Novel pyrrole derivatives

Abstract

There are provided inter alia compounds of formula (I) wherein R 1 , R 2 , R 3 , R 4a and R 4b are as defined in the specification and their use in therapy, especially in the treatment of bacterial (e.g. pneumococcal) infections.

1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  and R 2  are independently selected from —C(O)NR 5 R 6 , —C(O)OR 7 , CN, —C(O)R 7 , —C(O)NHC(O)R 7 , —NO 2 , —SO 3 R 7 , —SO 2 R 7 , —SOW, —SO 2 NR 5 R 6 , —SO 2 NH—C(O)OR 8 , —POR 21 R 22  and optionally substituted phenyl or heteroaryl; 
         R 3  is optionally substituted phenyl; 
         R 4a  and R 4b  are independently selected from hydrogen; C 1 -C 6  alkyl which alkyl group may optionally be substituted by hydroxyl, COOR 12  or CONR 13 R 14 ; aryl and —C 1 -C 3  alkylaryl in which said aryl groups may be optionally substituted; 
         R 5  and R 6  are independently selected from:
 (a) hydrogen, 
 (b) C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 10  cycloalkyl, C 5 -C 10  cycloalkenyl, heterocyclyl, —C 1 -C 3  alkyl-C 3 -C 10  cycloalkyl, —C 1 -C 3  alkyl-C 5 -C 10  cycloalkenyl or —C 1 -C 3  alkylheterocyclyl, or R 5  and R 6  together with the N to which they are attached may form a 5- or 6-membered heterocyclic ring optionally containing a further heteroatom selected from O, S and NR 9 , in which any of the aforementioned R 5  and R 6  groups may be optionally substituted by a group selected from cyano, C 1 -C 6  alkoxy, C 1 -C 6  fluoroalkoxy, C 1 -C 6  alkyl, C 1 -C 6  fluoroalkyl and —C(O)NR a R b , where R a  and R b  are independently selected from hydrogen and C 1 -C 6  alkyl, and any of the aforementioned R 5  and R 6  groups may be optionally substituted by one or more halogen atoms, and 
 (c) aryl, heteroaryl, C 1 -C 3  alkylaryl and —C 1 -C 3  alkylheteroaryl, said aryl and heteroaryl groups being optionally substituted; 
 
         R 7  is selected from:
 (a) C 1 -C 6  alkyl, C 2 C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 10  cycloalkyl, C 5 -C 10  cycloalkenyl, heterocyclyl, —C 1 -C 3  alkyl-C 3 -C 10  cycloalkyl, —C 1 -C 3  alkyl-C 5 -C 10  cycloalkenyl or —C 1 -C 3  alkylheterocyclyl, in which any of the aforementioned R 7  groups may be optionally substituted by a group selected from cyano, C 1 -C 6  alkoxy, C 1 -C 6  fluoroalkoxy, C 1 -C 6  alkyl, C 1 -C 6  fluoroalkyl and —C(O)NR a R b , where R a  and R b  are independently selected from hydrogen and C 1 -C 6  alkyl, and any of the aforementioned R 7  groups may be optionally substituted by one or more halogen atoms, and 
 (b) aryl, heteroaryl, C 1 -C 3  alkylaryl and —C 1 -C 3  alkylheteroaryl, said aryl and heteroaryl groups being optionally substituted; 
 
         R 8  is C 1 -C 6  alkyl; 
         R 9  is hydrogen, C 1 -C 6  alkyl; —C(O)R 19  or —C(O)OR 11 ; 
         R 10  is C 1 -C 6  alkyl; 
         R 11  is C 1 -C 6  alkyl; 
         R 12  is C 1 -C 6  alkyl; 
         R 13  is hydrogen or C 1 -C 6  alkyl; 
         R 14  is hydrogen or C 1 -C 6  alkyl; and 
         R 21  and R 22  are independently selected from C 1 -C 6  alkyl and C 1 -C 6  hydroxyalkyl; 
         or a pharmaceutically acceptable prodrug derivative thereof, or a pharmaceutically acceptable salt or solvate thereof; 
         provided that the compound is not: 
         a) diethyl 3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
         b) diethyl 3,4-dihydroxy-1-phenyl-1H-pyrrole-2,5-dicarboxylate; 
         c) dimethyl 3,4-dihydroxy-1-(4-bromophenyl)-1H-pyrrole-2,5-dicarboxylate; 
         d) dimethyl 3,4-dihydroxy-1-(4-chlorophenyl)-1H-pyrrole-2,5-dicarboxylate; 
         e) di-tert-butyl 3,4-dihydroxy-1-(4-nitrophenyl)-1H-pyrrole-2,5-dicarboxylate; 
         f) dimethyl 3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
         g) dimethyl 3,4-dihydroxy-1-phenyl-1H-pyrrole-2,5-dicarboxylate; 
         h) diethyl 3,4-bis(acetyloxy)-1-phenyl-1H-pyrrole-2,5-dicarboxylate; or 
         i) dimethyl 3,4-bis(acetyloxy)-1-phenyl-1H-pyrrole-2,5-dicarboxylate. 
       
