1,1′-(1,2-ethynediyl)bis-benzene derivatives as PTP 1-B inhibitors

1. A carboxylic acid of formula (I):

as well as its geometrical isomers, its optically active forms as enantiomers, diastereomers and its racemate forms, as well as pharmaceutically acceptable salts thereof, wherein

A is selected from the group consisting of C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkyl amine, C 1 -C 6 -alkyl alkoxy, aryl, heteroaryl, saturated or unsaturated 3-8-membered cycloalkyl, 3-8-membered heterocycloalkyl, C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, C 2 -C 6 -alkenyl aryl, C 2 -C 6 -alkenyl heteroaryl, C 2 -C 6 -alkynyl aryl, C 2 -C 6 -alkynyl heteroaryl, C 1 -C 6 -alkyl cycloalkyl, C 1 -C 6 -alkyl heterocycloalkyl, C 2 -C 6 -alkenyl cycloalkyl, C 2 -C 6 -alkenyl heterocycloalkyl, C 2 -C 6 -alkynyl cycloalkyl, C 2 -C 6 -alkynyl heterocycloalkyl;

R 1 is selected from the group consisting of H, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, halogen;

B is selected from the group consisting of:

D is either selected from the group consisting of

with m being an integer selected from 0, 1 or 2 and n being an integer selected from 1 or 2; or D is

with n being an integer selected from 0 or 1;

R is selected from the group consisting of C 1 -C 8 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkyl amine, C 1 -C 6 -alkyl alkoxy, aryl, heteroaryl, saturated or unsaturated 3-8-membered cycloalkyl, 3-8-membered heterocycloalkyl, C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, C 2 -C 6 -alkenyl aryl, C 2 -C 6 -alkenyl heteroaryl, C 2 -C 6 -alkynyl aryl, C 2 -C 6 -alkynyl heteroaryl, C 1 -C 6 -alkyl cycloalkyl, C 1 -C 6 -alkyl heterocycloalkyl, C 2 -C 6 -alkenyl cycloalkyl, C 2 -C 6 -alkenyl heterocycloalkyl, C 2 -C 6 -alkynyl cycloalkyl, C 2 -C 6 -alkynyl heterocycloalkyl; and

R 3 is H, or C 1 -C 6 -alkyl;

with the proviso that when B is an amide B3, R is not be a phenyl—optionally fused with a heterocycloalkyl—substituted by one or 2 moieties selected from hydroxy, C 1 -C 6 alkyl, carboxy, C 1 -C 6 alkoxy, C 1 -C 3 alkyl carboxy, C 2 -C 3 alkenyl carboxy, C 2 -C 3 alkynyl carboxy or amino.

2. A carboxylic acid according to claim 1 , having the formula

whereby A, B and D are as defined in claim 1 .

3. A carboxylic acid according to claim 1 , wherein R 1 is H.

4. A carboxylic acid according to claim 1 , wherein A is an aryl moiety, in particular a phenyl group, optionally substituted by a C 1 -C 8 -alkyl, a halogen or an alkoxy.

5. A carboxylic acid according to claim 4 , wherein A is a phenyl group substituted by a C 1 -C 4 -alkyl or a halogen.

6. A carboxylic acid according to claim 1 , wherein B is any of

whereby R is as defined in claim 1 .

7. A carboxylic acid according to claim 6 , wherein B is B1.

8. A carboxylic acid according to claim 1 , wherein D is either of

9. A carboxylic acid according to claim 1 , wherein D is

10. A carboxylic acid according to claim 1 , wherein R is a C 4 -C 6 -alkyl.

11. A carboxylic acid according to claim 1 , wherein A is a phenyl group substituted by a C 1 -C 4 -alkyl or a halogen, B is B1, R is a C 4 -C 6 -alkyl and D is

12. A carboxylic acid according to claim 1 , selected from the group consisting of:

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]-2-hydroxybenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol) salt,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]-2-hydroxybenzoic acid, hydrochloride salts,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]-2-hydroxybenzoic acid, lysine salt,

5-({4-[(4-Butylphenyl)ethynyl]benzyl}{[(E)-2-phenylvinyl]sulfonyl}amino)-2-hydroxybenzoic Acid,

4-({{4-[(4-Butylphenyl)ethynyl]benzyl}[2-(4-chlorophenyl)ethyl]amino}-methyl)benzoic acid, hydrochloride salt,

