New pyrrolidinium derivatives

Abstract

New pyrrolidinium derivatives having the chemical structure of general formula (I) are disclosed; as well as processes for their preparation, pharmaceutical compositions comprising them and their use in therapy as antagonists of M3 muscarinic receptors.

1 . A compound of formula (I):  
     
       
         
         
             
             
         
       
     
     wherein 
 B represents a group chosen from phenyl, naphthalenyl, 5,6,7,8-tetrahydronaphthalenyl, benzo[1,3]dioxolyl, biphenyl, and a 5 to 10-membered heteroaromatic group containing one or more heteroatoms chosen from N, O and S;  
 R 1 , R 2  and R 3  each independently represent a group chosen from a hydrogen atom, a halogen atom, hydroxy, phenyl, —OR 5 , —SR 5 , —NR 5 R 6 , —NHCOR 5 , —CONR 5 R 6 , —CN, —NO 2 , —COOR 5 —CF 3 , a straight optionally substituted lower alkyl group, and a branched optionally substituted lower alkyl group;  
 or R 1  and R 2  together form an aromatic or alicyclic ring or a heterocyclic group;  
 R 5  and R 6  each independently represent a group chosen from a hydrogen atom, a straight optionally substituted lower alkyl group and a branched optionally substituted lower alkyl group, or R 5  and R 6  together form an alicyclic ring;  
 n is an integer from 0 to 4;  
 A represents a group chosen from —CH 2 —, —CH═CR 7 —, —CR 7 ═CH—, —CR 7 R 8 —, —CO—, —O—, —S—, —S(O)—, —S(O) 2 — and —NR 7 —, wherein R 7  and R 8  each independently represent a group chosen from hydrogen atom, a straight optionally substituted lower alkyl group and a branched optionally substituted lower alkyl group, or R 7  and R 8  together form an alicyclic ring;  
 m is an integer from 0 to 8;  
 R 4  represents a lower alkyl group;  
 D represents a group of formula i) or ii)  
                     
 wherein  
 R 9  represents a group chosen from phenyl, 2-furyl, 3-furyl, 2-thienyl and 3-thienyl;  
 R 10  represents a group chosen from phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl and C 3 -C 7  cycloalkyl;  
 and R 11  represents a group chosen from a hydrogen atom, hydroxy, methyl, and CH 2 OH group;  
 wherein each of the cyclic groups represented by R 9  and R 10  is independently optionally substituted by one or two substituents chosen from halogen, straight optionally substituted lower alkyl, branched optionally substituted lower alkyl, hydroxy, optionally substituted lower alkoxy, nitro, cyano, —CO 2 R 12  and —NR 12 R 13 , wherein R 12  and R 13  are identical or different and are each independently chosen from a hydrogen atom, straight optionally substituted lower alkyl groups and branched optionally substituted lower alkyl groups;  
 Q represents a single bond or a group chosen from —CH 2 —, —CH 2 —CH 2 —, —O—, —O—CH 2 —, —S—, —S—CH 2 — and —CH═CH;  
 X −  represents a pharmaceutically acceptable anion of a mono or polyvalent acid;  
 or an individual stereoisomer of a compound of formula (I) or a mixtures of stereoisomers of a compound of formula (I);  
 with the proviso that in those compounds of formula (I) wherein B is phenyl, R 9  is unsubstituted phenyl, R 10  is unsubstitued phenyl or unsubstituted C 3 -C 7  cycloalkyl, and R 11  is hydrogen or hydroxy, the sequence —(CH 2 ) n —A—(CH 2 ) m — is not one of methylene, ethylene or propylene.  
 
   
   
       2 . A compound according to  claim 1 , wherein B represents a group chosen from phenyl, pyrrolyl, thienyl, furyl, biphenyl, naphthalenyl, 5, 6, 7, 8-tetrahydronaphthalenyl, benzo[1,3]dioxolyl, imidazolyl and benzothiazolyl.  
   
