AMINOALKYL SUBSTITUTED ARYL SULFAMIDE DERIVATIVES AND METHODS OF THEIR USE

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 —CH 2 —;

R 1 is, independently at each occurrence, H, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl, heteroaryl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide alkylamido, or arylamido; wherein each aryl or heteroaryl is independently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl groups; and each arylsulfonamide or arylamido is independently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido groups;

R 2 is aryl or heteroaryl substituted with 0-4 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide, alkylamido, arylamido, or aryl or heteroaryl optionally substituted with alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl;

R 3 and R 4 are, independently, H, alkyl, a heterocyclic ring, arylalkyl or heteroarylmethyl, wherein each of alkyl, heterocyclic ring, arylalkyl or heteroarylmethyl, are indepently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl groups, provided that neither R 3 or R 4 contain an aminoalkyl group;

and

wherein 1-3 carbon atoms in ring A may optionally be replaced with N.

2 . The compound of claim 1 , wherein each R 1 is H.

3 . The compound of claim 1 , wherein R 2 is:

wherein,

each R 5 , R 6 , R 7 , R 8 and R 9 are independently selected from the group consisting of H, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted, heteroaryl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide, alkylamido, or arylamido.

4 . The compound of claim 3 , wherein R 7 and R 9 are F.

5 . The compound of claim 4 , wherein R 5 R 6 and R 8 are H.

6 . The compound of claim 3 , wherein R 5 , R 6 , R 7 , R 8 and R 9 are independently H, halo, alkyl or alkoxy.

7 . The compound of claim 1 , wherein R 3 is methyl.

8 . The compound of claim 7 , wherein R 4 is H.

9 . The compound of claim 1 , wherein m is 1-2.

10 . The compound of claim 1 , wherein m is 1.

11 . The compound of claim 3 , wherein:

R 7 and R 9 are F; and

R 5 , R 6 and R 8 are H.

12 . The compound of claim 1 , wherein ring A comprises all carbon atoms.

13 . The compound of claim 1 , wherein R 2 is pyridinyl, methyl-pyridinyl, ethyl-pyridinyl, methoxy-pyridinyl, or quinolinyl.

14 . 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.

15 . The compound of claim 1 , wherein:

each R 1 is H;

m is 1;

R 3 is methyl; and

R 4 is H.

16 . The compound of claim 3 , wherein:

each R 1 is H;

R 7 and R 9 are F;

R 5 , R 6 and R 8 are H;

R 3 is methyl;

R 4 is H; and

m is 1.

17 . The compound of claim 1 , selected from the group consisting of:

18 . The compound of claim 1 , selected from the group consisting of:

3-[3-(4-chlorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(4-chlorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

N-{3-[3-(4-chlorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propyl}cyclopropanamine;

3-[3-(4-chlorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-ethylpropan-1-amine;

3-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-N-methylpropan-1-amine;

3-[3-(4-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(4-methoxyphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

N-methyl-3-[3-(4-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

3-[3-(2-methoxyphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(3-fluoro-2-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(3-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

N-methyl-3-[3-(1-naphthyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

N-methyl-3-[3-(2-naphthyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

N-methyl-3-[3-(3-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

N-methyl-3-[3-(2-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

3-[3-(3-methoxyphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

4-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-N-methylbutan-1-amine;

4-[3-(4-chlorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]butan-1-amine;

4-[3-(4-chlorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amine;

4-[3-(4-chlorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,N-dimethylbutan-1-amine;

n-butyl-4-[3-(4-chlorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1 (3H)-yl]butan-1-amine;

4-[3-(4-chlorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-ethyl-N-methylbutan-1-amine;

3-(2,2-dioxido-3-phenyl[1,2,5]thiadiazolo[3,4-b]pyridin-1(3H)-yl)-N-methylpropan-1-amine;

3-(2,2-dioxido-1-phenyl[1,2,5]thiadiazolo[3,4-c]pyridin-3(1H)-yl)-N-methylpropan-1-amine;

N-methyl-3-[3-(5-methylpyridin-2-yl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

N-methyl-3-[3-(3-methylpyridin-2-yl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

3-[3-(6-methoxypyridin-3-yl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(5-ethylpyridin-2-yl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

N-methyl-3-[3-(4-methylpyridin-2-yl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

3-(2,2-dioxido-3-pyridin-2-yl-2,1,3-benzothiadiazol-1(3H)-yl)-N-methylpropan-1-amine;

N-methyl-3-[3-(6-methylpyridin-2-yl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

N-methyl-3-[3-(4-methylpyridin-3-yl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

3-(2,2-dioxido-3-pyridin-3-yl-2,1,3-benzothiadiazol-1(3H)-yl)-N-methylpropan-1-amine;

3-(6-fluoro-2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-N-methylpropan-1-amine;

