Amino-pyridines As Inhibitors Of Beta-secretase

Abstract

The present invention provides an amino-pyridine compound of formula I The present invention also provides methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles.

1 . A compound of formula I 
     
       
         
         
             
             
         
       
     
     wherein
 X is CH 2  or NR; 
 R is H or alkyl; 
 R 1  and R 2  are each independently an alkyl, cycloalkyl, cycloheteroalkyl, phenyl or heteroaryl group each group optionally substituted; 
 R 3  and R 4  are each independently H, halogen, NR 6 R 7 , OR 8 , or an alkyl, haloalkyl or aryl group each group optionally substituted; 
 R 5  is H or an alkyl or haloalkyl group each optionally substituted; 
 R 6  and R 7  are each independently H or an optionally substituted alkyl group; and 
 R 8  is H or an alkyl or alkenyl group each group optionally substituted; or 
 a pharmaceutically acceptable salt thereof. 
 
   
   
       2 . The compound according to  claim 1  wherein X is CH 2  and R 5  is H. 
   
   
       3 . The compound according to  claim 1  wherein R 1  is an optionally substituted cycloalkyl or phenyl group and R 2  is an optionally substituted phenyl or heteroaryl group. 
   
   
       4 . The compound according to  claim 1  having the structure of formula Ia 
     
       
         
         
             
             
         
       
     
     wherein
 Y is CR 12  or N; 
 R 3 , R 4  and R 5  are as defined for formula I hereinabove; 
 R 9  is H, halogen, OR 12 , CO 2 R 12 , CONHR 12 , NHCOR 12 , or an alkyl, haloalkyl, aryl or heteroaryl group each group optionally substituted; 
 R 10  and R 11  are each independently H, halogen, OR 13 , or an alkyl or haloalkyl group each group optionally substituted; and 
 R 12  and R 13  are each independently H or an optionally substituted alkyl, haloalkyl, cycloheteroalkyl, aryl or heteroaryl group each group optionally substituted. 
 
   
   
       5 . The compound according to  claim 4  wherein R 3  is attached in the ring position ortho to the NHR 5  group and R 4  and R 5  are H. 
   
   
       6 . The compound according to  claim 4  wherein R 10  is H, halogen or an optionally substituted alkyl or alkoxy group and R 4 , R 5  and R 11  are H. 
   
   
       7 . The compound according to  claim 4  wherein Y is CH; R 4 , R 5 , and R 11  are H; R 3  is H, OR 5  or an optionally substituted alkyl group; R 9  is H, OR 12 , or an alkyl, aryl or heteroaryl group each optionally substituted; and R 10  is H, halogen, OR 13  or an optionally substituted alkyl group. 
   
   
       8 . The compound according to  claim 5  wherein R 3  is H or OR 8 . 
   