   
       3 . A compound according to  claim 2 , wherein B represents a group chosen from phenyl, thienyl and pyrrolyl.  
   
   
       4 . A compound according to  claim 1 , wherein R 1 , R 2  and R 3  each independently represents a group chosen from a hydrogen atom, a halogen atom, hydroxy, methyl, tert-butyl, —CH 2 OH, 3-hydroxypropyl, —OMe, —NMe 2 , —NHCOMe, —CONH 2 , —CN, —NO 2 , —COOMe and —CF 3 .  
   
   
       5 . A compound according to  claim 4 , wherein R 1 , R 2  and R 3  each independently represents a group chosen from hydrogen, fluorine, chlorine and hydroxy.  
   
   
       6 . A compound according to  claim 1 , wherein n=0 or 1; m is an integer from 1 to 6; and A represents a group chosen from —CH 2 —, —CH═CH—, —CO—, —NMe—, —O— and —S—.  
   
   
       7 . A compound according to  claim 6 , wherein A is a group chosen from —CH 2 —, —CH═CH— and —O—.  
   
   
       8 . A compound according to  claim 6 , wherein the pyrrolidinium group is substituted on the nitrogen atom with a C 1 -C 4  alkyl group and another group chosen from 3-phenoxypropyl, 2-phenoxyethyl, 3-phenylallyl, phenethyl, 3-phenylpropyl, 3-(3-hydroxyphenoxy)propyl, 3-(4-fluorophenoxy)propyl, 3-thien-2-ylpropyl, 4-oxo-4-thien-2-ylbutyl, 2-benzyloxyethyl, 3-o-tolyloxypropyl, 3-(3-cyanophenoxy)propyl, 3-(methylphenylamino)propyl, 3-phenylsulphanylpropyl, 4-oxo-4-phenylbutyl, 4-(4-fluorophenyl)-4-oxobutyl, 3-(2-chlorophenoxy)propyl, 3-(2,4-difluorophenoxy)propyl, 3-(4-methoxyphenoxy)propyl, and 3-(benzo[1,3]dioxol-5-yloxy)propyl.  
   
   
       9 . A compound according to  claim 8  wherein the pyrrolidinium group is substituted on the nitrogen atom with a C 1 -C 4  alkyl group and another group chosen from 3-phenoxypropyl, 2-phenoxyethyl, 3-phenylallyl, phenethyl, 3-phenylpropyl, 3-(3-hydroxyphenoxy)propyl, 3-(4-fluorophenoxy)propyl, 4-(4-fluorophenyl)-4-oxobutyl and 3-thien-2-ylpropyl.  
   
   
       10 . A compound according to  claim 1 , wherein D is a group of formula i), and wherein R 9  is a group chosen from phenyl, 2-thienyl and 2-furyl; R 10  is a group chosen from phenyl, 2-thienyl, cyclohexyl and cyclopentyl; and R 11  is a hydroxy group.  
   
   
       11 . A compound according to  claim 1 , wherein D is a group of formula ii), and wherein Q is a single bond or an oxygen atom and R 11  is a hydrogen atom or a hydroxy group.  
   
   
       12 . A compound according to  claim 1 , wherein X −  is chosen from chloride, bromide, trifluoroacetate and methanesulphonate.  
   
   
       13 . A compound according to  claim 1 , wherein the carbon at the 3-position of the pyrrolidinium ring has a R configuration.  
   
   
       14 . A compound according to  claim 1 , wherein the carbon at the 3-position of the pyrrolidinium ring has a S configuration.  
   
   
       15 . A compound according to  claim 1 , wherein D is a group of formula i) and the carbon substituted by R 9 , R 10  and R 11  has a R configuration.  
   
   
       16 . A compound according to  claim 1 , wherein D is a group of formula i) and the carbon substituted by R 9 , R 10  and R 11  has a S configuration.  
   
   
       17 . A compound according to  claim 1 , wherein said compound is a single isomer.  
   