     
     
         2 . The compound of  claim 1  wherein R 1  and R 2  are independently selected from —C(O)NR 5 R 6 , —C(O)OR 7 , CN, —C(O)R 7 , —C(O)NHC(O)R 7 , —NO 2 , —SO 3 R 7 , —SO 2 R 7 , —SOR 7 , —SO 2 NR 5 R 6 , —SO 2 NH—C(O)OR 8  and optionally substituted phenyl or heteroaryl. 
     
     
         3 - 6 . (canceled) 
     
     
         7 . The compound of  claim 1  wherein R 3  is substituted phenyl or phenyl having a substituent in the meta or para positions relative to the pyrrole ring. 
     
     
         8 . The compound of  claim 7  wherein R 3  is phenyl substituted by one or more substituents independently selected from halo, cyano, hydroxyl, C 1 -C 6  alkoxy, C 1 -C 6  hydroxyalkoxy, C 1 -C 6  fluoroalkoxy, C 1 -C 6  alkyl, C 1 -C 6  fluoroalkyl, —C(O)NR a R b , where R a  and R b  are independently selected from hydrogen and C 1 -C 6  alkyl; —O—R 15  wherein R 15  is —(CH 2 ) x —P(O)(OR 23 ) 2 , where x is 0, 1, 2, 3 or 4 and R 23  is independently selected from hydrogen and C 1 -C 3  alkyl, —(CH 2 ) y —S(O) 2 Me where y is 1, 2, 3 or 4, —C 1 -C 6  alkylheterocyclyl which heterocyclyl group may be optionally substituted by C 1 -C 3  alkyl, —C 1 -C 6  alkylphenyl which phenyl group may be optionally substituted by C 1 -C 3  alkoxy, or phenyl or 5- or 6-membered heteroaryl which phenyl or heteroaryl group may optionally be substituted by a group selected from C 1 -C 4  alkyl and halo; or —(O(CH 2 ) z ) p OR 24 , where each z, which may be the same or different, represents 2 or 3, p represents 1, 2, 3, 4 or 5 and R 24  is hydrogen or C 1 -C 3  alkyl; or two adjacent carbon atoms within R 3  may be linked by —O—CH 2 —O—. 
     
     
         9 . The compound of  claim 8  wherein R 3  is phenyl substituted by 1, 2 or 3 substituents independently selected from:
 (i) C 1 -C 6  alkoxy; —O—R 15  wherein R 15  is —(CH 2 ) x —P(O)(OR 23 ) 2 , where x is 0, 1, 2, 3 or 4 and R 23  is independently selected from hydrogen and C 1 -C 3  alkyl or R 15  is —(CH 2 ) y —S(O) 2 Me, where y is 1, 2, 3 or 4; 
 (ii) halo, cyano, C 1 -C 6  alkoxy, C 1 -C 6  fluoroalkoxy, C 1 -C 6  alkyl, C 1 -C 6  fluoroalkyl and —C(O)NR a R b , where R a  and R b  are independently selected from hydrogen and C 1 -C 6  alkyl; and 
 (iii) —(O(CH 2 ) z ) p OR 24 , where each z, which may be the same or different, represents 2 or 3, p represents 1, 2, 3, 4 or 5 and R 24  is hydrogen or C 1 -C 3  alkyl. 
 
