MXPA05013444A - Novel 8-aza-bicyclo[3.2.1]octane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors - Google Patents

Abstract

This invention relates to novel 8-aza-bicyclo[3.2.1]octane derivatives useful as monoamine, neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.

Description

NOVEDOSOS DERIVED FROM 8-AZA-BICICLO [3.2.1] OCTANO AND ITS USE AS INHIBITORS OF THE RE-CAPTATION OF MONOAMINIC NEUROTRANSMITORS FIELD OF THE INVENTION This invention relates to novel derivatives of the 8-aza-bicyclo [3.2.1] octane useful as inhibitors of the reuptake of monoarainic neurotranswers. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention. BACKGROUND OF THE INVENTION WO 97/30997 (NeuroSearch A / S) describes active trepane derivatives as inhibitors of neurotransmitter re-uptake. However, there is a great continuing need to find compounds with an optimized pharmacological profile with respect to the activity on the reuptake inhibitors of the monoamine neurotransmitters serotonin, dopamine and noradrenaine, such as the ratio between re-uptake of serotonin versus the activity of noradrenaline and dopamine. SUMMARY OF THE INVENTION In its first aspect, the invention provides a compound of Formula I: No. Ref.: 168300 or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof, * wherein Ra, Rb and X are as defined below. In its second aspect, the invention provides a pharmaceutical composition, comprising a therapeutically effective amount of a compound of the invention, or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof, together with less a vehicle, excipient or diluent acceptable for pharmaceutical use. In another aspect, the invention provides the use of a compound of the invention, or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for the treatment, prevention or alleviation of a disease or disorder or condition of a mammal, including a human, disease, disorder or condition that is sensitive to the inhibition of re-uptake of monoamine neurotransmitters in the central nervous system. In still another aspect, the invention relates to a method for the treatment, prevention or alleviation of a disease or a disorder or condition of a living animal organism, including a human, disorder, disease or condition that is responsive to re -procurement of monoamine neurotransmitters in the central nervous system, which method comprises the step of administering to a similar living animal organism in need thereof a therapeutically effective amount of a compound of the invention, or any of its isomers or any mixture of its isomers, or an acceptable salt for pharmaceutical use thereof. Other objects of the invention will be apparent to the person skilled in the art from the following detailed description and examples. DETAILED DESCRIPTION OF THE INVENTION Derivatives of 8-aza-bicyclo [3.2.1] octane In its first aspect the present invention provides compounds of formula I: or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof, wherein Ra represents hydrogen or alkyl; alkyl that is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitro, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl; X represents -O-, -S- or -NRC-; where Rc represents hydrogen, alkyl, -C (= 0) Rd or -S02Rd; where Ra represents hydrogen or alkyl; RD represents an aryl or heteroaryl group, aryl or heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitro, oxo, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkyl. In one embodiment, R represents hydrogen or alkyl; X represents -0-, -S- or -NRC-; where R c represents hydrogen, alkyl, -C (= 0) Ra or-S02Rd; where Ra represents hydrogen or alkyl; RD represents an aryl or heteroaryl group, aryl or heteroaryl group which is optionally substituted by one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitro, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl. In another embodiment, Ra represents hydrogen or alkyl. In yet another embodiment, Ra represents hydrogen. In another embodiment, R represents alkyl, such as methyl. In yet another embodiment, R represents alkyl substituted with hydroxy, cyano, cycloalkyl or alkenyl. In a special embodiment, Ra represents hydroxyalkyl, such as hydroxyethyl. In another embodiment, Ra represents cyanoalkyl, such as cyanomethyl. In still another embodiment, Ra represents cycloalkalkyl, such as cyclopropylmethyl. In another embodiment, Ra represents alkenylalkyl, such as allyl. In another modality, X represents -0-. In still another modality, X represents -S-. In another modality, X represents -NRC-. In a special embodiment, Ra represents hydrogen. In another embodiment, Rc represents -C (= 0) Rd. In a special embodiment, Rd represents hydrogen. In a special embodiment, X represents -NH- or -N ((C = 0) H) -. In another embodiment, Rb represents an aryl or heteroaryl group, aryl or heteroaryl group that is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, oxo and alkoxy. In yet another embodiment, Rb represents an aryl or heteroaryl group, aryl or heteroaryl group that is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy. In another embodiment, Rb represents an aryl or heteroaryl group, aryl or heteroaryl group that is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, oxo, alkyl and alkoxy. In yet another embodiment, Rb represents an aryl or heteroaryl group, aryl or heteroaryl group which is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, oxo and alkoxy. In another embodiment, Rb represents an aryl or heteroaryl group, aryl or heteroaryl group which is substituted with one or more substituents independently selected from the group consisting of: "halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy." In another embodiment, Rb represents a group unsubstituted, monosubstituted or disubstituted aryl or heteroaryl In another embodiment, Rb represents an optionally substituted monocyclic heteroaryl group In another embodiment, Rb represents an optionally substituted bicyclic heteroaryl group In yet another embodiment, Rb represents an optionally substituted polycyclic heteroaryl group. In a special embodiment, Rb represents an optionally substituted heteroaryl group and the compound of formula I is in the exo configuration In another embodiment, Ra represents hydrogen and Rb represents an optionally substituted heteroaryl group In another embodiment, Ra represents hydrogen, Rb represents an optionally substituted heteroaryl group gone and the compound of formula I is in the exo configuration. In yet another embodiment, Rb represents an optionally substituted phenyl group. In another embodiment, Rb represents an optionally substituted naphthyl group. In yet another embodiment, Rb represents an optionally substituted fluorenyl group.

In another embodiment, Rb represents an optionally substituted thienyl group. In yet another embodiment, Rb represents a benzoisothiazolyl group. In yet another embodiment, Rb represents a phenyl group, phenyl group which is optionally substituted. In still another it is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy. In another embodiment, Rb represents a phenyl group optionally substituted once or twice with halo, such as chlorine. In a special embodiment, Rb represents phenyl. In another embodiment, Rb represents monosubstituted phenyl. In a special embodiment, Rb represents chlorophenyl, such as 3-chlorophenyl. In another embodiment, Rb represents a disubstituted phenyl. In still another special embodiment, Rb represents dichlorophenyl, such as 2,3-dichlorophenyl or 3,4-dichlorophenyl. In another embodiment, R represents phenyl substituted with chloro and fluoro, such as 4-chloro-3-fluorophenyl or 4-fluoro-3-chlorophenyl. In yet another embodiment, Rb represents phenyl substituted with chloro and trifluoromethyl, such as 2-chloro-3-trifluoromethylphenyl or 4-chloro-3-trifluoromethylphenyl. In yet another embodiment, Rb represents phenyl substituted with fluoro and trifluoromethyl, such as 4-fluoro-3-trifluoromethylphenyl. In another embodiment, Rb represents phenyl substituted with chlorine and cyano, such as 3-chloro-4-cyanophenyl. In yet another embodiment, Rb represents phenyl substituted with chloro and methyl, such as 4-chloro-3-methylphenyl. In another embodiment, "Rb represents phenyl substituted with chlorine and bromine, such as 4-bromo-3-chlorophenyl In another embodiment, Rb represents a monosubstituted phenyl In another embodiment, Rb represents chlorophenyl, such as 3-chlorophenyl or chlorophenyl In another embodiment, Rb represents trifluoro-ethoxyphenyl, such as 3-trifluoromethoxyphenyl or 4-trifluoromethoxyphenyl In another embodiment, Rb represents trifluoromethylphenyl, such as 4-trifluoromethylphenyl In another embodiment, Rb represents methylphenyl, such as 4-methylphenyl In still another embodiment, Rb represents methoxyphenyl, such as 3-methoxyphenyl or 4-methoxyphenyl In another embodiment, Rb represents cyanophenyl, such as 4-cyanophenyl In another embodiment, Ra represents hydrogen and Rb represents a phenyl group, phenyl which is substituted twice with substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy In another embodiment, Rb represents a naphthyl group or, such as 1-naphthyl or 2-naphthyl. In yet another embodiment, Rb represents a naphthyl group substituted once or twice with halo, such as chlorine or bromine. In a special embodiment, Rb represents chloronaphthyl, such as 4-chloronaphthalen-1-yl. In another embodiment, Rb represents bromonaphthyl, such as 6-bromonaphthalen-2-yl. In yet another embodiment, Rb represents a naphthyl group substituted once or twice with alkoxy, such as methoxy. In a special embodiment, Rb represents methoxynaphthyl, such as 4-methoxynaphthalen-1-yl, 6-methoxynaphthalen-2-yl or 7-methoxynaphthalen-2-yl. In yet another embodiment, Rb represents a naphthyl group substituted once or twice with cyano. In a special embodiment, Rb represents cyanonaphthyl, such as 6-cyanonaphthalen-2-yl. In yet another embodiment, Rb represents a 1,2,3,4-tetrahydronaphthyl group, such as 1,2,3,4-tetrahydronaphthalen-6-yl. In another embodiment, Rb represents an indanyl group, such as 5-indanyl. In yet another embodiment, Rb represents a fluorenyl group substituted with oxo, such as fluoren-9-sna-2-yl. In still another embodiment, Rb represents a thienyl group, thienyl group which is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy. In another embodiment, Rb represents a thienyl group substituted one or more times with halo, such as chlorine or bromine. In a special embodiment, Rb represents bromothienyl, such as 4-bromothiophen-2-yl. In another modality, Rb represents dihalothienyl, such as bromo-chloro-thienyl, in particular 3-bromo-5-chloro-thiophen-2-yl or 4-bromo-5-chloro-thiophen-2-yl. In another embodiment, Rb represents dichlorothienyl, such as 3,4-dichloro-thiophen-2-yl. In another special embodiment, Rb represents trichlorothienyl, such as 3, 4, 5-trichloro-thiophen-2-yl. In still another special embodiment, Rb represents tribromothienyl, such as 3, 4, 5-tribromo-thiophen-2-yl. In yet another embodiment, Rb represents a benzoisothiazolyl group, such as 1,2-benzisothiazol-3-yl. In another embodiment, Rb represents an optionally substituted benzothiazolyl group. In a special embodiment, Rb represents benzothiazolyl, such as benzothiazol-2-yl. In another embodiment, Rb represents a benzothiazolyl group substituted once or twice with halo, such as chlorine. In a special embodiment, Rb represents chlorobenzothiazolyl, such as 6-chlorobenzothiazol-2-yl. In another embodiment, Rb represents a thiazolyl group substituted once or twice with halo, such as bromine. In a special embodiment, Rb represents bromothiazolyl, such as 5-bromothiazol-2-yl. In yet another embodiment, Rb represents a quinoxalinyl group, such as quinoxalin-2-yl. In another embodiment, Rb represents a quinazolinyl group, such as quinazolin-2-yl.