   
       18 . A compound according to  claim 1  chosen from: 
 3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-phenethylpyrrolidinium trifluoroacetate;    3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(2-phenoxyethyl)pyrrolidinium bromide;    3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(3-thien-2-ylpropyl)pyrrolidinium bromide;    3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(3-phenoxypropyl) pyrrolidinium bromide;    3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(-3-phenylallyl)pyrrolidinium trifluoroacetate;    3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(4-oxo-4-thien-2-ylbutyl)pyrrolidinium trifluoroacetate;    1-[4-(4-Fluorophenyl)-4-oxobutyl]-3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-methylpyrrolidinium trifluoroacetate;    1Ethyl-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-[3-(3-hydroxyphenoxy)propyl]pyrrolidinium trifluoroacetate;    3-(2-Hydroxy-2,2-dithien-2-yl-acetoxy)-1-methyl-1-(3-pyrrol-1-ylpropyl)pyrrolidinium trifluoroacetate;    3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-[6-(4-phenylbutoxy)hexyl]pyrrolidinium trifluoroacetate;    1-(2-Benzyloxyethyl )-3-(2-cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy)-1-methylpyrrolidinium trifluoroacetate;    1-[3-(3-Cyanophenoxy)propyl]-3-(2-cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy)-1-methyl pyrrolidinium trifluoroacetate;    3-(2-Cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy)-1-methyl-1-[3-(naphthalen-1-yloxy)propyl]pyrrolidinium trifluoroacetate;    3-(2-Cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy)-1-methyl-1-[3-(methylphenylamino)propyl]pyrrolidinium trifluoroacetate;    3-(2-Cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy)-1-ethyl-1-(3-phenylsulphanylpropyl)pyrrolidinium trifluoroacetate;    1-[3-(Benzothiazol-2-yloxy)propyl]-3-(2-cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy)-1-methylpyrrolidinium trifluoroacetate;    3-(2-Cyclopentyl-2-hydroxy-2-phenylacetoxy)-1-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide;    3-(2-Cyclopentyl-2-hydroxy-2-phenylacetoxy)-1-methyl-1-[3-(2,4,6-trimethylphenoxy)propyl]pyrrolidinium trifluoroacetate;    1-[3-(2-Chlorophenoxy)propyl]-3-(2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1-methylpyrrolidinium trifluoroacetate;    3-(2-Cyclopentyl-2-hydroxy-2-phenylacetoxy)-1-methyl-1-[3-(3-trifluoromethylphenoxy)propyl]pyrrolidinium trifluoroacetate;    1-[3-(Biphenyl-4-yloxy)propyl]-3-(2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1-methylpyrrolidinium trifluoroacetate;    3-(2-Cyclopentyl-2-hydroxy-2-phenylacetoxy)-1-[3-(2,4-difluorophenoxy)propyl]-1-methylpyrrolidinium trifluoroacetate;    3-(2-Cyclopentyl-2-hydroxy-2-phenylacetoxy)-1-ethyl-1-[3-(4-methoxyphenoxy)propyl]-pyrrolidinium trifluoroacetate;    3-(2-Cyclopentyl-2-hydroxy-2-phenylacetoxy)-1-methyl-1-[3-(5,6,7,8-tetrahydronaphthalen-2-yloxy)propyl]pyrrolidinium trifluoroacetate;    3-(2-Cyclopentyl-2-hydroxy-2-phenylacetoxy)-1-methyl-1-[3-( 1-methyl-1H-imidazol-2-ylsulphanyl)propyl]pyrrolidinium trifluoroacetate;    1-Methyl-1-phenethyl-3-(9H-xanthen-9-ylcarbonyloxy)pyrrolidinium bromide;    1-Methyl-1-(3-phenoxypropyl)-3-(9H-xanthen-9-ylcarbonyloxy)pyrrolidinium bromide;    1-[3-(Benzo[1,3]dioxol-5-yloxy)propyl]-1-methyl-3-(9H-xanthen-9-ylcarbonyloxy)pyrrolidinium trifluoroacetate;    1-[3-(2-Carbamoylphenoxy)propyl]-1-methyl-3-(9H-xanthen-9-ylcarbonyloxy)pyrrolidinium trifluoroacetate;    1-[3-(3-Dimethylaminophenoxy)propyl]-1-methyl-3-(9H-xanthen-9-ylcarbonyloxy)pyrrolidinium trifluoroacetate;    1-[3-(4-Acetylaminophenoxy)propyl]-1-methyl-3-(9H-xanthen-9-ylcarbonyloxy)pyrrolidinium trifluoroacetate;    1-[3-(4-Methoxycarbonylphenoxy)propyl]-1-methyl-3-(9H-xanthen-9-ylcarbonyloxy)pyrrolidinium trifluoroacetate;    1-Methyl-1-[3-(4-nitrophenoxy)propyl]-3-(9H-xanthen-9-ylcarbonyloxy)pyrrolidinium trifluoroacetate;    1-[3-(4-Hydroxymethylphenoxy)propyl]-1-methyl-3-(9H-xanthen-9-ylcarbonyloxy)pyrrolidinium trifluoroacetate;    3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-[3-(3-hydroxyphenoxy)propyl]-1-methylpyrrolidinium formate,    1-[3-(4-Fluorophenoxy)propyl]-3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-methylpyrrolidinium chloride;    3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(3-phenylpropyl)pyrrolidinium bromide;    1-Methyl-1-(3-o-tolyloxypropyl )-3-[(9H-xanthen-9-ylcarbonyl )oxy]pyrrolidinium bromide;    3-{[(9-hydroxy-9H-fluoren-9-yl)carbonyl]oxy}-1-methyl-1-(4-oxo-4-phenylbutyl)pyrrolidinium formate; and    3-(2-Cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy)-1-ethyl-1-(3-phenylsulfanylpropyl)pyrrolidinium bromide.    
   