     
     
         10 - 11 . (canceled) 
     
     
         12 . The compound of  claim 1  wherein:
 (i) R 4a  and R 4b  are independently selected from hydrogen or —C 1 -C 3  alkylaryl; 
 (ii) R 5  and R 6  are independently selected from hydrogen, C 1 -C 6  alkyl, aryl or C 1 -C 3  alkylaryl in which said aryl may be optionally substituted, or R 5  and R 6  together with the N to which they are attached form a 5- or 6-membered heterocyclic ring optionally containing a further heteroatom selected from O, S and NR 9  or R 5  and R 6  are or not both hydrogen; or 
 (iii) R 7  is C 1 -C 6  alkyl. 
 
     
     
         13 - 16 . (canceled) 
     
     
         17 . The compound of  claim 1  which is selected from the list consisting of:
 N 2 ,N 2 ,N 5 ,N 5 -tetraethyl-1-(4-fluorophenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxamide; 
 1-(4-ethoxyphenyl)-N 2 ,N 2 ,N 5 ,N 5 -tetraethyl-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxamide; 
 N 2 ,N 2 ,N 5 ,N 5 -tetraethyl-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxamide; 
 (3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-diyl)bis(morpholinomethanone); 
 3,4-dihydroxy-1-(4-methoxyphenyl)-N 2 ,N 2 ,N 5 ,N 5 -tetramethyl-1H-pyrrole-2,5-dicarboxamide; 
 (1-(4-fluorophenyl)-3,4-dihydroxy-1H-pyrrole-2,5-diyl)bis(morpholinomethanone); 
 1-(4-fluorophenyl)-3,4-dihydroxy-N 2 ,N 5 -dimethyl-N 2 ,N 5 -diphenyl-1H-pyrrole-2,5-dicarboxamide; 
 1-(4-fluorophenyl)-3,4-dihydroxy-N 2 ,N 2 ,N 5 ,N 5 -tetramethyl-1H-pyrrole-2,5-dicarboxamide; 
 di-tert-butyl-(4-fluorophenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarbonyl)bis(piperazine-1-carboxylate); 
 1,1′-(4,4′-(1-(4-fluorophenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarbonyl)bis(piperazine-4,1-diyl))diethanone; 
 (1-(4-fluorophenyl)-3,4-dihydroxy-1H-pyrrole-2,5-diyl)bis(piperidin-1-ylmethanone); 
 ethyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 1-(4-fluorophenyl)-3,4-dihydroxy-N 2 ,N 5 -diisopropyl-N 2 ,N 5 -dimethyl-1H-pyrrole-2,5-dicarboxamide; 
 N 2 ,N 5 -dibenzyl-1-(4-fluorophenyl)-3,4-dihydroxy-N 2 ,N 5 -dimethyl-1H-pyrrole-2,5-dicarboxamide; di-tert-butyl 4,4′-(3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarbonyl)bis(piperazine-1-carboxylate); 
 (3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-diyl)bis(piperazin-1-ylmethanone); 
 1-(4-fluorophenyl)-3,4-dihydroxy-N 2 ,N 2 ,N 5 ,N 5 -tetraisopropyl-1H-pyrrole-2,5-dicarboxamide; 
 (3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-diyl)bis(piperidin-1-ylmethanone); 
 3,4-dihydroxy-1-(2-methoxyphenyl)-N 2 ,N 2 ,N 5 ,N 5 -tetramethyl-1H-pyrrole-2,5-dicarboxamide; 
 (3,4-dihydroxy-1-(2-methoxyphenyl)-1H-pyrrole-2,5-diyl)bis(morpholinomethanone); 
 1-(4-ethoxyphenyl)-3,4-dihydroxy-N 2 ,N 2 ,N 5 ,N 5 -tetramethyl-1H-pyrrole-2,5-dicarboxamide; 
 (1-(4-ethoxyphenyl)-3,4-dihydroxy-1H-pyrrole-2,5-diyl)bis(morpholinomethanone); 
 (3,4-dihydroxy-1-(4-(trifluoromethyl)phenyl)-1H-pyrrole-2,5-diyl)bis(morpholinomethanone); 
 N 2 -ethyl-3,4-dihydroxy-1-(4-methoxyphenyl)-N 5 ,N 5 -dimethyl-1H-pyrrole-2,5-dicarboxamide; 
 3,4-dihydroxy-1-(4-methoxyphenyl)-N,N-dimethyl-5-(piperidine-1-carbonyl)-1H-pyrrole-2-carboxamide; 
 3,4-dihydroxy-1-(4-methoxyphenyl)-N,N-dimethyl-5-(morpholine-4-carbonyl)-1H-pyrrole-2-carboxamide; 
 3,4-dihydroxy-1-(4-methoxyphenyl)-N,N-dimethyl-5-(4-methylpiperazine-1-carbonyl)-1H-pyrrole-2-carboxamide; 
 3,4-dihydroxy-N 2 ,N 2 ,N 5 ,N 5 -tetramethyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrrole-2,5-dicarboxamide; 
 1-(4-(dimethylcarbamoyl)phenyl)-3,4-dihydroxy-N 2 ,N 2 ,N 5 ,N 5 -tetramethyl-1H-pyrrole-2,5-dicarboxamide; 
 tert-butyl (5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrol-2-yl)sulfonylcarbamate; 
 5-cyano-3,4-dihydroxy-1-(4-methoxyphenyl)-N,N-dimethyl-1H-pyrrole-2-carboxamide; 
 ethyl 5-(dimethylcarbamoyl)-1-(4-fluorophenyl)-3,4-dihydroxy-1H-pyrrole-2-carboxylate; 
 1,1′-(4,4′-(3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarbonyl)bis(piperazine-4,1-diyl))diethanone; 
 3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarbonitrile; 
 isopropyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 tert-butyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 3,4-dihydroxy-1-(4-methoxyphenyl)-5-(4-methylpiperazine-1-carbonyl)-1H-pyrrole-2-carboxylate; 