{4-[({[(4-tert-Butylphenyl)amino]carbonyl}{4-[(4-butylphenyl)ethynyl]-benzyl}amino)methyl]phenoxy}acetic acid,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(3-phenylpropyl)amino]-2-hydroxy-benzoic acid, hydrochloride salt,

{4-[({4-[(4-Butylphenyl)ethynyl]benzyl}{[(E)-2-phenylvinyl]sulfonyl}-amino) methyl]phenoxy}acetic acid,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(1-naphthylmethyl)amino]-2-hydroxy-benzoic acid, hydrochloride salt,

[4-({{4-[(4-Butylphenyl)ethynyl]benzyl}[(cyclohexylamino)carbonyl]amino}methyl)phenoxy]acetic acid,

[4-({{4-[(4-Butylphenyl)ethynyl]benzyl}[(cyclohexylamino)carbonyl]-amino}methyl)phenoxy]acetic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol) salt,

[4-({{4-[(4-Butylphenyl)ethynyl]benzyl}[(propylamino)carbonyl]-amino}methyl)-phenoxy]acetic acid,

{4-[({4-[(4-Butylphenyl)ethynyl]benzyl}{[(4-cyanophenyl)amino]carbonyl}amino)methyl]phenoxy}acetic acid,

5-((4-tert-Butylbenzyl){4-[(4-butylphenyl)ethynyl]benzyl}amino)-2-hydroxy-benzoic acid, hydrochloride salt,

(4-{[{4-[(4-Butylphenyl)ethynyl]benzyl}(2-thienylsulfonyl)amino]methyl}phenoxy)acetic acid,

5-[(1-{4-[(4-Butylphenyl)ethynyl]phenyl}pentyl)oxy]-2-hydroxybenzoic acid,

7-[(1-{4-[(4-Butylphenyl)ethynyl]phenyl}pentyl)oxy]-2,2-dimethyl-4H-1,3-benzodioxin-4-one, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)-glucitol) salt,

(4-{[{4-[(4-Butylphenyl)ethynyl]benzyl}(ethylsulfonyl)amino]-methyl}phenoxy)-acetic acid,

5-{[{4-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]carbonyl}-2-hydroxy-benzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)-glucitol) salt,

5-{[{4-[(4-Butylphenyl)ethynyl]benzoyl}(hexyl)amino]methyl}-2-hydroxybenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methyl-amino)glucitol) salt,

5-{[{4-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]sulfonyl}-2-hydroxy-benzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)-glucitol) salt,

4-[{4-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]-2-hydroxybenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol) salt,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]-2-fluorobenzoic acid,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol) salt,

5-{[{2-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]carbonyl}-2-hydroxybenzoic acid,

4-((3-Cyclopentylpropyl){4-[(4-fluorophenyl)ethynyl]benzoyl}amino)-2-hydroxybenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methyl-amino)glucitol) salt,

4-[{4-[(4-Butylphenyl)ethynyl]benzoyl}(3-cyclopentylpropyl)amino]-2-hydroxybenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methyl-amino)glucitol) salt,

5-{[{4-[(4-Fluorophenyl)ethynyl]benzoyl}(hexyl)amino]methyl}-2-hydroxy-benzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)-glucitol) salt,

5-{[{4-[(4-Chlorophenyl)ethynyl]benzoyl}(hexyl)amino]methyl}-2-hydroxybenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methyl-amino)glucitol) salt,

2-Fluoro-5-{hexyl[4-(phenylethynyl)benzyl]amino}benzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol) salt,

5-({4-[(4-Chlorophenyl)ethynyl]benzyl}(hexyl)amino)-2-hydroxybenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol) salt,

5-(Hexyl{4-[(4-methoxyphenyl)ethynyl]benzyl}amino)-2-hydroxybenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-[Hexyl(4-{[4-(trifluoromethyl)phenyl]ethynyl}benzyl)amino]-2-hydroxybenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(cyclopentylmethyl)amino]-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(3,3-dimethylbutyl)amino]-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-((Cyclopentylmethyl){4-[(4-methoxyphenyl)ethynyl]benzyl}amino)-2-hydroxybenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-({4-[(4-Butylphenyl)ethynyl]benzyl}(ethyl)amino)-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol) salt,

