Amino-5-(5-membered)heteroarylimidazolone Compounds And The Use Thereof For Beta-secretase Modulation

Abstract

The present invention provides a 2-amino-5-heteroaryl-5-phenylimidazolone 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 W is CO, CS or CH 2 ;
 X is N, NR, NO, S, SO m , O or CR 9 ; 
 Y is N, NR, NO, S, SO m , O or CR 10 ; 
 Z is C, N, NR, NO, S, SO m , O, CR 11  or CR 11 R 12  with the proviso that at least one of X, Y or Z must be N, NR, NO, S, SO m  or O; 
 m is 1 or 2; 
 R is H or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl or aryl(C 1 -C 6 )alkyl group each optionally substituted; 
 R 1  and R 2  are each independently H, COR 14 , CO 2 R 15  or an optionally substituted C 1 -C 4 alkyl group; 
 R 3  is H, OR 13  or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl or aryl(C 1 -C 6 )alkyl group each optionally substituted; 
 R 4  R 5 , R 9  and R 10  are each independently H, halogen, NO 2 , CN, OR 14 , CO 2 R 15 , COR 16 , NR 17 R 18 , SO p NR 19 R 20  or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 8 cycloalkyl group each optionally substituted; 
 R 6  and R 8  are each independently H, halogen, NO 2 , CN, OR 21 , NR 22 R 23  or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 8 cycloalkyl group each optionally substituted; 
 R 7  is H, halogen, NO 2 , CN, OR 24 , NR 25 R 26  or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, aryl or heteroaryl group each optionally substituted; 
 R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 21 , R 24 , R 27 , R 28  and R 29  are each independently H or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, cycloheteroalkyl or aryl group each optionally substituted; 
 R 17 , R 18 , R 19 , R 20 , R 22 , R 23 , R 25 , R 26 , R 30 , R 31 , R 32  and R 33  are each independently H, COR 34 , SO p R 35  or a C 1 -C 4 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8  cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or R 17 , R 18 , or R 19 , R 20  or R 22 , R 23 , or R 25 , R 26 , or R 30 , R 31 , or R 32 , R 33  may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing an additional heteroatom selected from O, N or S; 
 R 34  is H, or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted; and 
 R 35  is a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted; or 
 
     a tautomer thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof. 
   
   
       2 . The compound according to  claim 1  wherein W is CO; X is CR 9 ; Y is CR 10  and Z is NR or S. 
   
   
       3 . The compound according to  claim 1  wherein W is CO; X is N; Y is NR and Z is CR 11 R 12 . 
   
   
       4 . The compound according to  claim 1  wherein R 7  is phenyl or heteroaryl. 
   
   
       5 . The compound according to  claim 2  wherein R is H or C 1 -C 4 alkyl and R 4  is CN or COR 16 . 
   
   
       6 . The compound according to  claim 2  wherein R 7  is phenyl or heteroaryl. 
   
   
       7 . The compound according to  claim 3  wherein R 7  is phenyl or heteroaryl. 
   
   
       8 . The compound according to  claim 6  wherein R 1  and R 2  are H; and R 3  is methyl. 
   