 ethyl 5-(dibutylcarbamoyl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 5-cyano-1-(4-fluorophenyl)-3,4-dihydroxy-1H-pyrrole-2-carboxylate; 
 ethyl 3,4-dihydroxy-1-(4-methoxyphenyl)-5-(morpholine-4-carbonyl)-1H-pyrrole-2-carboxylate; 
 ethyl 5-(diethylcarbamoyl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-iodophenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(3-iodo-4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 3,4-bis(benzyloxy)-1-(4-ethoxyphenyl)-N 2 ,N 2 ,N 5 ,N 5 -tetraethyl-1H-pyrrole-2,5-dicarboxamide; 
 3,4-bis(benzyloxy)-N 2 ,N 2 ,N 5 ,N 5 -tetraethyl-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxamide; 
 3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-N 2 ,N 2 ,N 5 ,N 5 -tetramethyl-1H-pyrrole-2,5-dicarboxamide; 
 di-tert-butyl 4,4′-(3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarbonyl)bis(piperazine-1-carboxylate); 
 (3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-1H-pyrrole-2,5-diyl)bis(piperidin-1-ylmethanone); 
 3,4-bis(benzyloxy)-1-(2-methoxyphenyl)-N 2 ,N 2 ,N 5 ,N 5 -tetramethyl-1H-pyrrole-2,5-dicarboxamide; 
 (3,4-bis(benzyloxy)-1-(2-methoxyphenyl)-1H-pyrrole-2,5-diyl)bis(morpholinomethanone); 
 3,4-bis(benzyloxy)-1-(4-ethoxyphenyl)-N 2 ,N 2 ,N 5 ,N 5 -tetramethyl-1H-pyrrole-2,5-dicarboxamide; 
 (3,4-bis(benzyloxy)-1-(4-ethoxyphenyl)-1H-pyrrole-2,5-diyl)bis(morpholinomethanone); 
 3,4-bis(benzyloxy)-N 2 ,N 2 ,N 5 ,N 5 -tetramethyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrrole-2,5-dicarboxamide; 
 3,4-bis(benzyloxy)-N 2 -ethyl-1-(4-methoxyphenyl)-N 5 ,N 5 -dimethyl-1H-pyrrole-2,5-dicarboxamide; 
 3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-N,N-dimethyl-5-(4-methylpiperazine-1-carbonyl)-1H-pyrrole-2-carboxamide; 
 3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-N,N-dimethyl-5-(piperidine-1-carbonyl)-1H-pyrrole-2-carboxamide; 
 3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-N,N-dimethyl-5-(morpholine-4-carbonyl)-1H-pyrrole-2-carboxamide; 
 1,1′-(4,4′-(3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarbonyl)bis(piperazine-4,1-diyl))diethanone; 
 ethyl 3,4-bis(benzyloxy)-5-cyano-1-(4-fluorophenyl)-1H-pyrrole-2-carboxylate; 
 3,4-bis(benzyloxy)-5-cyano-1-(4-fluorophenyl)-N,N-dimethyl-1H-pyrrole-2-carboxamide; 
 ethyl 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-iodophenyl)-1H-pyrrole-2-carboxylate; 
 3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxamide; 
 3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxamide; 
 3,4-bis(benzyloxy)-N 2 ,N 5 -diethyl-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxamide; 
 3,4-bis(benzyloxy)-1-(4-fluorophenyl)-1H-pyrrole-2,5-dicarboxamide; 
 1-(4-fluorophenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxamide; 
 1-(4-ethoxyphenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxamide; 
 1-(4-ethoxyphenyl)-N 2 ,N 5 -diethyl-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxamide; 
 ethyl 3,4-bis(benzyloxy)-5-carbamoyl-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 5-carbamoyl-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 3,4-bis(benzyloxy)-5-(2-methoxyphenyl)-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-5-(pyridin-2-yl)-1H-pyrrole-2-carboxylate; 
 ethyl 3,4-dihydroxy-1-(4-methoxyphenyl)-5-(pyridin-2-yl)-1H-pyrrole-2-carboxylate; 
 ethyl 3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-5-(pyridin-4-yl)-1H-pyrrole-2-carboxylate; 
 ethyl 3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-5-(pyridin-3-yl)-1H-pyrrole-2-carboxylate; 
 ethyl 5-(4-ethylthiazol-2-yl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-5-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrrole-2-carboxylate; 
 ethyl 3,4-bis(benzyloxy)-5-(5-ethyl-1,3,4-oxadiazol-2-yl)-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 3,4-dihydroxy-1-(4-methoxyphenyl)-5-(2H-tetrazol-5-yl)-1H-pyrrole-2-carboxylate; 
 ethyl 3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-5-(2H-tetrazol-5-yl)-1H-pyrrole-2-carboxylate; 
