Mannose-derived antagonists of fimh useful for treating disease

Abstract

The present invention relates to mannoside derivative compounds useful as inhibitors of FimH and methods for the treatment or prevention of urinary tract infection.

What is claimed is: 
     
         1 .- 21 . (canceled) 
     
     
         22 . A compound of Formula I: 
       
         
           
           
               
               
           
         
         or a salt, ester, or prodrug thereof, wherein:
 R 1  is chosen from CH 3 , cyclopropyl, CN, CF 3 , OCH 3 , OAc, halogen, NH 2 , and NHR 4 ; 
 R 2  is chosen from H, NO 2 , NH 2 , and NHR 4 ; 
 L is absent, or O, S, and NR x ; 
 R 3  is an aryl, heterocyclyl, or heteroaryl group, any of which may be optionally substituted with cycloalkyl, heterocycloalkyl, halogen, oxo, OR 12 , SR 12 , NHR 12 , CN, COOH, CO 2 alkyl, NO 2 , NHCO-alkyl, SO 2 C 1-4 alkyl, SO 2 cycloalkyl, SO 2 NR 7 R 8 , CONR 7 R 8 , and C 1-4 alkyl, or an aryl or heteroaryl group optionally substituted with one or more of the following: 
 halogen, CN, COOH, NH 2 , CF 3 , NO 2 , and C 1-4 alkyl; 
 each R 4  is independently chosen from alkyl optionally substituted with OH, alkoxy, NH 2 , NHalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl; 
 each R 7  and R 12  is independently chosen from H, aryl, heteroaryl, alkyl optionally substituted with cycloalkyl, heterocycloalkyl, halogen, oxo, OR 12 , SR 12 , NHR 12 , CN, COOH, CO 2 alkyl, NO 2 , NHCO-alkyl, SO 2 C 1-4 alkyl, SO 2 cycloalkyl, SO 2 NR 7 R 8 , CONR 7 R 8 , and C 1-4 alkyl, or an aryl or heteroaryl group optionally substituted with one or more of the following: 
 halogen, CN, COOH, NH 2 , CF 3 , NO 2 , and C 1-4 alkyl; 
 R 8  is chosen from C 2-5 alkyl, aryl, heterocycloalkyl, heteroaryl, and alkylNHCOalkyl-Cyanine5.5; 
 or 
 R 7  and R 8  together form a heterocycloalkyl ring optionally substituted with alkyl; and 
 R x  is H, alkyl optionally substituted with OH, NH 2 , CO 2 H, CONH 2 , CO 2 Me, CN, N 3 , alkoxy, SO 2 alkyl, SO 2 NH 2 , COalkyl, and CONH 2 . 
 
       
     
     
         23 . The compound of  claim 22 , being a compound of Formula II: 
       
         
           
           
               
               
           
         
         or a salt, ester, or prodrug thereof, wherein:
 R 21  is chosen from CH 3 , cyclopropyl, CN, CF 3 , OCH 3 , OAc, halogen, NH 2 , NHR 24 ; 
 R 22  is chosen from H, NO 2 , NH 2 , NHR 24 ; 
 each R 24  is independently chosen from alkyl optionally substituted with OH, alkoxy, NH 2 , NHalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl; 
 and R 25  is an aryl or heteroaryl group optionally substituted with one or more of the following: 
 halogen, CN, COOH, NH 2 , NO 2 , NHCO-alkyl, NHalkyl, SO 2 C 1-4 alkyl, and C 1-4 alkyl. 
 
       
     
     
         24 . The compound of  claim 22 , being a compound of Formula IV: 
       
         
           
           
               
               
           
         
         or a salt, ester, or prodrug thereof, wherein:
 R 41  is chosen from CH 3 , CF 3 , OCH 3 , OAc, halogen, NH 2 , NHR 44 ; 
 R 42  is chosen from H, alkyl, NO 2 , NH 2 , NHR 44 ; 
 each R 44  is independently chosen from alkyl, aryl, and heteroaryl; 
 and R 45  is an alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group optionally substituted with one or more of the following: 
 halogen, CN, COOH, NH 2 , NO 2 , and C 1-4 alkyl. 
 