   
       9 . The compound according to  claim 1  selected from the group consisting essentially of:
 (5S)-2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   (5S)-2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-(5-propionyl-1-propyl-1H-pyrrol-3-yl)-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-(5-propionyl-1-propyl-1H-pyrrol-3-yl)-3,5-dihydro-4H-imidazol-4-one;   2-Amino-3-methyl-5-(3-pyridin-3-ylphenyl)-5-thien-2-yl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-3-methyl-5-(3-pyridin-3-ylphenyl)-5-thien-3-yl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(2′,5′-difluoro-1,1′-biphenyl-3-yl)-3-methyl-5-thien-2-yl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(2′,5′-difluoro-1,1′-biphenyl-3-yl)-3-methyl-5-thien-3-yl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[5-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-5-(1-isobutyl-1H-pyrazol-4-yl)-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-butyl-1H-pyrazol-4-yl)-5-[3-(2-fluoropyridin-3-yl)phenyl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-isobutyl-1H-pyrazol-4-yl)-3-methyl-5-(3-pyrimidin-5-ylphenyl)-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-butyl-1H-pyrazol-4-yl)-3-methyl-5-(3-pyrimidin-5-ylphenyl)-3,5-4H-imidazol-4-one;   2-Amino-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(4-fluoro-3-pyrimidin-5-ylphenyl)-3-methyl-5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-1H-pyrazol-4-yl)-5-(4-fluoro-3-pyrimidin-5-ylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-1H-pyrazol-4-yl)-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(5-butylthien-2-yl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one;   Methyl 4-[2-amino-4-(4-fluoro-3-pyrimidin-5-ylphenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[(4S)-2-amino-4-(4-fluoro-3-pyrimidin-5-ylphenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[(4R)-2-amino-4-(4-fluoro-3-pyrimidin-5-ylphenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(4-fluoro-3-pyrimidin-5-ylphenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2,2,2-trifluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2,2,2-trifluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-1H-pyrrole-2-carboxylate;   Isopropyl 4-{2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   Methyl 4-{(4S)-2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2,2,2-trifluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{(4R)-2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2,2,2-trifluoroethyl)-1H-pyrrole-2-carboxylate;   4-{2-Amino-4-[4-ethoxy-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-N-methyl-1H-pyrrole-2-carboxamide;   Isopropyl 4-[2-amino-4-(4-fluoro-3-pyrimidin-5-ylphenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   N-{3-[2-Amino-4-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-phenyl}-butyramide;   N-{3-[2-Amino-4-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-phenyl}-propionamide;   N-{3-[2-Amino-4-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-1-methyl-5-4,5-dihydro-1H-imidazol-4-yl]-phenyl}-2-methoxy-acetamide;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-5-(3-propoxyphenyl)-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-5-[3-(pentyloxy)phenyl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(3,3-dimethylbutoxy)phenyl]-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[3-(2-fluoroethoxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(3-butoxyphenyl)-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(cyclopropylmethoxy)phenyl]-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-(3-isobutoxyphenyl )-3-methyl-3,5-dihydro-4H-imidazol-4-one;   4-{3-[2-Amino-4-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-1-methyl-5-oxo-4,5-dihydro-H-imidazol-4-yl]phenoxy}butanenitrile;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[1-(3-methylbutyl)-5-propionyl-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[1-(3-fluoropropyl)-5-propionyl-1H-pyrrol-3-yl]-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-(5-propionyl-1-propyl-1H-pyrrol-3-yl)-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-(5-propionyl-1H-pyrrol-3-yl)-3,5-dihydro-4H-imidazol-4-one;   (5S)-2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   (5R)-2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   5-(5-Acetyl-1-ethyl-1H-pyrrol-3-yl)-2-amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   Methyl 4-{(4S)-2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{(4R)-2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-N-methyl-1H-pyrrole-2-carboxamide;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-N,1-diethyl-1H-pyrrole-2-carboxamide;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-N-propyl-1H-pyrrole-2-carboxamide;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-N-butyl-1-ethyl-1H-pyrrole-2-carboxamide;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-N-isopropyl-1H-pyrrole-2-carboxamide;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-N-cyclopentyl-1-ethyl-1H-pyrrole-2-carboxamide;   