In another embodiment, R represents a quinolinyl group, such as quinolin-2-yl, quinolin-6-yl or quinolin-8-yl. In another embodiment, Rb represents an isoquinolinyl group, such as isoquinolin-5-yl. In yet another embodiment, Rb represents a benzoxazolyl group, such as benzoxazol-2-yl. In another embodiment, Rb represents an optionally substituted pyridazinyl group. In yet another embodiment, Rb represents a pyridazinyl group substituted once or twice with halo, such as chlorine. In a special embodiment, Rb represents chloropyridazinyl, such as 6-chloropyridazin-3-yl. In another embodiment, Rb represents an optionally substituted pyridyl group. In another embodiment, Rb represents a pyridyl group, pyridyl group which is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy and alkoxy. In yet another embodiment, Rb represents a pyridyl group substituted once or twice with halo, such as chlorine or bromine. In a special embodiment, R represents chloropyridyl, such as 5-chloropyridin-2-yl or 6-chloropyridin-2-yl. In another embodiment, R represents bromopyridyl, such as 5-bromopyridin-2-yl or 6-bromopyridin-2-yl. In yet another embodiment, Rb represents a pyridyl group substituted once or twice with alkoxy, such as methoxy or ethoxy. In a special embodiment, Rb represents methoxypyridyl, such as 6-methox_L-pyridin-2-yl. In another special embodiment, Rb represents ethoxypyridyl, such as 6-ethoxypyridin-2-yl. In yet another embodiment, R represents a pyridine group substituted once or twice with trifluoromethyl. In a special embodiment, Rb represents trifluoromethylpyridyl, such as 5-trifluoromethylpyridin-2-yl. In another embodiment, Rb represents a pyridine group substituted once or twice with hydroxy. In a special embodiment, Rb represents a hydroxypyridyl, such as 6-hydroxypyridin-2-yl. In another embodiment, Rb represents an isoquinolinyl group, such as isoquinolin-1-yl. In another embodiment, Rb represents an optionally substituted pyrimidino group. In yet another mode, Rb represents a pyrimidine group substituted one or two times with halo, such as bromine. In a special embodiment, Rb represents bromopyrimidino, such as 5-bromopyrimidin-2-yl. In another embodiment, Rb represents a dibenzofuranyl group, such as di-benzofuran-2-yl. In yet another embodiment, Rb represents an indolyl group, such as 5-indolyl. In a special embodiment the chemical compound of the invention is endo-3- (3,4,5-Trichlorothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; endo-3- (3,4-Dichlorothiophen-2-yloxy) -8, -methyl-8-azabicyclo [3.2.1] octane; exo-3- (3,4,5-Trichlorothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (1,2-Benzoisothiazol-3-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (5-Bromothiazol-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (Benzothiazol-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-Chlorobenzothiazol-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (Quinoxalin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (quinolin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (Benzoxazol-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-chloro-pyridazin-3-yloxy-8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (5-chloro-pyridin-2-yloxy) -8-methyl-8 -azabicyclo [3.2.1] octane; exo-3- (isoquinolin-1-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-chloropyridin-2-yloxy) -8 -methyl-8-azabicyclo [3.2.1] octane; exo-3- (5-Bromopyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-Bromopyridine) 2-yloxy) -β-methyl-S-azabicyclo [3.2.1] octane; exo-3- (5-Bromopyrimidin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3 - (Quinazolin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (5-trifluoromethylpyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3,4,5-Tribromothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Bromothiophen-2-yloxy) -8-methyl -8-azabicyclo [3.2.1] octane; endo-3- (3-Bromo-5-chloro-thiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; endo-3- (4-Bromo-5-doro-thiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; endo-3- (3,4,5-Trichlorotiof en-2-yloxy) -8H-8-azabicyclo [3.2.2] 1 octane; exo-3- (2,3-Dichlorophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3,4-Dichlorophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3,4,5-Trichlorothiophen-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3-chloro-4-fluorophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3-Chloro-phenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloro-3-fluorophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloro-phenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (2-Chloro-3-trifluoromethyl-phendyo-8-H-8-azabicyclo [3.2.1] octane; exo-3- (Fluoren-9-one-2-yloxy) -8-H-8 -azabicyclo [3.2.1] octane; exo-3- (1,2-benzoisothiazol-3-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3,4-dichlorophenylthio) -8 ~ methyl-8-azabicyclo [3.2.1] octane; endo-3- (3,4-dichlorophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-chloro- 3-trifluoromethylphenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (2-Dibenzofuranyloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (1- Naphthyloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (2-Naphthyloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3-chloro- 4-cyanophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-chloro-3-methylphenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3 - (4-Chloronaph talen-1-yloxy) -8H-8-azabicyclo [3.2.2] octane; exo-3- (quinolin-2-yloxy) -8-H-8-azabicyclo [3.2. 1] octane; exo-3- (5-chloro-pyridin-2-yl) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-methoxyfenoxy) -8-H-8- azabicyclo [3.2.1] octane; exo-3- (isoquinolin-5-yl) xi) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (6-Bromo-naphthalen-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane, -exo-3- (4-Bromo-3-chloro-phenoxy) -8-H -8-azabicyclo [3.2.1] octane; exo-3- (quinolin-6-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Trifluorophenoxy) -8-H-8-aza cyclo [3.2.1] octane; exo-3- (4-Cyanophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (quinolin-8-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Methylphenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (6-Chloropyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (5-Bromopyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (6-Bromopyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (Isoquinolin-1-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3-Trifluoromethoxyphenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Trifluoromethoxyphenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (6-Methoxypyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (5-trifluoromethylpyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (6-Ethoxypyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Fluoro-3-trifluoromethylphenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (2,3-Dichlorophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3,4-Dichlorophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3-Chloro-4-fluorophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (Chloro-3-fluorophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; Exo-3- (2-Chloro-3-trifluoromethyl-phendxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3-Chloro-phenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloro-phenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (Fluoren-9-one-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3,4-dichlorophenylthio) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (1-Naphthyloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (2-Naphthyloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloro-3-trifluoromethyl-phenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3-Chloro-4-cyanophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (2-Dibenzofuranyloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloronaphthalen-1-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo3- (4-Chloro-3-methylphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Methoxyphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (7-Methoxynaphthalen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-Methoxynaphthalen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Bromo-3-chloro-phenoxy) -8-meiyl-8-azabicyclo [3.2.1] octane; exo-3- (Isoquinolin-5-yl) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-Bromo-naphthalen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3-Methoxyphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Cyanophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (quinolin-6-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (1,2,4,4-Tetrahydronaphthalen-6-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-T ifluoromethylphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Methylphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (8-quinolinyl) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (5-Indanyloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Methoxynaphthalen-1-yloxy) -8-methyl-8-azabicyclo [3.2.2] 1-octane; exo-3- (Indol-5-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3-Trifluoromethoxyphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Trifluoromethoxyphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Fluoro-3-trifluoromethylphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; endo-3- (3,4-Dichlorophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3,4-dichlorophenoxy) -8- (2-hydroxyethyl) -8-azabicyclo [3.2.1] octane; exo-3- (3,4-dichlorophenoxy) -8- (cyanomethyl) -8-azabicyclo [3.2.1] octane; exo-3- (3,4-dichlorophenoxy) -8- (cyclopropylmethyl) -8-azabicyclo [3.2.1] octane; exo-3- (3,4-dichlorophenoxy) -8- (allyl) -8-azabicyclo [3.2.1] octane; exo-3- (3, -Dichlorophenoxy) -8- (methoxyethyl) -8-azabicyclo [3.2.1] octane; exo-3- (6-Methoxypyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-Ethoxypyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-hydroxy-pyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-Cyano-naphthalen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo- (3,4-Dichloro-phenyl) - (8-methyl-8-aza-bicyclo [3.2.1] oct-3-yl) -amine; endo- (3,4-Dichloro-phenyl) - (8-methyl-8-aza-bicyclo [3.2.1] oct-3-yl) -formylamine; exo- (3, -Dichloro-phenyl) - (8-methyl-8-aza-bicyclo [3.2.1] oct-3-yl) -formylamine; or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof. Any combination of two or more embodiments such as those described above is considered within the scope of the present invention. Definition of Substituents In the context of this invention halo represents fluoro, chloro, bromo or iodo. In the context of this invention an alkyl group represents a saturated, straight or branched univalent hydrocarbon chain. The hydrocarbon chain preferably contains from one to six carbon atoms (C? _ Alkyl), including pentyl, isopentyl, neopentyl, tertiary pentyl, hexyl and isohexyl. In a preferred embodiment alkyl represents a C 1 - alkyl group, including butyl, isobutyl, secondary butyl, and tertiary butyl. In another preferred embodiment of this invention, alkyl represents a C? _3- alkyl group, which may be in particular methyl, ethyl, propyl or isopropyl. In the context of this invention, an alkenyl group represents a carbon chain containing one or more double bonds, including dienes, trienes and polyenes. In a preferred embodiment the alkenyl group of the invention comprises from two to six carbon atoms (C2_6 alkenyl), including at least one double bond. In a most preferred embodiment, the alkenyl group of the invention is ethenyl; 1- or 2-propenyl; 1-, 2- or 3-butenyl or 1,3-butadienyl; 1-, 2-, 3-, 4- or 5-hexenyl, or 1,3-hexadienyl, or 1, 3, 5-hexatrienyl. In the context of this invention, an alkynyl group represents a carbon chain containing one or more triple bonds, including diinos, trunnes and polyinos. In a preferred embodiment the alkynyl group of the invention comprises from two to six carbon atoms (C 2-6 alkynyl), including at least one triple bond. In its most preferred embodiment, the alkynyl group of the invention is ethynyl; 1-, or 2-propynyl; 1-, 2-, or 3-butynyl, or 1,3-butadiinyl; 1-, 2-, 3-, 4-pentynyl, or 1,3-pentadiinyl; 1-, 2-, 3-, 4-, or 5-hexinyl, or 1,3-hexadiinyl or 1, 3, 5-hexatriinyl. In the context of this invention a cycloalkyl group represents a cyclic alkyl group, preferably containing from three to seven carbon atoms (C3-7 cycloalkyl), including cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. Alkoxy is O-alkyl, in which alkyl is as defined above. Cycloalkoxy means O-cycloalsuyl, in which cycloalkyl is as defined above, Cycloalkylalkyl means cycloalkyl as above and alkyl as above, meaning, for example, cyclopropylmethyl. Amino is NH2 or NH-alkyl or N- (alkyl) _, where alkyl is as defined above. In the context of this invention an aryl group represents an aromatic carbocyclic ring system such as phenyl, naphthyl (1-naphthyl or 2-naphthyl) or fluorenyl. The term aryl is also intended to encompass a partially hydrogenated aromatic ring system, such as indanyl or 1, 2, 3, 4-tetrahydronaphthyl. In the context of this invention a heteroaryl group represents a heterocyclic mono- or bicyclic aromatic group, which contains one or more heteroatoms in its ring structure. Preferred heteroatoms include nitrogen (N), oxygen (O), and sulfur (S). Preferred monocyclic heteroaryl groups of the invention include 5- and 6-membered monocyclic aromatic heterocyclic groups, including for example, but not limited to, oxazolyl (oxazol-2-yl, -4-yl, or -5-yl), isoxazolyl (isoxazole) -3-yl), -4-yl, or -5-yl), thiazolyl (thiazol-2-yl, -4-yl, or -5-yl), isothiazolyl (isothiazol-3-yl, -4-yl) , or -5-yl), 1,2,4-oxadiazolyl (1, 2, 4-oxadiazol-3-yl or -5-yl), 1,2,4-thiadiazolyl (1, 2,4-thiadiazole- 3-yl or -5-yl), 1, 2, 5-oxadiazolyl (1, 2, 5-oxadiazol-3-yl or -4-yl), 1, 2, 5-thiadiazolyl (1, 2, 5 thiadiazol-3-yl or -4-yl), imidazolyl (2-, 4-, or 5-imidazolyl), pyrrolyl (2- or 3-pyrrolyl), furanyl (2- or 3-furanyl), thienyl (2- or 3-thienyl), pyridyl (2-, 3- or 4-pyridyl), pyridyl idyl (2-, 4-, 5- or 6-pyrimidyl), or pyridazinyl (3-, 4-pyridazinyl). Preferred bicyclic heteroaryl groups of the invention include indolizinyl, in particular 2-, 5- or 6-indolizinyl; indolyl, in particular 2-, 5- or β-indolyl; isoindolyl, in particular 2-, 5- or 6-isoindolyl; indazolyl, in particular 1- or 3-indazolyl; benzo [b] furanyl, in particular 2-, 5- or β-benzofuranyl; benzo [b] thienyl, in particular 2-, 5- or 6-benzothienyl; benzoimidazolyl, in particular 2-, 5- or β-benzoimidazolyl; benzoxazolyl, in particular 2-, 5- or 6-benzoxazolyl; benzothiazolyl, in particular 2-, 5- or 6-benzothiazolyl; benzisothiazolyl (1,2-benzisothiazolyl or 2,1-benzisothiazolyl), in particular 1,2-benzisothiazol-3-yl; purinyl, in particular 2- or 8-purinyl; quinolinyl, in particular 2-, 3-, 6-, 7- or 8-quinolinyl; isoquinolinyl, in particular 1-, 3-, 5-, 6- or 7-isoquinolinyl; cinolinyl, in particular 6- or 7-cynolinyl; phthalazinyl, in particular 6- or 7-phthalazinyl; quinazolinyl, in particular 2-, 6- or 7-quinazolinyl; quinoxalinyl, in particular 2- or 6-quinoxalinyl; 1,8-naphthyridinyl, in particular 1,8-naphthyridin-2-, 3-, 6- or 7-yl; pteridinyl, in particular 2-, 6- or 7-pteridinyl; and indenyl, in particular 1-, 2, 3-, 5- or 5-indenyl. Preferred polycyclic heteroaryl groups of the invention include dibenzofuranil, in particular 2-dibenzofuranyl. Acceptable Salts for Pharmaceutical Use The chemical compound of the invention can be delivered in any suitable form for the proposed administration. Suitable forms include pharmaceutically (i.e. physiological) acceptable salts, and pre- or pro-drug forms of the chemical compound of the invention. Examples of addition salts acceptable for pharmaceutical use include, without limitation, addition salts with non-toxic inorganic and organic acids such as hydrochloride derived from hydrochloric acid, hydrobromide derived from hydrobromic acid, nitrate derived from nitric acid, perchlorate derivative of perchloric acid, phosphate derived from phosphoric acid, sulphate derived from sulfuric acid, formiate derived from formic acid, acetate derived from acetic acid, acononate derived from aconitic acid, ascorbate derived from ascorbic acid. benzenesulfonate derived from benzenesulfonic acid, benzoate derived from benzoic acid, cinnamate derived from cinnamic acid, citrate derived from citric acid, embonate derived from embonic acid, enanthate derived from enanthic acid, fumarate derived from fumaric acid, glutamate derived from glutamic acid, glycolate derived from glycolic acid, lactate derived from lactic acid, maleate derived from maleic acid, malonate derived from malonic acid, mandelate derived from mandelic acid, methanesulfonate from methanesulfonic acid, naphthalene -2-sulphonate derived from naphthalene-2-sulfonic acid, phthalate derived from italic acid, salicylate derived from salicylic acid, sorbent derived from sorbic acid, stearate derived from stearic acid, succinate derived from succinic acid, tartrate derived from tartaric acid, p-toluenesulfonate derived from p-to acid sulfonic acid, and the like. Such salts can be obtained by methods well known and described in the art. Other acids such as oxalic acid, which can not be considered acceptable for pharmaceutical use, may be useful in the preparation of salts useful as intermediates in obtaining a chemical compound of the invention and its addition salts acceptable for pharmaceutical use. Examples of acceptable cation salts for pharmaceutical use of a chemical compound of the invention include, without limitation, the sodium, potassium, calcium, magnesium, zinc, aluminum, lithium, choline, lysine and of ammonium, and the like, of a chemical compound of the invention containing an anionic group. Such cation salts can be obtained by methods well known and described in the art. In the context of this invention the "onium salts" of compounds containing N are also considered acceptable salts for pharmaceutical use. Preferred "onium salts" include the alkyl-onium salts, the cycloalkyl-onium salts and the cycloalkylalkyl-onium salts. Examples of pre- or pro-drug forms of the chemical compound of the invention include examples of suitable prodrugs of the substances according to the invention and include compounds modified in one or more reactive or derivatizable groups of the parent compound. Of particular interest are compounds modified in a carboxyl group, a hydroxyl group or an amino group. Examples of suitable derivatives are esters or amides. The chemical compound of the invention can be supplied in soluble or insoluble forms together with a pharmaceutically acceptable solvent such as water, ethanol and the like. The soluble forms may also include hydrated forms such as the monohydrate, the dihydrate, the hemihydrate, the trihydrate, the tetrahydrate and the like. In general, soluble forms are considered equivalent to insoluble forms for the purposes of this invention. Stereoisomers Those skilled in the art will appreciate that the compounds of the present invention may contain one or more chiral centers, and that such compounds exist in the form of isomers. Moreover, the substituent -X-Rb in the 3-position of the 8-aza-bicyclo [3.2.1] octane skeleton of the formula I can be found in particular in exo or endo configuration. In one embodiment of the invention, the substituent in position 3 is in the exo configuration. In another embodiment of the invention, the substituent in position 3 is in the endo configuration. The invention includes all said isomers and any mixture thereof, including racemic mixtures. The racemic forms can be resolved in the optical antipodes by known methods and techniques. One way to separate the isomeric salts is by using an optically active acid, and by releasing the optically active amino compound by treatment with a base. Another method for resolving racemates in the optical antipodes is based on chromatography on an optically active matrix. Thus, the racemic compounds of the present invention can be resolved in their optical antipodes, for example, by fractional crystallization of d- or I- salts (tartrates, mandelates or camphor sulfonates), for example. The chemical compounds herein can also be resolved by formation of diastereomeric amides by reaction of the chemical compounds of the present invention with an optically active activated carboxylic acid such as the derivative of (+) or (-) phenylalanine, (+) or (-) Phenylglycine, acid. { +) or (-) canphaner or by formation of diastereomeric carbamates by reaction of the chemical compound of the present invention with an optically active chloroformate or the like. Additional methods for the resolution of optical isomers are known in the art. Such methods include those described by Jagues J, Collet A, &; Wilen S in "Enantio ers, Racemates, and Resolutions". John Wiley and Sons, New York (1981). Optically active compounds can also be prepared from optically active starting materials. Marked Compounds The compounds of the invention can be used in their labeled or unlabeled form. In the context of this invention "marked" represents the binding of a marker to the compound of interest that will allow the easy quantitative detection of said compound.

