2-(piperidin-1-yl)-4-heterocyclyl-thiazole-5-carboxylic acid derivatives against bacterial infections

Abstract

Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.

1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         R 1  is chloro or cyano; 
         R 2  is hydrogen, chloro, or cyano; 
         R 3  is halo, C 1-4 alkyl, C 1-4 alkoxy, or allyloxy; 
         R 4  is hydrogen or C 1-4 alkyl; 
         Ring A is selected from formula (a), (b) or (b′): 
       
       
         
           
           
               
               
           
         
         wherein: 
         “*” is the point of attachment to the thiazolyl ring; 
         X is CH, CR 6 , or N; 
         R 5  is H, a C 1-4 alkyl, or C 1-4 alkoxyC 1-4 alkyl; 
         R 6 , for each occurrence is independently selected from halo, —NR 7 R 8 , —OR 8 , and heterocycle wherein said heterocycle comprises at least one nitrogen ring member and is optionally substituted on one or more carbon atoms with one or more R 9  and is optionally substituted on one or more ring nitrogens with R 10 ; 
         R 6′  is hydrogen or R 6 ; 
         R 7  and R 8  are each, independently, selected from the group consisting of hydrogen and a C 1-6 alkyl wherein said alkyl is optionally substituted with one or more independently selected from —OH, N,N-di(C 1-4 alkyl)amino, a C 1-6 alkoxy, a C 1-6 alkoxyC 1-6 alkoxy, and heterocycle, wherein said heterocycle is optionally substituted on one or more carbon atoms with one or more independently selected halo, C 1-6 alkyl, and C 1-6 alkoxy, and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a C 1-4 alkyl; 
         R 9  is, for each occurrence, is independently selected from a C 1-4 alkyl, halo, hydroxy, C 1-4 alkoxy, amino, N—(C 1-4 alkyl)amino, and N,N-di(C 1-4 alkyl)amino; 
         R 10 , for each occurrence, is independently selected from a C 1-4 alkyl optionally substituted with N,N-di(C 1-4 alkyl)amino, —OH, heterocycle, and C 3-6 cycloalkyl, wherein the heterocycle may be optionally substituted with C 1-4 alkyl; and 
         n is 0, 1, 2, or 3. 
       
     
     
         2 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring A is represented by formula (a). 
     
     
         3 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein X is CR 6′ . 
     
     
         4 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein X is N. 
     
     
         5 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from the group consisting of 1-(2-methoxyethyl)-1H-imidazol-2-yl or 1-methyl-1H-1,2,4-triazol-5-yl. 
     
     
         6 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring A is represented by formula (b). 
     
     
         7 . The compound of  claim 6 , or a pharmaceutically acceptable salt thereof, wherein X is CH or CR 6 . 
     
     
         8 . The compound of  claim 6 , or a pharmaceutically acceptable salt thereof, wherein X is N. 
     
     
         9 . The compound of  claim 6 , or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from the group consisting of 3-fluoropyridin-2-yl or pyrazin-2-yl. 
     
     
         10 . The compound of  claim 6 , wherein n is 1 and R 6  is piperidino, piperazinyl, N-methylpiperazino or morpholino. 
     
     
         11 . The compound of  claim 6 , wherein n is 1 and R 6  is selected from 1-(1H-1,2,3-triazol-5-yl)methanamino, 2-(2-oxo-pyrrolidino)ethylamino, 2-methoxyethylamino, 2-(4-fluoropiperidino)ethylamino, 1-(1,3-dioxan-4-yl)-N-methylmethanamino, N-(1-methoxymethyl-2-methoxyethyl)amino, 2-(2-oxo-1,3-oxazolidin-3-yl)-ethylamino, 2-(2-methoxyethoxy)-ethylamino, 4-[2-(diethylamino)ethyl]piperazin-1-yl, 2-(4-methylpiperazin-1-yl)ethylamino, 2-(dimethylamino)ethoxy, 2-(4-methylpiperazin-1-yl)ethoxy, 2-morpholinoethylamino, or 2-(2-oxo-imidazolidin-1-yl)ethylamino. 
     
     
         12 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  is chloro. 
     
     
         13 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2  is hydrogen. 
     
     
         14 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2  is chloro. 
     
     
         15 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3  is selected from methyl, methoxy, ethoxy, or allyloxy. 
     
     
         16 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4  is hydrogen. 
     
     
         17 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4  is methyl or ethyl. 
     
     
         18 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is chloro;   R 2  is hydrogen, chloro or cyano;   R 3  is methyl, ethoxy, or allyloxy;   R 4  is hydrogen, methyl or ethyl;   Ring A is 1-(2-methoxyethyl)-1H-imidazol-2-yl, 1-methyl-1H-1,2,4-triazol-5-yl, 3-fluoropyridin-2-yl or pyrazin-2-yl.   
     
     
         19 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is chloro;   R 2  is hydrogen, chloro or cyano;   R 3  is methyl, ethoxy, or allyloxy;   R 4  is hydrogen, methyl or ethyl;   Ring A is formula (c):   
       
         
           
           
               
               
           
         
         wherein:
 X is CH or N; and 
 
         R 5  is H, a C 1-4 alkyl, or C 1-4 alkoxyC 1-4 alkyl. 
       