   
       19 . A compound according to  claim 1  chosen from: 
 (3R)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-phenethylpyrrolidinium bromide;    (3S)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-phenethylpyrrolidinium bromide;    (3R)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(2-phenoxyethyl)pyrrolidinium bromide;    (3S)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(2-phenoxyethyl)pyrrolidinium bromide;    (3R)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(3-thien-2-ylpropyl)pyrrolidinium bromide;    (3R)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide;    (3S)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide;    (3R)-3-[(2R)-2-Cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy]-1-ethyl-1-(3-phenylsulphanylpropyl)pyrrolidinium trifluoroacetate;    (3S)-3-[(2R)-2-Cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy]-1-ethyl-1-(3-phenylsulphanylpropyl)pyrrolidinium trifluoroacetate;    (3R)-3-[(2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide;    (3S)-3-[(2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide;    (3R)-3-[(2S)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide;    (3S)-3-[(2S)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide;    (3R)-1-Methyl-1-phenethyl-3-(9H-xanthen-9-ylcarbonyloxy)pyrrolidinium bromide;    (3S)-1-Methyl-1-phenethyl-3-(9H-xanthen-9-ylcarbonyloxy)pyrrolidinium bromide;    (3S)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-[3-(3-hydroxyphenoxy)propyl]-1-methylpyrrolidinium formate;    (3R)-3-{[(9-hydroxy-9H-fluoren-9-yl)carbonyl]oxy}-1-methyl-1-(4-oxo-4-phenylbutyl)pyrrolidinium formate;    (3R)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(4-oxo-4-thien-2-ylbutyl)pyrrolidinium chloride;    (3R)-1-[4-(4-Fluorophenyl)-4-oxobutyl]-3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-methylpyrrolidinium formate;    (3R)-1-[3-(3-Cyanophenoxy)propyl]-3-(2-cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy)-1-methylpyrrolidinium formate;    (3R)-3-(2-Cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy)-1-methyl-1-[3-(naphthalen-1-yloxy)propyl]pyrrolidinium formate;    (3R)-3-(2-Cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy)-1-methyl-1-[3-(methylphenylamino)propyl]pyrrolidinium chloride;    (3 R)-1-[3-(Benzothiazol-2-yloxy)propyl]-3-(2-cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy)-1-methylpyrrolidinium chloride;    (3R)-1-[3-(Biphenyl-4-yloxy)propyl]-3-[(2R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methylpyrrolidinium chloride;    (3R)-3-[(2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methyl-1-[3-(5,6,7,8-tetrahydronaphthalen-2-yloxy)propyl]pyrrolidinium bromide;    (3R)-3-[(2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methyl-1-[3-(1-methyl-1H-imidazol-2-ylsulfanyl)propyl]pyrrolidinium chloride;    (3R)-1-[3-(2-Chlorophenoxy)propyl]-3-[(2R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methylpyrrolidinium chloride;    3-[(2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-ethyl-1-[3-(4-methoxyphenoxy)propyl]pyrrolidinium bromide; and    (3R)-1-(2-Benzyloxyethyl)-3-(2-cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy)-1-methylpyrrolidinium bromide.    
   