The labeled compounds of the invention may be useful as diagnostic tools, radio-tracers, or monitoring agents in various diagnostic methods, and to have images of living receptors. The labeled isomer of the invention preferably contains at least one radionuclide as a label. Radionuclides that emit positrons are all candidates for use. In the context of this invention, the radionuclide is preferably selected from E (deuterium), 3 H (trithium), 13 C, 1 C, 131 I, 125 I, -23 I and 18 F. The physical method for detecting the labeled isomer of the present invention can be selected between Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), Magnetic Resonance Spectroscopy (MRS), for its Acronyms in English), Magnetic Resonance Imaging (MRI), and Axial Computed Tomography by X-ray (CAT, for its acronym in English), or combinations thereof. Methods of Preparation The chemical compounds of the invention can be prepared by conventional methods for chemical synthesis, e.g. those described in the working examples. The starting materials for the processes described in the present application are known or can be easily prepared by conventional methods from commercial chemicals. Also a compound of the invention can be converted to another compound of the invention using conventional methods. The final products of the reactions described herein can be isolated by conventional techniques, e.g. by extraction, crystallization, distillation, chromatography, etc. Biological Activity The compounds of the invention can be tested for their ability to inhibit the re-uptake of the monoamines dopamine, noradrenaline and serotonin in synaptosomes, for example as described in WO 97/30997. Based on the balanced activity observed in these assays, the compound of the invention is considered useful for the treatment, prevention or alleviation of a disease or disorder or condition of a mammal, including a human, disease, disorder or condition that is sensitive to the inhibition of re-uptake of monoamine neurotransmitters in the central nervous system. In a special embodiment, the compounds of the invention are considered useful for the treatment, prevention or relief of: mood disorder, depression, atypical depression, major depressive disorder, dysthymic disorder, bipolar disorder, bipolar I disorder, bipolar II disorder, disorder cyclothymic, mood disorder due to a general medical condition, mood disorder induced by chemical substances, pseudodemexicia, Ganser syndrome, obsessive-compulsive disorder, panic disorder, panic disorder without agoraphobia, panic disorder with agoraphobia, agoraphobia with no history of panic disorder, panic attack, memory deficits, memory loss, attention deficit hyperactivity disorder, obesity, anxiety, generalized anxiety disorder, eating disorder, Parkinson's disease, parkinsonism, dementia, dementia due to aging, dementia senile, Alzheimer's disease, immune complex syndrome acquired efficiency-dementia, memory dysfunction due to aging, specific phobia, social phobia, post-traumatic stress disorder, acute stress disorder, drug addiction, drug abuse, cocaine abuse, nicotine abuse, abuse of tobacco, alcohol addiction, alcoholism, pain, chronic pain, inflammatory pain, neuropathic pain, migrainous pain, tension headache, chronic tension headache, pain associated with depression, fibromyalgia, arthritis, osteoarthritis, rheumatoid arthritis, back pain, pain from cancer , irritable bowel pain, irritable bowel syndrome, post-operative pain, post-stroke pain, drug-induced neuropathy, diabetic neuropathy, pain maintained by the sympathetic system, trigeminal neuralgia, dental pain, myofacial pain, phantom limb pain, bulimia, premenstrual syndrome, late luteal phase syndrome, post-traumatic syndrome, chronic fatigue syndrome , urinary incontinence, stress incontinence, urgency incontinence, nocturnal incontinence, sexual dysfunction, premature ejaculation, erectile difficulty, erectile dysfunction, eating disorders, anorexia nervosa, sleep disorders, autism, mutism, trichotillomania, narcolepsy, post-depression stroke, brain damage induced by cerebrovascular accident, neuronal damage induced by cerebrovascular accident or Gilles de la Tourette's disease. In a preferred embodiment, the compounds are considered useful for the treatment, prevention or relief of depression. It is currently considered that an adequate dose of the active pharmaceutical component (CFA) is in the range of from about 0.1 to about 1000 mg of CFA per day, more preferably from about 10 to about 500 mg of CFA per day, most preferably from about 30 to about 100 mg of CFA per day, depending, however, on the exact mode of administration, the manner in which it is administered, the indication considered, the subject and in particular the body weight of the subject involved, and of the preference and experience of the doctor or veterinarian in charge. Preferred compounds of the invention exhibit biological activity in the sub-micro-olar and micromolar range, i.e. from below 1 to about 100 μM. Pharmaceutical Compositions In another aspect the invention provides novel pharmaceutical compositions comprising a therapeutically effective amount of the chemical compound of the invention. Although a chemical compound of the invention for use in therapy can be administered in the form of a crude chemical compound, it is preferred to introduce the active component, optionally in the physiologically acceptable salt form, into a pharmaceutical composition together with one or more adjuvants. , excipients, vehicles, buffers, diluents, and / or other usual pharmaceutical auxiliaries. In a preferred embodiment, the invention provides pharmaceutical compositions comprising the chemical compound of the invention, or a salt or derivative thereof acceptable for pharmaceutical use, together with one or more vehicles therefor acceptable for pharmaceutical use and, optionally, other ingredients therapeutic and / or prophylactic, known and used in the art. The vehicle (s) must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not detrimental to the recipient thereof. The pharmaceutical compositions of the invention may be those suitable for oral, rectal, bronchial, nasal, pulmonary, topical (including buccal and sub-lingual), transdermal, vaginal or parenteral administration (including cutaneous injection or infusion, subcutaneous, intramuscular, intraperitoneal, intravenous, intraarterial, intracerebral, infraocular), or those in a form suitable for administration by inhalation or insufflation, including administration of liquid aerosols and powders, or by sustained release systems. Suitable examples of sustained release systems include semipermeable matrices of solid hydrophobic polymers containing the compound of the invention, matrices which can take the form of articles with defined form, e.g. films or microcapsules. The chemical compound of the invention, together with a conventional adjuvant, vehicle or diluent, can thus be placed in the form of pharmaceutical compositions and unit dosages thereof. Such forms include solids, and in particular tablets, filled capsules, powder and pellet forms, and liquids, in particular solutions, suspensions, emulsions, aqueous or non-aqueous elixirs, and capsules filled therewith, all for oral use, suppositories for rectal administration, and sterile injectable solutions for parenteral use. Such pharmaceutical compositions and unit dosage forms thereof may comprise conventional ingredients in conventional proportions, with or without additional active compounds or principles, and such unit dosage forms may contain any suitable effective amount of the active component consistent with the daily dosage range proposed to use. The chemical compound of the present invention can be administered in a wide variety of oral and parenteral dosage forms. It will be obvious to those skilled in the art that the following dosage forms may comprise, as an active component, both a chemical compound of the invention and a pharmaceutically acceptable salt of a chemical compound of the invention. To prepare pharmaceutical compositions from a chemical compound of the present invention, vehicles acceptable for pharmaceutical use can be both solid and liquid. Solid form preparations include powders, tablets, pills, capsules, seals, suppositories and dispersible granules. A solid carrier may be one or more substances which may also act as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders, preservatives, debulking agents or an encapsulating material. In powders, the vehicle "is a finely divided solid, which is mixed with the finely divided active component." In tablets, the active component is mixed with the vehicle having the necessary binder capacity in suitable proportions in the desired shape and size. The powders and tablets preferably contain from five or ten to about seventy percent of the active compound, suitable carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethyl cellulose, a low melting point wax, cocoa butter and the like The term "preparation" aims to include the formulation of the active compound with the encapsulating material as a vehicle that provides a capsule in which the active component, with or without vehicles, it is surrounded by a vehicle, which is thus in association with it. seals and pills: Tablets, powders, capsules, pills, seals and pills can be used as solid forms suitable for oral administration. To prepare suppositories, a low melting point wax is first melted, such as a mixture of fatty acid glycerides or cocoa butter, and the active component is dispersed homogeneously therein, as by agitation. The molten homogeneous mixture is then poured into molds of suitable sizes, allowed to cool and, therefore, solidify. Compositions suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or sprays containing in addition to the active component vehicles such as those known in the art as appropriate. The preparations include solutions, suspensions and emulsions, for example, solutions in water or water-propylene glycol. For example, liquid preparations for parenteral injection can be formulated as solutions in aqueous polyethylene glycol solution. The chemical compound according to the present invention can thus be formulated for parenteral administration (eg by injection, for example bolus injection or continuous infusion) and can be presented in unit dosage form in ampoules, pre-filled syringes, infusion of small volume or in multi-dose containers with an added preservative. The compositions can adopt forms such as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and / or dispersing agents. Alternatively, the active component can be in powder form, obtained by aseptic isolation of a sterile solid or by "freeze-drying from a solution, for constitution with a suitable vehicle, eg sterile, pyrogen-free water, before use. Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding coloring, flavoring, stabilizing and thickening agents, as described.An aqueous suspensions for oral use can be made by dispersing the active component in water with viscous materials, such as gums natural or synthetic, resins, methylcellulose, sodium carboxymethylcellulose, or other well-known suspending agents Also included are preparations in solid form, intended for conversion, shortly before use, into liquid form preparations for oral administration. solutions, suspensions and emulsions. The active component such preparations may comprise colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents and the like. For topical administration to the epidermis, the chemical compound of the invention can be formulated as ointments, creams or lotions, or as a transdermal patch. The ointments and creams can be formulated, for example, with an aqueous or oily base with the addition of suitable thickeners and / or gelling agents. The lotions can be formulated with an aqueous or oily base and will generally also contain one or more emulsifying agents, stabilizing agents, dispersing agents, suspending agents, thickening agents or coloring agents. Compositions suitable for topical administration in the mouth include lozenges comprising the active agent in a flavored base, usually sucrose and acacia or tragacanth.; pills comprising the active component in an inert base such as gelatin and glycerin or sucrose and acacia; and mouth rinses comprising the active component in a suitable liquid vehicle. The solutions or suspensions are applied directly to the nasal cavity by conventional means, for example with a dropper, pipette or sprinkler. The compositions can be delivered in single dose or multi-dose form. Administration to the respiratory tract can also be achieved by means of an aerosol formulation in which the active component is provided in a pressurized container with a suitable oroprene such as a chlorofluorocarbon (CFC), for example dichlorodifluoromethane, trichlorofluoromethane or dichlorotetrafluoroethane, dioxide carbon or other suitable gas. The aerosol may also conveniently contain a surfactant such as lecithin. The dose of the drug can be controlled by providing a metering valve. Alternatively, the active components can be supplied as a dry powder, for example a powder mixture of the compound in a suitable powder base such as lactose, starch, starch derivatives such as hydroxypropylmethyl cellulose and polyvinylpyrrolidone (PVP). Conveniently, the powder vehicle will form a gel in the nasal cavity. The powder composition can be presented in unit dosage form, for example in capsules or cartridges, e.g.; gelatin, or blister packs from which the powder can be administered by means of an inhaler. In compositions intended for administration to the respiratory tract, including intranasal compositions, the compound will generally have a small particle size, for example of the order of 5 microns or less. Such a particle size can be obtained by means known in the art, for example by micronizing. When desired, compositions adapted to give sustained release of the active component may be employed.