 diethyl 1-(4-fluorophenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(3-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(4-(trifluoromethoxy)phenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(4-isopropylphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(4-phenoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 1-(4-ethoxyphenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 1-(4-ethylphenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(p-tolyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 1-(3,4-dimethoxyphenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 1-(4-chlorophenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(4-(trifluoromethyl)phenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(3,4,5-trimethoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 1-(2,4-dimethoxyphenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(4-propoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 1-(4-ethoxy-3,5-difluorophenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(3-phenoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 1-(benzo[d][1,3]dioxol-5-yl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxylate; 
 diisopropyl 3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 2-ethyl 5-isopropyl 3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 di-tert-butyl 3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(2-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 1-(4-cyanophenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 1-(4-fluorophenyl)-3-hydroxy-4-(2-hydroxyethoxy)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3-hydroxy-4-(2-hydroxyethoxy)-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3-(2-(tert-butoxy)-2-oxoethoxy)-1-(4-fluorophenyl)-4-hydroxy-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3-(benzyloxy)-4-(2-(tert-butoxy)-2-oxoethoxy)-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3-(2-amino-2-oxoethoxy)-1-(4-fluorophenyl)-4-hydroxy-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3-(2-(tert-butoxy)-2-oxoethoxy)-4-hydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3-(2-amino-2-oxoethoxy)-4-hydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 1-(4-(tert-butyl)phenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(3-iodo-4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate; 
 5-acetyl-3,4-dihydroxy-1-(4-methoxyphenyl)-N,N-dimethyl-1H-pyrrole-2-carboxamide; 
 ethyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-(2-methoxyethoxy)phenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 3-((diethoxyphosphoryl)oxy)-5-(dimethylcarbamoyl)-4-hydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 1-(4-(2,5,8,11-tetraoxatridecan-13-yloxy)phenyl)-5-(dimethylcarbamoyl)-3,4-dihydroxy-1H-pyrrole-2-carboxylate; 
 ethyl 3,4-dihydroxy-1-(4-methoxyphenyl)-5-(methylcarbamoyl)-1H-pyrrole-2-carboxylate; 
 ethyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-hydroxyphenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-(phosphonooxy)phenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-(3-morpholinopropoxy)phenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 1-(4-(3-(diethoxyphosphoryl)propoxy)phenyl)-5-(dimethylcarbamoyl)-3,4-dihydroxy-1H-pyrrole-2-carboxylate; 
 (3-(4-(2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-3,4-dihydroxy-1H-pyrrol-1-yl)phenoxy)propyl)phosphonic acid; 
 ethyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-(3-(methylsulfonyl)propoxy)phenyl)-1H-pyrrole-2-carboxylate; 
 neopentyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 2,6-dimethylcyclohexyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 cyclopentyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 5-(dimethylphosphoryl)-3,4-dihydroxy-1-(4-methoxyphenyl)-N,N-dimethyl-1H-pyrrole-2-carboxamide; 
 diethyl 3,4-dihydroxy-1-(4-(2-methoxyethoxy)phenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(4-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 1-(4-(2,5,8,11-tetraoxatridecan-13-yloxy)phenyl)-3,4-dihydroxy-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(4-(3-morpholinopropoxy)phenyl)-1H-pyrrole-2,5-dicarboxylate; 
 diethyl 3,4-dihydroxy-1-(4-((4-methoxybenzyl)oxy)phenyl)-1H-pyrrole-2,5-dicarboxylate; 
 or a pharmaceutically acceptable prodrug derivative of any one thereof; and 
 pharmaceutically acceptable salts and solvates of any one thereof. 
 
