Indian Patents. 227197:8-AZA-BICYCLO[3,2,1]OCTANE DERIVATIVE OF THE FORMULA I

Title of Invention	8-AZA-BICYCLO[3,2,1]OCTANE DERIVATIVE OF THE FORMULA I
Abstract	ABSTRACT 8-A2A-BICYCLO[3.2.1lOCTANE DERIVATIVES OF THE FORMULA I 3509/CHENP/2005 The present invention relates to novel 8-aza-bicyclo[3.2.1]octane derivatives useful as monoamine neurotransmitter re-uptake inhibitors. This invention also relates topharmaceutlcal compositions comprising the compounds of the invention.

Full Text	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. BACKGROUND ART WO 97/30997 (NeuroSearch A/S) describes tropane derivatives active as neurotransmitter re-uptake inhibitors. However, there is a continued strong need to find compounds with an optimised pharmacological profile as regards the activity on reuptake of the monoamine neurotransmitters senstonin, dopamine and noradrenaline, such as the ratio of the serotonin reuptake versus the noradrenaline and dopamine activity. SUMMARY OF THE INVENTION In a further 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 pharmaceuticaliy acceptable salt thereof, for the manufacture of a pharmaceutical composition for the treatment, prevention or alleviation of a disease or a disorder or a condition of a mammal, Including a human, which disease, disorder or condition is responsive to inhibition of monoamine neurotransmitter re-uptaite in the central nervous system. In a still further aspect, the invention relates to a method for treatment, prevention or alleviation of a disease or a disorder or a condition of a living animal body, Including a human, which disorder, disease or condition Is responsive to responsive to Inhibition of monoamine neurotransmitter re-uptai(e In the central nervous system, which method comprises the step of administering to such a living animal body 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 a pharmaceuticaliy acceptable salt thereof. Other objects of the invention will be apparent to the person skilled in the art fr-om the following detailed description and examples. DETAILED DISCLOSURE OF THE [NVENTION 3-aza-bicyclo[3.2.1]octane derivatives In Its first aspect the present Invention provides compounds of fomiuia I: )r any of its isomers or any mixture of its isomers, )r a pharmaceuticaliy acceptable salt thereof, vherein \^ represents hydrogen or alkyi; which aikyi is optionally substituted with one or more substituents Independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitro, alkoxy, cycioalkoxy, alkyl, cydoalkyl, cycloalkylalkyi, alkenyl and alkynyl; C represents -0-, -S- or -NR°-; wherein R° represents hydrogen, alkyl, -C(=b)R' or-SOaR'; wherein R' represents hydrogen or alkyl; R represents an aryl or a heteroaryl group, which aryl or heteroaryl group is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitre, oxo, ' ali In one embodiment, R^ represents hydrogen or alkyl; X represents -0-, -S- or -NR"-; wherein R represents hydrogen, alkyl, -C(=0)R'* or-SOaR^; wherein R" represents hydrogen or alkyl; R" represents an aryl or a heteroaryl group, which aryl or heteroaryl group 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, cycloalkyi, cycloalkylalkyl, alkenyl and alkynyl. In a further embodiment, R" represents hydrogen or alkyl. In a still further embodiment, Rrepresents hydrogen. In a further embodiment, R^represents alkyl, such as methyl. In a still further embodiment, R°represents alkyl substituted with hydroxy, cyano, cycloalkyi or alkenyl. In a special embodiment, R° represents hydroxyalkyl, such as hydroxyethyl. In a further embodiment, R° represents cyanoalkyi, such as cyanomethyl. In a still further embodiment, R represents cycloalkylalkyl, such as cyclopropylmethyl. In a further embodiment, R° represents alkenylalkyl, such as allyl. In a further embodiment, X represents -0-. In a still further embodiment, X represents -S-. In a further embodiment, X represents -NR'-. In a special embodiment, R'* represents hydrogen. In a further embodiment, R° represents -C(=:0)R'. In a special embodiment, R' represents hydrogen. In a special embodiment, X represents -NH- or -N((C=0)H)- In a further embodiment, R** represents an aryl or a heteroaryl group, which aryl or heteroaryl group Is optionally substituted with one or more substituents Independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, oxo and alkoxy. In a still further embodiment, R' represents an aryl or a heteroaryl group, which aryl or heteroaryl group is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy. In a further embodiment, R" represents an aryl or a heteroaryl group, which aryl or heteroaryl group is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, oxo, alkyl and alkoxy. In a still further embodiment, R" represents an aryl or a heteroaryl group, which aryi or heteroaryl group is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyi, trifluoromethoxy, cyano, oxo and allcoxy.ln a further embodiment, R' represents an aryl or a heteroaryl group, which aryl or heteroaryl group is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyi, trifluoromethoxy, cyano and alkoxy. In a further embodiment, R* represents an unsubstltuted, monosubstituted or disubstituted aryl or heteroaryl group. In a still further embodiment, R^ represents an optionally substituted monocytic heteroaryl group. In a further embodiment, R' represents an optionally substituted bicylic heteroaryl group. In a still further embodiment, R"" represents an optionally substituted polycylic heteroaryl group. in a special embodiment, R^ represents an optionally substituted heteroaryl group and the compound of formula I Is In the exo configuration. In a further embodiment. R^ represents hydrogen and R" represents an optionally substituted heteroaryl group. In a still further embodiment, R° represents hydrogen, R' represents an optionally substituted heteroaryl group and the compound of formula I is in the exo configuration. In a still further embodiment, R' represents an optionally substituted phenyl group. In a further embodiment, R' represents an optionally substituted naphthyl group. In a still further embodiment, R" represents an optionally substituted fluorenyl group. In a further embodiment, R represents an optionally substituted thienyl group. In a still further embodiment, R' represents an optionally substituted benzoisothlazolyl group. In a still further embodiment, R' represents a phenyl group, which phenyl group Is optionally substituted with one or more substituents Independently selected from the group consisting of: halo, trifluoromethyi, trifluoromethoxy, cyano and alkoxy. In a further embodiment, R' represents a phenyl group optionally substituted once or twice with halo, such as chloro. In a special embodiment, R' represents phenyl, in a further embodiment, R' represents monosubstituted phenyl, in a special embodiment, R" represents chlorophenyl, such as 3-chlorophenyl. In a further embodiment, R^ represents a disubstituted phenyl. In a still further special embodiment, R" represents dichlorophenyl, such as 2,3-dichIorophenyl or 3,4-dlchlorophenyi. In a further embodiment, R represents phenyl substituted with chloro and fluoro, such as 4-chloro-3-fluoraphenyl or 4-fluoro-3-chlorophenyi. In a still further embodiment, R' represents phenyl substituted with chloro and trifluoromethyi, such as 2-chloro-3-trifluoromethyiphenyl or4-chloro-3-trlfluoromethyiphenyl. In a still further smbodiment, R" represents phenyl substituted with fluoro and trifluoromethyi, such as 4-fluoro-3-trifIuoromethylphenyl. In a further embodiment, R' represents phenyl substituted with chloro and cyano, such as 3-chloro-4-cyanophenyl. In still a further embodiment, R represents phenyl substituted with chloro and methyl, such as 4-chloro-3-methylphenyl. In a further embodiment, R" represents phenyl substituted with chloro and bromo, such as 4-bromo-3-chlorophenyl. In a further embodiment, R' represents a monosubstituted phenyl. In a still further embodiment, R^ represents chlorophenyl, such as 3-chlorophenyl or4-chlGrophenyl. In a further embodiment, R' represents trifluoromethoxyphenyl, such as 3-trifluoromethoxyphenyl or4-trlfluoromethoxyphenyl. In a still further embodiment, R represents trifluoromethylphenyl, such as 4-trifluoromethylphenyl. In a further embodiment, R' represents methylphenyl, such as 4-methylphenyl. In a still further embodiment, R' represents methoxyphenyl, such as 3-methoxyphenyl or 4-methoxyphenyl. In a still further embodiment, R' represents cyanophenyl, such as 4-cyanophenyl. In a further embodiment, R' represents hydrogen and R** represents a phenyl group which phenyl group Is substituted twice with substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy. In a further embodiment, R^ represents a naphthyl group, such as 1 -naphthyl or 2-naphthyl. In a still further embodiment, R'* represents a naphthyl group substituted once or twice with halo, such as chloro or bromo. In a special embodiment, R^ represents chloronaphthyl, such as4-chioronaphthalen-1-yl. In a further embodiment, R** represents bromonaphthyl, such as 6-bromonaphthalen-2-yl. In a still further embodiment, R' represents a naphthyl group substituted one or twice with alkoxy, such as methoxy. In a special embodiment, R" represents methoxynaphthyl, such as 4-methoxynaphthalen-1-yl, 6-methoxynaphthalen-2-y! or 7-methoxynaphthalen-2-yl. In a still further embodiment, R' represents a naphthyl group substituted one or twice with cyano. In a special embodiment, R' represents cyanonaphthyi, such as 6-cyanonaphthalen-2-yl. In a still further embodiment, R" represents a 1,2,3,4-tetrahydronaphthyl group, such as 1,2,3,4-Tetrahydronaphthalen-6-yl. In a further embodiment, R** represents an indanyl group, such as 5-indanyl. In a still further embodiment, R' represents a fluorenyl group substituted with 0X0, such as fluoren-9-one-2-yl. In a still further embodiment, R" represents a thienyi group, which thienyl group is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy. In a further embodiment, R" represents a thienyl group substituted one or more times with halo, such as chloro or bromo. In a special embodiment, R'^ represents bromothienyl, such as 4-bromothiophen-2-yl. In a further embodiment, R" represents dihalothienyl, such as bromo-chioro-thienyl, in particular 3-bromo-5-chioro-thiophen-2-yl or4-bromo-5-chloro-thlophen-2-yl. In a further embodiment, R represents di-chlorothienyl, such as 3,4-dichloro-thiophen-2-yi. In a further special embodiment, R" represents trichlorothienyl, such as 3,4,5-trichloro-thiophen-2-yl. In a stiil further spe¬cial embodiment, R' represents tribromothlanyl, such as 3,4,5-tribromo-thiophen-2-yl. In a still further embodiment, R" represents a benzoisothlazolyl group, such as 1,2-benzoisothiazoi-3-yl. In a further embodiment, R represents an optionally substituted benzothiazolyl group. In a special embodiment, R" represents benzothiazoiyi, such as benzothiazol-2-yi. In a further embodiment, R'* represents a benzothiazolyl group substituted once or twice with halo, such as chloro. In a special embodiment, R represents chioroben-zothiazoiyl, such as 6-chlorobenzothiazol-2-yi. In a further embodiment, R" represents a thiazolyl group substituted once or twice with halo, such as bromo. in a speclai embodiment, R represents bromothla-zolyi, such as 5-bromothiazoi-2-yi. in a stiii further embodiment, R' represents a quinoxaiinyi group, such as qui-noxalin-2-yl. in a further embodiment, R" represents a quinazolinyl group, such as quina-zolin-2-yi. In a further embodiment, R' represents a quinolinyl group, such as quinolin-2-yi, quinolin-6-yi orquinolin-8-yl. in a further embodiment, R' represents a isoquinolinyl group, such as isoquino- I lin-5-yi. In a still further embodiment, R' represents a benzoxazolyl group, such as ben-zoxazol-2-yi. In a further embodiment, R'* represents an optionally substituted pyridazinyi group. In a still further embodiment, R' represents a pyridazinyi group substituted on¬ce or twice with halo, such as chloro. in a speclai embodiment, R' represents chloro-pyrldazinyl, such as 6-chloropyridazin-3-yl. in a further embodiment, R represents an optionally substituted pyridyl group. In a Hirther embodiment, R represents a pyridyl group, which pyridyl group is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy and aikoxy. In a still further em¬bodiment, R'^ represents a pyridyl group substituted once or twice with halo, such as chloro or bromo. In a special embodiment, R' represents chloropyridyl, such as 5-chloropyridin-2-yl or 6-chloropyridin-2-yl. In a further embodiment, R" represents bro-mopyridyl, such as 5-bromopyridln-2-yl or6-bromopyridin-2-yl. in a still further em¬bodiment, R' represents a pyridyl group substituted once or twice with aikoxy, such as methoxy or ethoxy. In a special embodiment, R' represents methoxypyridyl, such as 6-methoxypyridin-2-yl. In a further special embodiment, R* represents ethoxypyridyl, such as 6-ethoxypyridin-2-yl. In a still further embodiment, R" represents a pyridin group substituted once or twice with trifluoromethyl. In a special embodiment, R' I represents trifluoromethylpyridyl, such as 5-trlfluoromethylpyridln-2-yl. In a further em¬bodiment, R' represents a pyridin group substituted once or twice with hydroxy. In a special embodiment, R" represents a hydroxypyridyl, such as 6-hydroxy-pyridin-2-yl. In a further embodiment, R' represents a isoquinolinyl group, such as isoquino- lin-1-yl. I In a further embodiment, R'* represents an optionally substituted pyrlmidin group. In a still further embodiment, R' represents a pyrlmidin group substituted once or twice with halo, such as bromo. In a special embodiment, R* represents bro-mopyrimidin, such as 5-bromopyrimidin-2-yl. In a further embodiment, R' represents a dibenzofuranyl group, such as diben-zofuran-2-yl. In a still further embodiment, R' represents an indolyl group, such as 5-indolyl. In a special embodiment the chemical compound of the invention is encfo-3-(3,4,5-Trichlorothiophen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; ' ©n(/o-3-(3,4-Dichlorothlophen-2-yloxy)-8-methyl-8-azablcyclo[3.2.1]octane; exo-3-(3,4,5-Trichlorothiophen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(1,2-Benzolsothlazol-3-yloxy)-8-methyl-8-azabicycio[3.2.1]octane; exo-3-(5-Bromothiazol-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(Benzothlazol-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-(Qulnolln-2-yioxy)-8-methyi-8-azabicyclo[3.2.1]octane; Gxo-3-(Benzoxazol-2-yloxy)-8-methy!