       
     
     
         25 . A compound of formula V: 
       
         
           
           
               
               
           
         
         or a salt, ester, or prodrug thereof, wherein:
 R 51  is chosen from CH 3 , CF 3 , OCH 3 , OAc, halogen, NH 2 , NHR 54 ; 
 R 52  is chosen from H, NO 2 , NH 2 , NHR 54 , and alkyl; 
 each R 54  is independently chosen from alkyl, COR 510 , SO 2 R 511 , aryl, and heteroaryl; 
 R 56  is chosen from CN, CO 2 alkyl, halogen, aryl, heteroaryl, SO 2 alkyl, SO 2 cycloalkyl, SO 2 NR 57 R 58 , and CONR 57 R 58 ; 
 each R 57  and R 512  is independently chosen from H, alkyl optionally substituted with halogen, CN, COOH, NH 2 , NO 2 , and C 1-4 alkyl, aryl, and heteroaryl; 
 R 58  is chosen from C 2-8 alkyl, aryl, heterocycloalkyl, heteroaryl, and alkylNHCOalkyl-Cyanine5.5; 
 or 
 R 57  and R 58  together form a heterocycloalkyl ring; 
 R 510  and R 511  are each independently selected from alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; 
 R 516  is chosen from H, OR 512 , SR 512 , NHR 512 , COOR 517  and CONR 518 R 519 ; and 
 each of R 517 , R 518 , and R 519  is independently chosen from H, cycloalkyl, aryl, heteroaryl, and heterocycloalkyl and alkyl optionally substituted with halogen, CN, COOH, NH 2 , NO 2 , and C 1-4 alkyl, 
 wherein the compound is not: 
 
         3′-chloro-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-4-carbonitrile, 
         3′-methyl-N-(pyridin-3-yl)-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3-carboxamide, 
         3′-methyl-N-(pyridin-4-yl)-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3-carboxamide, 
         methyl 3′-methoxy-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-4-carboxylate, 
         methyl 3′-methyl-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-4-carboxylate, 
         methyl 3′-fluoro-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-4-carboxylate, 
         3′-fluoro-N 3 ,N 5 -dimethyl-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3,5-dicarboxamide, 
         3′-methoxy-N 3 ,N 5 -dimethyl-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3,5-dicarboxamide, 
         3′-chloro-N 3 N 5 -dimethyl-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3,5-dicarboxamide, 
         N,3′-dimethyl-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3-carboxamide, 
         3′-chloro-N-methyl-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3-carboxamide, 
         methyl 3′-methoxy-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3-carboxylate, 
         methyl 3′-fluoro-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3-carboxylate, 
         methyl 3′-methyl-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3-carboxylate, 
         N 3 ,N 5 ,3′-trimethyl-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3,5-dicarboxamide, 
         (3′-chloro-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-4-yl)(morpholino)methanone, 
         (2R,3S,4S,5S,6R)-2-(3-chloro-4′-(1H-tetrazol-5-yl)biphenyl-4-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, 
         methyl 3′-chloro-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3-carboxylate, 
         methyl 3′-chloro-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-4-carboxylate, 
         methyl 3′-(trifluoromethyl)-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-4-carboxylate, 
         methyl 3′-(trifluoromethyl)-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3-carboxylate, 
         N-methyl-3′-(trifluoromethyl)-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3-carboxamide, 
         N 3 ,N 5 -dimethyl-3′-(trifluoromethyl)-4′-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)biphenyl-3,5-dicarboxamide. 
       
     
     
         26 . A compound of Formula (VI), Formula (VII), Formula (VIII), or Formula (IX): 
       
         
           
           
               
               
           
         
         or a salt, ester, or prodrug thereof, wherein:
 R 61  is chosen from CH 3 , CF 3 , OCH 3 , OAc, halogen, NH 2 , NHR 64 ; 
 R 62  is chosen from H, NO 2 , NH 2 , NHR 64 ; 
 each R 64  is independently chosen from alkyl, aryl, and heteroaryl; 
 R 69  is chosen from COOH, COOalkyl, halogen, or alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl optionally substituted with halo, heteroaryl optionally substituted with halo, and CONR 610 R 611 ; 
 R 610  is chosen from H, alkyl, aryl, and heteroaryl; 
 R 611  is chosen from C 2-8 alkyl, aryl, and heteroaryl; 
 or 
 R 610  and R 611  together form a cycloalkyl or heterocycloalkyl ring; 
 