     
     
         18 . The compound of  claim 1  in the form of a prodrug derivative. 
     
     
         19 . The compound of  claim 18  wherein the prodrug derivative is selected from carboxylate ester, sulfamate ester, phosphate ester and carbamate ester derivatives. 
     
     
         20 . (canceled) 
     
     
         21 . The compound of  claim 19  wherein one or both of R 4a  and R 4b  are independently selected from —C(O)R 16 , —SO 2 NH 2 , —PO(OR 19 )(OR 20 ), —CHR 26 —OPO(OR 19 )(OR 20 ) where R 26  is hydrogen or C 1 -C 6  alkyl, and —C(O)NR 17 R 18 , wherein R 16 , R 17 , R 18 , R 19  and R 20  are independently selected from:
 (a) C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 10  cycloalkyl, C 5 -C 10  cycloalkenyl, heterocyclyl, —C 1 -C 3  alkyl-C 3 -C 10  cycloalkyl, —C 1 -C 3  alkyl-C 5 -C 10  cycloalkenyl or —C 1 -C 3  alkylheterocyclyl, or R 17  and R 18  together with the N to which they are attached may form a 5- or 6-membered heterocyclic ring optionally containing a further heteroatom selected from O, S and NR 25a R 25b  where R 25a  is hydrogen, C 1 -C 6  alkyl, —CH 2 —OPO(OR 19 )(OR 20 ) or a 5- or 6-membered heterocyclic ring, and R 25b  is absent or C 1 -C 6  alkyl; and in which any of the aforementioned R 16 , R 17  or R 18  groups may be optionally substituted by one or more groups selected from cyano, —OPO(OR 19 )(OR 20 ), —(O(CH 2 ) z ) r OR 24 , wherein each z, which may be the same or different, represents 2 or 3, r represents an integer selected from 1 to 20, and R 24  is hydrogen, C 1 -C 3  alkyl or —PO(OR 19 )(OR 2 ), C 1 -C 6  alkoxy, C 1 -C 6  fluoroalkoxy, C 1 -C 6  alkyl, C 1 -C 6  fluoroalkyl and —C(O)NR a R b , where R a  and R b  are independently selected from hydrogen and C 1 -C 6  alkyl, and any of the aforementioned R 16 , R 17  or R 18  groups may be optionally substituted by one or more halogen atoms; and 
 (b) aryl, heteroaryl, C 1 -C 3  alkylaryl and —C 1 -C 3  alkylheteroaryl, said aryl and heteroaryl groups being optionally substituted; 
 
       or R 18 , R 19  and R 20  may independently represent hydrogen. 
     