3-(5-Chloro-2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-N-methylpropan-1-amine;

3-(6-bromo-2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-N-methylpropan-1-amine;

N-methyl-3-(5-methyl-2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)propan-1-amine;

3-(7-fluoro-2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-N-methylpropan-1-amine;

N-methyl-3-(6-methyl-2,2-dioxido-3-phenyl-2,1,3-benzo-thiadiazol-1(3H)-yl)propan-1-amine;

3-(4-fluoro-2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-N-methylpropan-1-amine;

3-[7-fluoro-3-(3-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(methylamino)propyl]-1-phenyl-1,3-dihydro-2,1,3-benzothiadiazole-5-carbonitrile 2,2-dioxide;

3-(5-fluoro-2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)-N-methylpropan-1-amine;

3-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1 (3H)-yl]-N-methylpropan-1-amine;

3-[3-(2,3-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(3,5-difluorophenyl)-2,2-dioxido-2,13-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(2,5-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-{2,2-dioxido-3-[3-(trifluoromethoxy)phenyl]-2,1,3-benzothiadiazol-1(3H)-yl}-N-methylpropan-1-amine;

3-{2,2-dioxido-3-[2-(trifluoromethoxy)phenyl]-2,1,3-benzothiadiazol-1(3H)-yl}-N-methylpropan-1-amine;

3-{2,2-dioxido-3-[3-(trifluoromethyl)phenyl]-2,1,3-benzothiadiazol-1(3H)-yl}-N-methylpropan-1-amine;

3-[3-(2-chlorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(3-bromophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

2-[3-(4-chlorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethanamine;

2-[3-(4-chlorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylethanamine;

3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

N-ethyl-3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

4-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]butan-1-amine;

4-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amine;

3-[3-(2-Chloro-4-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(2-Chloro-4-fluorophenyl)-2,2-dioxido-2,13-benzothiadiazol-1(3H)-yl]propan-1-amine;

3-[3-(4-fluoro-2-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(4-fluoro-2-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

3-[3-(4-fluoro-2-methoxyphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

5-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]pentan-1-amine;

5-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpentan-1-amine;

5-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,N-dimethylpentan-1-amine;

3-[3-(3-Chlorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(2,6-Difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

3-[2,2-Dioxido-3-(2,4,6-trifluorophenyl)-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

3-[3-(2-fluorophenyl)-2,2-dioxido-5-phenyl-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

3-[4-fluoro-3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[4-fluoro-3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propan-1-amine;

3-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[7-fluoro-3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1 (3H)-yl]-N-methylpropan-1-amine;

3-[2,2-Dioxido-3-(2,4,6-trifluorophenyl)-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(2,4-Difluorophenyl)-7-fluoro-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(2,4-Difluorophenyl)-4-fluoro-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(2,4-Difluorophenyl)-7-fluoro-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,N-dimethylpropan-1-amine;

4-[2,2-Dioxido-3-(2,4,6-trifluorophenyl)-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amine;

4-[3-(4-Fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amine;

4-[3-(2,6-Difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amine;

N-{3-[3-(2,6-Difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propyl}cyclopropanamine;

N-{3-[3-(2,4-Difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1 (3H)-yl]propyl}cyclopropanamine;

N-{4-[3-(2,6-Difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]butyl}cyclopropanamine;

4-[3-(2-chloro-4-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amine;

4-[3-(2-chloro-4-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1 (3H)-yl]-N,N-dimethylbutan-1-amine;

5-[3-(2-chloro-4-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpentan-1-amine;

5-[3-(2-chloro-4-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,N-dimethylpentan-1-amine;

3-[3-(2-fluoro-4-methoxyphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-fluoro-4-{3-[3-(methylamino)propyl]-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl}phenol;

3-fluoro-4-{3-[4-(methylamino)butyl]-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl}phenol;

4-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amine;

3-[3-(4-chloro-2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

N-[3-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)propyl]cyclopropanamine;

N-{3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propyl}cyclopropanamine;

N-[3-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)butyl]cyclopropanamine;

N-{3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]butyl}cyclopropanamine;

3-[3-(4-chloro-2-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

6-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylhexan-1-amine;

6-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]hexan-1-amine;

6-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,N-dimethylhexan-1-amine;

4-[3-(2-fluoro-4-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amine;

4-[3-(2-fluoro-4-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]butan-1-amine;

4-[3-(2-fluoro-4-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1 (3H)-yl]-N,N-dimethylbutan-1-amine;

N-ethyl-4-[3-(2-fluoro-4-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]butan-1-amine;

3-[3-(2-fluoro-4-methylphenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(3,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

4-[3-(3,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amine;

3-[3-(3,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-(2,2,2-trifluoroethyl)propan-1-amine;