2-Amino-5-[1-ethyl-5-(piperidin-1-ylcarbonyl)-1H-pyrrol-3-yl]-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[1-ethyl-5-(morpholin-4-ylcarbonyl)-1H-pyrrol-3-yl]-5-[3-(3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-N,N-dimethyl-1H-pyrrole-2-carboxamide;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-N-(4-fluorobenzyl)-1H-pyrrole-2-carboxamide;   (5S)-2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   Methyl 4-{(4S)-2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-1H-pyrrole-2-carboxylate;   (5S)-5-(5-Acetyl-1-ethyl-1H-pyrrol-3-yl)-2-amino-5-[3-(2-fluoropyridin-3yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[1-ethyl-5-(methylsulfonyl)-1H-pyrrol-3-yl]-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   Methyl 4-[2-amino-1-methyl-5-oxo-4-(3-pyrimidin-5-ylphenyl)-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-4-[3-(6-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(2′,5′-difluorobiphenyl-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(3′,5′-difluorobiphenyl-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(3′-cyanobiphenyl-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(5′-cyano-2′-fluorobiphenyl-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(3′-methoxybiphenyl-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-1-methyl-5-oxo-4-[3′-(trifluoromethoxy)biphenyl-3-yl]-4,5-dihydro-1H-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(3′,4′-difluorobiphenyl-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-4-[3-(1,3-benzodioxol-5-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   4-[2-Amino-4-(3-bromophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-methyl-1H-pyrrole-2-carbonitrile;   4-[2-Amino-4-(3-bromophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carbonitrile;   4-[2-Amino-4-(3-bromophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-propyl-1H-pyrrole-2-carbonitrile;   4-[2-Amino-1-methyl-5-oxo-4-(3-pyrimidin-5-ylphenyl)-4,5-dihydro-1H-imidazol-4-yl]-1-methyl-1H-pyrrole-2-carbonitrile;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-methyl-1H-pyrrole-2-carbonitrile;   4-{2-Amino-4-[3-(2-chloro-5-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-methyl-1H-pyrrole-2-carbonitrile;   4-[2-Amino-1-methyl-5-oxo-4-(3-pyrimidin-5-ylphenyl)-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carbonitrile;   4-[2-Amino-1-methyl-5-oxo-4-(3-pyrimidin-5-ylphenyl)-4,5-dihydro-1H-imidazol-4-yl]-1-propyl-1H-pyrrole-2-carbonitrile;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-propyl-1H-pyrrole-2-carbonitrile;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carbonitrile;   4-{2-Amino-4-[3-(2-chloro-5-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-propyl-1H-pyrrole-2-carbonitrile;   5-(5-Acetyl-1H-pyrrol-3-yl)-2-amino-5-(3-bromophenyl)-3-methyl-3,5-dihydro-imidazol-4-one;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-1H-pyrrole-2-carbaldehyde;   4-[2-Amino-4-(3-bromophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-H-pyrrole-2-carbaldehyde;   4-[2-Amino-4-(3-bromophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-ethyl-1H-pyrrole-2-carbaldehyde;   4-[2-Amino-4-(3-bromophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carbaldehyde;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-1H-pyrrole-2-carbaldehyde;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carbaldehyde;   2-Amino-5-[5-[(diethylamino)methyl]-1-(2-fluoroethyl)-1H-pyrrol-3-yl]-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-{1-(2-fluoroethyl)-5-[(isopropylamino)methyl]-1H-pyrrol-3-yl}-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[1-(2-fluoroethyl)-5-(pyrrolidin-1-ylmethyl)-1H-pyrrol-3-yl]-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[5-[(dimethylamino)methyl]-1-(2-fluoroethyl)-1H-pyrrol-3-yl]-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[5-[(dimethylamino)methyl]-1-(2-fluoroethyl)-1H-pyrrol-3-yl]-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[1-ethyl-5-(1-hydroxypropyl)-1H-pyrrol-3-yl]-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-1H-pyrrole-2-carbaldehyde O-methyloxime hydrochloride;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(3-bromophenyl)-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-3,5-dihydro-4H-imidazol-4-one;   (5S)-2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   (5R)-2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-5-(3-pyrimidin-5-ylphenyl)-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(3′-methoxybiphenyl-3-yl)-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(3′,5′-difluorobiphenyl-3-yl)-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(3′-chlorobiphenyl-3-yl)-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(3′-chloro-4′-fluorobiphenyl-3-yl)-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   3′-{2-Amino-1-methyl-5-oxo-4-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-4,5-dihydro-1H-imidazol-4-yl}biphenyl-3-carbonitrile;   2-Amino-5-(3-bromo-4-fluorophenyl)-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(4-fluoro-3-pyrimidin-5-ylphenyl)-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   a tautomer thereof,   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 a therapeutically effective amount of a compound of formula I 
     