-8-azabicyclo[3.2.1]octane; exo-3-(6-Chloro-pyridazin-3-yloxy)-8-methyl-8-azablcycio[3.2.1]octane,-exo-3-(5-Chloro-pyridin-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(lsoquinolin-1-yloxy)-8-methyl-8-azabicyclo[3,2.1]octane; exo-3-(6-Chloropyridin-2-yloxy)-8-methyi-B-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; ©xo-3-(5-Bromopyrlmldin-2-yloxy)-8-methyl-8-azablcyGlo[3.2.1]octane; ©xo-3-(Quinazolln-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(5-Trlfluoromethylpyrldln-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(3,4,5-Tribromothiophen-2-yloxy)-8-methyl-8-azablcyclo[3.2.1]octane; €xo-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; encfo-3-(4-Bromo-5-chloro-thiophen-2-yloxy)-8-methyl-8-azabicycIo[3.2.1]octane; e/7do-3-(3,4,5-Trichlorothiopen-2-yloxy)-8-H-8-azabicyclo[3.2.1loctane; exo-3-(2,3-Dichloroph©noxy)-8-H-8-azabicyclo[3.2.1]octane; exo-3-(3,4-DichlorophGnoxy)-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-B-azabicyclo[3.2.1]octane; exo-3-(4-Chloro-3-fIuorophenoxy)-8-H-8-azabicyclo[3.2.1]octane; ejfo-3-(4-ChIoro-phenoxy)-8-H-8-azabicyclo[3.2.1 ]octane; exo-3-(2-Chloro-3-trifluoromethyl-phenoxy)-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; enoto-3-(3,4-Dichlorophenoxy)-8-H-8-azabicyclo[3.2.1]octane; ©xo-3-(4-Chloro-3-trif!uoromethylphenoxy)-8-H-8-azabicyclo[3.2.1 ]octanG; exo-3-(2-DIbenzofuranyloxy)-8-H-8-azablcyclo[3.2.1]oclane; ©xo-3-(1 -Naphthyloxy)-8-H-B-azabicyclo[3.2.1]octane; ©xo-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; oxo-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-Metho)^phGno>cy)-8-H-8-azabicyclo[3.2.1]octane; exo-3-(lsoquinolin-5-yloxy)-8-H-8-azabicyclo[3.2.1 ]octane; ©xo-3-(6-Bromo-naphthal0n-2-yloxy)-B-H-8-azabicyclo[3.2.1]octane; exo-3-(4-Bromo-3-chloro-phenoxy)-8-H-8-azabicyclo[3.2.1 Joclane; Bxo-3-(Qulnolin-6-yloxy)-8-H-8-azabicyclo[3.2.1]octane; exo-3-(4-Trifluorophenoxy)-8-H-8-azabicyclo[3.2.1 Joctane; exo-3-(4-Cyanophenoxy)-8-H-B-azabicycIo[3.2.1 ]octane; 0xo-3-(Qulnolin-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-yioxy)-8-H-8-azabicyclo[3.2.1]octane; Bxo-3-(5-Bromopyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane; Bxo-3-(6-Bromopyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1 Joctane; Bxo-3-(lsoquinolin-1-yloxy)-8-H-8-azablcyclo[3.2.1]octanG; 9xo-3-(3-Trifluoromethoxyphenoxy)-8-H-8-azabicyclo[3.2.1]oc1ane; sxo-3-(4-TrifIuoramethoxyphenoxy)-8-H-8-azabicyclo[3.2.1]octane; exo-3-(6-Methoxypyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1 Joctane; ©xo-3-(5-trlfluoromethylpyrldln-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-Dlchloraphenoxy)-8-mGthyl-8-azabicyclo[3.2.1]octane; exo-3-(3,4-Dichlorophenoxy)-8-methyl-8-azabicyclo[3.2.1 Joctane; oxo-3-(3-Chloro-4-fluorophenoxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(4-Chloro-3-fluoraphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(2-Chloro-3-trifluoromethyl-phenoxy)-8-methyl-8-azabicyclb[3.2.1]octane; ©xo-3-(3-Chloro-phenoxy)-8-methyl-8-azabicyclo[3.2.1]od:ane; 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; ©xo-3-(1-Naphthyloxy)-8-methyl-8-azabicyclo[3.2.1]octane; 6xo-3-(2-Naphthyloxy)-8-methyl-8-azablcyclo[3.2.1 ]octane; exo-3-(4-Chloro-3-trifluoromethyl-phenoxy)-8-methyl-8-azabicycIo[3,2.1]octane; exo-3-(3-Chloro-4-cyanophenoxy)-8-methyl-8-azablcyclo[3.2.1]octane; exo-3-(2-Dibenzofuranyloxy)-8-methyl-8-azablcyclo[3.2.1]octane; ©xo-3-(4-Chloronaphthalen-1-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; ©xo3-(4-Chloro-3-methylphenoxy)-8-methyl-8-azablcyclo[3.2.1]octan6; ©xo-3-(4-Methoxyphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane; ©xo-3-(7-Methoxynaphthalen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; ©xo-3-(6-Methoxynaphthalen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; ©xo-3-(4-Bromo-3-chloro-phenoxy)-8-methyl-8-azabicyclo[3.2.1]octane; ©xo-3-(lsoquinolin-5-yl)-8-methyl-8-a2abicyclo[3.2.1]octane; exo-3-(6-Bromo-naphthalen-2-yloxy)-B-methyl-8-azabicyclo[3.2.1]octanB; ©xo-3-(3-Methoxyphenoxy)-8-methyl-8-azabicyclo[3.2.1 joctane; exo-3-(4-Cyanophenoxy)-8-methyl-8-azabicyclo[3.2.1]ootane; exo-3-(Qui nol ln-e-yloxy)-8-methyl-8-azabicyclo[3.2.1 ]octane; ©xo-3-(1,2,3,4-Tetrahydronaphthalen-6-yloxy)-8-methyl-8-azabicyclo[3.2.1]oGtane; ©xo-3-(4-Trifluoramethylphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(4-Methylphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane; ©xo3-(8-QuinolinyI)-8-methyI-8-azabicyclo[3.2.1]octane; ©xo-3-(5-lndanyloxy)-8-nnethyl-8-azabicyclo[3.2.1]octane; exo-3-(4-Methoxynaphthalen-1-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; ©xo-3-(lndol-5-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; ©xo-3-(3-Trifluoromethoxyphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(4-Trifluoromethoxyphenoxy)-8-mBthyl-8-azabicyclD[3.2.1]octane; ©xo-3-(4-Fluoro-3-trifluoromethylphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane; enGfo-3-(3,4-Dichiorophenoxy)-8-methyl-8-azabicycIo[3.2.1]octane; exo-3-(3,4-Dichlorophenoxy)-8-(2-hydroxyethyi)-8-azablcycio[3.2.1]actane; exo-3-(3,4-Dichlorophenoxy)-8-(cyanomethyi)-8-azabicycio[3.2.1]octane; ©xo-3-(3,4-Dlchlorophenoxy)-8-(cyclopropylmethyl)-8-azabicyclo[3.2.13octane; GXO-3-(3,4-Dichlorophenoxy)-8-(aliyl)-8-azabicyclo[3.2.1]octane; exo-3-(3,4-Dichlorophenoxy)-8-(methoxyethyl)-8-azabicycio[3.2.1]octane; exo-3-(6-Methoxypyridin-2-yioxy)-8-methyi-8-azablcyolo[3.2.1]octane; ©xo-3-(6-Ethoxypyridin-2-yloxy)-8-methyi-8-azabicyclo[3.2.1]octane; ©xo-3-(6-hydroxy-pyridin-2-yioxy)-8-methyl-B-azabicyclo[3.2.1]octane; exo-3-(6-Cyano-naphthalGn-2-yioxy)-8-methyl-8-azabicyclo[3.2.1]octane; ©xo-(3,4-Dichloro-phenyl)-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-amlne; encto-(3,4-Dichloro-phenyl)-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-formylamine; exo-(3,4-Dichloro-phenyi)-(8-methyl-8-aza-bicyGlo[3.2.1]oct-3-yi)-formylamine; or any of Its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof. Any combination of two or more of the embodiments as described above is considered within the scope of the present Invention. Definition of Substituents in the context of this invention haio represents fluoro, chloro, bromo or iodo. In the context of this invention an allq^l group designates a univalent saturated, straight or branched hydrocarbon chain. The hydrocarbon chain preferably contain of [irom one to six carbon atoms (Ci^-alkyl), including pentyi, isopentyl, neopentyl, Brtiary pentyi, hexyi and isohexyi. In a preferred embodiment alkyl represents a C^-alicyl group, including butyl, isobutyl, secondary butyl, and tertiary butyl. In another Dreferred embodiment of this invention ailcyi represents a Ci^-aliQrl group, which may n particular be methyl, ethyl, propyl or Isopropyl. In the context of this invention an allcenyl group designates a carbon chain X}ntaining one or more double bonds, including di-enes, tri-enes and poly-enes. In a jreferred embodiment the ail In the context of this invention an allcynyl group designates a carbon chain iontaining one or more triple bonds, including di-ynes, tri-ynes and poiy-ynes. In a )referred embodiment the all 3-butynyl, or 1,3-butdiynyl; 1-, 2-, 3-, 4-p9ntynyl, or 1,3-pentdiynyl; 1-, 2-, 3-, 4-, or5-hexynyl, or 1,3-hexdiynyl or 1,3,5-he)ctriynyl. In Vne context of this invention a cycloalkyi group designates a cyclic a\ky\ group, preferably containing of from three to seven carbon atoms (Ca-rcycloalkyl), including cyclopropyl, cyclobutyl, cyclopentyi, cyciohexyi and cycloheptyi. Alkoxy Is 0-aikyl, wherein alkyl is as defined above. Cycloaikoxy means 0-cycloalkyl, wherein cycloalkyi is as defined above. CycloalkylalkyI means cycloalkyi as above and alkyl as above, meaning for example, cyclopropylmethyl. Amino Is NHa or NH-alkyI or N-(alkyl)2, wherein alkyl is as defined above. In the context of this invention an aryi group designates a carbocycllc aromatic ring system such as phenyl, naphthyl (1-naphthyl or 2-naphthyl) orfluorenyl. The term aryi is also intended to cover a partially hydrogenated carbocycllc aromatic ring system, such as Indanyl or 1,2,3,4-tetrahydronaphthyl. In the context of this invention a heteroaryi group designates an aromatto mono- or bicyclic heterocyclic group, which holds one or more heteroatoms in its ring staicture. Pre¬ferred heteroatoms Include nitrogen (N), oxygen (O), and sulphur (S). Preferred monocyclic heteroaryi groups of the invention include aromatic 5- and 6 membered heterocyclic monocyclic groups, including for example, but not limited to, oxazolyl (oxazol-2-yl, -4-yl, or -5-yl), isoxazolyl (lsoxazol-3-yl, -4-yl, or -5-yl), thiazolyl (thiazol-2-yl, -4-yI, or-5-yl), Isothiazoiyi (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-thiadiazol-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-lmidazolyl), pyrrolyl (2- or 3-pyrrolyl), furanyl (2- or 3-furanyl), thienyl (2-or3-thienyl), pyridyl (2-, 3-or 4-pyridyl), pyrimidyl (2-, 4-, 5-or6-pyrimidyl), or pyrldazlnyi (3-or4-pyridazinyl). Preferred bicyclic heteroaryi groups of the invention include indolizinyl, in particular2-, 5-or 6-indolizinyl; Indolyl, in particular 2-, 5-or6-indolyl; isoindolyl, in particular 2-, 5- or6-lsolndolyl; Indazolyl, in particular 1 - or 3-indazolyl; benzo[b]furanyl, In particular 2-, 5- or 6-benzofuranyl; benzo[b]thienyl, in particular 2-, 5-or 6-benzothienyl; benzlmidazolyl, in particular 2-, 5-or6-benzimidazolyl; benzoxazolyl, in particular 2-, 5-or6-benzoxazolyl; benzothiazolyl, in particular 2-, 5-or6-benzothiazolyl; benzoisothiazolyl (1,2-benzoisothiazoiyl or 2,1-benzoisothiazolyl), in particular 1,2-benzoisothiazol-3-yl; purinyl, in particular 2-or 8-purinyl; quinolinyi. In particular 2-, 3-, 6-, 7- or8-qulnollnyl; isoquinolinyl, In particular 1-, 3-, 5-, 6-or 7-isoquinolinyl; cinnolinyl, in particular 6-or 7-cinnolinyl; phthalazinyl, in particular 6- or 7-phthalazinyl; quinazolinyl. In particular 2-, 6-or 7-qulnazolinyl; quinoxalinyl, in particular 2- or 6-qulnoxallnyl; 1,8-naphthyrldInyl, In particular 1,8-naphthyridin-2-, 3-, 6- or7-yl; pteridinyl, in particular 2-, 6-or 7-pteridinyl; and indenyl, in particular 1-, 2-, 3-, 5-or5-indenyl. Preferred polycyclic heteroaryl groups of the Invention include dibenzofuranyl, in particular 2-dibenzofuranyl. Pharmaceuticallv Acceptable Salts The chemical compound of the invention may be provided In any form suitable for the intended administration. Suitable forms include pharmaceutically (i.e. physiologically) acceptable salts, and pre- or prodrug forms of the chemical compound of the invention. Examples of pharmaceutically acceptable addition salts include, without limitation, the ncn-toxic inorganic and organic acid addition salts such as the hydrochloride derived from hydrochloric acid, the hydrabromida derived from hydrobromicacld, the nitrate de¬rived from nitric add, the perchlorate derived from perchloric acid, the phosphate derived from phosphoric add, the sulphate derived fiiom sulphuric acid, the formate derived from formic acid, the acetate derived from acetic acid, the aconate derived from aconitic acid, the ascorisate derived firom ascorbic add, the benzenesulphonate derived from benzen-sulphonic add, the benzoate derived from benzoic acid, the cinnamate derived from cin-namic acid, the citrate derived from citric acid, the embonate derived from embonic acid, the enantate derived from enanthic acid, the fumarate derived from fumaric acid, the glu-tamate derived from glutamic acid, the glycolate derived from glycolic acid, the lactate de¬rived from ladle acid, the maleate derived firom maleic add, the malonate derived from malonic acid, the mandelate derived from mandelic acid, the methanesulphonate derived from methane sulphonic acid, the naphthalene-2-sulphonate derived from naphtalene-2-sulphonic acid, the phthalate derived from phthalic acid, the salicylate derived from sali¬cylic acid, the sorisate derived from sorisic add, the stearate derived fit)m stearic acid, the succinate derived firom succinic add, the tartrate derived from tartaric acid, the toluene-p-sulphonate derived from p-toluene sulphonic acid, and the like. Such salts may be formed by procedures well known and described in the art. Other acids such as oxalic acid, which niay not be considered pharmaceutically acceptable, may be useful in the preparation of salts useful as intermediates in obtaining a chemical compound of the Invention and its pharmaceutically acceptable acid addition salt. Examples of pharmaceutically acceptable catlonic salts of a chemical compound of the Invention include, without limitation, the sodium, the potassium, the calcium, the magnesium, the zinc, the aluminium, the lithium, the choline, the lysine, and the ammonium salt, and the like, of a chemical compound of the invention containing an anionic group. Such catlonic salts may be formed by procedures well known and described In the art. In the context of this invention the "onium salts" of N-containing compounds are also contemplated as phamiaceutically acceptable salts. Preferred "onium salts" include the alkyl-onium salts, the cycloalkyl-onium salts, and the cycloalkylalkyl-onium salts. Examples of pre- or prodrug forms of the chemical compound of the invention include examples of suitable prodrugs of the substances according to the invention include compounds modified at one or more reactive or derivatizabie groups of the parent compound. Of particular Interest are compounds modified at a carboxyl group, a hydroxyl group, or an amino group. Examples of suitable derivatives are esters or amides. The chemical compound of the invention may be provided in dissoluble or indissoluble forms together with a pharmaceutically acceptable solvent such as water, ethanol, and the like. Dissoluble forms may also Include hydrated forms such as the monohydrate, the dihydrate, the hemihydrate, the trihydrate, the tetrahydrate, and the like. In general, the dissoluble forms are considered equivalent to indissoluble forms for the purposes of this invention. Steric Isomers It will be appreciated by those