The pharmaceutical preparations are preferably in unit dosage forms. In such form, the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as tablets, capsules and powders packed in vials or ampoules. Also, the unit dosage form can be the capsule itself, tablet, seal or tablet, or it can be the appropriate number of any of these in packaged form. Tablets or capsules for oral administration and liquids for intravenous administration and continuous infusion are preferred compositions. More details on techniques for formulation and administration can be found in the latest edition of Reminqton's Pharmaceutical Sciences (Maack Publishing Co., Easton, PA). A therapeutically effective dose refers to that amount of active component that alleviates the symptoms or condition. Therapeutic efficacy and toxicity, eg. ED50 and LD5n can be determined by standard pharmacological procedures in cell cultures or experimental animals. The dose ratio between the therapeutic and toxic effects is the therapeutic index and can be expressed by the LD5c / ED5c ratio. Pharmaceutical compositions exhibiting high therapeutic indices are preferred. The dose administered must, of course, be carefully adjusted to the age, weight and condition of the individual treated, as well as to the route of administration, dosage form and regimen, and the desired result, and the exact dose should be determined, by course, by the intervening doctor. The actual dose depends on the nature and severity of the treatment, and is within the good judgment of the physician, and can be varied by titration of the dose to the particular circumstances of this invention to produce the desired therapeutic effect. However, it is currently considered that pharmaceutical compositions containing from about 0.1 to about 500 mg of the active component per individual dose, preferably from about 1 to about 100 mg, most preferably from about 1 to about 10 mg, are suitable for treatments therapeutic The active component can be administered in one or several doses per day. A satisfactory result can be obtained, in certain cases, at a dose as low as 0.1 (μg / kg iv and 1 μg / kg po It is currently considered that the upper limit of the dosage range is approximately 10 mg / kg iv and 100 mg / kg po Preferred ranges are from about 0.1 μg / kg to about 10 mg / kg / day iv, and from about 1 μg / kg to about 100 mg / kg / day po Therapeutic Methods In another aspect the invention provides a method for the treatment, prevention or alleviation of a disease or a disorder or condition of a living animal organism, including a human, disease, disorder or condition that is sensitive to the inhibition of re-uptake of monoamine neurotransmitters in the system central nervous system, and which method comprises administering to a living animal organism, including a human, in need thereof, an effective amount of a chemical compound of the invention. suitable dosing doses are from 0.1 to 1000 milligrams daily, 10-500 milligrams daily, and especially 30-100 milligrams daily, depending as usual on the exact modality of administration, of the way it is administered, of the indication to which is directed the administration, the subject involved and the body weight of the subject involved, and in addition to the preference and experience of the doctor or veterinarian in charge.