   
       9 . The compound according to  claim 4  selected from the group consisting of:
 N-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenyl}-3-methyl-benzamide;   N-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenyl}-3-bromo-benzamide;   N-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenyl}-benzamide;   6-[2-(4-bromo-phenyl)-5-(2-chloro-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine;   6-[2-(2-Chloro-phenyl)-5-(4-methoxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine;   4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenol;   6-[2-(2-Chloro-phenyl)-5-(4-propoxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   6-[2-(4-Butoxy-phenyl)-5-(2-chloro-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   6-[2-(2-Chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   6-[2-(2-Chloro-phenyl)-5-(4-hexyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   4-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenoxy}-butyronitrile hydrochloride;   5-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenoxy}-pentanenitrile hydrochloride;   6-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenoxy}-hexanenitrile hydrochloride;   6-{2-(2-Chloro-phenyl)-5-[4-(pyridin-4-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine dihydrochloride;   6-{2-(2-Chloro-phenyl)-5-[2-(pyridin-4-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine dihydrochloride;   6-[2-(2-Chloro-phenyl)-5-(4-phenoxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   6-[2-Biphenyl-4-yl-5-(2-chloro-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine;   6-{2-(2-Chloro-phenyl)-5-[4-(1,2-dihydro-pyridin-3-yl)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine;   6-[2-(2-Chloro-phenyl)-5-(4-pyrimidin-5-yl-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine;   6-[2-(2-Chloro-phenyl)-5-(4-pyridin-3-yl-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine;   6-{2-(2-Chloro-phenyl)-5-[4-(pyrimidin-2-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine hydrochloride;   6-{2-(2-Chloro-phenyl)-5-[4-(thiazol-2-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine hydrochloride;   6-{2-(2-Chloro-phenyl)-5-[4-(pyridazin-3-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine hydrochloride;   6-{2-(2-Chloro-phenyl)-5-[4-(pyrazin-2-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine hydrochloride;   6-{2-(2-Chloro-phenyl)-5-[4-(pyridin-3-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine hydrochloride   6-{2-(2-Chloro-phenyl)-5-[4-(pyrimidin-5-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine hydrochloride;   1-(4-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenoxy}-phenyl)-ethanone hydrochloride;   6-[2-[4-(4-Bromo-phenoxy)-phenyl]-5-(2-chloro-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   6-[2-(2-Chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   6-[2-(2-Chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-3-methoxy-2-nitro-pyridine;   6-[2-(2-Chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-3-methoxy-pyridin-2-ylamine hydrochloride;   3-{6-[2-(2-Chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-3-methoxy-pyridin-2-ylamino}-propan-1-ol hydrochloride;   2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-ol hydrochloride;   6-[2-(2-Chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridine-2,3-diamine hydrochloride;   3-{2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-yloxy}-propan-1-ol hydrochloride;   4-{2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-yloxy}-butyronitrile hydrochloride;   2-{2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-ylamino}-ethanol hydrochloride;   3-{2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-ylamino}-propan-1-ol hydrochloride;   2-{2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-yloxy}-ethanol hydrochloride;   2-{2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-yloxy}-ethanol hydrochloride;   2-{2-Amino-6-[2-(4-bromo-phenyl)-5-(2-chloro-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-yloxy}-ethanol;   {4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenyl}-pyrimidin-5-yl-amine;   2-(2-Amino-6-{2-(2-chloro-phenyl)-5-[4-(pyrimidin-5-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-3-yloxy)-ethanol;   2-(2-Amino-6-{2-(2-chloro-phenyl)-5-[4-(pyrimidin-5-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-3-ylamino)-ethanol;   Pentanoic acid {4-[1-(6-amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenyl}-amide;   6-[2-(2-Chloro-phenyl)-5-(4-pentylamino-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   2-[(2-amino-6-{[2-(2-chlorophenyl)-5-(4-propoxyphenyl)-1H-pyrrol-1-yl]methyl}pyridine-3-yl)oxy]ethanol;   6-[(2,5-diphenyl-1H-pyrrol-1-yl)methyl]pyridin-2-amine;   6-{[2-phenyl-5-(4-propoxyphenyl)-1H-pyrrol-1-yl]methyl}pyridin-2-amine;   Ethyl 4-[1-[(6-aminopyridin-2-yl)methyl]-5-(4-fluorophenyl)-1H-pyrrol-2-yl]benzoate;   Ethyl 4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}benzoate;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-cyclopropylbenzamide;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-ethylbenzamide;   4-[1-[(6-aminopyridin-2-yl)methyl]-5-(4-fluorophenyl)-1H-pyrrol-2-yl]-N-ethylbenzamide;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-isopropylbenzamide;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-butylbenzamide;   N-allyl-4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}benzamide;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-propylbenzamide;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-(tetrahydrofuran-2-ylmethyl)benzamide;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-cyclobutylbenzamide;   a stereoisomer thereof; and   a pharmaceutically acceptable salt thereof.   
   
   
       10 . A method for the treatment of a disease or disorder associated with excessive BACE activity in a patient in need thereof which comprises providing to said patient an effective amount of a compound of formula I 
     
       
         
         
             
             
         
       
     
     wherein
 X is CH 2  or NR; 
 R is H or alkyl; 
 R 1  and R 2  are each independently an alkyl, cycloalkyl, cycloheteroalkyl, phenyl or heteroaryl group each group optionally substituted; 
 R 3  and R 4  are each independently H, halogen, NR 6 R 7 , OR 8 , or an alkyl, haloalkyl or aryl group each group optionally substituted; 
 R 5  is H or an alkyl or haloalkyl group each optionally substituted; 
 R 6  and R 7  are each independently H or an optionally substituted alkyl group; and 
 R 8  is H or an alkyl or alkenyl group each group optionally substituted; or 
 a pharmaceutically acceptable salt thereof. 
 
   
   
       11 . The method according to  claim 10  wherein said disease or disorder is selected from the group consisting of: Alzheimer's disease; cognitive impairment; Down's Syndrome; HCHWA-D; cognitive decline; senile dementia; cerebral amyloid angiopathy; and a neurodegenerative disorders. 
   
   
       12 . The method according to  claim 10  wherein said disease or disorder is characterized by production of β-amyloid deposits or neurofibrillary tangles. 
   
   
       13 . The method according to  claim 12  wherein said disease or disorder is Alzheimer's disease. 
   