skilled In the art 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 substltuent -X-R' on position 3 of the 8-a2a-bicyclo[3.2.1]octane skeleton of formula I may in particular be in the exo orendo configuration, in one embodiment of the invention the substltuent at position 3 is in the exo configuration. In another embodiment of the invention the substltuent at position 3 is in the endo configuration. The Invention includes all such isomers and any mixtures thereof including racemic mixtures. Racemic forms can be resolved into the optical antipodes by known methods and techniques. One way of separating the isomeric salts is by use of an optically active acid, and liberating the optically active amine compound by treatment with a base. Another method for resolving racemates into the optical antipodes is based upon chromatography on an optical active matrix. Racemic compounds of the present invention can thus be resolved into their optical antipodes, e.g., by fractional crystallisation of d- or I- (tartrates, mandelates, or camphorsulphonate) salts for example. The chemical compounds of the present invention may also be resolved by the formation of diastereomeric amides by reaction of the chemical compounds of the present Invention with an optically active activated carboxylic acid such as that derived from (+) or (-) phenylalanine, (+) or (-) phenylglycine, (+) or (-) camphanic acid or by the 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 resolving the optical isomers are known in the art. Such methods include those described by Jaques J, Collet A, & Wilen S in "Enantiomers. Racemates. and Resolutions". John Wiley and Sons, New York (1981). Optical active compounds can also be prepared from optical active starting materials. Labelled Compounds The compounds of the invention may be used in their labelled or unlabelled form. In the context of this invention "label" stands for the binding of a marker to the compound of interest that will allow easy quantitative detection of said compound. The labelled compounds of the invention may be useful as diagnostic tools, radio tracers, or monitoring agents in various diagnostic methods, and for in vivo receptor imaging. The labelled isomer of the Invention preferably contains at least one radto-nuclide as a label. Positron emitting radionuclides are all candidates for usage. In the context of this invention the radionuclide is preferably selected from ^H (deuterium), ^H (tritium), "C,^C,^'l,^^i,^=^l, and ^«F. The physical method for detecting the labelled isomer of the present invention may be selected from Position Emission Tomography (PET), Single Photon Imaging Computed Tomography (SPECT), iVIagnetIc Resonance Spectroscopy (i\/IRS), Magnetic Resonance Imaging (l\/iRI), and Computed Axial X-ray Tomography (CAT), or combinations thereof. Methods of Preparation The chemical compounds of the invention may 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 may readily be prepared by conventional methods from commercially available chemicals. Also one compound of the invention can be converiied to another compound of the Invention using conventional methods. The end products of the reactions described herein may be Isolated by conventional techniques, e.g. by extraction, crystallisation, distillation, chromatography, etc. Biological Activity Compounds of the Invention may be tested for their ability to Inhibit reuptalte of the monoamines dopamine, noradrenaline and serotonin in synaptosomes eg such as lescribed in WO 97/30997. Based on the balanced activity observed In these tests he compound of the invention Is considered useful for the treatment the treatment, )revention or alleviation of a disease or a disorder or a condition of a mammal, includ-ng a human, which disease, disorder or condition is responsive to inhibition of nonoamlne neurotransmitter re-uptake in the central nervous system. In a special embodiment, the compounds of the Invention are considered useful or the treatment, prevention or alleviation of: mood disorder, depression, atypical lepresslon, major depressive disorder, dysthymic disorder, bipolar disorder, bipolar I lisorder, bipolar II disorder, cyclothymic disorder, mood disorder due to a general ledical condition, substance-induced mood disorder, pseudodementia, Ganser's yndrome, obsessive compulsive disorder, panic disorder, panic disorder without goraphobia, panic disorder with agoraphobia, agoraphobia without history of panic isorder, panic attack, memory deficits, memory loss, attention deficit hyperactivity isorder, obesity, anxiety, generalized anxiety disorder, eating disorder, Parkinson's isease, parkinsonism, dementia, dementia of ageing, senile dementia, Alzheimer's isease, acquired immunodeficiency syndrome dementia complex, memory ysfunction In ageing, specific phobia, social phobia, post-traumatic stress disorder, cute stress disorder, drug addiction, drug misuse, cocaine abuse, nicotine abuse, )bacco abuse, alcohol addiction, alcoholism, pain, chronic pain, inflammatory pain, europathic pan, migraine pain, tension-type headache, chronic tension-type eadache, pain associated with depression, fibromyalgia, arthritis, osteoarthritis, leumatoid arthritis, back pain, cancer pain, irritable bowel pain, irritable bowel /ndrome, post-operative pain, post-stroke pain, drug-induced neuropathy, diabetic suropathy, sympathetically-maintained pain, trigeminal neuralgia, dental pain, lyofacial pain, phantom-limb pain, bulimia, premenstrual syndrome, late luteal phase yndrome, post-traumatic syndrome, chronic fatigue syndrome, urinary incontinence, ress incontinence, urge incontinence, nocturnal incontinence, sexual dysfunction, 'emature ejaculation, erectile difficulty, erectile dysfunction, eating disorders, lorexla nervosa, sleep disorders, autism, mutism, triohotiiiomania, narcolepsy, post-roke depression, stroke-induced brain damage, stroke-induced neuronal damage or ilies de la Tourettes disease. In a preferred embodiment, the compounds are )nsidered useful for the treatment, prevention or alleviation of depression. It is at present contemplated that a suitable dosage of the active jarmaceutical Ingredient (API) is within the range of from about 0.1 to about 1000 mg 'I per day, more preferred of from about 10 to about 500 mg API per day, most eferred of from about 30 to about 100 mg API per day, dependent, however, upon the exact mode of administration, the form in which it is administered, the indication considered, the subject and in particular the body weight of the subject involved, and further the preference and experience of the physician or veterinarian in charge. Preferred compounds of the invention show a biological activity in the sub-micromolar and micromoiar range, i.e. of from below 1 to about 100 ^M. Pharmaceutical Compositions In another aspect the Invention provides novel phamnaceutical compositions comprising a therapeutically effective amount of the chemical compound of the invention. While a chemical compound of the invention for use in therapy may be administered In the form of the raw chemical compound, it Is preferred to introduce the active ingredient, optionally in the form of a physiologically acceptable salt, in a pharmaceutical composition together with one or more adjuvants, excipients, can-Jers, buffers, diluents, and/or other customary pharmaceutical auxiliaries. in a prefenred embodiment, the invention provides pharmaceutical compositions comprising the chemical compound of the invention, or a pharmaceutlcaliy acceptable salt or derivative thereof, together with one or more pharmaceutlcaliy acceptable carriers therefore, and, optionally, other therapeutic and/or prophylactic ingredients, know and used in the art. The carrier(s) must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not harmful to the recipient thereof. Pharmaceutical compositions of the invention may be those suitable for oral, rectal, bronchial, nasal, pulmonal, topical (including buccal and sub-lingual), tnansdemnal, vaginal or parenteral (including cutaneous, subcutaneous, intramuscular, intraperitoneal, intrave¬nous, intraarterial. Intracerabnal, intraocular injection or infusion) administnation, or those in a form suitable for administration by inhalation or Insufflation, including powders and liquid aerosol administration, or by sustained release systems. Suitable examples of sustained release systems include semipemneable matrices of solid hydrophobic polymers contain¬ing the compound of the invention, which matrices may be in form of shaped articles, e.g. films or microcapsules. The chemical compound of the inventbn, together with a conventional adjuvant, :;arrier, or diluent, may thus be placed Into the fomi of phamiaceutical compositions and jnit dosages thereof. Such forms Include solids, and in pariicuiar tablets, filled capsules, 3owder and pellet forms, and liquids, in particular aqueous or non-aqueous solutions, suspensions, emulsions, elixirs, and capsules filled with the same, all for oral use, sup-jositories for rectal administration, and sterile Injectable solutions for parenteral use. Such jhannaceutical compositions and unit dosage forms thereof may comprise conventional igredients 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 ingredient commensurate with the Intended daily dosage range to be employed. 1 The chemical compound of the present invention can be administered In a wide va¬riety of oral and parenteral dosage forms, it will be obvious to those skilled in the art that the following dosage forms may comprise, as the active component, either a chemical compound of the invention or a phanmaoeutically acceptable salt of a chemical compound of the invention. For preparing pharmaceutical compositions firom a chemical compound of the pre¬sent invention, pharmaceutically acceptable earners can be either solid or liquid. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersibie granules. A solid earner can be one or more subslances which may also act as diluents, flavouring agents, solubilizers. lubricants, suspending agents, binders, preserva-b'ves, tablet disintegrating agents, or an encapsulating material. In powders, the earner is a finely divided solid, which is in a mixture with the finely divided active component. In tablets, the active component is mixed with the carrier having the necessary binding capacity in suitable propori:lons and compacted In the shape and size desired. The powders and tablets preferably contain from five or ten to about seventy per-[;entcf the active compound. Suitable caniers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylceliulose, sodium carisoxymethylceliulose, a low melting wax, cocoa butter, and the like. The term 'preparation" is intended to include the formulation of the active compound with encapsu-ating material as canler providing a capsule In which the active component, with or with-3ut caniers, is surrounded by a carrier, which is thus in association with it. Similariy, ca¬chets and lozenges are Included. Tablets, powders, capsules, pills, cachets, and lozenges :»n be used as solid forms suitable for oral administration. For preparing suppositories, a low melting wax, such as a mixture of fatty acid glyc-}ride or cocoa butter, is first melted and the active component is dispersed homogene-)usly therein, as by stinring. The molten homogenous mixture is then poured into conven-ent sized moulds, allowed to cool, and thereby to solidify. Compositions suitable tor vaginal administration may be presented as pessaries, ampons, creams, gels, pastes, foams or sprays containing in addition to the active ingre-iient such caniers as are known in tiie art to be appropriate. Liquid preparations include solutions, suspensions, and emulsions, for example, i/ater or water-propylene glycol solutions. For example, parenteral injection liquid prepara-lons can be fonmulated as solutions in aqueous polyethylene glycol solution. The chemical compound according to the present invention may thus be fomnulated 3r parenteral administration (e.g. by Injection, for example bolus injection or continuous ifusion) and may be presented in unit dose fomn in ampoules, pre-filled syringes, small volume infusion or in multi-dose containers with an added preservative. The compositions may talce such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulation agents such as suspending, stabilising and/or dispersing agents. Alternatively, the active ingredient may be in powder form, obtained by aseptic iso¬lation of sterile solid or by lyophiiization from solution, for constitution with a suitable vehi¬cle, e.g. sterile, pyrogen-free water, before use. Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavours, stabilising and thicl Aqueous suspensions suitable for oral use can be made by dispersing the finely di¬vided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, or other well l Also included are solid form preparations, intended for conversion shortly before use to liquid form preparations lor oral administration. Such liquid forms include solutions, suspensions, and emulsions. In addition to the active component such preparations may comprise colorants, flavours, stabilisers, buflisrs, artificial and natural sweeteners, dis-persants, thiclceners, solubilizing agents, and the lil For topical administration to the epidermis the chemical compound of the invention may be formulated as ointments, creams or lotions, or as a transdermal patch. Ointments and creams may, for example, be formulated with an aqueous or oily base with the addi¬tion of suitable thicl Compositions suitable for topical administration in the mouth include lozenges comprising the active agent In a flavoured base, usually sucrose and acada or tragacanth; pastilles comprising the active ingredient in an inert base such as gelatin and glycerine or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier. Solutions or suspensions are applied directiy to tiie nasal cavity by conventional means, for example with a dropper, pipette or spray. The compositions may be provided in single or multi-dose fonn. Administration to tiie respiratory tract may also be achieved by means of an aerosol formulation In which Une active Ingredient is provided in a pressurised pacl Alternatively the active ingredients may be provided In the form of a dry powder, for example a powder mix of the compound in a suitable powder base such as lactose, starch, starch derivatives such as hydroxypropylmethyl cellulose and polyvinylpyrrolidone (PVP). Conveniently the powder carrier will form a gel in the nasal cavity. The powder composi¬tion may be presented in unit dose form for example in capsules or cartridges of, e.g., gelatin, or blister packs from which the powder may be administered by means of an in¬haler. In compositions intended for administration to the respiratory tract, including intra¬nasal compositions, the compound will generally have a small particle size for example of the order of 5 microns or less. Such a particle size may be obtained by means known in the art, for example by micronization. When desired, compositions adapted to give sustained release of the active ingre¬dient 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 ac¬tive component. The unit dosage form can be a packaged preparation, the package con¬taining discrete quantities of preparation, such as packaged tablets, capsules, and pow¬ders in vials or ampoules. Also, the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or It can be the appropriate number of any of these in packaged form. Tablets or capsules for oral administration and liquids for intravenous administra-tkMi and continuous infusion are preferred compositions. Further details on techniques for formulation and administration may be found in the latest edition of Remington's Pharmaceutical Sciences (l\/laack Publishing Co., Easton, PA). A therapeutically effective dose refers to that amount of active ingredient, which ameliorates the symptoms or condition. Therapeutic efficacy and toxiclly, e.g. EDeo and LDso, may be detenmlned by standard pharmacological procedures in cell cultures or ex¬perimental animals. The dose ratio between therapeutic and toxic effects is the tiierapeutic index and may be expressed by the ratio LD50/ED50. Phamiaceutlcal compositions exhibit¬ing large therapeutic indexes are preferred. The dose administered must of course be carefully adjusted to tiie age, weight and condition of the Individual being treated, as well as the route of administration, dosage form and regimen, and tiie result desired, and tiie exact dosage should of course be de¬termined by the practitioner. The actual dosage depend on the nature and severity of the disease being treated, and Is within the discretion of the physician, and may be varied by titration of the dosage to the particular circumstances of this invention to produce tiie desired therapeutic effect. However, it is presently contemplated that pharmaceutical Mmpositi'ons containing of from about 0.1 to about 500 mg of active ingredient per individual dose, preferably of from about 1 to about 100 mg, most preferred of from about 1 to about 10 mg, are suitable for therapeutic treatments. The active Ingredient may be administered in one or several doses per day. A satisfactory result can, in certain instances, be obtained at a dosage as low as 0.1 jxg/kg i.v. and 1 \|ig/kg p.o. The upper limit of the dosage range is presently considered to be about 10 mg/kg i.v. and 100 mg/kg p.o. Preferred ranges are from about 0.1 p,g/kg to about 10 mg/kg/day I.v., and from about 1 \|.ig/kg to about 100 mg/kg/day p.o. Methods of Therapy in another aspect the invention provides a method for the treatment, prevention or alleviation of a disease or a disorder or a condition of a living animal body, including a human, which disease, disorder or condition Is responsive to Inhibition of monoamine neurotransmitter re-uptake in the central nervous system, and which method comprises administering to such a living animal body, including a human, In need thereof an effective amount of a chemical compound of the invention. 11 is at present contemplated that suitable dosage ranges are 0.1 to 1000 milligrams daily, 10-500 milligrams daily, and especially 30-100 milligrams daily, dependent as usual upon the exact mode of administration, form in which administered, the Indication toward which the administration is directed, the subject Involved and the body weight of the subject Involved, and further the preference and axperience of the physician or veterinarian in charge. EXAMPLES The invention Is further Illustrated with reference to the following examples, which are not intended to be in anyway limiting to the scope of the Invention as claimed. General: Ail reactions Involving air sensitive reagents or Intermediates were lerformed under nitrogen and in anhydrous solvents. Magnesium sulphate was used IS drying agent In the workup-procedures and solvents were evaporated under re¬duced pressure. Method A )ndo-3-(3,4,5-Trichloroth!open-2-yloxy)-8-nnethyl-8-azabicyclo[3.2.1]octane umaric acid salt V mixture of tetrachlorothiophene (5.48 g, 24.69 mmol), troplne (enrfo-8-methyl-8-izabicycio[3.2.1]octan-3-ol) (3.48 g, 24.69 mmol), potasslum-terf-butoxide (4.16 g, 37.04 mmol), 18-crown-6-ether (6.53 g, 24.69 mmol) and DI\/IF (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 addition of a diethyl ether and methanol mixture (9:1) saturated with fumaric acid. l\/lp 200.4-206.4°C. encfo-3-(3,4-Dichlorothlopen-2-ylox/)-8-methyl-8-azabicyclo[3.2.1]octane Was prepared according to method A from 2,3,4-trichlorothiophene and tropine {endo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol) isolated as the free base and oil. exo-3-(3,4,5-Trichlorothiopen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane hydrochloric acid salt Was prepared according to method A from tetratrichlorothiophene and pseudo-tropine (©xo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol). Mp 249-250'C. exo-3-(1,2-Benzol8othiazol' Was prepared according to method A from 3-chloro-1,2-benzoisothiazole and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol). Mp 259.4-261.2°C. ejro-3-(5-Bromothlazol-2-yloxy)-8-methyl>8-azabicyclo[3.2.1]octane Was prepared according to method A from 2,5-dibromothiazole and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1loctan-3-ol). Isolated as the free base. Mp 104-106°C. exo-3-(Benzothlazol-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octanefun(iarfcacid salt Was prepared according to method A from 2-chlorobenzothiazole and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.11octan-3-ol). Mp 160-162°C. exo-3-(6-Chlorobenzothlazol-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt i/Vas prepared according to method A from 2,6-dichlorobenzothiazole and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-oi). Mp 163-164.5°C. 0jco-3-(Quinoxalin-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt Was 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. I exo-3-(QuiaoIin-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method A from 2-chloroquinoline and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2,1]octan-3-ol). iVIp 192.5-195°C. exO'^-(Benzoxazol-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt \ Was prepared according to method A from 2-chlorobenzoxazole and pseudo-tropine (exo-8-methyl-8-azablcyclo[3.2.1]octan-3-oi). Mp 141-144°C. exo-3-(6-Ciiloro-pyridazin-3-yloxy}-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid aait I Was prepared according to method A from 3,6-dichloropyridazine and pseudo-tropine (exo-8-methyl-8-azablcyclo[3.2.1]octan-3-ol). Mp 181-183°C. e)ro-3-(5-Ciiioro-pyridin-2-yloxy)>^-methyl-8-azabicycio[3.2.1]octane fumaric acid salt Was prepared according to method A from 2,5-dichioropyridine and pseudo-tropine (exo-8-methyl-8-azab!cycio[3.2.1]oclan-3-ol). Mp 214-216°C. euro-3-(isoquinolin-1-yioxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method A from 1-chloroisoquinoline and pseudo-tropine ^ (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol). Mp 180-181.5°C. exo-3-(6-Cliloropyridin-2-yioxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid sait Was 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-Bromopyrldin-2-yloxy)-8-methyl-8-azablcyclo[3.2.1]octane fumaric acid salt Was prepared according to method A from 2,5-dibromopyrldine and pseudo-tropine (exo-8-methyl-8-azablcyclo[3.2.1]octan-3-ol). Mp 213-215°C. €!)ro-3-(8-Bromopyridin-2-yioxy)-8-methyl-8-azabicyelo[3.2.1]octane fumaric acid salt Was prepared according to method A from 2,6-dibromopyrldlne and pseudo-tropine (exo-8-methyl-8-azablcyclo[3.2.1]octan-3-ol). Mp 198-200°C. exo-3-(5-Bromopyrimidin-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octanefumaric acid salt Was prepared according to method A from 5-bromo-2-chioropyrimidine and pseudo-tropine (©xo-8-methyl-8-azabicycloI3.2.1]octan-3-oi). Mp 198-200°C. exo-3-(Quinazolin-2-yloxy)-8-methyl-B-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method A from 2-chloroquinazoline and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol). Mp 209-211°C. exo-3-(5-Trifluoromethylpyridln-2-yloxy)-8-methy[-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method A from 2-chloro-5-trifluoromethyIpyridlne and pseudo-tropine (exo-8-m0thyl-8-azabicyclo[3.2.1]octan-3-ol). IVIp 190-191.5 "C. exo-3-(3,4,5-Tribromothlophen-2-yloxy}-8-methyl-8-azabicyclo[3.2.1]octane hydrochloric acid salt Was prepared according to method A from tetrabromothiophene and pseudo-tropine (©xo-8-methyl-8-azabicyclo[3.2.1]octan-3-oI). I^p 223.3-223.9 °C. exo-3-(4-Bromothiophen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane hydrochloric acid salt Was prepared from exo-3-(3,4,5-Tribromothiophen-2-yioxy)-8-methyl-8-azabicyclo [3.2.1]octane by stirring with 5 eq of zincpowder in concentrated acetic acid at 75 °C for 15 h. Worlcup procedure was performed according to method A. IVIp 222.1 °C. endo-3-(3-Bromo-5-chloro-thiophen-2-yloxy)-8-methyl-B-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method A from 3-bromo-2,5-dichiorothiophene and tropine (enQfo-8-methyl-8-azabicyclo[3.2.1]octan-3-oi) IWp 171 -173 "C. end'o-3-(4-Bromo-5-chloro-th!ophen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method A from 3-bromo-2,5-dichlorothiophene and tropine (e/7do-8-methyl-8-azabicyclo[3.2.1]octan-3-ol) Mp 136 -139 °C. Method B e/}cro-3-(3,4,5-Trichlorothiopen-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane A mixture of ©/7c/o-3-(3,4,54richlorothlophen-2-yloxy)-8-methyl-8-f azabicyclo[3.2.1]octane (0.50 g, 1.53 mmol), 1-chloroethyl chloroformate (1.27 ml, 11.5 mmol) and toluene (20 ml) was stirred at reflux for 15 h. Water (10 ml) was added and the was stin-ed at reflux for 3.5 h. The mixture was evaporated. Sodium methoxide in methanol (5 mi, 1 M) and silica gel 60 (2 g) was added and was followed by evaporation. Chromatography, of the crude mixture, on silica gel with \ dichloromethane, methanol and cone, ammonia (89:10:1) gave the title compound in quantitative yield as free base and oil. exo-3-(2,3-D!chlorophenoxy)-8-H-8-azablcyclo[3.2.1]octane Was prepared according to method B. Isolated as the free base. Mp 62.3-65.4°C. ejro-3-(3,4-Dichlorophenoxy)-8-H-8-azabicyclo[3.2.1]octane hydrochloric acid salt Was prepared according to method B. Mp 160.1°C. ejro-3-(3,4,5-Trichlorothiophen-2-yloxy)-8-H-8-«zabicyclo[3.2.1]octane hydrochloric acid salt Was prepared according to method B. Mp 255-256°C. axo-3-(3-Ctiloro-4-fluorophenoxy)-8-H-8-azabicyclo[3.2.1]octanefumaricacid salt Was prepared according to method B. Mp 151-154°C. ex'o-3-(3-Chloro-phenoxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 195-196°C. exo-3-(4-Ctiloro-3-fiuorophsnoxy)-8-H-8-azabicyclo[3.2.1]octane Was prepared according to method B. Isolated as free base and oil. exo-3-(4-Chloro-phenoxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 188-188.5°C. exo-^-(2-Chioro-3-trifluoromethyl-phenoxy)-8-iHI-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 190-193°C. e)ro-3-(Fluoren-9-one-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane Was prepared according to method B. Isolated as the free base. Mp 242.8 - 256.3°C. exo-3-(1,2-Benzoisothiazol-3-yloxy)-8-H-8-azabicyclo[3.2.1]octane hydrochloric acid salt Was prepared according to method B from 3-chloro-1,2-benzoisothiazolG and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol). Mp252.5'C. exo-3-(3,4-Dichlorophenylthio)-8-methyl-8-azablcycIo[3.2.1]octanefumaricacid salt Was prepared according to method B. Mp 194-196°C. en Was prepared according to method B from. Mp 287°C. ajro-3-(4-Chioro-3-trifluoromethylphenoxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 215-217°C. ejro-3-(2-Dibenzofuranyloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 217-221°C. exo-3-(1-Naphthyloxy)-8-H-8-azablcycloI3.2.1loctane fumaric acid salt i/Vas prepared according to method B. Mp 223-224°C. Bxo-3-(2-Naphthyloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt \Nas prepared according to method B. Mp 202-204°C. exo-3-(3-Chloro-4-cyanophenoxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Nas prepared according to method B. Mp 176.3-178.9°C. axo-3-(4-Chloro-3-methylphenoxy}-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 192.5-194.5°C. »ro-3-(4-Chloronaphthalen-1-yloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid talt Vas prepared according to method B. Mp 226-227°C. ajro-3-(Quinolin-2-yloxy)-8-H-8-azablcyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 211 -213°C. ejro-3-(5-Chloro-pyridin-2-yl)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 196-198°C. exo-3-(4-Mothoxyphenoxy)-8-H-8-azablcyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 137-147°C. exo-3-(lsoquinoiln-5-yloxy)-8-IHi-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 192-194°C. axo-3-(6-Bromo-naphthalen-2-yloxy)-8-H-8'azabicyclo[3.2.1]octane hydrochloric acid salt Was prepared according to method B. Isolated as free base. Mp 270-274°C. exo-3-(4-Bromo-3-chioro-phanoxy)-8-H-8-azablcyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 207-209°C. ejro-^-(Quinolin-6-yloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric add salt Was prepared according to method B. Mp 237-239°C. exo-3-(4-Ti1fluorophenoxy)-8-H-8-azabicyclo[3.2.1]octane hydrochloric acid salt Was prepared according to method B. Mp 178-180°C. exo-^-(4-Cyanophenoxy)-8-H-8-azablcyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 188.9-191.6°C. exo-3-(Quinolin-8-yloxy)>8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 