   
       20 . A compound according to  claim 1  chosen from: 
 (1*,3R)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-phenethylpyrrolidinium bromide (diastereomer 1);    (1*,3R)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-phenethylpyrrolidinium bromide (diastereomer 2);    (1*,3R)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(2-phenoxyethyl)pyrrolidinium bromide (diastereomer 1);    (1*,3R)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(2-phenoxyethyl)pyrrolidinium bromide (diastereomer 2);    (1*,3S)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(2-phenoxyethyl)pyrrolidinium bromide (diastereomer 1);    (1*,3S)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(2-phenoxyethyl)pyrrolidinium bromide (diastereomer 2);    (1*,3R)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide (diastereomer 1);    (1*,3R)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide (diastereomer 2);    (1*,3S)-3-[(2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide (diastereomer 1);    (1*,3S)-3-[(2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide (diastereomer 2);    (1*,3R)-1-Methyl-1-phenethyl-3-(9H-xanthen-9-ylcarbonyloxy)pyrrolidinium bromide (diastereomer 1);    (1*,3R)-1-Methyl-1-phenethyl-3-(9H-xanthen-9-ylcarbonyloxy)pyrrolidinium bromide (diastereomer 2);    (1*,3R)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(3-phenylallyl)pyrrolidinium bromide (diastereomer 1);    (1*,3R)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(3-phenylallyl)pyrrolidinium bromide (diastereomer 2);    (1*,3R)-1-[4-(4-Fluorophenyl)-4-oxobutyl]-3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-methylpyrrolidinium chloride (diastereomer 1);    (1*,3S)-1-[3-(4-Fluorophenoxy)propyl]-3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-methylpyrrolidinium chloride (diastereomer 1);    (1*,3S)-1-[3-(4-Fluorophenoxy)propyl]-3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-methylpyrrolidinium chloride (diastereomer 2);    (1*,3S)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(3-phenylpropyl)pyrrolidinium bromide (diastereomer 1);    (1*,3S)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-methyl-1-(3-phenylpropyl)pyrrolidinium bromide (diastereomer 2);    (1*,3R)-3-[(2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide (diastereomer 1);    (1*,3R)-3-[(2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide (diastereomer 2);    (1*,3R)-1-[3-(Benzo[1,3]dioxol-5-yloxy)propyl]-1-methyl-3-[(9H-xanthen-9-ylcarbonyl)oxy]pyrrolidinium bromide (diastereomer 1);    (1*,3R)-1-[3-(Benzo[1,3]dioxol-5-yloxy)propyl]-1-methyl-3-[(9H-xanthen-9-ylcarbonyl)oxy]pyrrolidinium bromide (diastereomer 2);    (1*,3S)-1-Methyl-1-(3-o-tolyloxypropyl)-3-[(9H-xanthen-9-ylcarbonyl)oxy]pyrrolidinium bromide (diastereomer 1);    (1*,3S)-1-Methyl-1-(3-o-tolyloxypropyl)-3-[(9H-xanthen-9-ylcarbonyl)oxy]pyrrolidinium bromide (diastereomer 2);    (1*,3R)-1-[3-(Biphenyl-4-yloxy)propyl]-3-[(2R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methylpyrrolidinium chloride (diastereomer 1);    (1*,3R)-1-[3-(Biphenyl-4-yloxy)propyl]-3-[(2R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methylpyrrolidinium chloride (diastereomer 2);    (1*,3R)-3-[(2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methyl-1-[3-(5,6,7,8-tetrahydronaphthalen-2-yloxy)propyl]pyrrolidinium bromide (diastereomer 1); and    (1*,3R)-3-[(2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methyl-1-[3-(5,6,7,8-tetrahydronaphthalen-2-yloxy)propyl]pyrrolidinium bromide (diastereomer 2).    
   