       
       
         
           
           
               
               
           
         
         or a salt, ester, or prodrug thereof, wherein:
 R 71  is chosen from CH 3 , CF 3 , OCH 3 , OAc, halogen, NH 2 , NHR 74 ; 
 R 72  is chosen from H, NO 2 , NH 2 , NHR 74 ; 
 each R 74  is independently chosen from alkyl, aryl, and heteroaryl; 
 and R 75  is amino, alkyl, or an aryl or heteroaryl group optionally substituted with one or more of the following: 
 halogen, CN, COOH, NH 2 , NO 2 , and C 1-4 alkyl; 
 
       
       
         
           
           
               
               
           
         
         or a salt, ester, or prodrug thereof, wherein:
 “ ” represents a single or double bond; 
 R 81  is chosen from CH 3 , CF 3 , OCH 3 , OAc, halogen, NH 2 , NHR 84 ; 
 R 82  is chosen from H, NO 2 , NH 2 , NHR 84 ; 
 each R 84  is independently chosen from alkyl, aryl, and heteroaryl; 
 X is chosen from H, ═O, —OH, OR 812 ; —NH 2 , and —NHR 812 ; 
 Y is chosen from absent, alkyl, H, and R 813 ; 
 R 86  is chosen from H, CN, COOalkyl, halogen, aryl, heteroaryl, SO 2 alkyl, SO 2 cycloalkyl, SO 2 NR 87 R 88 , and CONR 87 R 88 ; 
 each R 87  and R 814  is independently chosen from H, aryl, heteroaryl, and alkyl optionally substituted with halogen, CN, COOH, NH 2 , CF 3 , NO 2 , and C 1-4 alkyl; 
 R 88  is chosen from C 2-8 alkyl, aryl, heterocycloalkyl, and heteroaryl; 
 or 
 R 87  and R 88  together form a heterocycloalkyl ring; 
 R 816  is chosen from H, OR 814 , SR 814 , NHR 814 , COOR 817  and CONR 818 R 819 ; and 
 each of R 817 , R 818 , and R 819  is independently chosen from H, cycloalkyl, aryl, heteroaryl, heterocycloalkyl and alkyl optionally substituted with halogen, CN, COOH, NH 2 , CF 3 , NO 2 , and C 1-4 alkyl; 
 R 812  is an aryl or heteroaryl group optionally substituted with one or more of the following: 
 halogen, CN, COOH, NO 2 , and C 1-4 alkyl. 
 and R 813  is an aryl or heteroaryl group optionally substituted with one or more of the following: 
 halogen, CN, COOH, NO 2 , and C 1-4 alkyl; 
 wherein the compound of Formula (VIII) is not 
 
         7-(3-methyl-4-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)phenyl)isoquinolin-1 (2H)-one; 
       
       
         
           
           
               
               
           
         
         or a salt, ester, or prodrug thereof, wherein:
 “ ” represents a single or double bond; 
 A is chosen from S, O, NR 917 ; 
 R 91  is chosen from CH 3 , CF 3 , OCH 3 , OAc, halogen, NH 2 , NHR 94 ; 
 R 92  is chosen from H, NO 2 , NH 2 , NHR 94 ; 
 each R 94  is independently chosen from alkyl, aryl, and heteroaryl; 
 each R 915  and R 916  is independently chosen from H, cycloalkyl, aryl, heteroaryl, heterocycloalkyl and alkyl optionally substituted with halogen, CN, COOH, NH 2 , CF 3 , NO 2 , and C 1-4 alkyl; 
 or 
 R 915  and R 916  together form a cycloalkyl, aryl, heterocycloalkyl or heteroaryl ring, optionally substituted with one or more of the following: 
 oxo, halogen, CN, COOH, NH 2 , CF 3 , NO 2 , and C 1-4 alkyl; and 
 R 917  is chosen from absent, H, and alkyl; 
 wherein the compound of Formula (IX) is not: 
 