5-(Hexyl{4-[(4-propylphenyl)ethynyl]benzyl}amino)-2-hydroxybenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]-2-fluorobenzoic acid, lysine salt,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]-2-fluorobenzoic acid, tromethamine (i.e. (2-amino-2-hydroxymethyl)-1,3-propanediol) salt,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(pentyl)amino]-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol) salt,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(methyl)amino]-2-fluorobenzoic acid,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(cyclopropylmethyl)amino]-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-{Butyl[4-(phenylethynyl)benzyl]amino}-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol) salt,

2-Fluoro-5-{[4-(phenylethynyl)benzyl](propyl)amino}benzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol) salt,

2-Fluoro-5-[{4-[(4-fluorophenyl)ethynyl]benzyl}(hexyl)amino]benzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

2-Fluoro-5-(hexyl{4-[(4-propylphenyl)ethynyl]benzyl}amino)benzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-{{4-[(4-Butylphenyl)ethynyl]benzyl}[(2-carboxycyclopropyl)methyl]amino}-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-[{4-[(4-Ethylphenyl)ethynyl]benzyl}(hexyl)amino]-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-[{4-[(4-tert-Butylphenyl)ethynyl]benzyl}(hexyl)amino]-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-{[{4-[(4-Butylphenyl)ethynyl]phenyl}(hexyl)amino]methyl}-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

4-({(3,3-Dimethylbutanoyl)-4-[(4-hexylphenyl)ethynyl]anilino}methyl)-2-hydroxybenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol) salt,

5-[{4-[(4-Butylphenyl)ethynyl]benzyl}(isobutyl)amino]-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-{[{4-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]carbonyl}-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-[{4-[(4-Butylphenyl)ethynyl]benzoyl}(hexyl)amino]-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-[({4-[(4-Butylphenyl)ethynyl]phenyl}sulfonyl)(hexyl)amino]-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-{[{4-[(4-Butylphenyl)ethynyl]benzoyl}(hexyl)amino]methyl}-2-fluorobenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt,

5-{[({4-[(4-Butylphenyl)ethynyl]phenyl}sulfonyl)(hexyl)amino]methyl}-2-fluorobenzoic acid,

5-{{4-[(4-Butylphenyl)ethynyl]benzyl}[(propylamino)carbonyl]amino }-2-fluorobenzoic acid,

5-{{4-[(4-Butylphenyl)ethynyl]benzyl}[(cyclohexylamino)carbonyl]amino}-2-fluorobenzoic acid, and

4-[{4-[(4-Chlorophenyl)ethynyl]benzoyl}(3-cyclopentylpropyl)amino]-2-hydroxybenzoic acid, N-methyl-D-glucamine (i.e. 1-deoxy-1-(methylamino)glucitol)salt.

13. A medicament comprising a carboxylic acid according to claim 1 .

14. The medicament according to claim 13 for the modulation of the activity of PTPs.

15. The medicament according to claim 14 wherein the PTP is PTP1B, GLEPP-1.

16. The medicament according to claim 15 wherein said modulation consists in the inhibition of PTP1B.

17. A pharmaceutical composition containing at least one carboxylic acid according to claim 1 and a pharmaceutically acceptable carrier, diluent or excipient thereof.

18. A pharmaceutical composition according to claim 17 further comprising at least one supplementary drug selected from the group consisting of insulin, aldose reductase inhibitors, alpha-glucosidase inhibitors, sulfonyl urea agents, biguanides (e.g. metformin), thiazolidines, PPARs agonists, c-Jun Kinase or GSK-3 inhibitors.

19. A pharmaceutical composition according to claim 18 wherein said supplementary drug is selected from the group consisting of a rapid acting insulin, an intermediate acting insulin, a long acting insulin, a combination of intermediate and rapid acting insulins, Minalrestat, Tolrestat, Sorbinil, Methosorbinil, Zopolrestat, Epalrestat, Zenarestat, Imirestat, Ponalrestat, ONO-2235, GP-1447, CT-112, BAL-ARI 8, AD-5467, ZD5522, M-16209, NZ-314, M-79175, SPR-210, ADN 138, or SNK-860, Miglitol, Acarbose, Glipizide, Glyburide, Chlorpropamide, Tolbutamide, Tolaz-amide, or Glimepriride.

20. A method of preparing a carboxylic acid according to claim 1 , comprising the step of:

whereby the moieties A, B 1-22 , R 1 , D are as above defined and D′ is a protected form of the moiety D.

