one of said R 4 , together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with alkyl; 
         or 
         both of said R 4 , together with the nitrogen through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, hydroxyalkyl, aminoalkyl, a heterocyclic ring, F, or CF 3 ; and where any additional N atom may be optionally substituted with alkyl; 
         or 
         one of said R 6  or one of said R 7  and one of said R 4 , together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two C 1 -C 4  alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl; provided that R 4  and R 7 , taken together, do not form a piperidinyl ring; 
         R 9  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R 11 , heteroaryl substituted with 0-3 R 11 , alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide, alkylamido, or arylamido; 
         R 10  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; 
         R 11  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; 
         R 12  and R 13  are each, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, hydroxyalkyl, aminoalkyl, a heterocyclic ring, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; and 
         wherein 1-3 carbon atoms in ring A may optionally be replaced with N; 
         the process comprising: 
         (d) reacting a compound of formula IA: 
       
       
         
           
           
               
               
           
         
         with a compound of formula IB: 
       
       
         
           
           
               
               
           
         
         wherein, 
         T is an —N(R 4 ) 2  or an activating group; 
         wherein, 
         if T is —N(R 4 ) 2 , then the compound of formula I is formed; or 
         if T is an activating group, then a compound of formula IC is formed: 
       
       
         
           
           
               
               
           
         
         and the process further comprises: 
         (e) reacting the compound formula IC with —N(R 4 )R P  to form a compound of formula ID: 
       
       
         
           
           
               
               
           
         
         wherein, 
         R P  is R 4  or a protecting group; 
         wherein, 
         if R P  is R 4 , the compound of formula I is formed; or 
         if R P  is a protecting group, the process further comprises: 
         (f) deprotecting the compound of formula ID to form a deprotected compound; and 
         (g) reacting the deprotected compound with an activated-R 4  group, provided that R 4  in the activated-R 4  group is not H; 
         wherein the compound of formula I is formed. 
       
     
     
         51 . The process of  claim 50 , wherein step (d) further comprises contacting the compound of formula IA and IB with dialkyl azodicarboxylate and triphenylphosphine. 
     
     
         52 . The process of  claim 51 , wherein the dialkyl azodicarboxylate is diisopropyl azodicarboxylate. 
     
     
         53 . The process of  claim 50 , wherein the activating group is selected from the group consisting of halo, tosylate, mesylate, triflate, and oxo. 
     
     
         54 . The process of  claim 53 , wherein the activating group is Br. 
     
     
         55 . The process of  claim 50 , wherein the protecting group is selected from the group consisting of BOC, benzyl, acetyl, PMB, alkyl, Fmoc, Cbz, trifluoroacetyl, tosyl and triphenylmethyl. 
     
     
         56 . The process of  claim 55 , wherein the protecting group is BOC. 
     
     
         57 . The process of  claim 50 , wherein the deprotecting step is performed in the presence of at least one agent selected from hydrochloric acid (HCl), tin(II)chloride, ammonium chloride, zinc, trifluoroacetic acid (TFA), tosic acid, a halotrimethylsilane, or aluminum chloride. 
     
     
         58 . The process of  claim 50 , wherein any one of steps (d)-(g) is performed at or above 30° C. or any one of steps (d)-(g) includes a purification step comprising at least one of: filtration, extraction, chromatography, trituration, or recrystallization. 
     
     
         59 . The process of  claim 50 , wherein the activated-R 4  group is halo-R 4  or O═R 4 . 
     
     
         60 . The process of  claim 50 , wherein the compound of formula IA is prepared by:
 (a) reacting a compound of formula IE:   
       
         
           
           
               
               
           
         
         wherein R B  is F or Cl; 
         with R 2 —NH 2  to form a compound of formula IF: 
       
       
         
           
           
               
               
           
         
         (b) hydrogenating the compound of formula IF to form a compound of formula IG: 
       
       
         
           
           
               
               
           
         
         and (c) reacting the compound of formula IG with sulfamide in diglyme to form the compound of formula IA. 
       
     
     
         61 . The process of  claim 60 , wherein the hydrogenating step is performed in the presence of hydrogen (H 2 ) and Pd/C. 
     
     
         62 . The process of  claim 60 , wherein any one of steps (a)-(c) is performed at or above 30° C. 
     
     
         63 . The process of  claim 60 , wherein any one of steps (a)-(c) includes a purification step comprising at least one of: filtration, extraction, chromatography, trituration, or recrystallization. 
     