     
         22 . The compound of  claim 19  wherein one or both of R 4a  and R 4b  are independently selected from —C(O)R 16 , —SO 2 NH 2 , —PO(OR 19 )(OR 20 ) and —C(O)NR 17 R 18 , wherein R 16 , R 17 , R 18 , R 19  and R 20  are independently selected from
 (a) C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 10  cycloalkyl, C 5 -C 10  cycloalkenyl, heterocyclyl, —C 1 -C 3  alkyl-C 3 -C 10  cycloalkyl, —C 1 -C 3  alkyl-C 5 -C 10  cycloalkenyl or —C 1 -C 3  alkylheterocyclyl, in which any of the aforementioned R 16 , R 17  or R 18  groups may be optionally substituted by a group selected from cyano, C 1 -C 6  alkoxy, C 1 -C 6  fluoroalkoxy, C 1 -C 6  alkyl, C 1 -C 6  fluoroalkyl and —C(O)NR a R b , where R a  and R b  are independently selected from hydrogen and C 1 -C 6  alkyl, and any of the aforementioned R 16 , R 17  or R 18  groups may be optionally substituted by one or more halogen atoms, and 
 (b) aryl, heteroaryl, C 1 -C 3  alkylaryl and —C 1 -C 3  alkylheteroaryl, said aryl and heteroaryl groups being optionally substituted; 
 
       or R 18 , R 19  and R 20  may independently represent hydrogen. 
     
     
         23 . The compound of  claim 19  wherein:
 (i) both of R 4a  and R 4b  are independently selected from —C(O)R 16 , —SO 2 NH 2 , —PO(OR 19 )(OR 20 ), or —CHR 26 —OPO(OR 19 )(OR 20 ) where R 26  is hydrogen or C 1 -C 6  alkyl, and —C(O)NR 17 R 18 ; or 
 (ii) one of R 4a  and R 4b  is selected from —C(O)R 16 , —SO 2 NH, —PO(OR 19 )(OR 20 ), or —CHR 26 —OPO(OR 19 )(OR 20 ) where R 26  is hydrogen or C 1 -C 6  alkyl, and —C(O)NR 17 R 18 ; and the other of R 4a  and R 4b  is hydrogen. 
 
     
     
         24 - 25 . (canceled) 
     
     
         26 . The compound of  claim 23  wherein R 16  is C 1 -C 6  alkyl or C 3 -C 10  cycloalkyl in which either of the aforementioned groups may be optionally substituted by a group selected from —OPO(OR 19 )(OR 20 ) and —(O(CH 2 ) z ) r OR 24 , where each z, which may be the same or different, represents 2 or 3, r represents an integer selected from 1 to 20, and R 24  is hydrogen, C 1 -C 3  alkyl or —PO(OR 19 )(OR 20 ) or R 16  is phenyl optionally substituted by —(CHR 26 ) q —OPO(OR 19 )(OR 20 ) wherein q represents 0 or 1. 
     