         1-(3-chloro-4-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)phenyl)-1H-indole-5-carboxylic acid, 
         1-(3-chloro-4-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)phenyl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile, 
         (2R,3S,4S,5S,6R)-2-(2-chloro-4-(5-chloro-1H-pyrrolo[2,3-b]pyridin-1-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, 
         (2R,3S,4S,5S,6R)-2-(hydroxymethyl)-6-(2-methoxy-4-(5-nitro-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, 
         (2R,3S,4S,5S,6R)-2-(2-fluoro-4-(5-nitro-1H-indol-1-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, 
         (2R,3S,4S,5S,6R)-2-(2-fluoro-4-(1H-indol-1-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, 
         (2R,3S,4S,5S,6R)-2-(2-chloro-4-(5-(trifluoromethyl)-1H-indol-1-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, 
         1-(3-chloro-4-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)phenyl)-1H-indole-6-carboxylic acid, 
         (2R,3S,4S,5S,6R)-2-(2-chloro-4-(1H-indol-1-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, 
         (2R,3S,4S,5S,6R)-2-(2-chloro-4-(5-nitro-1H-indol-1-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol. 
       
     
     
         27 . The compound of  claim 26 , being a compound of Formula (VI): 
       
         
           
           
               
               
           
         
         or a salt, ester, or prodrug thereof, wherein:
 R 61  is chosen from CH 3 , CF 3 , OCH 3 , OAc, halogen, NH 2 , NHR 64 ; 
 R 62  is chosen from H, NO 2 , NH 2 , NHR 64 ; 
 each R 64  is independently chosen from alkyl, aryl, and heteroaryl; 
 R 69  is chosen from COOH, COOalkyl, halogen, or alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl optionally substituted with halo, heteroaryl optionally substituted with halo, and CONR 610 R 611 ; 
 R 610  is chosen from H, alkyl, aryl, and heteroaryl; 
 R 611  is chosen from C 2-8 alkyl, aryl, and heteroaryl; 
 or 
 R 610  and R 611  together form a cycloalkyl or heterocycloalkyl ring. 
 
       
     
     
         28 . The compound of  claim 26 , being a compound of Formula (VII): 
       
         
           
           
               
               
           
         
         or a salt, ester, or prodrug thereof, wherein:
 R 71  is chosen from CH 3 , CF 3 , OCH 3 , OAc, halogen, NH 2 , NHR 74 ; 
 R 72  is chosen from H, NO 2 , NH 2 , NHR 74 ; 
 each R 74  is independently chosen from alkyl, aryl, and heteroaryl; 
 and R 75  is amino, alkyl, or an aryl or heteroaryl group optionally substituted with one or more of the following: 
 halogen, CN, COOH, NH 2 , NO 2 , and C 1-4 alkyl. 
 
       
     
     
         29 . The compound of  claim 26 , being a compound of Formula (VIII): 
       
         
           
           
               
               
           
         
         or a salt, ester, or prodrug thereof, wherein:
 “ ” represents a single or double bond; 
 R 81  is chosen from CH 3 , CF 3 , OCH 3 , OAc, halogen, NH 2 , NHR 84 ; 
 R 82  is chosen from H, NO 2 , NH 2 , NHR 84 ; 
 each R 84  is independently chosen from alkyl, aryl, and heteroaryl; 
 X is chosen from H, ═O, —OH, OR 812 ; —NH 2 , and —NHR 812 ; 
 Y is chosen from absent, alkyl, H, and R 813 ; 
 R 86  is chosen from H, CN, COOalkyl, halogen, aryl, heteroaryl, SO 2 alkyl, SO 2 cycloalkyl, SO 2 NR 87 R 88 , and CONR 87 R 88 ; 
 each R 87  and R 814  is independently chosen from H, aryl, heteroaryl, and alkyl optionally substituted with halogen, CN, COOH, NH 2 , CF 3 , NO 2 , and C 1-4 alkyl; 
 R 88  is chosen from C 2-8 alkyl, aryl, heterocycloalkyl, and heteroaryl; 
 or 
 R 87  and R 88  together form a heterocycloalkyl ring; 
 R 816  is chosen from H, OR 814 , SR 814 , NHR 814 , COOR 817  and CONR 818 R 819 ; and 
 each of R 817 , R 818 , and R 819  is independently chosen from H, cycloalkyl, aryl, heteroaryl, heterocycloalkyl and alkyl optionally substituted with halogen, CN, COOH, NH 2 , CF 3 , NO 2 , and C 1-4 alkyl; 
 R 812  is an aryl or heteroaryl group optionally substituted with one or more of the following: 
 halogen, CN, COOH, NO 2 , and C 1-4 alkyl. 
 and R 813  is an aryl or heteroaryl group optionally substituted with one or more of the following: 
 halogen, CN, COOH, NO 2 , and C 1-4 alkyl; 
 wherein the compound is not 
 