182-184.5°C. exo-3-(4-ltflethylphenoxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 174-177°C. exo-3-(&'Chloropyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method B from 2,6-dichloropyridine and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-oi). Mp 202-204°C. exo-3-(5-Bromopyridin-2-yloxy)-8-l4-8-azabicycio[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 216-218°C. exo-3-(6-Bromopyridin-2-yioxy)-8-H-8'-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to metiiod B. Mp 218-220°C. exo-3-(lsoqulnolin-1-yloxy)-8-l-l-8-azablcyclo[3.2.1]octane fumaric acid sait Was prepared according to metiiod B from 1 -cliloroisoqulnoline and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol). Mp 215-217°C. exo-3-(3-Trtfluoromethoxyphenoxy}-8-H-8-azabicycIo[3.2.1]octane Was prepared according to metiiod B. isoiated as thie free base. i\/lp 185.5-187°C. exo-3-(4-TrifIuoromethoxyphenoxy}-8-H-8-azabicyclo[3.2.1]octane Was prepared according to metiiod B. isolated as tlie free base. l\/lp. 192.5-194°C. «xo-3-(6-IMethoxypyrldin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to metiiod B). l\/ip 200-202°C. ejro-3-(5-Trifiuoromethylpyridin-2-yioxy)-8-H-8-azabicycio[3.2.1]octane fumaric acid salt Was prepared according to metiiod B. Mp 196.5-198.5°C. exo-3-(6-Etlioxypyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to metiiod B. iVIp 192.5-194.5°C. exo-3-(4-Fluoro-3-trifIuoromethylphBnoxy)-8-H-8-azablcyclo[3.2.1]octane fumaric acid salt Was prepared according to metiiod B. Mp 182-185°C. Method C eiro-3-(2,3-Dlchlorophenoxy)-8-methyl-B-azabicyclo[3.2.1]octane fumaric acid salt DIetiiylazodicarboxylate (8.36 ml, 53.1 mmol) was added dropwise at room-temperature to a mixture of tropine (e/7£/o-8-metliyl-8-azablcyclo[3.2.1]octan-3-ol) (5.0 g, 35.4 mmol), 2,3-diciiloropiienoi (6.93 g, 42.5 mmoi), tripiienyipliospliine (13.9 g, 53.1 mmol) and dioxane (55 ml). Tlie mixture was stirred for 40 ii at 100°C. Aqueous sodium iiydroxide (100 ml, 1 M) was added to tiie mixture. Tlie mixture was extracted witii diciilorometliane (2 x 100 mi). Chromatograpiiy on silica gel witii metiianol, diciiloromethane and acetone (1:4:1) gave tiie title compound. Yield 6.22 g, (61%). The corresponding salt was obtained by addition of a dietliyl ether and methanol mixture (9:1) saturated withfumaric acid. I\1p 171.3-194.7°C. exO'3-(3,4-Dichlorophenoxy)-B-methyl-8-azablcycio[3.2.1]octanBfuniaricacid salt Was prepared according to method C. I\4p 225.6°C. exo-3-(3-Chloro-4-fiuorophenoxy)-8-nnethyl-8-azabicyclo[3.2.1]octane Was prepared according to method C. Isolated as free base and oil. ejro-3-(4-Chloro-3-fluorophenoxy)-8-methyl-8-azabicyclo[3.2.1]octane Was prepared according to method C. Isolated as free base and oil. exo-3-(2-Chloro-3-4rifluoromethylphenoxy)-8-methyl-8-azabicyc[o[3.2.1]octane Was prepared according to method C. isolated as free base and oil. flixo-3-(3-Chloro-phenoxy)-8-m9thyl-8-azabicyclD[3.2.1]octane oxalic acid salt Was prepared according to method C. i\/lp 208-209°C. exo-3-(4-Chloro-phenoxy)-8-methyl-8-azabicyclo[3.2.1]octane oxalic acid salt Was prepared according to method C. Mp 150.5-154.0°C. ejro-3-(Fiuordn-9-ona-2-yloxy)-8-methyi-8-azabicyclo[3.2.1]octane hydrochloric acid salt Was prepared according to method C. Mp Decomp. earo-3-(3,4-DichlorophenyKhio)-8-methyl-8-azabicyclo[3.2.1]octanefumaricacid salt Was prepared according to method C from 3,4-dichiorothiophenoi. Mp 179-181°C. sxo-3-(1 -Naphthyloxy)-8-nfiethyl-8-azabicyclo[3.2.1 Joctane Was prepared according to method C. Isolated as free base. iVIp 72-74°C. exo-3-(2-Naphthyloxy)-8-niethyl-8-azabicyclo[3.2.1]octane Was prepared according to method C. isolated as free base. Mp 83-86°C. exo-3-(4-Chloro-3-trifluoromethylphenoxy)-8-nn8thyl-8-azabicyclc[3.2.1]octane fumaric acid salt Was prepared according to method C. Mp 172.3-174.2°C. 6xO'-3-(3-Chloro-4-cyanophenoxy)-8-methyl-8-azabicyclo[3.2.1]octanefumaric acid salt Was prepared according to method C. Mp 191.7-194.3°C. ajro-3-(2-Dibenzofuranyloxy)-8-methyl-8-azabicyclo[3.2.1]octanefumaricacid salt Was prepared according to metliod C. l\/lp 199.9-202.0°C. e)ro-3-(4-ChloronaphthaIen-1-yloxy}-8-methyl-8-azablcyclo[3.2.1]octanefunfiaric acid salt Was prepared according to metiiod C. ly^p 198-199°C. exo-3-(4-Ch[oro-3-methylphenoxy)-8-niethyl-8azabicycio[3.2.1]octanefumaric acid salt \Nas prepared according to method C. Mp 230-232°C. sxo-3-(4-Methoxyphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt iA/as prepared according to method C. Mp 164.5-166.5°C. Bjro-3-(7-Methoxynaphthalen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt ^as prepared according to method C. Mp 143-145°C. axo-3-(6-Methoxyiiaphthalen-2-yloxy)-8-methyl-8-azabicyc[o[3.2.1]octane fumaric icid salt ^as prepared according to method C. Mp 78.5-81.5°C. 3XO-3-(4-Bromo-3-chloro-phenoxy)-8-methyl-8-azabicyclo[3.2.1 ]octane fumaric icid salt Nas prepared according to method C. Mp 218-220°C. }XO-3-(lsoquinoIin-5-yl)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt Nas prepared according to method C. Mp 193-196°C. ?xo-3-(6-BromoHnaphthalen-2-yioxy)-8-methyl-8-azabicyc[o[3.2.1]octane fumaric icid salt Vas prepared according to method C. Mp 227-229°C. !xo-3-(3-Methoxyphenoxy)-8-mathyl-8-azablcyclo[3.2.1]octane fumaric acid salt Vas prepared according to method C. Mp 144-147°C. exo-3-(4-Cyanoph8noxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method C. Mp 177.9-181.9°C. exo-3-(QuinDlin-6-yloxy)-8-methyl-8*azablcyclo[3.2.1]octane fumaric acid salt Was prepared according to metliod C. I\4p 221-223°C. ejro-3-(1,2,3,4-TGtrahydronaphthal8n-6-yloxy)-8-mgthyl-8-azabicycio[3.2.1]octane Fumaric acid salt Was prepared according to metliod C. Mp 165.9-167.2°C. B)ro-3-(4-TrlfluoromethyIphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt i/Vas prepared according to method C. I^p 184.1-186.5°C. axo-3-(4-IVIetliylpiienoxy]-8-metiiyl-8-azabicycio[3.2.1]octane fumaric acid salt yVas prepared according to method C. Mp 178-181 °C. »ro-3-(8-Quinol!nyl)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid saltWas Drepared according to method C. Mp 158-160°C, »ro-3-(5-lndanyloxy)-8-methyi-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method C. Mp 184.7-185.9°C. }xo-3-(4-l\/lethoxynaphthalen-1-yIoxy)-8-methyi-8-azabicyclo[3.2.1]octane fumaric icid salt Vas prepared according to method C. Mp 185-188°C. ixo-3-(lndol-5-yloxy)-8-metiiyl-8-azabicyclo[3.2.1]octane fumaric acid salt Vas prepared according to method C. Mp 176.3-178.3°C. uro-3-(3-Trifluoromethoxyphenoxy)-8-methyI-8'«utabicyclo[3.2.l]octane Vas prepared according to method C. Isolated as the free base. Oil. ixo-3-(4-TrifiuoromGthoxyphenoxy)-8-methyl-8'azabicycio[3.2.1]octane Vas prepared according to method C. isolated as the free base. Oil. ixo-3-(4-Fiuoro-3-trifluoromethyiphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane umaric acid salt Vas prepared according to method C. Mp 167-169'C. Method D endo-3-(3,4-Dichlorophenoxy)-8-methyl-8-azablcyclo[3.2.1]octane fumaric acid salt A mixture of e/70fo-3-chloro-8-m9thyl-8-azabicyclo[3.2.1]octan (3.9, 24 mmol), (prepared from exo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol and thionylchlorlde at reflux for 3 h), 3,4-dichiorophenol (5.9 g, 36 mmoi), sodium hydride 60% (1.2 g, 36 mmol) and ethanol (30 mi) 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 diethylether (3 x 50 ml). Chromatography, of the crude mixture, on silica gel with dichloromethane, methanol and cone, ammonia (89:10:1) gave the title compound. The corresponding salt was obtained by addition of a diethyl ether and methanol mixture (9:1) saturated with fumaric acid. Yield 0.90 g (9%). Mp 19B.0-207.7'C. IVIethod E exo-3-(3,4-Dichlorophenoxy)-8-(2-hydroxyethyl)-8-azablcyclo[3.2.1]octane \ mixture of ©xo-3-(3,4-Dlchlorophenoxy)-8-H-8-azablcyclo[3.2.1]octane (2.2 g, 8.1 nmol), 2-bromoethanol (0.6 ml, 8.9 mmol), potassium carbonate (1.1 g, 8.1 mmol) and sthanoi (20 mi) was stirred at reflux for 15 h. Aqueous sodium hydroxide (50 mi, 4IVI) A/as added. The mixture was extracted with dichloromethane (3 x 50 ml). Chromatog-■aphy, of the crude mixture, on silica gel with dichloromethane, methanol and cone, ammonia (89:10:1) gave the title compound as free base and oil. Yield 0.40 g (16%). »ro-3-(3,4-Dlchlorophenoxy)-8-(cyanomethyl)-8-azablcyclo[3.2.1]octane fumaric icid salt A/as prepared according to method E. Mp 79-82°C. Mro-3-(3,4-Dichlorophenoxy)-8-(cyclopropylmethyl)-8-azabicyclo[3.2.1]octane umaric acid salt Vas prepared according to method E. Mp 187-189.5°C. uro-3-(3,4-Dichlorophenoxy)-8-(allyl)-8-azablcyclo[3.2.1]od:ane fumaric acid salt Vas prepared according to method E. 202-206'C. exo-3-(3^-Dichlorophenoxy)-8-(methoxyetliyl}-8-azabicyclo[3.2.1]octanefumaric acid salt Was prepared according to method E. Mp 177.8-179.5 "C. IVIethodF e]ro-3- A mixture of exo-3-(6-Chloropyridin-2-yioxy)-8-methyi-B-azabicyclo[3.2.1]octane (6.5 g, 25.8 mmol), sodium methoxide (6.5 g, 0.12 mol) and NIVIP (30 mi) was stirred at 1 SO'C for 15 h. Water (300 ml) was added. The mixture was extracted with d 1-ethylether (3 x 150 ml). The con-esponding salt was obtained by addition of a diethyl ether and methanol mixture (9:1) saturated with fumaric acid. Yield 3.0 g (32%). Mp 176-177.5 exo-3-(6-Ethoxypyrldin-2-yloxy)-8-methyl-8-azabicyclo[3.2.1 ]octane fumaric acid saltWas prepared according to method F, l\/lp 177-179°C. exo-3-(6-hydroxy-pyridln-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared from exo-3-(6-(cls-methylvinyloxy)-pyridin-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane by stirring it with concentrated hydrochloric acid at reflux for 0.5 h. Worl Method G exo-3-(6-Cyano-naphttialen-2-yloxy)-8-mothyl-B-azabicyclo[3.2.1]octane fumaric acid salt A mixture of exo-3-(6-bromo-napiith-2-yioxy)-8-methyl-8-azablcycio[3.2.1]octane (2.6 g, 7.5 mmol), Zn(CN)2 (2.2 g, 18 mmol), palladacycle (50 mg) and dioxane (30 ml) was stirred at reflux for 70 h. Aqueous sodium hydroxide (50 ml, 1 M) was added to the mixture. The mixture was extracted with dichloromethane (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 addition of a diethyl ether and methanol mixture (9:1) saturated with fumaric acid. Mp 230-232'C. Method H exo-(3,4-Dichloro-phenyi)-(8-methyl-B-aza-blcyclo[3i!.1]oct-3-yl)-aminefumaric acid salt ^ mixture of 3,4-dichloroformanllide (0.6 g, 3.17 mmoi), tropine methanesulfonate loiuenesuifonic acid salt (1.24 g, 3.17 mmoi) [S.Archer et ai. JACS 80,4677-4691 [1958], sodium hydride (0.17 g, 6.97 mmoi) and DIVIF (5 mi) was prepared at 0 °C. The nixture was stirred for 15 h at room temperature. Aqueous sodium hydroxide (5 ml, 1 \H) was added to the mixture. The mixture was extracted with dichioromethane (2x5 Til). Chromatography on silica gel with methanol, dichioromethane and aqueous am-■nonia (10: 89:1) gave the title compound. The corresponding salt was obtained by idditlon of a diethyl ether and methanol mixture (9:1) saturated with fumaric add. Kield 23 mg, (2%). Mp 193.5-202.0°C. )n(/o-(3,4-Dichioro-phanyl)-(8-methyl-8-aza-bicyGio[3.2.1]oct-3-yi)-1brmyiamine umaric acid salt IVas Isolated from the reaction mixture above according to method I. Yield 32 mg, 3%). Mp 206.3°C. »xo-(3,4-Dichloro-phenyl)-(8-'nethyl-8-aza-bicyclo[3.2.1]oct-3-yl)-formylamine umaric acid salt Vas prepared by formylation with concentrated formic acid from exo-(3,4-Dichloro-ihenyl)-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yi)-amine. Workup was performed ac-lording to method I. Mp 150.5-153.0°C. We claim: 1, An 8-aza-bicyclo[3,2,l]octane derivative of the Formula I: 2. The chemical compound as claimed in claim 1, wherein R represents a phenyl group, which phenyl group is substituted with one or two substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy. 3. The chemical compound as claimed in claim 1, wherein R"' represents a pyridyl group, which pyridyl group is substituted with one or two substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy and alkoxy, 4. The chemical compound as claimed in claim 1, wherein exo-3-(2,3-Dichlorophenoxy)-8-H-8-azabicyclo[3,2,l]octane; exo-3-(3,4-Dichlorophenoxy)-8-H-8-azabicyclo[3,2,l]octane; exo-3-(3-Chloro-4-fluorophenoxy)-8-H-8-azabicyclo[3,2,1 ]octane; ejco-3-(3-Chloro-phenoxy)-8-H-8-azabicyclo[3,2,l]octane; ejco-3-(4-Chloro-3-fluorophenoxy)-8-H-8-azabicyclo[3,2,l]octane; ejco-3-(4-Chloro-phenoxy)-8-H-8-azabicyclo[3,2,l]octane; exo-3-(2-Chloro-3-trifluoromethyl-phenoxy)-8-H-8-azabicyclo[3,2,l]octane; e«c/o-3-(3,4-Dichlorophenoxy)-8-H-8-azabicyclo[3,2,1 Joctane; exo-3-(4-Chloro-3-trifluoromethylphenoxy)-8-H-8-azabicyclo[3,2,l]octane; ejco-3-(3-Chloro-4-cyanophenoxy)-8-H-8-azabicyclo[3,2,l]octane; ew-3-(4-Chloro-3-methylphenoxy)-8-H-8-azabicyclo[3,2,l]octane; exo-3-(4-Chloronaphthalen-l-yloxy)-8-H-8-azabicyclo[3,2,l]octane; exo-3-(5-Chloro-pyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane; exo-3-(4-Methoxyphenoxy)-8-H-8-azabicyclo[3,2,l]octane; exo-3-(6-Bromo-naphthalen-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane; ^xo-3-(4-Bromo-3-chloro-phenoxy)-8-H-8-azabicyclo[3,2,1 ]octane; ejco-3-(4-Cyanophenoxy)-8-H-8-azabicyclo[3,2,1 Joctane; exo-3-(4-Methylphenoxy)-8-H-8-azabicyclo[3,2,l]octane; exo-3-(6-Chloropyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane; exo-3-(5-Bromopyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane; exo-3-(6-Bromopyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane; exo-3-(3-TrifIuoromethoxyphenoxy)-8-H-8-azabicyclo[3,2,1 ]octane; exo-3-(4-Trifluoromethoxyphenoxy)-8-H-8-azabicyclo[3,2,1 ]octane; eA;o-3-(6-Methoxypyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane; exo-3-(5-Trifluoromethylpyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane; ejco-3-(6-Ethoxypyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane; exo-3-(4-Fluoro-3-trifluoromethylphenoxy)-8-H-8-azabicyclo[3,2,l]octane; or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof. 5. A pharmaceutical composition having monoamine neurotransmitter re-uptake inhibitory activity comprising a therapeutically effective amount of a compound as claimed in claim 1, or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof, together with at least one pharmaceutically acceptable carrier, excipient or diluent.