       
         
         
             
             
         
       
     
     wherein W is CO, CS or CH 2 ;
 X is N, NR, NO, S, SO m , O or CR 9 ; 
 Y is N, NR, NO, S, SO m , O or CR 10 ; 
 Z is C, N, NR, NO, S, SO m , O, CR 11  or CR 11 R 12  with the proviso that at least one of X, Y or Z must be N, NR, NO, S, SO m , or O; 
 m is 1 or 2; 
 R is H or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl or aryl(C 1 -C 6 )alkyl group each optionally substituted; 
 R 1  and R 2  are each independently H, COR 14 , CO 2 R 15  or an optionally substituted C 1 -C 4 alkyl group; 
 R 3  is H, OR 13  or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl or aryl(C 1 -C 6 )alkyl group each optionally substituted; 
 R 4 , R 5 , R 9  and R 10  are each independently H, halogen, NO 2 , CN, OR 14 , CO 2 R 15 , COR 16 , NR 17 R 18 , SO p NR 19 R 20  or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 8 cycloalkyl group each optionally substituted; 
 R 6  and R 8  are each independently H, halogen, NO 2 , CN, OR 21 , NR 22 R 23  or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 8 cycloalkyl group each optionally substituted; 
 R 7  is H, halogen, NO 2 , CN, OR 24 , NR 25 R 26  or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, aryl or heteroaryl group each optionally substituted; 
 R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 21 , R 24 , R 27 , R 28  and R 29  are each independently H or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, cycloheteroalkyl or aryl group each optionally substituted; 
 R 17 , R 18 , R 19 , R 20 , R 22 , R 23 , R 25 , R 26 , R 30 , R 31 , R 32  and R 33  are each independently H, COR 34 , SO p R 35  or a C 1 -C 4 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8  cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or R 17 , R 15 , or R 19 , R 20  or R 22 , R 23 , or R 25 , R 26 , or R 30 , R 31 , or R 32 , R 33  may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing an additional heteroatom selected from O, N or S; 
 R 34  is H, or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted; and 
 R 35  is a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted; or 
 a tautomer thereof, a stereoisomer thereof 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 disorder. 
   
   
       12 . The method according to  claim 10  wherein said disease or disorder is characterized by the production of β-amyloid deposits or neurofibrillary tangles. 
   
   
       13 . A method for modulating the activity of BACE which comprises contacting a receptor thereof with an effective amount of a compound of  claim 1 . 
   
   
       14 . A method for the treatment of Alzheimer's disease in a patient in need thereof which comprises providing to said patient an effective amount of a compound of  claim 1 . 
   
   
       15 . A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and an effective amount of a compound of formula I 
     
       
         
         
             
             
         
       
     