3-[2,2-dioxido-3-(2,3,4-trifluorophenyl)-2,13-benzothiadiazol-1(3H)-yl]-N-ethylpropan-1-amine;

3-[2,2-dioxido-3-(2,3,4-trifluorophenyl)-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

3-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpropan-1-amine;

5-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylpentan-1-amine;

5-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]pentan-1-amine;

5-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,N-dimethylpentan-1-amine;

3-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,N-dimethylpropan-1-amine;

3-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-ethylpropan-1-amine;

4-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N,N-dimethylbutan-1-amine;

4-[3-(2,4-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-ethylbutan-1-amine;

4-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-ethylbutan-1-amine;

4-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-isopropylbutan-1-amine;

N-{4-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]butyl}cyclobutanamine;

N-{4-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]butyl}cyclohexanamine;

3-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-ethylpropan-1-amine;

3-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-isopropylpropan-1-amine;

N-{3-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propyl}cyclobutanamine;

N-{3-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propyl}cyclopentanamine;

N-{3-[3-(2,6-difluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propyl}cyclohexanamine;

N-{3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propyl}piperidin-4-amine;

N-[3-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)propyl]piperidin-4-amine;

N-{3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]ethyl}piperidin-4-amine;

N-[2-(2,2-dioxido-3-phenyl-2,1,3-benzothiadiazol-1(3H)-yl)ethyl]piperidin-4-amine;

2-({3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]propyl}amino) ethanol; and

pharmaceutically acceptable salts thereof.

19 . The compound of claim 1 ,

wherein said pharmaceutically acceptable salt is a hydrochloride or dihydrochloride.

20 . 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 —CH 2 —;

R 1 is, independently at each occurrence, H, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl, heteroaryl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide alkylamido, or arylamido; wherein each aryl or heteroaryl is independently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl groups; and each arylsulfonamide or arylamido is independently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido groups;

R 2 is aryl or heteroaryl substituted with 0-4 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide, alkylamido, arylamido, or aryl or heteroaryl optionally substituted with alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl;

R 3 and R 4 are, independently, H, alkyl, a heterocyclic ring, arylalkyl or heteroarylmethyl, wherein each of alkyl, heterocyclic ring, arylalkyl or heteroarylmethyl, are indepently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl groups, provided that neither R 3 or R 4 contain an aminoalkyl group; and

wherein 1-3 carbon atoms in ring A may optionally be replaced with N; and

b. at least one pharmaceutically acceptable carrier.

21 . 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 —CH 2 —;

R 1 is, independently at each occurrence, H, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl, heteroaryl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide alkylamido, or arylamido; wherein each aryl or heteroaryl is independently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl groups; and each arylsulfonamide or arylamido is independently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido groups;

R 2 is aryl or heteroaryl substituted with 0-4 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide, alkylamido, arylamido, or aryl or heteroaryl optionally substituted with alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl;

R 3 and R 4 are, independently, H, alkyl, a heterocyclic ring, arylalkyl or heteroarylmethyl, wherein each of alkyl, heterocyclic ring, arylalkyl or heteroarylmethyl, are indepently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl groups, provided that neither R 3 or R 4 contain an aminoalkyl group; and

wherein 1-3 carbon atoms in ring A may optionally be replaced with N.

22 . The method of claim 21 ,

wherein said vasomotor symptom is hot flush.

23 . The method of claim 21 ,

wherein said sexual dysfunction is desire-related or arousal-related.

24 . The method of claim 21 ,

wherein said gastrointestinal disorder or said genitourinary disorder is stress incontinence or urge incontinence.

25 . The method of claim 21 ,

wherein said condition is chronic fatigue syndrome or fibromyalgia syndrome.

26 . The method of claim 21 ,

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.

27 . The method of claim 21 ,

wherein said condition is diabetic neuropathy.

28 . The method of claim 21 ,

wherein said condition is pain.

29 . The method of claim 28 ,

wherein said pain is acute centralized pain, acute peripheral pain, or a combination thereof.

30 . The method of claim 28 ,

wherein said pain is chronic centralized pain, chronic peripheral pain, or a combination thereof.

31 . The method of claim 28 ,

wherein said pain is neuropathic pain, visceral pain, musculoskeletal pain, bony pain, cancer pain, inflammatory pain, or a combination thereof.

32 . The method of claim 31 ,

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.

33 . The method of claim 32 ,

wherein said neuropathic pain is post-herpetic neuralgia.

34 . The method of claim 31 ,

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.

35 . The method of claim 28 ,

wherein said subject is female; and

the pain is female-specific pain.