EXAMPLES The invention is further illustrated with reference to the following examples, which are not intended to be in any way limiting the scope of the claimed invention. General: All reactions involving reagents or air-sensitive intermediates were carried out under nitrogen atmosphere and in anhydrous solvents. Magnesium sulfate was used as a drying agent in the processing processes and the solvents were evaporated under reduced pressure. Method A endo-3- (3, 4,5-Trichlorothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, fumaric acid salt A mixture of tetrachlorothiophene (5.48 g, 24.69 mmol), tropine (endo-8-methyl- 8-azabicyclo [3.2.1] octan-3-ol) (3.48 g, 24.69 mmol), potassium tert-butoxide (4.16 g, 37.04 mmol), 18-crown-6-ether (6.53 g, 24.69 mmol) and DMF (50 mL) was stirred at 100 ° C for 15 h . Aqueous hydrochloric acid (50 ml, 4 M) was added to the mixture. The mixture was washed with diethyl ether (2 x 100 mL). Aqueous sodium hydroxide (100 ml, 4 M) was added. The mixture was extracted with ethyl acetate (3 x 100 mL). The organic phase was washed with aqueous sodium chloride (3 x 50 mL). Yield 2.65 g (33%). The corresponding salt was obtained by adding a mixture of diethyl ether and methanol (9: 1) saturated with fumaric acid. Pf. 200. -206.4 ° C. endo-3- (3,4-Dichlorothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane It was prepared according to method A from 2, 3, 4-trichlorothiophene and trppine ( endo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol), isolating as free and oily base. exo-3- (3, 4,5-Trichlorothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane hydrochloride Prepared according to method A from tetrachlorothiophene and pseudo-tropine (exo) -8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Mp. 249-250 ° C. exo-3- (1,2-Benzoisothiazol-3-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane hydrochloride Prepared according to method A from 3-chloro-l, 2-benzoisothiazole and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Pf. 259.4-261.2 ° C. exo-3- (5-Bro-thothiazol-2-yloxy) -8-methyl-8-azabiecyclo [3.2.1] octane It was prepared according to method A from 2, 5-dibromothiazole and pseudo-tropine (exo- 8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Isolated as a free base. Mp. 104-106 ° C. exo-3- (Benzothiazol-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method A from 2-chlorobenzothiazole and pseudo-tropine (exo) -8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Mp. 160-162 ° C. EXO-3- (6-Chlorobenzothiazol-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method A from 2,6-dichlorobenzothiazole and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Mp. 163-164.5 ° C. exo-3- (Quinoxalin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, salt of phthamaric acid Prepared according to method A from 2-chloroquinoxaline and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Mp. 208-210 ° C. exo-3- (quinolin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method A from 2-chloroquinoline and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Pf. 192.5-195 ° C. exo-3- (Benzoxazol-2-yloxy) -8-methyl-8-azabisyclo [3.2.1] octane, salt of fumaric acid Prepared according to method A from 2-chlorobenzoxazole and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Pf. 141-144 ° C. exo-3- (6-chloro-pyridazin-3-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method A from 3,6-dichloropyridazine and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Mp. 181-183 ° C. EXO-3- (5-Chloro-pyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, salt of fumaric acid It was prepared according to method A from 2, 5-dichloropyridine and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-oI). Mp. 214-216 ° C. exo-3- (lsoquinolin-1-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method A from 1-chloroisoquinoline and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Pf. 180-181.5 ° C. exo-3- (6-chloropyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method A from 2,6-dichloropyridine and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Mp. 202-204 ° C. exo-3- (5-Bromopyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method A from 2, 5-dibromopyridine and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Mp. 213-215 ° C. exo-3- (6-Bromopyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method A from 2,6-dibromopyridine and pseudo -tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Mp. 198-200 ° C. exo-3- (5-Bromopyrimidin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method A from -bromo-2-chloropyrimidine and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Mp. 198-200 ° C. exo-3- (Quinazolin-2-yloxy) -8-methyl-8-azabicyclo [3.2.13 octane, fumaric acid salt] Prepared according to method A from 2-chloroquinazolin and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Pf. 209-211 ° C. EXO-3- (5-Trifluoromethylpyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method A from 2-chloro-5-trifluoromethylpyridine and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Pf. 190-191.5 ° C. exo-3- (3,4,5-Tribromothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane hydrochloride Prepared according to method A from tetrabromothiophene and pseudo-tropine (exo) -8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Pf. 223.3-223.9 ° C. exo-3- (4-Bromothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane hydrochloride Prepared from exo-3- (3,4,5-tribromothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane with 5 eq. of zinc powder in concentrated acetic acid at 75 ° C during h. The processing procedure was carried out according to method A. Pf. 222.1 ° C. endo-3- (3-Bromo-5-chloro-thiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method A from 3-bromo-2, 5-dichlorothiophene and tropine (endo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol) Mp. 171-173 ° C. endo-3- (4-Bromo-5-chloro-thiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method A from 3-bromo-2, 5-dichlorothiophene and tropine (endo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol) Mp. 136-139 ° C. Method B endo-3- (3,4,5-Trichlorothio-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane A mixture of endo-3- (3,4,5-trichlorothiophene) 2-yloxy) -8-methyl-8-azabicyclo- [3.2.1J octane (0.50 g, 1.53 mmol), 1-chloroethyl chloroformate (1.27 ml, 11.5 mmol) and toluene (20 ml) was stirred under reflux for 15 h . Water (10 ml) was added and the mixture was stirred at reflux for 3.5 h. The mixture was evaporated. Sodium methoxide in methanol (5 ml, 1 M) and silica gel 60 (2 g) was added and evaporation was continued. Chromatography of the crude mixture on silica gel with dichloromethane, methanol and conc. Ammonia. (89: 10: 1) gave the title compound with quantitative yield as a free and oily base. exo-3- (2,3-Dichlorophenoxy) -8-H-8-azabicyclo [3.2.1] octane It was prepared according to method B. It was isolated as free base. Mp. 62.3-65.4 ° C. exo-3- (3,4-dichlorophenoxy) -8-H-8-azabicyclo [3.2.1] octane hydrochloride Prepared according to the method B. Pf. 160.1 ° C. EXO-3- (3,4,5-Trichlorothiophen-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane hydrochloride Prepared according to Method B. Pf. 255-256 ° C. EXO-3- (3-Chloro-4-fluorophenoxy) -8-H-8-azabicyclo [3.2, 1] octane, fumaric acid salt Prepared according to method B. Pp. 151-154 ° C. EXO-3- (3-Chloro-phenoxy) -8-H-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to the method B. Pf. 195-196 ° C. exo-3- (4-chloro-3-fluorophenoxy) -8-H-8-azabicyclo [3.2.1] octane It was prepared according to method B. It was isolated as free and oily base. exo-3- (4-chloro-phenoxy) -8-H-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method B. Pp. 188-188.5 ° C. exo-3- (2-Chloro-3-trifluoro and yl-phenoxy) -8-H-8-azabicylo [3.2.1] octane, salt of fumaric acid Prepared according to method B. Pf. 190-193 ° C. exo-3- (Fluoren-9-one-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane It was prepared according to method B. It was isolated as free base. Pf. 242.8-256.3 ° C. exo-3- (1, 2-Benzoisothiazol-3-yloxy) -8-H-8-azabicyclo [3.2.1] octane hydrochloride Prepared according to method B from 3-chloro-l, 2-benzoisothiazole and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Pf. 252.5 ° C. exo-3- (3,4-dichlorophenylthio) -8-methyl-8-azabisyclo [3.2.1], octane, salt of fumaric acid Prepared according to method B. Pf. 194-196 ° C. endo-3- (3,4-Dichlorophenoxy) -8-H-8-azabicyclo [3.2.1] octane hydrochloride Prepared according to "the method B. Pf. 287 ° C. exo-3- (4-chloro) -3-trifluoromethylphenoxy) -8-H-8-azabicyclo [3.2.1] octane salt of fumaric acid Prepared according to the method B. Pf. 215-217 ° C. Exo-3- (2-Dibenzofuranyloxy) - 8-H-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method B. Pf. 217-221 ° C. Exo-3- (1-Naphthyloxy) -8-H-8 -azabisyclo [3.2.1] octane, salt of fumaric acid Prepared according to Method B. Pf. 223-224 ° C. exo-3- (2-Naphoryloxy) -8-H-8-azabicyclo [3.2 .1] octane, fumaric acid salt It was prepared according to the method B. Pp. 202-204 ° C. exo-3- (3-Chloro-4-cyanophenoxy) -8-H-8-azabicyclo [3.2. 1] octane, salt of fumaric acid Prepared according to method B. Pf. 176.3-178.9 ° C. exo-3- (4-Chloro-3-methylphenoxy) -8-H-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to the method B. Pf. 192.5-194.5 ° C. exo-3- (4-chloronaf-alen-1-yloxy) -8-H-8-azabisislo [3.2.1] octane, salt of fumaric acid Prepared according to method B. Pf. 226-227 ° C. exo-3- (quinolin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method B. Pf. 211-213 ° C. exo-3- (5-chloro-pyridin-2-yl) -8-H-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method B. Pp. 196-199 ° C . exo-3- (4-Methoxyphenoxy) -8-H-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to the method B. Pf. 137-147 ° C. EXO-3- (Isoquinolin-5-yloxy) -8-H-8-azabicyclo [3.2.1] Octane, fumaric acid salt Prepared according to the method B. Pf. 192-194 ° C. exo-3- (6-Bromo-naphthalen-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane hydrochloride Prepared according to method B. It was isolated as free base. Mp. 270-274 ° C. exo-3- (4-Bromo-3-chloro-phenoxy) -8-H-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method B. Pf. 207-209 ° C . exo-3- (quinolin-6-yloxy) -8-H-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method B. Pf. 237-239 ° C. EXO-3- (4-Trifluorophenoxy) -8-H-8-azabicyclo [3.2.1] octane hydrochloride Prepared according to method B. Pp. 178-180 ° C. EXO-3- (4-Cyanophenoxy) -8-H-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to the method B. Pf. 188.9-191.6 ° C. exo-3- (quinolin-8-yloxy) -8-H-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method B. Pp. 182-184.5 ° C.