Full Text

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.
BACKGROUND ART
WO 97/30997 (NeuroSearch A/S) describes tropane derivatives active as neurotransmitter re-uptake inhibitors.
However, there is a continued strong need to find compounds with an optimised pharmacological profile as regards the activity on reuptake of the monoamine neurotransmitters senstonin, dopamine and noradrenaline, such as the ratio of the serotonin reuptake versus the noradrenaline and dopamine activity.
SUMMARY OF THE INVENTION

In a further 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 pharmaceuticaliy acceptable salt thereof, for the manufacture of a pharmaceutical composition for the treatment, prevention or alleviation of a disease or a disorder or a condition of a mammal, Including a human, which disease, disorder or condition is responsive to inhibition of monoamine neurotransmitter re-uptaite in the central nervous system.
In a still further aspect, the invention relates to a method for treatment, prevention or alleviation of a disease or a disorder or a condition of a living animal body, Including a human, which disorder, disease or condition Is responsive to responsive to Inhibition of monoamine neurotransmitter re-uptai(e In the central nervous system, which method comprises the step of administering to such a living animal body 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 a pharmaceuticaliy acceptable salt thereof.
Other objects of the invention will be apparent to the person skilled in the art fr-om the following detailed description and examples.
DETAILED DISCLOSURE OF THE [NVENTION
3-aza-bicyclo[3.2.1]octane derivatives
In Its first aspect the present Invention provides compounds of fomiuia I:

)r any of its isomers or any mixture of its isomers,
)r a pharmaceuticaliy acceptable salt thereof,
vherein
\^ represents hydrogen or alkyi;
which aikyi is optionally substituted with one or more substituents Independently selected from the group consisting of:
halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitro, alkoxy, cycioalkoxy, alkyl, cydoalkyl, cycloalkylalkyi, alkenyl and alkynyl; C represents -0-, -S- or -NR°-;
wherein R° represents hydrogen, alkyl, -C(=b)R' or-SOaR'; wherein R' represents hydrogen or alkyl;

R** represents an aryl or a heteroaryl group,
which aryl or heteroaryl group is optionally substituted with one or more substituents independently selected from the group consisting of:
halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitre, oxo,
' ali In one embodiment, R^ represents hydrogen or alkyl; X represents -0-, -S- or -NR"-;
wherein R** represents hydrogen, alkyl, -C(=0)R'* or-SOaR^; wherein R*" represents hydrogen or alkyl; R"* represents an aryl or a heteroaryl group,
which aryl or heteroaryl group 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, cycloalkyi, cycloalkylalkyl, alkenyl and alkynyl.
In a further embodiment, R" represents hydrogen or alkyl. In a still further embodiment, R*represents hydrogen. In a further embodiment, R^represents alkyl, such as methyl. In a still further embodiment, R°represents alkyl substituted with hydroxy, cyano, cycloalkyi or alkenyl. In a special embodiment, R° represents hydroxyalkyl, such as hydroxyethyl. In a further embodiment, R° represents cyanoalkyi, such as cyanomethyl. In a still further embodiment, R* represents cycloalkylalkyl, such as cyclopropylmethyl. In a further embodiment, R° represents alkenylalkyl, such as allyl.
In a further embodiment, X represents -0-. In a still further embodiment, X represents -S-. In a further embodiment, X represents -NR'-. In a special embodiment, R'* represents hydrogen. In a further embodiment, R° represents -C(=:0)R'. In a special embodiment, R' represents hydrogen. In a special embodiment, X represents -NH- or -N((C=0)H)-
In a further embodiment, R** represents an aryl or a heteroaryl group, which aryl or heteroaryl group Is optionally substituted with one or more substituents Independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, oxo and alkoxy. In a still further embodiment, R' represents an aryl or a heteroaryl group, which aryl or heteroaryl group is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy. In a further embodiment, R" represents an aryl or a heteroaryl group, which aryl or heteroaryl group is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, oxo, alkyl and alkoxy. In a still further

embodiment, R*" represents an aryl or a heteroaryl group, which aryi or heteroaryl group is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyi, trifluoromethoxy, cyano, oxo and allcoxy.ln a further embodiment, R' represents an aryl or a heteroaryl group, which aryl or heteroaryl group is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyi, trifluoromethoxy, cyano and alkoxy.
In a further embodiment, R** represents an unsubstltuted, monosubstituted or disubstituted aryl or heteroaryl group.
In a still further embodiment, R^ represents an optionally substituted monocytic heteroaryl group. In a further embodiment, R' represents an optionally substituted bicylic heteroaryl group. In a still further embodiment, R"" represents an optionally substituted polycylic heteroaryl group.
in a special embodiment, R^ represents an optionally substituted heteroaryl group and the compound of formula I Is In the exo configuration. In a further embodiment. R^ represents hydrogen and R" represents an optionally substituted heteroaryl group. In a still further embodiment, R° represents hydrogen, R' represents an optionally substituted heteroaryl group and the compound of formula I is in the exo configuration.
In a still further embodiment, R' represents an optionally substituted phenyl group. In a further embodiment, R' represents an optionally substituted naphthyl group. In a still further embodiment, R" represents an optionally substituted fluorenyl group.
In a further embodiment, R** represents an optionally substituted thienyl group. In a still further embodiment, R' represents an optionally substituted benzoisothlazolyl group.
In a still further embodiment, R' represents a phenyl group, which phenyl group Is optionally substituted with one or more substituents Independently selected from the group consisting of: halo, trifluoromethyi, trifluoromethoxy, cyano and alkoxy.
In a further embodiment, R' represents a phenyl group optionally substituted once or twice with halo, such as chloro. In a special embodiment, R' represents phenyl, in a further embodiment, R' represents monosubstituted phenyl, in a special embodiment, R" represents chlorophenyl, such as 3-chlorophenyl. In a further embodiment, R^ represents a disubstituted phenyl. In a still further special embodiment, R" represents dichlorophenyl, such as 2,3-dichIorophenyl or 3,4-dlchlorophenyi. In a further embodiment, R** represents phenyl substituted with chloro and fluoro, such as 4-chloro-3-fluoraphenyl or 4-fluoro-3-chlorophenyi. In a still further embodiment, R' represents phenyl substituted with chloro and trifluoromethyi, such as 2-chloro-3-trifluoromethyiphenyl or4-chloro-3-trlfluoromethyiphenyl. In a still further smbodiment, R" represents phenyl substituted with fluoro and trifluoromethyi, such as