     wherein W is CO, CS or CH 2 ;
 X is N, NR, NO, S, SO m , O or CR 9 ; 
 Y is N, NR, NO, S, SO m , O or CR 10 ; 
 Z is C, N, NR, NO, S, SO m , O, CR 11  or CR 11  R 12  with the proviso that at least one of X, Y or Z must be N, NR, NO, S, SO m  or O; 
 m is 1 or 2; 
 R is H or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl or aryl(C 1 -C 6 )alkyl group each optionally substituted; 
 R 1  and R 2  are each independently H, COR 14 , CO 2 R 15  or an optionally substituted C 1 -C 4 alkyl group; 
 R 3  is H, OR 13  or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl or aryl(C 1 -C 6 )alkyl group each optionally substituted; 
 R 4 , R 5 , R 9  and R 10  are each independently H, halogen, NO 2 , CN, OR 14 , CO 2 R 15 , COR 16 , NR 17 R 18 , SO p NR 19 R 20  or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 8 cycloalkyl group each optionally substituted; 
 R 6  and R 8  are each independently H, halogen, NO 2 , CN, OR 21 , NR 22 R 23  or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 8 cycloalkyl group each optionally substituted; 
 R 7  is H, halogen, NO 2 , CN, OR 24 , NR 25 R 26  or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, aryl or heteroaryl group each optionally substituted; 
 R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 21 , R 24 , R 27 , R 28  and R 29  are each independently H or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, cycloheteroalkyl or aryl group each optionally substituted; 
 R 17 , R 18 , R 19 , R 20 , R 22 , R 23 , R 25 , R 26 , R 30 , R 31 , R 32  and R 33  are each independently H, COR 34 , SO p R 35  or a C 1 -C 4 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8  cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or R 17 , R 18 , or R 19 , R 20  or R 22 , R 23 , or R 25 , R 26 , or R 30 , R 31 , or R 32 , R 33  may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing an additional heteroatom selected from O, N or S; 
 R 34  is H, or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted; and 
 R 35  is a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted; or 
 
     a tautomer thereof, a stereoisomer thereof or a pharmaceutically acceptable salt thereof. 
   
   
       16 . The composition according to  claim 15  having a formula I compound wherein W is CO; X is CR 9 ; Y is CR 10  and Z is NR or S. 
   
   
       17 . The composition according to  claim 15  having a formula I compound wherein W is CO; X is N; Y is NR and Z is CR 11 R 12 . 
   
   
       18 . The composition according to  claim 16  having a formula I compound wherein R 7  is phenyl or heteroaryl. 
   
   
       19 . The composition according to  claim 18  having a formula I compound wherein R is H or C 1 -C 4 alkyl; R 4  is COR 16 , R 1  and R 2  are H; and R 3  is methyl 
   