21. An intermediate compound (I′) selected from the group consisting of:

6-[{4-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]-2,2-dimethyl-4H-1,3-benzodioxin-4-one,

Methyl 5-[{4-[(4-butylphenyl)ethynyl]benzyl}(hexyl)amino]-2-hydroxybenzoate,

(E)-N-{4-[(4-Butylphenyl)ethynyl]benzyl}-N-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-6-yl)-2-phenylethylenesulfonamide,

Methyl 4-({{4-[(4-butylphenyl)ethynyl]benzyl}[2-(4-chlorophenyl)ethyl]amino}-methyl)-benzoate,

Methyl {4-[({[(4-tert-butylphenyl)amino]carbonyl}{4-[(4-butylphenyl)ethynyl]-benzyl}amino)methyl]phenoxy}acetate,

6-[{4-[(4-Butylphenyl)ethynyl]benzyl}(3-phenylpropyl)amino]-2,2-dimethyl-4H-1,3-benzodioxin-4-one,

Methyl {4-[({4-[(4-butylphenyl)ethynyl]benzyl}{[(E)-2-phenylvinyl]sulfonyl}-amino)methyl]phenoxy}acetate,

6-[{4-[(4-Butylphenyl)ethynyl]benzyl}(1-naphthylmethyl)amino]-2,2-dimethyl-4H-1,3-benzodioxin-4-one,

Methyl [4-({{4-[(4-butylphenyl)ethynyl]benzyl}[(cyclohexylamino)carbonyl]-amino}-methyl)phenoxy]acetate,

Methyl [4-({{4-[(4-butylphenyl)ethynyl]benzyl}[(propylamino)carbonyl]amino}-methyl)phenoxy]acetate,

Methyl [4-({{4-[(4-butylphenyl)ethynyl]benzyl}[(4-cyanoanilino)carbonyl]amino}-methyl)phenoxy]acetate,

6-((4-tert-Butylbenzyl){4-[(4-butylphenyl)ethynyl]benzyl}amino)-2,2-dimethyl-4H-1,3-benzodioxin-4-one,

Methyl (4-{[{4-[(4-butylphenyl)ethynyl]benzyl}(2-thienylsulfonyl)amino]methyl}-phenoxy)acetate,

6-[(1-{4-[(4-Butylphenyl)ethynyl]phenyl}pentyl)oxy]-2,2-dimethyl-4H-1,3-benzodioxin-4-one,

Methyl (4-{[{4-[(4-butylphenyl)ethynyl]benzyl}(ethylsulfonyl)amino]methyl}-phenoxy)acetate,

N-{4-[(4-Butylphenyl)ethynyl]benzyl}-N-hexyl-2,2-dimethyl-4-oxo-4H-1,3-benzodioxine-6-carboxamide,

4-[(4-Butylphenyl)ethynyl]-N-[(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-6-yl)methyl]-N-hexylbenzamide,

7-[{4-[(4-Butylphenyl)ethynyl]benzyl}(hexyl)amino]-2,2-dimethyl-4H-1,3-benzodioxin-4-one,

Methyl 5-[{4-[(4-butylphenyl)ethynyl]benzyl}(hexyl)amino]-2-fluorobenzoate,

N-{2-[(4-Butylphenyl)ethynyl]benzyl}-N-hexyl-2,2-dimethyl-4-oxo-4H-1,3-benzodioxine-6-carboxamide,

4-Bromo-N-(3-cyclopentylpropyl)-N-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl)benzamide,

N-(3-Cyclopentylpropyl)-N-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl)-4-[(4-fluorophenyl)ethynyl]benzamide,

4-[(4-Butylphenyl)ethynyl]-N-(3-cyclopentylpropyl)-N-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl)benzamide,

N-[(2,2-Dimethyl-4-oxo-4H-1,3-benzodioxin-6-yl)methyl]-4-[(4-fluorophenyl) -ethynyl]-N-hexylbenzamide,

4-[(4-Chlorophenyl)ethynyl]-N-[(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-6-yl)methyl]-N-hexylbenzamide,

Methyl 2-fluoro-5-{hexyl[4-(phenylethynyl)benzyl]amino}benzoate,

6-({4-[(4-Chlorophenyl)ethynyl]benzyl}(hexyl)amino)-2,2-dimethyl-4H-1,3-benzodioxin-4-one,

6-(Hexyl{4-[(4-methoxyphenyl)ethynyl]benzyl}amino)-2,2-dimethyl-4H-1,3-benzodioxin-4-one,