     
         64 . A process for the preparation of a compound of formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof; 
         wherein: 
         n is an integer from 0 to 4; 
         m is an integer from 0 to 6; 
         X is, independently at each occurrence, C(R 7 ) 2 , N(R 3 ), O, S, S(═O), or S(═O) 2 ; 
         Y is C; or 
         Y and an adjacent X together form —CR 7 ═CR 7 —, —C≡C—, or arylenyl substituted with 0-3 R 10 ; 
         R 1  is, independently at each occurrence, H, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R 11 , heteroaryl substituted with 0-3 R 11 , alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide substituted with 0-3 R 5 , alkylamido, or arylamido substituted with 0-3 R 5 ; 
         R 2  is aryl substituted with 0-3 R 9  or heteroaryl substituted with 0-3 R 9 ; 
         R 3  is, independently at each occurrence, H, halo, hydroxy, alkyl substituted with 0-3 R 13 , a heterocyclic ring, aryl substituted with 0-3 R 12 , or heteroaryl substituted with 0-3 R 12 ; 
         R 4  is, independently at each occurrence, H, alkyl substituted with 0-3 R 13 , arylalkyl substituted with 0-3 R 13  or heteroarylmethyl substituted with 0-3 R 13 ; 
         R 5  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido; 
         R 6  is, independently at each occurrence, H, hydroxy, C 1 -C 4  alkyl, C 1 -C 6  alkoxy, halo, aryl substituted with 0-3 R 1 , heteroaryl substituted with 0-3 R 1 , —N(R 3 ) 2 , —S(R 3 ), or —R 8 —O—R 3 ; or both R 6  groups form a cycloalkyl, a heterocyclic ring, ═O or ═N—OH; 
         provided that if each R 3  is H, each X is CH 2 , and either each R 6  is H or one R 6  is hydroxy; then, both of said R 4 , together with the nitrogen through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, hydroxyalkyl, aminoalkyl, or a heterocyclic ring, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl; 
         R 7  is, independently at each occurrence, H, hydroxy, alkoxy, or C 1 -C 4  alkyl; 
         R 8  is, independently at each occurrence, straight or branched alkylenyl; 
         or 
         one of said R 3  and one of said R 4 , together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with alkyl; 
         or 
         both of said R 4 , together with the nitrogen through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two alkyl, hydroxyalkyl, aminoalkyl, a heterocyclic ring, F, or CF 3 ; and where any additional N atom may be optionally substituted with alkyl; 
         or 
         one of said R 6  or one of said R 7  and one of said R 4 , together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO 2 , and where any carbon ring atom may be optionally substituted with one or two C 1 -C 4  alkyl, F, or CF 3 ; and where any additional N atom may be optionally substituted with C 1 -C 4  alkyl; provided that R 4  and R 7 , taken together, do not form a piperidinyl ring; 
         R 9  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R 11 , heteroaryl substituted with 0-3 R 11 , alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide, alkylamido, or arylamido; 
         R 10  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; 
         R 11  is, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; 
         R 12  and R 13  are each, independently at each occurrence, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, hydroxyalkyl, aminoalkyl, a heterocyclic ring, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl; and 
         wherein 1-3 carbon atoms in ring A may optionally be replaced with N; 
         the process comprising: 
         (d) reacting R 2 (BOH) 2  and a transitional metal salt with a compound of formula IH: 
       
       
         
           
           
               
               
           
         
         wherein, 
         R P  is R 4  or a protecting group; and 
         if R P  is R 4 , the compound of formula I is formed; or 
         if R P  is a protecting group, the process further comprises: 
         (e) deprotecting the compound of formula IH to form a deprotected compound; and 
         (g) reacting the deprotected compound with an activated-R 4  group, provided that R 4  group in the activated-R 4  group is not H; 
         wherein the compound of formula I is formed. 
       
     
     
         65 . The process of  claim 64 , wherein the transitional metal salt is copper(II)acetate. 
     
     
         66 . The process of  claim 64 , wherein the activated-R 4  group is halo-R 4  or O═R 4 . 
     
     
         67 . The process of  claim 64 , wherein the protecting group is selected from the group consisting of BOC, benzyl, acetyl, PMB, alkyl, Fmoc, Cbz, trifluoroacetyl, tosyl and triphenylmethyl. 
     
     
         68 . The process of  claim 67 , wherein the protecting group is BOC. 
     
     
         69 . The process of  claim 64 , wherein the deprotecting step is performed in the presence of at least one agent selected from hydrochloric acid (HCl), tin(II)chloride, ammonium chloride, zinc, trifluoroacetic acid (TFA), tosic acid, a halotrimethylsilane, or aluminum chloride. 
     
     
         70 . The process of  claim 64 , wherein any one of steps (d)-(g) is performed at or above 30° C. or any one of steps (d)-(g) includes a purification step comprising at least one of: filtration, extraction, chromatography, trituration, or recrystallization. 
     
     
         71 . The process of  claim 64 , wherein the compound of formula IH is prepared by:
 (a) reacting a compound of formula IJ:   
       
         
           
           
               
               
           
         
         wherein R B  is F or Cl; 
         with a compound of formula IK: 
       
       
         
           
           
               
               
           
         
         to form a compound of formula IL: 
       
       
         
           
           
               
               
           
         
         (b) hydrogenating the compound of formula IL to form a compound of formula IM: 
       
       
         
           
           
               
               
           
         
         and (c) reacting the compound of formula IM with sulfamide and diglyme to form the compound of formula IH. 
       
     
     
         72 . The process of  claim 71 , wherein the hydrogenating step is performed in the presence of hydrogen (H 2 ) and Pd/C. 
     
     
         73 . The process of  claim 71 , wherein any one of steps (a)-(c) is performed at or above 30° C. 
     
     
         74 . The process of  claim 71 , wherein any one of steps (a)-(c) includes a purification step comprising at least one of: filtration, extraction, chromatography, trituration, or recrystallization.