   
       21 . A process for producing a compound of formula (I), as claimed in  claim 1 , comprising reacting an alkylating agent of formula R4-W with an intermediate of formula (II)  
     
       
         
         
             
             
         
       
     
     wherein W is a leaving group.  
   
   
       22 . A process according to  claim 21 , wherein the compound of formula (II) is obtained by reaction of a compound of formula (V)  
     
       
         
         
             
             
         
       
     
     wherein L is a leaving group, with a compound of formula (VI).  
     
       
         
         
             
             
         
       
     
   
   
       23 . A compound chosen from: 
 2-Hydroxy-2,2-dithien-2-ylacetic acid (3R)-1-(2-phenoxyethyl)pyrrolidin-3-yl ester;    2-Hydroxy-2,2-dithien-2-ylacetic acid (3R)-1-(3-phenoxypropyl)pyrrolidin-3-yl ester;    2-Hydroxy-2,2-dithien-2-ylacetic acid (3R)-1-(3-thien-2-yl propyl)pyrrolidin-3-yl ester; and    2-Hydroxy-2,2-dithien-2-ylacetic acid (3R)-1- phenethylpyrrolidin-3-yl ester.    
   
   
       24 . A compound chosen from: 
 (3R)-1-(3-phenoxypropyl)pyrrolidin-3-ol and    (3R)-1-(3-thien-2-ylpropyl)pyrrolidin-3-ol.    
   
   
       25 . A process for producing a compound as claimed in  claim 1 , comprising 
 reacting an alkylating agent of formula (IV)                          wherein W represents a leaving group, with an intermediate of formula (III)                          
   
   
       26 . A pharmaceutical composition comprising a compound as claimed in  claim 1  and at least one pharmaceutically acceptable carrier or diluent.  
   
   
       27 - 29 . (canceled)  
   
   
       30 . A method for treating a subject afflicted with a pathological condition or disease susceptible to amelioration by antagonism of M3 muscarinic receptors, comprising administering to said subject an effective amount of a compound as claimed in  claim 1 .  
   
   
       31 . A method according to  claim 30  wherein the pathological condition is a respiratory, urological or gastrointestinal disease or disorder.  
   
   
       32 . A composition comprising 
 (i) a compound as claimed in  claim 1;  and    (ii) a compound effective in the treatment of a respiratory, urological or gastrointestinal disease or disorder.    
   
   
       33 . A composition according to  claim 32  comprising 
 (i) a compound as claimed in  claim 1;  and    (ii) at least one compound chosen from: a ∃2 agonist, steroid, antiallergic drug, phosphodiesterase IV inhibitor and a leukotriene D4 (LTD4) antagonist.    
   
   
       34 . A pharmaceutical composition according to  claim 26 , wherein the composition is an admixture.