EXO-3- (4-Methylphenoxy) -8-H-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method B. Pf. 174-177 ° C. exo-3- (6-chloropyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method B from 2,6-dichloropyridine and pseudo -tropine (exo-'8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Mp. 202-204 ° C. exo-3- (5-Bromopyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to the method B. Pf. 216-218 ° C. exo-3- (6-Bromopyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to the method B. Pf. 218-220 ° C. exo-3- (lsoquinolin-1-yloxy) -8-H-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method B from 1-chloroisoquinoline and pseudo-tropine (exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol). Mp. 215-217 ° C. EXO-3- (3-Trifluoromethoxy-noxy) -8-H-8-azabicyclo [3.2.1] octane It was prepared according to method B. It was isolated as free base. Mp. 185.5-187 ° C. EXO-3- (4-Trifluoromethoxyphenoxy) -8-H-8-azabicyclo [3.2.1] O-one. Method B was prepared according to COTI. It was isolated as a free base. Mp. 192.5-194 ° C. exo-3- (6-Methoxypyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method B). Pf. 200-202 ° C. EXO-3- (5-Trifluoromethylpyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to the method B. Pf. 196.5-198.5 ° C. exo-3- (6-Ethoxypyridin-2-yloxy) -8-H-8-azabisyclo [3.2.1] octane, fumaric acid salt Prepared according to the method B. Pf. 192.5-194.5 ° C. EXO-3- (4-Fluoro-3-trifluoromethylphenoxy) -8-H-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method B. Pp. 182-185 ° C. Method C exo-3- (2,3-Dichlorophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane, fumaric acid salt Diethylazodicarboxylate (8.36 ml, 53.1 mmol) was added dropwise at room temperature to a mixture of tropine (endo-S-methyl-S-azabicyclo- [3.2.1] octan-3-ol) (5.0 g, 35.4 mmol), 2,3-dichlorophenol (6.93 g, 42.5 mmol), triphenylphosphine (13.9 g) , 53.1 mmol) and dioxane (55 ml). The mixture was stirred for 40 h at 100 ° C. Aqueous sodium hydroxide (100 ml, 1 M) was added to the mixture. The mixture was extracted with dichloromethane (2 x 100 mL). Chromatography on silica gel with methanol, dichloromethane and acetone (1: 4: 1) gave the title compound. Yield 6.22 g (61%). The corresponding salt was obtained by adding a mixture of diethyl ether and methanol (9: 1) saturated with fumaric acid. Pf. 171.3-194.7 ° C. exo-3- (3,4-dichlorophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method C. Pf. 225.6 ° C. exo-3- (3-Chloro-4-fluorophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane It was prepared according to method C. It was isolated as free and oily base. exo-3- (4-chloro-3-fluorophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane It was prepared according to method C. It was isolated as free and oily base. exo-3- (2-Chloro-3-trifluoromethylphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane It was prepared according to method C. It was isolated as free and oily base. exo-3- (3-Chloro-phenoxy) -8-methyl-8-azabicyclo [3.2.1] octane salt of oxalic acid Prepared according to method C. Pf. 208-209 ° C. exo-3- (4-chloro-phenoxy) -8-methyl-8-azabicyclo [3.2.1] octane oxalic acid salt Prepared according to method C. Pf. 150.5-154.0 ° C. exo-3- (Fluoren-9-one-2-yloxy) -8-methyl-8-azabicyclo [3.2.13 octane hydrochloride] Prepared according to the method C. Pf. decomp. EXO-3- (3,4-Dichlorophenyl) -8-methyl-8-azabicyclo [3.2.13 octane, salt of fumaric acid Prepared according to method C from 3,4-dichlorothiophenol. Mp. 179-181 ° C. exo-3- (1-Naphoryloxy) -8-methyl-8-azabicyclo [3.2.13 octane] Prepared according to method C. It was isolated as free base. Mp. 72-74 ° C. exo-3- (2-Naphthyloxy) -8-methyl-8-azabicyclo [3.2.13 octane] Prepared according to method C. It was isolated as free base. Mp. 83-86 ° C. EXO-3- (4-Chloro-3-trifluoromethylphenoxy) -8-methyl-8-azabicyclo [3.2.1] -octane, fumaric acid salt Prepared according to method C. Pf. 172.3-174.2 ° C. exo-3- (3-Chloro-4-cyanophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method C. Pf. 191.7-194.3 ° C. exo-3- (2-Dibenzofuranyloxy) -8-methyl-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method C. Pf. 199.9-202.0 ° C. EXO-3- (4-Chloronaphthalen-1-yloxy) -8-methyl-8-azabicyclo [3.2.13 octane, fumaric acid salt] Prepared according to method C. Pf. 198-199 ° C. EXO-3- (4-Chloro-3-methylphenoxy) -8-methyl-8-azab-cyclo [3.2.1] octane, salt of fumaric acid Prepared according to method C. Pf. 230-232 ° C. exo-3- (4-Me-oxyphenoxy) -8-methyl-8-azabicyclo [3.2.13 octane, fumaric acid salt] Prepared according to method C. Pf. 164.5-166.5 ° C. exo-3- (7-Methoxynaphthalen-2-yloxy) -8-methyl-8-azabicyclo [3.2.13 octane, fumaric acid salt] Prepared according to method C. Pf. 143-145 ° C. exo-3- (6-methoxy-naph-alen-2-yloxy) -8-methyl-8-azabisyclo [3.2. I] octane, salt of fumaric acid Prepared according to method C. Pf. 78.5-81.5 ° C. exo-3- (4-Bromo-3-chloro-phenoxy) -8-methyl-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method C. Pf. 218-220 ° C . exo-3- (lsoquinolin-5-yl) -8-methyl-8-azabicyclo [3.2.13 octane, fumaric acid salt] Prepared according to the method C. Pf. 193-196 ° C. EXO-3- (6-Bromo-naphthalen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane, salt of fumaric acid Prepared according to method C. Pf. 227-229 ° C. exo-3- (3-Methoxyphenoxy) -8-methyl-8-azabisislo [3.2.13 octane, salt of fumaric acid Prepared according to method C. Pf. 144-147 ° C. EXO-3- (4-Cyanofinoxy) -8-methyl-8-azabisislo [3.2.13 octane, salt of fumaric acid Prepared according to method C. Pf. 177.9-181.9 ° C. exo-3- (quinolin-6-yloxy) -8-methyl-8-azabicyclo [3.2.13 octane, fumaric acid salt] Prepared according to method C. Pf. 221-223 ° C. exo-3- (1,2,3,4-Tetrahydronaphthalen-6-yloxy) -8-methyl-8-azabicialo [3.2.13 -octane, fumaric acid salt] Prepared according to method C. Pf. 165.9 - 167.2 ° C. EXO-3- (4-Trifluoromethylphenoxy) -8-methyl-8-azabisyclo [3.2.13 octane, salt of fumaric acid Prepared according to method C. Pf. 184.1-186.5 ° C. exo-3- (4-Methylphenoxy) -8-methyl-8-azabisislo [3.2.1] ostano, salt of fumaric acid Prepared according to method C. Pf. 178-181 ° C.