4-fluoro-3-trifIuoromethylphenyl. In a further embodiment, R' represents phenyl substituted with chloro and cyano, such as 3-chloro-4-cyanophenyl. In still a further embodiment, R** represents phenyl substituted with chloro and methyl, such as 4-chloro-3-methylphenyl. In a further embodiment, R" represents phenyl substituted with chloro and bromo, such as 4-bromo-3-chlorophenyl. In a further embodiment, R' represents a monosubstituted phenyl. In a still further embodiment, R^ represents chlorophenyl, such as 3-chlorophenyl or4-chlGrophenyl. In a further embodiment, R' represents trifluoromethoxyphenyl, such as 3-trifluoromethoxyphenyl or4-trlfluoromethoxyphenyl. In a still further embodiment, R** represents trifluoromethylphenyl, such as 4-trifluoromethylphenyl. In a further embodiment, R' represents methylphenyl, such as 4-methylphenyl. In a still further embodiment, R' represents methoxyphenyl, such as 3-methoxyphenyl or 4-methoxyphenyl. In a still further embodiment, R' represents cyanophenyl, such as 4-cyanophenyl.
In a further embodiment, R' represents hydrogen and R** represents a phenyl group which phenyl group Is substituted twice with substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy.
In a further embodiment, R^ represents a naphthyl group, such as 1 -naphthyl or 2-naphthyl. In a still further embodiment, R'* represents a naphthyl group substituted once or twice with halo, such as chloro or bromo. In a special embodiment, R^ represents chloronaphthyl, such as4-chioronaphthalen-1-yl. In a further embodiment, R** represents bromonaphthyl, such as 6-bromonaphthalen-2-yl. In a still further embodiment, R*' represents a naphthyl group substituted one or twice with alkoxy, such as methoxy. In a special embodiment, R" represents methoxynaphthyl, such as 4-methoxynaphthalen-1-yl, 6-methoxynaphthalen-2-y! or 7-methoxynaphthalen-2-yl. In a still further embodiment, R' represents a naphthyl group substituted one or twice with cyano. In a special embodiment, R' represents cyanonaphthyi, such as 6-cyanonaphthalen-2-yl.
In a still further embodiment, R"* represents a 1,2,3,4-tetrahydronaphthyl group, such as 1,2,3,4-Tetrahydronaphthalen-6-yl.
In a further embodiment, R** represents an indanyl group, such as 5-indanyl.
In a still further embodiment, R' represents a fluorenyl group substituted with 0X0, such as fluoren-9-one-2-yl.
In a still further embodiment, R*" represents a thienyi group, which thienyl group is substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy.
In a further embodiment, R*" represents a thienyl group substituted one or more times with halo, such as chloro or bromo. In a special embodiment, R'^ represents bromothienyl, such as 4-bromothiophen-2-yl. In a further embodiment, R" represents

dihalothienyl, such as bromo-chioro-thienyl, in particular 3-bromo-5-chioro-thiophen-2-yl or4-bromo-5-chloro-thlophen-2-yl. In a further embodiment, R** represents di-chlorothienyl, such as 3,4-dichloro-thiophen-2-yi. In a further special embodiment, R" represents trichlorothienyl, such as 3,4,5-trichloro-thiophen-2-yl. In a stiil further spe¬cial embodiment, R' represents tribromothlanyl, such as 3,4,5-tribromo-thiophen-2-yl.
In a still further embodiment, R" represents a benzoisothlazolyl group, such as 1,2-benzoisothiazoi-3-yl.
In a further embodiment, R** represents an optionally substituted benzothiazolyl group. In a special embodiment, R" represents benzothiazoiyi, such as benzothiazol-2-yi. In a further embodiment, R'* represents a benzothiazolyl group substituted once or twice with halo, such as chloro. In a special embodiment, R** represents chioroben-zothiazoiyl, such as 6-chlorobenzothiazol-2-yi.
In a further embodiment, R" represents a thiazolyl group substituted once or twice with halo, such as bromo. in a speclai embodiment, R** represents bromothla-zolyi, such as 5-bromothiazoi-2-yi.
in a stiii further embodiment, R' represents a quinoxaiinyi group, such as qui-noxalin-2-yl.
in a further embodiment, R" represents a quinazolinyl group, such as quina-zolin-2-yi.
In a further embodiment, R' represents a quinolinyl group, such as quinolin-2-yi, quinolin-6-yi orquinolin-8-yl.
in a further embodiment, R' represents a isoquinolinyl group, such as isoquino-
I lin-5-yi.
In a still further embodiment, R' represents a benzoxazolyl group, such as ben-zoxazol-2-yi.
In a further embodiment, R'* represents an optionally substituted pyridazinyi group. In a still further embodiment, R' represents a pyridazinyi group substituted on¬ce or twice with halo, such as chloro. in a speclai embodiment, R' represents chloro-pyrldazinyl, such as 6-chloropyridazin-3-yl.
in a further embodiment, R** represents an optionally substituted pyridyl group. In a Hirther embodiment, R** represents a pyridyl group, which pyridyl group is substituted with one or more substituents independently selected from the group consisting of:
halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy and aikoxy. In a still further em¬bodiment, R'^ represents a pyridyl group substituted once or twice with halo, such as chloro or bromo. In a special embodiment, R' represents chloropyridyl, such as 5-chloropyridin-2-yl or 6-chloropyridin-2-yl. In a further embodiment, R*" represents bro-mopyridyl, such as 5-bromopyridln-2-yl or6-bromopyridin-2-yl. in a still further em¬bodiment, R' represents a pyridyl group substituted once or twice with aikoxy, such as

methoxy or ethoxy. In a special embodiment, R' represents methoxypyridyl, such as 6-methoxypyridin-2-yl. In a further special embodiment, R** represents ethoxypyridyl, such as 6-ethoxypyridin-2-yl. In a still further embodiment, R" represents a pyridin group substituted once or twice with trifluoromethyl. In a special embodiment, R' I represents trifluoromethylpyridyl, such as 5-trlfluoromethylpyridln-2-yl. In a further em¬bodiment, R' represents a pyridin group substituted once or twice with hydroxy. In a special embodiment, R" represents a hydroxypyridyl, such as 6-hydroxy-pyridin-2-yl.
In a further embodiment, R' represents a isoquinolinyl group, such as isoquino-
lin-1-yl.
I In a further embodiment, R'* represents an optionally substituted pyrlmidin
group. In a still further embodiment, R*' represents a pyrlmidin group substituted once or twice with halo, such as bromo. In a special embodiment, R** represents bro-mopyrimidin, such as 5-bromopyrimidin-2-yl.
In a further embodiment, R' represents a dibenzofuranyl group, such as diben-zofuran-2-yl.
In a still further embodiment, R' represents an indolyl group, such as 5-indolyl.
In a special embodiment the chemical compound of the invention is encfo-3-(3,4,5-Trichlorothiophen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; ' ©n(/o-3-(3,4-Dichlorothlophen-2-yloxy)-8-methyl-8-azablcyclo[3.2.1]octane; exo-3-(3,4,5-Trichlorothiophen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(1,2-Benzolsothlazol-3-yloxy)-8-methyl-8-azabicycio[3.2.1]octane; exo-3-(5-Bromothiazol-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(Benzothlazol-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-(Qulnolln-2-yioxy)-8-methyi-8-azabicyclo[3.2.1]octane; Gxo-3-(Benzoxazol-2-yloxy)-8-methy!-8-azabicyclo[3.2.1]octane; exo-3-(6-Chloro-pyridazin-3-yloxy)-8-methyl-8-azablcycio[3.2.1]octane,-exo-3-(5-Chloro-pyridin-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(lsoquinolin-1-yloxy)-8-methyl-8-azabicyclo[3,2.1]octane; exo-3-(6-Chloropyridin-2-yloxy)-8-methyi-B-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; ©xo-3-(5-Bromopyrlmldin-2-yloxy)-8-methyl-8-azablcyGlo[3.2.1]octane; ©xo-3-(Quinazolln-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(5-Trlfluoromethylpyrldln-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane; exo-3-(3,4,5-Tribromothiophen-2-yloxy)-8-methyl-8-azablcyclo[3.2.1]octane; €xo-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;
encfo-3-(4-Bromo-5-chloro-thiophen-2-yloxy)-8-methyl-8-azabicycIo[3.2.1]octane;
e/7do-3-(3,4,5-Trichlorothiopen-2-yloxy)-8-H-8-azabicyclo[3.2.1loctane;
exo-3-(2,3-Dichloroph©noxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(3,4-DichlorophGnoxy)-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-B-azabicyclo[3.2.1]octane;
exo-3-(4-Chloro-3-fIuorophenoxy)-8-H-8-azabicyclo[3.2.1]octane;
ejfo-3-(4-ChIoro-phenoxy)-8-H-8-azabicyclo[3.2.1 ]octane;
exo-3-(2-Chloro-3-trifluoromethyl-phenoxy)-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;
enoto-3-(3,4-Dichlorophenoxy)-8-H-8-azabicyclo[3.2.1]octane;
©xo-3-(4-Chloro-3-trif!uoromethylphenoxy)-8-H-8-azabicyclo[3.2.1 ]octanG;
exo-3-(2-DIbenzofuranyloxy)-8-H-8-azablcyclo[3.2.1]oclane;
©xo-3-(1 -Naphthyloxy)-8-H-B-azabicyclo[3.2.1]octane;
©xo-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;
oxo-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-Metho)^phGno>cy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(lsoquinolin-5-yloxy)-8-H-8-azabicyclo[3.2.1 ]octane;
©xo-3-(6-Bromo-naphthal0n-2-yloxy)-B-H-8-azabicyclo[3.2.1]octane;
exo-3-(4-Bromo-3-chloro-phenoxy)-8-H-8-azabicyclo[3.2.1 Joclane;
Bxo-3-(Qulnolin-6-yloxy)-8-H-8-azabicyclo[3.2.1]octane;
exo-3-(4-Trifluorophenoxy)-8-H-8-azabicyclo[3.2.1 Joctane;
exo-3-(4-Cyanophenoxy)-8-H-B-azabicycIo[3.2.1 ]octane;
0xo-3-(Qulnolin-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-yioxy)-8-H-8-azabicyclo[3.2.1]octane;
Bxo-3-(5-Bromopyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane;
Bxo-3-(6-Bromopyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1 Joctane;
Bxo-3-(lsoquinolin-1-yloxy)-8-H-8-azablcyclo[3.2.1]octanG;
9xo-3-(3-Trifluoromethoxyphenoxy)-8-H-8-azabicyclo[3.2.1]oc1ane;
sxo-3-(4-TrifIuoramethoxyphenoxy)-8-H-8-azabicyclo[3.2.1]octane;

exo-3-(6-Methoxypyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1 Joctane;
©xo-3-(5-trlfluoromethylpyrldln-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-Dlchloraphenoxy)-8-mGthyl-8-azabicyclo[3.2.1]octane;
exo-3-(3,4-Dichlorophenoxy)-8-methyl-8-azabicyclo[3.2.1 Joctane;
oxo-3-(3-Chloro-4-fluorophenoxy)-8-methyl-8-azabicyclo[3.2.1]octane;
exo-3-(4-Chloro-3-fluoraphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane;
exo-3-(2-Chloro-3-trifluoromethyl-phenoxy)-8-methyl-8-azabicyclb[3.2.1]octane;
©xo-3-(3-Chloro-phenoxy)-8-methyl-8-azabicyclo[3.2.1]od:ane;
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;
©xo-3-(1-Naphthyloxy)-8-methyl-8-azabicyclo[3.2.1]octane;
6xo-3-(2-Naphthyloxy)-8-methyl-8-azablcyclo[3.2.1 ]octane;
exo-3-(4-Chloro-3-trifluoromethyl-phenoxy)-8-methyl-8-azabicycIo[3,2.1]octane;
exo-3-(3-Chloro-4-cyanophenoxy)-8-methyl-8-azablcyclo[3.2.1]octane;
exo-3-(2-Dibenzofuranyloxy)-8-methyl-8-azablcyclo[3.2.1]octane;
©xo-3-(4-Chloronaphthalen-1-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane;
©xo3-(4-Chloro-3-methylphenoxy)-8-methyl-8-azablcyclo[3.2.1]octan6;
©xo-3-(4-Methoxyphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane;
©xo-3-(7-Methoxynaphthalen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane;
©xo-3-(6-Methoxynaphthalen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane;
©xo-3-(4-Bromo-3-chloro-phenoxy)-8-methyl-8-azabicyclo[3.2.1]octane;
©xo-3-(lsoquinolin-5-yl)-8-methyl-8-a2abicyclo[3.2.1]octane;
exo-3-(6-Bromo-naphthalen-2-yloxy)-B-methyl-8-azabicyclo[3.2.1]octanB;
©xo-3-(3-Methoxyphenoxy)-8-methyl-8-azabicyclo[3.2.1 joctane;
exo-3-(4-Cyanophenoxy)-8-methyl-8-azabicyclo[3.2.1]ootane;
exo-3-(Qui nol ln-e-yloxy)-8-methyl-8-azabicyclo[3.2.1 ]octane;
©xo-3-(1,2,3,4-Tetrahydronaphthalen-6-yloxy)-8-methyl-8-azabicyclo[3.2.1]oGtane;
©xo-3-(4-Trifluoramethylphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane;
exo-3-(4-Methylphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane;
©xo3-(8-QuinolinyI)-8-methyI-8-azabicyclo[3.2.1]octane;
©xo-3-(5-lndanyloxy)-8-nnethyl-8-azabicyclo[3.2.1]octane;
exo-3-(4-Methoxynaphthalen-1-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane;
©xo-3-(lndol-5-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane;
©xo-3-(3-Trifluoromethoxyphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane;
exo-3-(4-Trifluoromethoxyphenoxy)-8-mBthyl-8-azabicyclD[3.2.1]octane;
©xo-3-(4-Fluoro-3-trifluoromethylphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane;