6-[Hexyl(4-{[4-(trifluoromethyl)phenyl]ethynyl}benzyl)amino]-2,2-dimethyl-4H-1,3-benzodioxin-4-one,

5-{[4-(4-Butyl-phenylethynyl)-benzyl]-cyclopentylmethyl-amino}-2-fluoro-benzoic acid methyl ester,

Methyl 5-[{4-[(4-butylphenyl)ethynyl]benzyl}(3,3-dimethylbutyl)amino]-2-fluorobenzoate,

6-((Cyclopentylmethyl){4-[(4-methoxyphenyl)ethynyl]benzyl}amino)-2,2-dimethyl-4H-1,3-benzodioxin-4-one,

Methyl 5-((cyclopentylmethyl){4-[(4-methoxyphenyl)ethynyl]-benzyl}amino)-2-hydroxybenzoate,

Methyl 5-({4-[(4-butylphenyl)ethynyl]benzyl}(ethyl)amino)-2-fluorobenzoate,

6-(Hexyl{4-[(4-propylphenyl)ethynyl]benzyl}amino)-2,2-dimethyl-4H-1,3-benzodioxin-4-one,

Methyl 5-(hexyl{4-[(4-propylphenyl)ethynyl]benzyl}amino)-2-hydroxybenzoate,

Methyl 5-[{4-[(4-butylphenyl)ethynyl]benzyl}(pentyl)amino]-2-fluorobenzoate,

Methyl 5-[{4-[(4-butylphenyl)ethynyl]benzyl}(methyl)amino]-2-fluorobenzoate,

Methyl 5-[{4-[(4-butylphenyl)ethynyl]benzyl}(cyclopropylmethyl)amino]-2-fluorobenzoate,

Methyl 5-{butyl[4-(phenylethynyl)benzyl]amino}-2-fluorobenzoate,

Methyl 2-fluoro-5-{[4-(phenylethynyl)benzyl](propyl)amino}benzoate,

Methyl 2-fluoro-5-[{4-[(4-fluorophenyl)ethynyl]benzyl}-(hexyl)amino]benzoate,

Methyl 2-fluoro-5-(hexyl{4-[(4-propylphenyl)ethynyl]-benzyl}amino) benzoate,

Methyl 5-({4-[(4-butylphenyl)ethynyl]benzyl}{[2-(ethoxycarbonyl) cyclopropyl]methyl}amino)-2-fluorobenzoate,

Methyl 5-[{4-[(4-ethylphenyl)ethynyl]benzyl}(hexyl)amino]-2-fluorobenzoate,

Methyl 5-[{4-[(4-tert-butylphenyl)ethynyl]benzyl}(hexyl)amino]-2-fluorobenzoate,

Methyl 5-{[4-[(4-butylphenyl)ethynyl](hexyl)anilino]methyl}-2-fluorobenzoate,

N-[(2,2-Dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl)methyl]-N-{4-[(4-hexylphenyl)ethynyl]phenyl}-3,3-dimethylbutanamide,

Methyl 5-[{4-[(4-butylphenyl)ethynyl]benzyl}(isobutyl)amino]-2-fluorobenzoate,

Methyl 5-{[{4-[(4-butylphenyl)ethynyl]benzyl}(hexyl)amino]carbonyl}-2-fluorobenzoate,

Methyl 5-[{4-[(4-butylphenyl)ethynyl]benzoyl}(hexyl)amino]-2-fluorobenzoate,

Methyl 5-[({4-[(4-butylphenyl)ethynyl]phenyl}sulfonyl)(hexyl)amino]-2-fluorobenzoate,

Methyl 5-{[{4-[(4-butylphenyl)ethynyl]benzoyl}(hexyl)amino]methyl}-2-fluorobenzoate,

Methyl 5-{[({4-[(4-butylphenyl)ethynyl]phenyl}sulfonyl)(hexyl)amino]methyl)-2-fluorobenzoate,

Methyl 5-{{4-[(4-butylphenyl)ethynyl]benzyl}[(propylamino)carbonyl]amino}-2-fluorobenzoate,

Methyl 5-{{4-[(4-butylphenyl)ethynyl]benzyl}[(cyclohexylamino)carbonyl]amino}-2-fluorobenzoate, and

4-[(4-Chlorophenyl)ethynyl]-N-(3-cyclopentylpropyl)-N-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl)benzamide.