EXO-3- (8-Quinolinyl) -8-methyl-8-azabicyclo [3.2.1] octane, fumaric acid salt Prepared according to method C. Pf. 158-160 ° C. EXO-3- (5-LNANYLYOXY) -8-METHYL-8-AZABYSTIDE [3.2.1] OSTANE, FUMARIC ACID SALT It was prepared according to method C. Pf. 184.7-185.9 ° C. exo-3- (4-methoxy-naph-alen-1-yloxy) -8-methyl-8-azabicialo [3.2.13 ostano, fumaric acid salt] Prepared according to method C. Pf. 185-188 ° C. exo-3- (indol-5-yloxy) -8-methyl-8-azabicyclo [3.2.13 ostano, fumaric acid salt] Prepared according to method C. Pf. 176.3- 178.3 ° C. EXO-3- (3-Trifluoromethoxyphenoxy) -8-methyl-8-azabicyclo [3.2.13 octane] Prepared according to method C. It was isolated as free base. Oil. EXO-3- (4-Trifluoromethoxyphenoxy) -8-methyl-8-azabicyclo [3.2.13 octane] Prepared according to method C. It was isolated as a free base. Oil.

EXO-3- (4-Fluoro-3-trifluoromethylphenoxy) -8-methyl-8-azabicyclo [3.2.13 -octane, fumaric acid salt] Prepared according to method C. Pf. 167-169 ° C. Method D endo-3- (3,4-Dichlorophenoxy) -8-methyl-8-azabisislo [3.2.13 ostano, salt of the fumiduous acid A mixture of endo-3-chloro-8-methyl-8-azabicyclo [3.2. 1] octane (3.9, 24 mmol), (prepared from exo-8-methyl-8-azabicyclo [3.2.1] octan-3-ol and thionic chloride at reflux for 3 h), 3,4-dichlorophenol (5.9 g, 36 mmol), 60% sodium hydride (1.2 g, 36 mmol) and ethanol (30 mL) was stirred at reflux for 15 h. Aqueous hydrochloric acid (50 ml, 4 M) was added to the mixture. The ethanol was evaporated. The mixture was washed with diethyl ether (3 x 50 mL). Aqueous sodium hydroxide (50 ml, 4 M) was added. The mixture was extracted with diethyl ether (3 x 50 mL). Chromatography of the crude mixture on silica gel with dichloromethane, methanol and conc. Ammonia. (89: 10: 1) gave the title compound. The corresponding salt was obtained by adding a mixture of diethyl ether and methanol (9: 1) saturated with fumaric acid. Yield 0.90 g (9%). Pp. 198.0-207.7 ° C.

Method E exo-3- (3,4-Dichlorophenoxy) -8- (2-hydroxyethyl) -8-azabicyclo [3.2.13 octane A mixture of exo-3- (3,4-dichlorophenoxy) - 8-H- 8-azabicyclo [3.2.1] octane (2.2 g, 8.1 mmol), 2-bromoethanol (0.6 ml, 8.9 mmol), potassium carbonate (1.1 g, 8.1 mmol) and ethanol (20 ml) was stirred under reflux for 15 h. h. Aqueous sodium hydroxide (50 ml, 4 M) was added. The mixture was extracted with dichloromethane (3 x 50 mL). Chromatography of the crude mixture on silica gel with dichloromethane, methanol and conc. Ammonia. (89: 10: 1) gave the title compound as a free and oily base. Yield 0.40 g (16%). EXO-3- (3,4-DICHOROPHENOXY) -8- (Cyanomethyl) -8-azabicyclo [3.2.13 OSTANATE, FUMARISM ACID SALT It was prepared according to the method E.Pf. 79-82 ° C. exo-3- (3,4-Dichlorophenoxy) -8- (cyclopropylmethyl) -8-azabicyclo [3.2.1] -octane, fumaric acid salt Prepared according to the method E. Pf. 187-189.5 ° C. exo-3- (3,4-dichlorophenoxy) -8- (allyl) -8-azabisislo [3.2.13 ostano, salt of the fumidic acid was prepared according to the method E. Pf. 202-20ß ° C. exo-3- (3,4-dichlorophenoxy) -8- (methoxyethyl) -8-azabisislo [3.2.1] ostano, salt of the fumidic acid Was prepared according to the method E. Pf. 177.8-179.5 ° C. Method F exo-3- (6-methoxypyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.13 ostano, fumaric acid salt A mixture of exo-3- (6-chloropyridin-2-yloxy) - 8-Methyl-8-azabicyclo [3.2.1] -octane (6.5 g, 25.8 mmol), sodium methoxide (6.5 g, 0.12 mol) and NMP (30 mL) was stirred at 130 ° C for 15 h. Water (300 ml) was added. The mixture was extracted with diethyl ether (3 x 150 mL). The corresponding salt was obtained by adding a mixture of diethyl ether and methanol (9: 1) saturated with fumaric acid. Performance 3.0 g - (32%). Mp. 176-177.5 ° C. exo-3- (6-Ethoxypyridin-2-yloxy) -8-methyl-8-azabicialo [3.2.13 ostano, salt of fumaric acid Prepared according to method F, MP 177-179 ° C. exo-3- (6-Hydroxy-pyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.13 octane, salt of fumaric acid Prepared from exo-3- (6- (cis-methylvinyloxy) -pyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane by stirring with concentrated hydrochloric acid at reflux for 0.5 h. The processing was carried out according to the method F. Pf. 196.5-200 ° C. Method G exo-3- (6-Cyano-naphthalen-2-lloxy) -8-methyl-8-azabisislo [3.2.13 ostano, salt of the fumaric acid a mixture of exo-3- (6-bromo-naft -2-yloxy) -8-methyl-8-azabicyclo [3.2.1] -octane (2.6 g, 7.5 mmol), Zn (CN) 2 (2.2 g, 18 mmol), paladacycle (50 mg) and dioxane (30 mg). mi) was stirred at reflux for 70 h. Aqueous sodium hydroxide (50 ml, 1 M) was added to the mixture. The mixture was extracted with dichlorocethane (2 x 50 mL). Chromatography on silica gel with methanol, dichloromethane and aqueous ammonia (1: 9: 1%) gave the title compound. Yield 2.06 g, (94%). The corresponding salt was obtained by adding a mixture of diethyl ether and methanol (9: 1) saturated with fumaric acid. Mp. 230-232 ° C. Method H exo- (3, 4-Dichloro-phenyl) - (8-methyl-8-aza-bicyclo [3.2.13 ost-3-yl) -amine salt of the fumidic acid) A mixture of 3,4-dichloroformanilide (0.6 was prepared at 0 ° C. g, 3.17 mmol), tropine methanesulfonate toluenesulfonate (1.24 g, 3.17 mmol) [S. rcher et. to the. JACS 80, 4677-4691 (1958)], sodium hydride (0.17 g, 6.97 mmol) and DMF (5 ml). The mixture was stirred for 15 h at room temperature. Aqueous sodium hydroxide (5 ml, 1 M) was added to the mixture. The mixture was extracted with dichloromethane (2 x 5 mL).

Chromatography on silica gel with methanol, dichloromethane and aqueous ammonia (10: 89: 1) gave the title compound. The corresponding salt was obtained by adding a mixture of diethyl ether and methanol * (9: 1) saturated with fumaric acid. Yield 23 mg, (2%). Pf. 193.5-202.0 ° C. endo- (3, 4-Dichloro-phenyl) - (8-methyl-8-aza-bicyclo [3.2.13 ost-3-yl) -formylamine, salt of fumaric acid) It was isolated from the above reaction mixture in accordance with Method I. Yield 32 mg, (3%). Mp. 206.3 ° C. EXO- (3, 4-Dichloro-phenyl) - (8-methyl-8-aza-bicyclo [3.2.13 oct-3-yl) -formylamine, fumaric acid salt) Prepared by formylation with concentrated formic acid from exo- (3,4-dichloro-phenyl) - (8-methyl-8-aza-bicyclo [3.2.1] oct-3-yl) -amine. The processing was carried out according to the method I. Pf. 150.5-153.0 ° C. It is noted that in relation to this date, the best method known by the applicant to carry out the said invention is that which is clear from the present description of the invention.