     
         27 . The compound of  claim 18  selected from the list consisting of:
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl diacetate; 
 ethyl 5-(dimethylcarbamoyl)-3,4-bis((dimethylcarbamoyl)oxy)-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(4-methylpiperazine-1-carboxylate); 
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis([1,4′-bipiperidine]-1′-carboxylate); 
 ethyl 5-(dimethylcarbamoyl)-4-((dimethylcarbamoyl)oxy)-3-hydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(2-methylpropanoate); 
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(2,2-dimethylpropanoate); 
 ethyl 5-(dimethylcarbamoyl)-3-hydroxy-1-(4-methoxyphenyl)-4-(sulfamoyloxy)-1H-pyrrole-2-carboxylate; 
 ethyl 5-(dimethylcarbamoyl)-3-hydroxy-1-(4-methoxyphenyl)-4-(phosphonooxy)-1H-pyrrole-2-carboxylate; 
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-4-hydroxy-1-(4-methoxyphenyl)-1H-pyrrol-3-yl[1,4′-bipiperidine]-1′-carboxylate; 
 ethyl 3,4-bis((diethoxyphosphoryl)oxy)-5-(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 3-((diethoxyphosphoryl)oxy)-5-(dimethylcarbamoyl)-4-hydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 ethyl 4-((diethoxyphosphoryl)oxy)-5-(dimethylcarbamoyl)-3-hydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate; 
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)phenyl)-1H-pyrrole-3,4-diyl bis(2-methylpropanoate); 
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(3-methoxypropanoate); 
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(3-(2-methoxyethoxy)propanoate); 
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(3-(2-methoxyethoxy)-2,2-dimethylpropanoate); 
 ethyl 5-(dimethylcarbamoyl)-3-hydroxy-1-(4-methoxyphenyl)-4-((phosphonooxy)methoxy)-1H-pyrrole-2-carboxylate; 
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(3-(2-(2-methoxyethoxy)ethoxy)-2,2-dimethylpropanoate); 
 2,5-bis(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(2-methylpropanoate); 
 ethyl 5-(dimethylcarbamoyl)-4-hydroxy-1-(4-methoxyphenyl)-3-((phosphonooxy)methoxy)-1H-pyrrole-2-carboxylate; 
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(2,2-dimethyl-3-(2-(2-(phosphonooxy)ethoxy)ethoxy)propanoate); 
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(2,2-dimethyl-3-(3-(phosphonooxy)propoxy)propanoate); 
 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(25,25-dimethyl-2,5,8,11,14,17,20,23-octaoxahexacosan-26-oate); 
 2,5-bis(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(25,25-dimethyl-2,5,8,11,14,17,20,23-octaoxahexacosan-26-oate); 
 2,5-bis(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(2,2-dimethyl-3-(2-(2-(phosphonooxy)ethoxy)ethoxy)propanoate); 
 2-(dimethylcarbamoyl)-5-(isopropoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(2,2-dimethyl-3-(2-(2-(phosphonooxy)ethoxy)ethoxy)propanoate); 
 2,5-bis(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(piperidine-4-carboxylate); 
 2,5-bis(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(4-((phosphonooxy)methyl)benzoate); 
 (1R,1′R,4R,4′R)-2,5-bis(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(4-((phosphonooxy)methyl)cyclohexanecarboxylate); 
 and pharmaceutically acceptable salts and solvates of any one thereof. 
 
     
     
         28 . The compound of  claim 1  which is ethyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate, or a pharmaceutically acceptable prodrug derivative, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         29 . A pharmaceutical composition comprising a compound according to  claim 1 , without provisos a) to i), optionally in combination with one or more pharmaceutically acceptable diluents or carriers. 
     
     
         30 . The pharmaceutical composition of  claim 29  comprising one or more other therapeutically active ingredients. 
     
     
         31 . A method of treatment of bacterial infections caused by bacteria producing pore-forming toxins which comprises administering to a subject in need thereof an effective amount of:
 (i) a compound according to  claim 1  without provisos a) to i); or   (ii) diethyl 3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylate or a pharmaceutically acceptable prodrug derivative thereof, or a pharmaceutically acceptable salt or solvate thereof.   
     
     
         32 . (canceled) 
     
     
         33 . The method according toot  claim 31  wherein the bacterial infection is:
 (i) caused by  Streptococcus  spp.,  Clostridium  spp.,  Listeria  spp.,  Bacillus  spp., or  Streptococcus pneumoniae ; or 
 (ii) is selected from the group consisting of pneumococcal pneumonia, pneumococcal meningitis, pneumococcal septicaemia/bacteraemia, pneumococcal keratitis, pneumococcal otitis media, gas gangrene, gastrointestinal anthrax, inhalational anthrax, porcine meningitis, encephalitis, septicaemia/bacteraemia, and pneumonia. 
 
     
     
         34 - 36 . (canceled) 
     
     
         37 . The method of  claim 31  wherein:
 (i) the compound is administered to the subject in combination with one or more other therapeutically active ingredients; 
 (ii) the compound and the one or more other therapeutically active ingredients are administered to the subject in separate formulations; or 
 (iii) the compound is administered to the subject in combination with one or more antibiotic agents selected from the group consisting of a β-lactam, a β-lactam in combination with a β-lactamase inhibitor, a cephalosporin a fluoroquinolone, a tetracycline, a macrolide antibiotic a lipopeptide antibiotic an aminoglycoside antibiotic, a glycopeptide antibiotic, a lincosamide antibiotic, and a rifamycin. 
 
     
     
         38 . (canceled) 
     
     
         39 . The method of  claim 31  wherein the one or more other therapeutically active ingredients is one or more antimicrobial or immunomodulatory agents. 
     
     
         40 . (canceled) 
     
     
         41 . The method of  claim 31  wherein the subject is a human.