Pharmacologically-active vanilloid carbamates

1. The Compound of the formula (I)

wherein

R 1 , R 2 , and R* are hydrogen, (C 1 -C 15 )alkyl, (C 1 -C 15 )alkyl(C 1 -C 6 )alkoxy, aryl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 6 )alkyl, (C 1 -C 6 )alkaryl, heterocyclic, (C 1 -C 6 )alkyl heterocyclic, and amino acyl and pharmaceutically acceptable addition salts thereof and optical and geometric isomers or racemic mixtures thereof.

2. The compound of claim 1 wherein

R 1 and R 2 are alike or different and selected from hydrogen, (C 1 -C 15 )alkyl, (C 1 -C 15 )alkyl(C 1 -C 6 )alkoxy, aryl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 6 )alkyl, (C 1 -C 6 )alkaryl, heterocyclic, (C 1 -C 6 )alkyl heterocyclic, and amino acyl;

R* is (C 1 -C 6 )alkyl or aryl; and

pharmaceutically acceptable acid addition salts thereof and optical and geometric isomers or racematic mixtures thereof.

3. The compound of claim 2 wherein

R 1 is hydrogen (C 1 -C 15 )alkyl;

R 2 is hydrogen (C 1 -C 15 )alkyl, (C 1 -C 15 )alkyl(C 1 -C 6 )alkoxy, aryl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 6 )alkyl, (C 1 -C 6 )alkaryl, heterocyclic, (C 1 -C 6 )alkyl heterocyclic, and amino acyl; and

R* is (C 1 -C 6 )alkyl.

4. The compound of the formula (I)

wherein

R 1 is hydrogen or n-butyl;

R 2 is ethyl, n-butyl, n-hexyl, n-octyl, n-heptyl, 2ethylhexyl, n-dodecyl, cyclohexyl, cyclohexylmethyl, 2-phenoxyethyl, phenethyl, 2-indanyl, 2-methoxyethyl, 33-dimethylbutyl,

2-(4-morpholino)ethyl, ethyl 2-glycinyl or ethyl 2-valinyl; and

R* is methyl.

5. The compound which is

4-{[(cyclohexylcarbamoyl)oxy]methyl}-2-methoxyphenyl acetate,

4-{[(butylcarbamoyl)oxy]methyl}-2-methoxyphenyl acetate,

4-{[(hexylcarbamoyl)oxy]methyl}-2-methoxyphenyl acetate,

4-{[(octylcarbamoyl)oxy]methyl}-2-methoxyphenyl acetate,

4-{[(decyclacarbamoyl)oxy]methyl}-2-methoxyphenyl acetate,

2-methoxy-4({[(2-methoxyethyl)carbamoyal]oxy}methyl)phenyl acetate,

4-(acetyloxy)-3-methoxybenzyl 2-thioxo-13 thiazolidine-3carboxylate,

4-{[(heptylcarbamoyl)oxy]methyl}-2methoxyphenyl acetate,

4-{[(dibutylcarbamoyl)oxy]methyl}-2-methoxyphenyl acetate,

4-{[(benzylcarbamoyl)oxy]methyl}-2-methoxyphenyl acetate,

4-{[(2-ethylhexycarbamoyl)oxy]methyl}-2-methoxyphenyl acetate

4-{[(dodecylcarbamoyl)oxy]methyl}-2-methoxyphenyl acetate,

2-methoxy-4({[(2-phenoxyethyl)carbamoyal]oxy}methyl)phenyl acetate,

2-methoxy-4({[(2-phenylethyl)carbamoyal]oxy}methyl)phenyl acetate,

4-({[(cyclohexylmethyl)carbamoyl]oxy}methyl)-2-methoxyphenyl acetate

4-{[(2,3-dihydro-1H-inden-2-ylcarbamoyl)oxy]methyl}-2-methoxyphenyl acetate,

4-({[(3,3-dimethylbutyl)carbamoyl]oxy}methyl)-2-methoxyphenyl acetate,

2-methoxy-4-[({[2-(morpholin-4-yl)ethyl]carbamoyl}oxy)methyl]phenyl acetate,

4-{[(ethylcarbamoyl)oxy]methyl}-2-methoxyphenyl acetate,

ethyl 2[({[4-(acetyloxy)-3-methoxybenzyl]oxy}carbonyl)amino]acetate, or

ethyl 2[({[4-(acetoxy)-3-methoxybenzyl]oxy}carbonyl)amino]-3-methylbutanoate.

6. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and a pharmaceutically effective amount of claim 1 .

7. A method of treating Alzheimer's dementia, Parkinson's disease, depression, pain, rheumatoid arthritis, multiple sclerosis, or inflammation which comprises administering to a patient an effective amount of the compound of claim 1 .

8. A method of treating Huntington's disease, hypertension, arthritis, allergic airway inflammation, Crohn's disease, ulcerative colitis, or neuropathic pain which comprises administering to a patient an effective amount of the compound of claim 1 .

9. A method of preparing a compound of formula (I)

wherein

R 1 is hydrogen;

R 2 is n-butyl, n-hexyl, n-octyl or cyclohexyl; and

R* is methyl, which comprises

reacting a benzyl alcohol compound of formula (I)

with an isocyanate of formula (b)

RNCO (b)

wherein

R is n-butyl, n-hexyl, n-octyl or cyclohexyl;

and obtaining the compound of formula (I).

10. A method of preparing a compound of formula (I)

wherein

R 1 , R 2 , and R* are hydrogen, (C 1 -C 15 )alkyl, (C 1 -C 15 )alkyl(C 1 -C 6 )alkoxy, aryl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 6 )alkyl, (C 1 -C 6 )alkaryl, heterocyclic, (C 1 -C 6 )alkyl heterocyclic, and amino acyl and pharmaceutically acceptable addition of salts thereof and optical and geometric isomers or racemic mixtures thereof, which comprises

reacting a benzyl alcohol compound of formula (a)

with carbonyldiimidazole (CDI) of formula (c)

(c) to obtain the compound of formula (d)

reacting the compound of formula (d) with NHR 1 R 2 and obtaining the compound of formula (I).

11. A method of preparing a compound of formula (I)

wherein, R 1 , R 2 and R* are hydrogen, (C 1 -C 15 )alkyl, (C 1-15 )alkyl(C 1 -C 6 )alkoxy, aryl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 6 )alkyl, (C 1 -C 6 )alkaryl, heterocyclic, (C 1 -C 6 )alkyl heterocyclic, and amino acyl and pharmaceutically acceptable addition of salts thereof and optical and geometric isomers or racemic mixtures thereof, which comprises reacting a benzyl alcohol compound of formula (a)

with N-chloroformylthiazolidine-2-thione of formula (e)

to obtain the compound of formula (f)

reacting the compound of formula (f) with NHR 1 R 2 and obtaining the compound of formula (I).