     
     
         20 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is chloro;   R 2  is hydrogen, chloro or cyano;   R 3  is methyl, ethoxy, or allyloxy;   R 4  is hydrogen, methyl or ethyl;   Ring A is selected from formula (d) or (e):   
       
         
           
           
               
               
           
         
         wherein:
 X is CH or N; and 
 
         R 6  is a halo. 
       
     
     
         21 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is chloro;   R 2  is hydrogen, chloro or cyano;   R 3  is methyl, methoxy, ethoxy, or allyloxy;   R 4  is hydrogen, methyl or ethyl;   Ring A is selected from formula (d) or (e):   
       
         
           
           
               
               
           
         
         wherein: 
         R 6  is —OR 8  or —NR 7 R 8 ; 
         R 7  is hydrogen or a C 1-4 alkyl; and 
         R 8  is selected from the group consisting of 1-(1H-1,2,3-triazol-5-yl)methyl, 2-(2-oxo-pyrrolidino)ethyl, 2-methoxyethyl, 2-(4-fluoropiperidino)ethyl, 1-(1,3-dioxan-4-yl)-N-methylmethyl, 1-methoxymethyl-2-methoxyethyl, 2-(4-methylpiperazin-1-yl)ethyl, 2-(dimethylamino)ethyl, 2-(4-methylpiperazin-1-yl)ethyl, 2-(2-oxo-1,3-oxazolidin-3-yl)-ethyl, 2-(2-methoxyethoxy)-ethyl, 2-morpholinoethyl, or 2-(2-oxo-imidazolidin-1-yl)ethyl. 
       
     
     
         22 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is chloro;   R 2  is hydrogen, chloro or cyano;   R 3  is methyl, methoxy, ethoxy, or allyloxy;   R 4  is hydrogen, methyl or ethyl;   Ring A is selected from formula (d) or (e):   
       
         
           
           
               
               
           
         
         wherein: 
         R 6  is piperidino, piperazinyl, N-methylpiperazino or morpholino. 
       
     
     
         23 . The compound of  claim 21  or  22 , or a pharmaceutically acceptable salt thereof, wherein R 1  and R 2  are both chloro; and R 3  is methoxy. 
     
     
         24 . A compound selected from the group consisting of:
 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-[1-(2-methoxyethyl)-1H-imidazol-2-yl]-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-[1-(2-methoxyethyl)-1H-imidazol-2-yl]-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-[1-(2-methoxyethyl)-1H-imidazol-2-yl]-1,3-thiazole-5-carboxylic acid;   Ethyl 2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylate;   2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-[1-(2-methoxyethyl)-1H-imidazol-2-yl]-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-[1-(2-methoxyethyl)-1H-imidazol-2-yl]-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylic acid;   2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylic acid;   Methyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylate;   Methyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-[1-(2-methoxyethyl)-1H-imidazol-2-yl]-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylate;   Methyl 2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylate;   Methyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylate;   Methyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-[1-(2-methoxyethyl)-1H-imidazol-2-yl]-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylate;   Methyl 2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylate;   Methyl 2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-[1-(2-methoxyethyl)-1H-imidazol-2-yl]-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylate;   Methyl 2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylate;   Methyl 2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylate;   Methyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylate;   Methyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-[1-(2-methoxyethyl)-1H-imidazol-2-yl]-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylate;   Methyl 2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(1-methyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-5-carboxylate;   Methyl 2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-[1-(2-methoxyethyl)-1H-imidazol-2-yl]-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(3-fluoropyridin-2-yl)-1,3-thiazole-5-carboxylate;   Ethyl 2-[(3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methylpiperidin-1-yl]-4-(pyrazin-2-yl)-1,3-thiazole-5-carboxylate;   2-[(3R,4S)-4-{[(3,4-Dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]-1,3-thiazole-5-carboxylic acid; and   pharmaceutically acceptable salts thereof.   
     
     
         25 . A pharmaceutical composition comprising a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier. 
     
     
         26 . A method of inhibiting bacterial DNA gyrase and/or bacterial topoisomerase IV in a warm-blooded animal in need of such treatment, comprising administering to the animal an effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
         27 . A method of producing an antibacterial effect in a warm-blooded animal in need of such treatment, comprising administering to the animal an effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
         28 . A method of treating a bacterial infection in a warm-blooded animal in need thereof, comprising administering to the animal an effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
         29 . The method of  claim 28 , wherein the bacterial infection is selected from the group consisting of community-acquired  pneumoniae , hospital-acquired  pneumoniae , skin and skin structure infections, acute exacerbation of chronic bronchitis, acute sinusitis, acute otitis media, catheter-related sepsis, febrile neutropenia, osteomyelitis, endocarditis, urinary tract infections and infections caused by drug resistant bacteria such as Penicillin-resistant  Streptococcus pneumoniae , methicillin-resistant  Staphylococcus aureus , methicillin-resistant  Staphylococcus epidermidis  and Vancomycin-Resistant Enterococci.