   
       14 . The method according to  claim 13  having a formula I compound of the structure 
     
       
         
         
             
             
         
       
       wherein 
       Y is CR 12  or N; 
       R 3 , R 4  and R 5  are as defined for formula I hereinabove; 
       R 9  is H, halogen, OR 12 , CO 2 R 12 , CONHR 12 , NHCOR 12 , or an alkyl, haloalkyl, aryl or heteroaryl group each group optionally substituted; 
       R 10  and R 11  are each independently H, halogen, OR 13 , or an alkyl or haloalkyl group each group optionally substituted; and 
       R 12  and R 13  are each independently H or an optionally substituted alkyl, haloalkyl, cycloheteroalkyl, aryl or heteroaryl group each group optionally substituted. 
     
   
   
       15 . A method for modulating the activity of BACE which comprises contacting a receptor thereof with an effective amount of a compound of formula I 
     
       
         
         
             
             
         
       
     
     wherein
 X is CH 2  or NR; 
 R is H or alkyl; 
 R 1  and R 2  are each independently an alkyl, cycloalkyl, cycloheteroalkyl, phenyl or heteroaryl group each group optionally substituted; 
 R 3  and R 4  are each independently H, halogen, NR 8 R 7 , OR 8 , or an alkyl, haloalkyl or aryl group each group optionally substituted; 
 R 5  is H or an alkyl or haloalkyl group each optionally substituted; 
 R 6  and R 7  are each independently H or an optionally substituted alkyl group; and 
 R 8  is H or an alkyl or alkenyl group each group optionally substituted; or 
 a pharmaceutically acceptable salt thereof. 
 
   
   
       16 . The method according to  claim 15  having a formula I compound wherein the structure is 
     
       
         
         
             
             
         
       
     
     wherein
 Y is CR 12  or N; 
 R 3 , R 4  and R 5  are as defined for formula I hereinabove; 
 R 9  is H, halogen, OR 12 , CO 2 R 12 , CONHR 12 , NHCOR 12 , or an alkyl, haloalkyl, aryl or heteroaryl group each group optionally substituted; 
 R 10  and R 11  are each independently H, halogen, OR 13 , or an alkyl or haloalkyl group each group optionally substituted; and 
 R 12  and R 13  are each independently H or an optionally substituted alkyl, haloalkyl, cycloheteroalkyl, aryl or heteroaryl group each group optionally substituted. 
 
   
   
       17 . A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and an effective amount of a compound of formula I 
     
       
         
         
             
             
         
       
     
     wherein
 X is CH 2  or NR; 
 R is H or alkyl; 
 R 1  and R 2  are each independently an alkyl, cycloalkyl, cycloheteroalkyl, phenyl or heteroaryl group each group optionally substituted; 
 R 3  and R 4  are each independently H, halogen, NR 6 R 7 , OR 8 , or an alkyl, haloalkyl or aryl group each group optionally substituted; 
 R 5  is H or an alkyl or haloalkyl group each optionally substituted; 
 R 6  and R 7  are each independently H or an optionally substituted alkyl group; and 
 R 8  is H or an alkyl or alkenyl group each group optionally substituted; or a pharmaceutically acceptable salt thereof. 
 
   
   
       18 . The composition according to  claim 17  having a formula I compound wherein the structure is 
     
       
         
         
             
             
         
       
     
     wherein
 Y is CR 12  or N; 
 R 3 , R 4  and R 5  are as defined for formula I hereinabove; 
 R 9  is H, halogen, OR 12 , CO 2 R 12 , CONHR 12 , NHCOR 12 , alkyl, haloalkyl, aryl or heteroaryl; 
 R 10  and R 11  are each independently H, halogen, OR 13 , alkyl orhaloalkyl; and 
 R 12  and R 13  are each independently H, alkyl, haloalkyl, cycloheteroalkyl, aryl or heteroaryl. 
 
   
   
       19 . The composition according to  claim 18  having a compound wherein Y is CH; R 4 , R 5 , and R 11  are H; R 3  is H, OR 8  or an optionally substituted alkyl group; R 9  is H, OR 12  or an alkyl, aryl or heteroaryl group each optionally substituted; and R 10  is H, halogen, OR 13  or an optionally substituted alkyl group. 
   