         7-(3-methyl-4-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)phenyl)isoquinolin-1 (2H)-one. 
       
     
     
         30 . The compound of  claim 26 , being a compound of Formula (DC): 
       
         
           
           
               
               
           
         
         or a salt, ester, or prodrug thereof, wherein:
 “ ” represents a single or double bond; 
 A is chosen from S, O, NR 917 ; 
 R 91  is chosen from CH 3 , CF 3 , OCH 3 , OAc, halogen, NH 2 , NHR 94 ; 
 R 92  is chosen from H, NO 2 , NH 2 , NHR 94 ; 
 each R 94  is independently chosen from alkyl, aryl, and heteroaryl; 
 each R 915  and R 916  is independently chosen from H, cycloalkyl, aryl, heteroaryl, heterocycloalkyl and alkyl optionally substituted with halogen, CN, COOH, NH 2 , CF 3 , NO 2 , and C 1-4 alkyl; 
 or 
 R 915  and R 916  together form a cycloalkyl, aryl, heterocycloalkyl or heteroaryl ring, optionally substituted with one or more of the following: 
 oxo, halogen, CN, COOH, NH 2 , CF 3 , NO 2 , and C 1-4 alkyl; and 
 R 917  is chosen from absent, H, and alkyl; 
 wherein the compound is not: 
 
         1-(3-chloro-4-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)phenyl)-1H-indole-5-carboxylic acid, 
         1-(3-chloro-4-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)phenyl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile, 
         (2R,3S,4S,5S,6R)-2-(2-chloro-4-(5-chloro-1H-pyrrolo[2,3-b]pyridin-1-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, 
         (2R,3S,4S,5S,6R)-2-(hydroxymethyl)-6-(2-methoxy-4-(5-nitro-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol, 
         (2R,3S,4S,5S,6R)-2-(2-fluoro-4-(5-nitro-1H-indol-1-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, 
         (2R,3S,4S,5S,6R)-2-(2-fluoro-4-(1H-indol-1-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, 
         (2R,3S,4S,5S,6R)-2-(2-chloro-4-(5-(trifluoromethyl)-1H-indol-1-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, 
         1-(3-chloro-4-((2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)phenyl)-1H-indole-6-carboxylic acid, 
         (2R,3S,4S,5S,6R)-2-(2-chloro-4-(1H-indol-1-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, 
         (2R,3S,4S,5S,6R)-2-(2-chloro-4-(5-nitro-1H-indol-1-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol. 
       
     
     
         31 . A method of treatment of a FimH-mediated disease comprising the administration of a therapeutically effective amount of a compound as recited in  claim 22  to a human patient in need thereof. 
     
     
         32 . The method of  claim 31 , wherein said disease is chosen from a bacterial infection, Crohn's disease (CD), and Inflammatory Bowel Disease (IBD). 
     
     
         33 . The method of  claim 32 , wherein said bacterial infection is a urinary tract infection. 
     
     
         34 . The method of  claim 33 , wherein said urinary tract infection is recurrent. 
     
     
         35 . The method of  claim 33 , wherein said urinary tract infection is chronic. 
     
     
         36 . The method of  claim 33 , wherein said bacterial infection is an antibiotic-resistant bacterial infection. 
     
     
         37 . The method of  claim 32 , wherein said disease is Crohn's disease. 
     
     
         38 . The method of  claim 32 , wherein said disease is Inflammatory Bowel Disease.