Claims (4)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. A derivative of 8-aza-bicyclo [3.2.1] octane of Formula I: or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof, characterized in that Ra represents hydrogen or alkyl; alkyl that is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitro, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl; X represents -O-, -S- or -NRC-; where Rc represents hydrogen, alkyl, -C (= 0) Rd or -S02R2 where R ->. d represents hydrogen or alkyl; Rb represents an aryl or heteroaryl group, aryl or heteroaryl group which is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitro, oxo, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl.
2. 2. The chemical compound according to claim 1, characterized in that Ra represents hydrogen.
3. 3. The chemical compound according to claim 1, characterized in that Ra represents methyl.
4. 4. The chemical compound according to any of claims 1-3, characterized in that X represents -O-. 5t ~ The chemical compound according to any of claims 1-3, characterized in that X represents -S-. 6. The chemical compounds according to any of claims 1-5, characterized in that Rb represents an aryl or heteroaryl group, aryl or heteroaryl group that is -substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, oxo, alkyl and alkoxy. 7. The chemical compound according to any of claims 1-5, characterized in that Rb represents a phenyl group, phenyl group which is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy. 8. The chemical compound according to any of claims 1-5, characterized in that Rb represents a thienyl group, thienyl group which is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy. 9. The chemical compound according to any of claims 1-5, characterized in that Rb represents a pyridyl group, pyridyl group which is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, * trifluoromethoxy, cyano, hydroxy and alkoxy. 10. The chemical compound according to claim 1, characterized in that it is: endo-3- (3,4,5-Trichlorothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; endo-3- (3,4-Dichlorothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3,4,5-Trichlorothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (1, 2-Benzoisothiazol-3-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (5-Bromothiazol-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (Benzothiazol-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; Exo-3- (6-Chlorobenzothiazol-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (Quinoxalin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; Exo-3- (Quinolin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (Benzoxazol-2-yloxy) -8-methyl-8-azabicyclo [3.2.2] 1-octane; exo- 3- (6-chloro-pyridazin-3-yloxy-8-methyl-8-azabicyclo [3.2.1] octane; * exo-3- (5-chloro-pyridin-2-yloxy) -8-methyl- 8-azabicyclo [3.2.1] octane; exo-3- (isoquinolin-1-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-Chloropyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (5-Bromopyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-Bromopyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (5-Bromopyrimidin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (Quinazolin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (5-Trifluoromethylpyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3,4,5-Tribromothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Bromothiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; endo-3- (3-Bromo-5-chloro-thiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; endo-3- (4-Bromo-5-doro-thiophen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; endo-3- (3,, 5-Trichlorothiophen-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (2,3-Dichlorophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3,4-dichlorophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3,4,5-Trichlorothiophen-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3-Chloro-4-fluorophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3-Chloro-phenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloro-3-fluorophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloro-phenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (2-Chloro-3-trifluoromethyl-phenoxy-dHd-azabicyclo [3.2.1] octane; exo-3- (Fluoren-9-one-2-yloxy) -8-H-8-azabicyclo [3.2 .1] octane; exo-3- (1, 2-Benzoisothiazol-3-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3, -Dichlorophenylthio) -8-methyl-8-azabicyclo [3.2.1] octane; endo-3- (3,4-Dichlorophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloro-3-trifluoromethylphenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (2-Dibenzofuranyloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (1-Naphthyloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (2-Naphthyloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3-Chloro-4-cyanophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloro-3-methylphenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloronaphthalen-1-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (quinolin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (5-Chloro-pyridin-2-yl) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Methoxyphenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (isoquinolin-5-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (6-Bromo-naphthalen-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Bromo-3-chloro-phenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (quinolin-6-yloxy) -8 * -H-8-azabicyclo [3.2.1] octane; exo-3- (4-Trifluorophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Cyanophenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (quinolin-8-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Methylphenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (6-Chloropyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (5-Bromopyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (6-Bromopyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (Isoquinolin-1-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (3-Trifluoromethoxyphenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Trifluoromethoxyphenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (6-Methoxypyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (5-trifluoromethylpyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (6-Ethoxypyridin-2-yloxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (4-Fluoro-3-trifluoromethylphenoxy) -8-H-8-azabicyclo [3.2.1] octane; exo-3- (2,3-Dichlorophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3,4-Dichlorophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3-Chloro-4-fluorophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloro-3-fluorophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; Exo-3- (2-Chloro-3-trifluoromethyl-phenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3-Chloro-phenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloro-phenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (Fluoren-9-one-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3,4-dichlorophenylthio) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (1-Naphthyloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (2-Naphthyloxy) -8-methyl-l-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloro-3-trifluoromethyl-phenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3-Chloro-4-cyanophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (2-Dibenzofuranyloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Chloronaphthalen-1-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo3- (4-Chloro-3-methylphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Methoxyphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (7-Methoxynaphthalen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-Methoxynaphthalen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Bromo-3-chloro-phenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (Isoquinolin-5-yl) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-Bromo-naphthalen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3-Methoxyphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Cyanophenoxy) -8-methyl-8-azabicyclo [3.2.1] octane, -exo-3- (quinolin-6-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (1,2,3,4-Tetrahydronaphthalen-6-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Trifluoromethylphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Methylphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (8-quinolinyl) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (5-Indanyloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3 - (4-methoxy-naphthalen-1-yloxy) -8-methyl-8-azabicyclo [3. 2 . 1] octane; exo- 3 - (Indol-5-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (3-Trifluoromethoxyphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Trifluoromethoxyphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (4-Fluoro-3-trifluoromethylphenoxy) -8-methyl-8-azabicyclo [3.2.1] octane; endo-3- (3,4 -Dichlorophenoxy) '- 8 -methyl-8-azabicyclo [3.2.1] octane; exo-3- (3,4 -Dichlorophenoxy) -8- (2-hydroxyethyl) -8-azabicyclo [3.2.1] octane; exo-3- (3,4 -Dichlorophenoxy) -8- (cyanomethyl) -8-azabicyclo [3.2.1] octane; exo-3- (3,4 -Dichlorophenoxy) -8- (cyclopropylmethyl) -8-azabicyclo [3.2.1] octane; exo-3- (3,4-dichlorophenoxy) -8- (allyl) -8-azabicyclo [3.2.1] octane; EXO-3- (3,4-Dichlorophenoxy) -8- (methoxyethyl) -8-azabicyclo [3.2.1] octane; exo-3- (6-Methoxypyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-Ethoxypyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-hydroxy-pyridin-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo-3- (6-Cyano-naphthalen-2-yloxy) -8-methyl-8-azabicyclo [3.2.1] octane; exo- (3,4-Dichloro-phenyl) - (8-methyl-8-aza-bicyclo [3.2.1] oct-3-yl) -amine; endo- (3, -Dichloro-phenyl) - (8-methyl-8-azabicyclo [3.2.1] oct-3-yl) -formylamine; - exo- (3,4-Dichloro-phenyl) - (8-methyl-8-azabicyclo [3.2.1] oct-3-yl) -fo'rmilamine; or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof. 11. A pharmaceutical composition, characterized in that it comprises a therapeutically effective amount of a compound of any of claims 1-10, or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof, together with the less a vehicle, excipient or diluent acceptable for pharmaceutical use. 12. Use of the chemical compound according to any of claims 1-10, or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament. The use according to claim 12, for the manufacture of a pharmaceutical composition for the treatment, prevention or alleviation of a disease or disorder or condition of a mammal, including a human, disease, disorder or condition that is sensitive to the inhibition of the reuptake of monoamine neurotransmitters in the central nervous system. 14. The use of (In accordance with claim 13, wherein the disease, disorder or condition is mood disorder, depression, atypical depression, major depressive disorder, dysthymic disorder, bipolar disorder, bipolar I disorder, bipolar II disorder, cyclothymic disorder, mood disorder due to a general medical condition, chemical-induced mood disorder, pseudodementia, Ganser syndrome, obsessive-compulsive disorder, panic disorder, panic disorder without agoraphobia, panic disorder with agoraphobia, agoraphobia with no history of mood disorder panic, panic attack, memory deficits, memory loss, hyperactivity disorder with attention deficit, obesity, anxiety, generalized anxiety disorder, eating disorder, Parkinson's disease, parkinsonism, dementia, dementia due to aging, senile dementia, Alzheimer's disease, complex acquired immunodeficiency syndrome-dementia ia, memory dysfunction due to aging, specific phobia, social phobia, post-traumatic stress disorder, acute stress disorder, drug addiction, drug abuse, cocaine abuse, nicotine abuse, tobacco abuse, addiction alcohol, alcoholism, pain, chronic pain, inflammatory pain, neuropathic pain, migrainous pain, tension headache, chronic tension headache, pain associated with depression, fibromyalgia, arthritis, osteoarthritis, rheumatoid arthritis, back pain, pain from cancer, pain Irritable bowel syndrome, irritable bowel syndrome, "post-operative pain, post-stroke pain, drug-induced neuropathy, diabetic neuropathy, pain maintained by the sympathetic system, trigeminal neuralgia, dental pain, myofacial pain, limb pain ghost, bulimia, premenstrual syndrome, late luteal phase syndrome, post-traumatic syndrome, chronic fatigue syndrome, incontinence urinary, stress incontinence, urgency incontinence, nocturnal incontinence, sexual dysfunction, premature ejaculation, erectile dysfunction, erectile dysfunction, eating disorders, anorexia nervosa, sleep disorders, autism, mutism, trichotillomania, narcolepsy, post-apoplexy depression, brain damage induced by cerebrovascular accident, neuronal damage induced by cerebrovascular accident or Gilíes de la Tourette's disease. 15. A method for the treatment, prevention or alleviation of a disease or disorder or condition of a living animal organism, including a human, disorder, disease or condition that is sensitive to the inhibition of the reuptake of monoamine neurotransmitters in the central nervous system, method characterized in that it comprises the step of administering to said living animal organism in need thereof a therapeutically effective amount of a compound according to any of claims 1-10, or any of its isomers or any mixture of its isomers , or an acceptable salt for pharmaceutical use thereof.