Pyrrolidinium derivatives

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 O—, —S—, —S(O)—, and —S(O) 2 —;

m is an integer from 0 to 8;

R 4 represents a lower alkyl group;

D represents a group of formula i)

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, or - and CH 2 OH;

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; and

X − represents a pharmaceutically acceptable anion of a mono or polyvalent acid;

or an individual stereoisomers of a compound of formula (I) or mixture 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 unsubstituted 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 —O— and —S—.

7. A compound according to claim 6 , wherein A is —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-(3-hydroxyphenoxy)propyl, 3-(4-fluorophenoxy)propyl, 2-benzyloxyethyl, 3-o-tolyloxypropyl, 3-(3-cyanophenoxy)propyl, 3-phenylsulphanylpropyl, 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-(3-hydroxyphenoxy)propyl, and 3-(4-fluorophenoxy)propyl.

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 X − is chosen from chloride, bromide, trifluoroacetate and methanesulphonate.

12. A compound according to claim 1 , wherein the carbon at the 3-position of the pyrrolidinium ring has a R configuration.

13. A compound according to claim 1 , wherein the carbon at the 3-position of the pyrrolidinium ring has a S configuration.

14. 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.

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 S configuration.

16. A compound according to claim 1 wherein said compound is a single isomer.

17. A compound according to claim 1 chosen from:

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-phenoxypropyl)pyrrolidinium bromide;

1-Ethyl-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-[3-(3-hydroxyphenoxy)propyl]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-methylpyrrolidinium 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-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;

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-Cyclohexyl-2-fur-2-yl-2-hydroxyacetoxy)-1-ethyl-1-(3-phenylsulfanylpropyl)pyrrolidinium bromide.

18. A compound according to claim 1 chosen from:

(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-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;

(3S)-3-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-[3-(3-hydroxyphenoxy)propyl]-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)-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.

19. A compound according to claim 1 chosen from:

(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*,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*,3R)-3-[(2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-2-methyl-1-(3-phenoxypropyl)pyrrolidinium bromide (disatereomer 1);

(1*,3R)-3-[(2R)-2-Cyclopentyl-2-hydroxy-2-phenylacetoxy]-1-methyl-1-(3-phenoxypropyl)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-1-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-1-yloxy)propyl]pyrrolidinium bromide (diastereomer 2).

20. A compound chosen from:

2-Hydroxy-2,2-dithien-2-ylacetic acid (3R)-1-(2-phenoxyethyl)pyrrolidin-3-yl ester; and

2-Hydroxy-2,2-dithien-2-ylacetic acid (3R)-1-(3-phenoxypropyl)pyrrolidin-3-yl ester.

21. A compound

(3R)-1-(3-phenoxypropyl)pyrrolidin-3-ol.

22. A pharmaceutical composition comprising a compound as claimed in claim 1 and at least one pharmaceutically acceptable carrier or diluent.

23. A composition according to claim 22 comprising

(i) a compound as claimed in claim 1 ; and

(ii) at least one compound chosen from steroid.