   
       20 . The composition according to  claim 15  having a formula I compound selected from the group consisting essentially of:
 (5S)-2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   (5S)-2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-(5-propionyl-1-propyl-1H-pyrrol-3-yl)-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-(5-propionyl-1-propyl-1H-pyrrol-3-yl)-3,5-dihydro-4H-imidazol-4-one;   2-Amino-3-methyl-5-(3-pyridin-3-ylphenyl)-5-thien-2-yl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-3-methyl-5-(3-pyridin-3-ylphenyl)-5-thien-3-yl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(2′,5′-difluoro-1,1′-biphenyl-3-yl)-3-methyl-5-thien-2-yl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(2′,5′-difluoro-1,1′-biphenyl-3-yl)-3-methyl-5-thien-3-yl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[5-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-5-(1-isobutyl-1H-pyrazol-4-yl)-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-butyl-1H-pyrazol-4-yl)-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-isobutyl-1H-pyrazol-4-yl)-3-methyl-5-(3-pyrimidin-5-ylphenyl)-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-butyl-1H-pyrazol-4-yl)-3-methyl-5-(3-pyrimidin-5-ylphenyl)-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(4-fluoro-3-pyrimidin-5-ylphenyl)-3-methyl-5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-1H-pyrazol-4-yl)-5-(4-fluoro-3-pyrimidin-5-ylphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-1H-pyrazol-4-yl)-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(5-butylthien-2-yl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one;   Methyl 4-[2-amino-4-(4-fluoro-3-pyrimidin-5-ylphenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[(4S)-2-amino-4-(4-fluoro-3-pyrimidin-5-ylphenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[(4R)-2-amino-4-(4-fluoro-3-pyrimidin-5-ylphenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(4-fluoro-3-pyrimidin-5-ylphenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2,2,2-trifluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2,2,2-trifluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-1H-pyrrole-2-carboxylate;   Isopropyl 4-{2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   Methyl 4-{(4S)-2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2,2,2-trifluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{(4R)-2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2,2,2-trifluoroethyl)-1H-pyrrole-2-carboxylate;   4-{2-Amino-4-[4-ethoxy-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-N-methyl-1H-pyrrole-2-carboxamide;   Isopropyl 4-[2-amino-4-(4-fluoro-3-pyrimidin-5-ylphenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   N-{3-[2-Amino-4-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-phenyl}-butyramide;   N-{3-[2-Amino-4-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-phenyl}-propionamide;   N-{3-[2-Amino-4-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-phenyl}-2-methoxy-acetamide;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-5-(3-propoxyphenyl)-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-5-[3-(pentyloxy)phenyl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(3,3-dimethylbutoxy)phenyl]-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[3-(2-fluoroethoxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(3-butoxyphenyl)-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(cyclopropylmethoxy)phenyl]-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-(3-isobutoxyphenyl)-3-methyl-3,5-dihydro-4H-imidazol-4-one;   4-{3-[2-Amino-4-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-1-methyl-5-oxo-4,5-dihydro-H-imidazol-4-yl]phenoxy}butanenitrile;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[1-(3-methylbutyl)-5-propionyl-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[1-(3-fluoropropyl)-5-propionyl-1H-pyrrol-3-yl]-5-[3-(2-fluropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-(5-propionyl-1-propyl-1H-pyrrol-3-yl)-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-(5-propionyl-1H-pyrrol-3-yl)-3,5-dihydro-4H-imidazol-4-one;   (5S)-2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   (5R)-2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   5-(5-Acetyl-1-ethyl-1H-pyrrol-3-yl)-2-amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   Methyl 4-{(4S)-2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{(4R)-2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-N-methyl-1H-pyrrole-2-carboxamide;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-N,1-diethyl-1H-pyrrole-2-carboxamide;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-N-propyl-1H-pyrrole-2-carboxamide;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-N-butyl-1-ethyl-1H-pyrrole-2-carboxamide;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-N-isopropyl-1H-pyrrole-2-carboxamide;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-N-cyclopentyl-1-ethyl-1H-pyrrole-2-carboxamide;   2-Amino-5-[1-ethyl-5-(piperidin-1-ylcarbonyl)-1H-pyrrol-3-yl]-5-[3-(2-fluropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[1-ethyl-5-(morpholin-4-ylcarbonyl)-1H-pyrrol-3-yl]-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-N,N-dimethyl-1H-pyrrole-2-carboxamide;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-N-(4-fluorobenzyl)-1H-pyrrole-2-carboxamide;   (5S)-2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   Methyl 4-{(4S)-2-amino-4-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-1H-pyrrole-2-carboxylate;   (5S)-5-(5-Acetyl-1-ethyl-1H-pyrrol-3-yl)-2-amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[1-ethyl-5-(methylsulfonyl)-1H-pyrrol-3-yl]-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   Methyl 4-[2-amino-1-methyl-5-oxo-4-(3-pyrimidin-5-ylphenyl)-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-4-[3-(6-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(2′,5′-difluorobiphenyl-3-yl)-1-methyl-5-oxo-4,5dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(3′,5′-difluorobiphenyl-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(3′-cyanobiphenyl-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(5′-cyano-2′-fluorobiphenyl-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(3′-methoxybiphenyl-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-1-methyl-5-oxo-4-[3′-(trifluoromethoxy)biphenyl-3-yl]-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-[2-amino-4-(3′,4′-difluorobiphenyl-3-yl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   Methyl 4-{2-amino-4-[3-(1,3-benzodioxol-5-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carboxylate;   4-[2-Amino-4-(3-bromophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-methyl-1H-pyrrole-2-carbonitrile;   4-[2-Amino-4-(3-bromophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carbonitrile;   4-[2-Amino-4-(3-bromophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-propyl-1H-pyrrole-2-carbonitrile;   4-[2-Amino-1-methyl-5-oxo-4-(3-pyrimidin-5-ylphenyl)-4,5-dihydro-1H-imidazol-4-yl]-1-methyl-1H-pyrrole-2-carbonitrile;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-methyl-1H-pyrrole-2-carbonitrile;   4-{2-Amino-4-[3-(2-chloro-5-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-methyl-1H-pyrrole-2-carbonitrile;   4-[2-Amino-1-methyl-5-oxo-4-(3-pyrimidin-5-ylphenyl)-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carbonitrile;   4-[2-Amino-1-methyl-5-oxo-4-(3-pyrimidin-5-ylphenyl)-4,5-dihydro-1H-imidazol-4-yl]-1-propyl-1H-pyrrole-2-carbonitrile;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-propyl-1H-pyrrole-2-carbonitrile;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carbonitrile;   4-{2-Amino-4-[3-(2-chloro-5-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-propyl-1H-pyrrole-2-carbonitrile;   5-(5-Acetyl-1H-pyrrol-3-yl)-2-amino-5-(3-bromophenyl)-3-methyl-3,5-dihydro-imidazol-4-one;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-1H-pyrrole-2-carbaldehyde;   4-[2-Amino-4-(3-bromophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-pyrrole-2-carbaldehyde;   4-[2-Amino-4-(3-bromophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-ethyl-1H-pyrrole-2-carbaldehyde;   4-[2-Amino-4-(3-bromophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-1-(2-fluoroethyl)-1H-pyrrole-2-carbaldehyde;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-1H-pyrrole-2-carbaldehyde;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-(2-fluoroethyl)-1H-pyrrole-2-carbaldehyde;   2-Amino-5-[5-[(diethylamino)methyl]-1-(2-fluoroethyl)-1H-pyrrol-3-yl]-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-{1-(2-fluoroethyl)-5-[(isopropylamino)methyl]-1H-pyrrol-3-yl}-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[1-(2-fluoroethyl)-5-(pyrrolidin-1-ylmethyl)-1H-pyrrol-3-yl]-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[5-[(dimethylamino)methyl]-1-(2-fluoroethyl)-1H-pyrrol-3-yl]-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[5-[(dimethylamino)methyl]-1-(2-fluoroethyl)-1H-pyrrol-3-yl]-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[1-ethyl-5-(1-hydroxypropyl)-1H-pyrrol-3-yl]-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   4-{2-Amino-4-[3-(2-fluoropyridin-3-yl)phenyl]-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl}-1-ethyl-1H-pyrrole-2-carbaldehyde O-methyloxime hydrochloride;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(3-bromophenyl)-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-3,5-dihydro-4H-imidazol-4-one;   (5S)-2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   (5R)-2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(1-ethyl-5-propionyl-1H-pyrrol-3-yl)-3-methyl-5-(3-pyrimidin-5-ylphenyl)-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(3′-methoxybiphenyl-3-yl)-3-methyl-5-[5-propionyl-1-(2,2,2-triflouroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(3′,5′-difluorobiphenyl-3-yl)-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(3′-chlorobiphenyl-3-yl)-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(3′-chloro-4′-fluorobiphenyl-3-yl)-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   3′-{2-Amino-1-methyl-5-oxo-4-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-4,5-dihydro-1H-imidazol-4-yl}biphenyl-3-carbonitrile;   2-Amino-5-(3-bromo-4-fluorophenyl)-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   2-Amino-5-(4-fluoro-3-pyrimidin-5-ylphenyl)-3-methyl-5-[5-propionyl-1-(2,2,2-trifluoroethyl)-1H-pyrrol-3-yl]-3,5-dihydro-4H-imidazol-4-one;   a tautomer thereof,   a stereoisomer thereof; and   a pharmaceutically acceptable salt thereof.