   
       20 . The composition according to  claim 18  having a compound selected from the group consisting of:
 N-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenyl}-3-methyl-benzamide;   N-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenyl}-3-bromo-benzamide;   N-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenyl}-benzamide;   6-[2-(4-bromo-phenyl)-5-(2-chloro-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine;   6-[2-(2-Chloro-phenyl)-5-(4-methoxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine;   4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenol;   6-[2-(2-Chloro-phenyl)-5-(4-propoxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   6-[2-(4-Butoxy-phenyl)-5-(2-chloro-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   6-[2-(2-Chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   6-[2-(2-Chloro-phenyl)-5-(4-hexyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   4-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenoxy}-butyronitrile hydrochloride;   5-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenoxy}-pentanenitrile hydrochloride;   6-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenoxy}-hexanenitrile hydrochloride;   6-{2-(2-Chloro-phenyl)-5-[4-(pyridin-4-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine dihydrochloride;   6-{2-(2-Chloro-phenyl)-5-[2-(pyridin-4-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine dihydrochloride;   6-[2-(2-Chloro-phenyl)-5-(4-phenoxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   6-[2-Biphenyl-4-yl-5-(2-chloro-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine;   6-{2-(2-Chloro-phenyl)-5-[4-(1,2-dihydro-pyridin-3-yl)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine;   6-[2-(2-Chloro-phenyl)-5-(4-pyrimidin-5-yl-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine;   6-[2-(2-Chloro-phenyl)-5-(4-pyridin-3-yl-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine;   6-{2-(2-Chloro-phenyl)-5-[4-(pyrimidin-2-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine hydrochloride;   6-{2-(2-Chloro-phenyl)-5-[4-(thiazol-2-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine hydrochloride;   6-{2-(2-Chloro-phenyl)-5-[4-(pyridazin-3-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine hydrochloride;   6-{2-(2-Chloro-phenyl)-5-[4-(pyrazin-2-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine hydrochloride;   6-{2-(2-Chloro-phenyl)-5-[4-(pyridin-3-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine hydrochloride   6-{2-(2-Chloro-phenyl)-5-[4-(pyrimidin-5-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-2-ylamine hydrochloride;   1-(4-{4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenoxy}-phenyl)-ethanone hydrochloride;   6-[2-[4-(4-Bromo-phenoxy)-phenyl]-5-(2-chloro-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   6-[2-(2-Chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   6-[2-(2-Chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-3-methoxy-2-nitro-pyridine;   6-[2-(2-Chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-3-methoxy-pyridin-2-ylamine hydrochloride;   3-{6-[2-(2-Chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-3-methoxy-pyridin-2-ylamino}-propan-1-ol hydrochloride;   2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-ol hydrochloride;   6-[2-(2-Chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridine-2,3-diamine hydrochloride;   3-{2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-yloxy}-propan-1-ol hydrochloride;   4-{2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-yloxy}-butyronitrile hydrochloride;   2-{2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-ylamino}-ethanol hydrochloride;   3-{2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-ylamino}-propan-1-ol hydrochloride;   2-{2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-yloxy}-ethanol hydrochloride;   2-{2-Amino-6-[2-(2-chloro-phenyl)-5-(4-pentyloxy-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-yloxy}-ethanol hydrochloride;   2-{2-Amino-6-[2-(4-bromo-phenyl)-5-(2-chloro-phenyl)-pyrrol-1-ylmethyl]-pyridin-3-yloxy}-ethanol;   {4-[1-(6-Amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenyl}-pyrimidin-5-yl-amine;   2-(2-Amino-6-{2-(2-chloro-phenyl)-5-[4-(pyrimidin-5-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-3-yloxy)-ethanol;   2-(2-Amino-6-{2-(2-chloro-phenyl)-5-[4-(pyrimidin-5-yloxy)-phenyl]-pyrrol-1-ylmethyl}-pyridin-3-ylamino)-ethanol;   Pentanoic acid {4-[1-(6-amino-pyridin-2-ylmethyl)-5-(2-chloro-phenyl)-1H-pyrrol-2-yl]-phenyl}-amide;   6-[2-(2-Chloro-phenyl)-5-(4-pentylamino-phenyl)-pyrrol-1-ylmethyl]-pyridin-2-ylamine hydrochloride;   2-[(2-amino-6-{[2-(2-chlorophenyl)-5-(4-propoxyphenyl)-1H-pyrrol-1-yl]methyl}pyridine-3-yl)oxy]ethanol;   6-[(2,5-diphenyl-1H-pyrrol-1-yl)methyl]pyridin-2-amine;   6-{[2-phenyl-5-(4-propoxyphenyl)-1H-pyrrol-1-yl]methyl}pyridin-2-amine;   Ethyl 4-[1-[(6-aminopyridin-2-yl)methyl]-5-(4-fluorophenyl)-1H-pyrrol-2-yl]benzoate;   Ethyl 4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}benzoate;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-cyclopropylbenzamide;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-ethylbenzamide;   4-[1-[(6-aminopyridin-2-yl)methyl]-5-(4-fluorophenyl)-1H-pyrrol-2-yl]-N-ethylbenzamide;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-isopropylbenzamide;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-butylbenzamide;   N-allyl-4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}benzamide;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-propylbenzamide;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-(tetrahydrofuran-2-ylmethyl)benzamide;   4-{1-[(6-aminopyridin-2-yl)methyl]-5-phenyl-1H-pyrrol-2-yl}-N-cyclobutylbenzamide;   a stereoisomer thereof; and   a pharmaceutically acceptable salt thereof.