36 . 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 —CH 2 —;

R 1 is, independently at each occurrence, H, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl, heteroaryl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide alkylamido, or arylamido; wherein each aryl or heteroaryl is independently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl groups; and each arylsulfonamide or arylamido is independently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido groups;

R 2 is aryl or heteroaryl substituted with 0-4 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide, alkylamido, arylamido, or aryl or heteroaryl optionally substituted with alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl;

R 3 and R 4 are, independently, H, alkyl, a heterocyclic ring, arylalkyl or heteroarylmethyl, wherein each of alkyl, heterocyclic ring, arylalkyl or heteroarylmethyl, are indepently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl groups, provided that neither R 3 or R 4 contain an aminoalkyl group; 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 3 )(R 4 ) or an activating group;

wherein,

if T is —N(R 3 )(R 4 ), 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 3 , 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 3 group, provided that R 3 in the activated-R 3 group is not H;

wherein the compound of formula I is formed.

37 . The process of claim 36 , wherein step (d) further comprises contacting the compound of formula IA and IB with dialkyl azodicarboxylate and triphenylphosphine.

38 . The process of claim 37 , wherein the dialkyl azodicarboxylate is diisopropyl azodicarboxylate.

39 . The process of claim 36 , wherein the activating group is selected from the group consisting of halo, tosylate, mesylate, triflate, and oxo.

40 . The process of claim 39 , wherein the activating group is Br.

41 . The process of claim 36 , wherein the protecting group is selected from the group consisting of BOC, benzyl, acetyl, PMB, C 1 -C 6 alkyl, Fmoc, Cbz, trifluoroacetyl, tosyl and triphenylmethyl.

42 . The process of claim 41 , wherein the protecting group is BOC.

43 . The process of claim 36 , 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.

44 . The process of claim 36 , 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.

45 . The process of any one of claims 36 , wherein the activated-R 3 group is halo-R 3 .

46 . The process of claim 36 , 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.

47 . The process of claim 46 , wherein the hydrogenating step is performed in the presence of hydrogen (H 2 ) and Pd/C.

48 . The process of claim 46 , wherein any one of steps (a)-(c) is performed at or above 30° C.

49 . The process of claim 46 , wherein any one of steps (a)-(c) includes a purification step comprising at least one of: filtration, extraction, chromatography, trituration, or recrystallization.

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 —CH 2 —;

R 1 is, independently at each occurrence, H, alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl, heteroaryl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide alkylamido, or arylamido; wherein each aryl or heteroaryl is independently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl groups; and each arylsulfonamide or arylamido is independently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido groups;

R 2 is aryl or heteroaryl substituted with 0-4 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide, alkylamido, arylamido, or aryl or heteroaryl optionally substituted with alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl;

R 3 and R 4 are, independently, H, alkyl, a heterocyclic ring, arylalkyl or heteroarylmethyl, wherein each of alkyl, heterocyclic ring, arylalkyl or heteroarylmethyl, are indepently substituted with 0-3 alkyl, alkoxy, halo, CF 3 , OCF 3 , hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl groups, provided that neither R 3 or R 4 contain an aminoalkyl group; 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 3 or a protecting group; and

if R P is R 3 , 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

(f) reacting the deprotected compound with an activated-R 3 group, provided that R 3 group in the activated-R 3 group is not H;

wherein the compound of formula I is formed.

51 . The process of claim 50 , wherein the transitional metal salt is copper(II) acetate.

52 . The process of claim 50 , wherein the activated-R 3 group is halo-R 3 .

53 . The process of claim 50 , wherein the protecting group is selected from the group consisting of BOC, benzyl, acetyl, PMB, C 1 -C 6 alkyl, Fmoc, Cbz, trifluoroacetyl, tosyl and triphenylmethyl.

54 . The process of claim 53 , wherein the protecting group is BOC.

55 . 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.

56 . The process of claim 50 , wherein any one of steps (d)-(f) is performed at or above 30° C. or any one of steps (d)-(f) includes a purification step comprising at least one of: filtration, extraction, chromatography, trituration, or recrystallization.

57 . The process of claim 50 , 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.

58 . The process of claim 57 , wherein the hydrogenating step is performed in the presence of hydrogen (H 2 ) and Pd/C.

59 . The process of claim 57 , wherein any one of steps (a)-(c) is performed at or above 30° C.

60 . The process of claim 57 , wherein any one of steps (a)-(c) includes a purification step comprising at least one of: filtration, extraction, chromatography, trituration, or recrystallization.

61 . The process of claim 36 , wherein any one of the steps is performed in: a protic solvent, an aprotic solvent, a polar solvent, a nonpolar solvent, a protic polar solvent, an aprotic nonpolar solvent, or an aprotic polar solvent.

62 . The process of claim 50 , wherein any one of the steps is performed in: a protic solvent, an aprotic solvent, a polar solvent, a nonpolar solvent, a protic polar solvent, an aprotic nonpolar solvent, or an aprotic polar solvent.