enGfo-3-(3,4-Dichiorophenoxy)-8-methyl-8-azabicycIo[3.2.1]octane;
exo-3-(3,4-Dichlorophenoxy)-8-(2-hydroxyethyi)-8-azablcycio[3.2.1]actane;
exo-3-(3,4-Dichlorophenoxy)-8-(cyanomethyi)-8-azabicycio[3.2.1]octane;
©xo-3-(3,4-Dlchlorophenoxy)-8-(cyclopropylmethyl)-8-azabicyclo[3.2.13octane;
GXO-3-(3,4-Dichlorophenoxy)-8-(aliyl)-8-azabicyclo[3.2.1]octane;
exo-3-(3,4-Dichlorophenoxy)-8-(methoxyethyl)-8-azabicycio[3.2.1]octane;
exo-3-(6-Methoxypyridin-2-yioxy)-8-methyi-8-azablcyolo[3.2.1]octane;
©xo-3-(6-Ethoxypyridin-2-yloxy)-8-methyi-8-azabicyclo[3.2.1]octane;
©xo-3-(6-hydroxy-pyridin-2-yioxy)-8-methyl-B-azabicyclo[3.2.1]octane;
exo-3-(6-Cyano-naphthalGn-2-yioxy)-8-methyl-8-azabicyclo[3.2.1]octane;
©xo-(3,4-Dichloro-phenyl)-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-amlne;
encto-(3,4-Dichloro-phenyl)-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-formylamine;
exo-(3,4-Dichloro-phenyi)-(8-methyl-8-aza-bicyGlo[3.2.1]oct-3-yi)-formylamine;
or any of Its isomers or any mixture of its isomers, or a pharmaceutically acceptable
salt thereof.
Any combination of two or more of the embodiments as described above is considered within the scope of the present Invention.
Definition of Substituents
in the context of this invention haio represents fluoro, chloro, bromo or iodo.
In the context of this invention an allq^l group designates a univalent saturated, straight or branched hydrocarbon chain. The hydrocarbon chain preferably contain of [irom one to six carbon atoms (Ci^-alkyl), including pentyi, isopentyl, neopentyl, Brtiary pentyi, hexyi and isohexyi. In a preferred embodiment alkyl represents a C^-alicyl group, including butyl, isobutyl, secondary butyl, and tertiary butyl. In another Dreferred embodiment of this invention ailcyi represents a Ci^-aliQrl group, which may n particular be methyl, ethyl, propyl or Isopropyl.
In the context of this invention an allcenyl group designates a carbon chain X}ntaining one or more double bonds, including di-enes, tri-enes and poly-enes. In a jreferred embodiment the ail In the context of this invention an allcynyl group designates a carbon chain iontaining one or more triple bonds, including di-ynes, tri-ynes and poiy-ynes. In a )referred embodiment the all
3-butynyl, or 1,3-butdiynyl; 1-, 2-, 3-, 4-p9ntynyl, or 1,3-pentdiynyl; 1-, 2-, 3-, 4-, or5-hexynyl, or 1,3-hexdiynyl or 1,3,5-he)ctriynyl.
In Vne context of this invention a cycloalkyi group designates a cyclic a\ky\ group, preferably containing of from three to seven carbon atoms (Ca-rcycloalkyl), including cyclopropyl, cyclobutyl, cyclopentyi, cyciohexyi and cycloheptyi.
Alkoxy Is 0-aikyl, wherein alkyl is as defined above.
Cycloaikoxy means 0-cycloalkyl, wherein cycloalkyi is as defined above.
CycloalkylalkyI means cycloalkyi as above and alkyl as above, meaning for example, cyclopropylmethyl.
Amino Is NHa or NH-alkyI or N-(alkyl)2, wherein alkyl is as defined above.
In the context of this invention an aryi group designates a carbocycllc aromatic ring system such as phenyl, naphthyl (1-naphthyl or 2-naphthyl) orfluorenyl. The term aryi is also intended to cover a partially hydrogenated carbocycllc aromatic ring system, such as Indanyl or 1,2,3,4-tetrahydronaphthyl.
In the context of this invention a heteroaryi group designates an aromatto mono- or bicyclic heterocyclic group, which holds one or more heteroatoms in its ring staicture. Pre¬ferred heteroatoms Include nitrogen (N), oxygen (O), and sulphur (S).
Preferred monocyclic heteroaryi groups of the invention include aromatic 5- and 6 membered heterocyclic monocyclic groups, including for example, but not limited to, oxazolyl (oxazol-2-yl, -4-yl, or -5-yl), isoxazolyl (lsoxazol-3-yl, -4-yl, or -5-yl), thiazolyl (thiazol-2-yl, -4-yI, or-5-yl), Isothiazoiyi (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-thiadiazol-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-lmidazolyl), pyrrolyl (2- or 3-pyrrolyl), furanyl (2- or 3-furanyl), thienyl (2-or3-thienyl), pyridyl (2-, 3-or 4-pyridyl), pyrimidyl (2-, 4-, 5-or6-pyrimidyl), or pyrldazlnyi (3-or4-pyridazinyl).
Preferred bicyclic heteroaryi groups of the invention include indolizinyl, in particular2-, 5-or 6-indolizinyl; Indolyl, in particular 2-, 5-or6-indolyl; isoindolyl, in particular 2-, 5- or6-lsolndolyl; Indazolyl, in particular 1 - or 3-indazolyl; benzo[b]furanyl, In particular 2-, 5- or 6-benzofuranyl; benzo[b]thienyl, in particular 2-, 5-or 6-benzothienyl; benzlmidazolyl, in particular 2-, 5-or6-benzimidazolyl; benzoxazolyl, in particular 2-, 5-or6-benzoxazolyl; benzothiazolyl, in particular 2-, 5-or6-benzothiazolyl; benzoisothiazolyl (1,2-benzoisothiazoiyl or 2,1-benzoisothiazolyl), in particular 1,2-benzoisothiazol-3-yl; purinyl, in particular 2-or 8-purinyl; quinolinyi. In particular 2-, 3-, 6-, 7- or8-qulnollnyl; isoquinolinyl, In particular 1-, 3-, 5-, 6-or 7-isoquinolinyl; cinnolinyl, in particular 6-or 7-cinnolinyl; phthalazinyl, in particular 6- or 7-phthalazinyl; quinazolinyl. In particular 2-, 6-or 7-qulnazolinyl; quinoxalinyl, in particular 2- or 6-qulnoxallnyl; 1,8-naphthyrldInyl, In particular 1,8-naphthyridin-2-, 3-,

6- or7-yl; pteridinyl, in particular 2-, 6-or 7-pteridinyl; and indenyl, in particular 1-, 2-, 3-, 5-or5-indenyl.
Preferred polycyclic heteroaryl groups of the Invention include dibenzofuranyl, in particular 2-dibenzofuranyl.
Pharmaceuticallv Acceptable Salts
The chemical compound of the invention may be provided In any form suitable for the intended administration. Suitable forms include pharmaceutically (i.e. physiologically) acceptable salts, and pre- or prodrug forms of the chemical compound of the invention.
Examples of pharmaceutically acceptable addition salts include, without limitation, the ncn-toxic inorganic and organic acid addition salts such as the hydrochloride derived from hydrochloric acid, the hydrabromida derived from hydrobromicacld, the nitrate de¬rived from nitric add, the perchlorate derived from perchloric acid, the phosphate derived from phosphoric add, the sulphate derived fiiom sulphuric acid, the formate derived from formic acid, the acetate derived from acetic acid, the aconate derived from aconitic acid, the ascorisate derived firom ascorbic add, the benzenesulphonate derived from benzen-sulphonic add, the benzoate derived from benzoic acid, the cinnamate derived from cin-namic acid, the citrate derived from citric acid, the embonate derived from embonic acid, the enantate derived from enanthic acid, the fumarate derived from fumaric acid, the glu-tamate derived from glutamic acid, the glycolate derived from glycolic acid, the lactate de¬rived from ladle acid, the maleate derived firom maleic add, the malonate derived from malonic acid, the mandelate derived from mandelic acid, the methanesulphonate derived from methane sulphonic acid, the naphthalene-2-sulphonate derived from naphtalene-2-sulphonic acid, the phthalate derived from phthalic acid, the salicylate derived from sali¬cylic acid, the sorisate derived from sorisic add, the stearate derived fit)m stearic acid, the succinate derived firom succinic add, the tartrate derived from tartaric acid, the toluene-p-sulphonate derived from p-toluene sulphonic acid, and the like. Such salts may be formed by procedures well known and described in the art.
Other acids such as oxalic acid, which niay not be considered pharmaceutically acceptable, may be useful in the preparation of salts useful as intermediates in obtaining a chemical compound of the Invention and its pharmaceutically acceptable acid addition salt.
Examples of pharmaceutically acceptable catlonic salts of a chemical compound of the Invention include, without limitation, the sodium, the potassium, the calcium, the magnesium, the zinc, the aluminium, the lithium, the choline, the lysine, and the ammonium salt, and the like, of a chemical compound of the invention containing an anionic group. Such catlonic salts may be formed by procedures well known and described In the art.

In the context of this invention the "onium salts" of N-containing compounds are also contemplated as phamiaceutically acceptable salts. Preferred "onium salts" include the alkyl-onium salts, the cycloalkyl-onium salts, and the cycloalkylalkyl-onium salts.
Examples of pre- or prodrug forms of the chemical compound of the invention include examples of suitable prodrugs of the substances according to the invention include compounds modified at one or more reactive or derivatizabie groups of the parent compound. Of particular Interest are compounds modified at a carboxyl group, a hydroxyl group, or an amino group. Examples of suitable derivatives are esters or amides.
The chemical compound of the invention may be provided in dissoluble or indissoluble forms together with a pharmaceutically acceptable solvent such as water, ethanol, and the like. Dissoluble forms may also Include hydrated forms such as the monohydrate, the dihydrate, the hemihydrate, the trihydrate, the tetrahydrate, and the like. In general, the dissoluble forms are considered equivalent to indissoluble forms for the purposes of this invention.
Steric Isomers
It will be appreciated by those skilled In the art 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 substltuent -X-R' on position 3 of the 8-a2a-bicyclo[3.2.1]octane skeleton of formula I may in particular be in the exo orendo configuration, in one embodiment of the invention the substltuent at position 3 is in the exo configuration. In another embodiment of the invention the substltuent at position 3 is in the endo configuration.
The Invention includes all such isomers and any mixtures thereof including racemic mixtures.
Racemic forms can be resolved into the optical antipodes by known methods and techniques. One way of separating the isomeric salts is by use of an optically active acid, and liberating the optically active amine compound by treatment with a base. Another method for resolving racemates into the optical antipodes is based upon chromatography on an optical active matrix. Racemic compounds of the present invention can thus be resolved into their optical antipodes, e.g., by fractional crystallisation of d- or I- (tartrates, mandelates, or camphorsulphonate) salts for example.
The chemical compounds of the present invention may also be resolved by the formation of diastereomeric amides by reaction of the chemical compounds of the present Invention with an optically active activated carboxylic acid such as that

derived from (+) or (-) phenylalanine, (+) or (-) phenylglycine, (+) or (-) camphanic acid or by the 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 resolving the optical isomers are known in the art. Such methods include those described by Jaques J, Collet A, & Wilen S in "Enantiomers. Racemates. and Resolutions". John Wiley and Sons, New York (1981).
Optical active compounds can also be prepared from optical active starting materials.
Labelled Compounds
The compounds of the invention may be used in their labelled or unlabelled form. In the context of this invention "label" stands for the binding of a marker to the compound of interest that will allow easy quantitative detection of said compound.
The labelled compounds of the invention may be useful as diagnostic tools, radio tracers, or monitoring agents in various diagnostic methods, and for in vivo receptor imaging.
The labelled isomer of the Invention preferably contains at least one radto-nuclide as a label. Positron emitting radionuclides are all candidates for usage. In the context of this invention the radionuclide is preferably selected from ^H (deuterium), ^H (tritium), "C,^*C,^'l,^^i,^=^l, and ^«F.
The physical method for detecting the labelled isomer of the present invention may be selected from Position Emission Tomography (PET), Single Photon Imaging Computed Tomography (SPECT), iVIagnetIc Resonance Spectroscopy (i\/IRS), Magnetic Resonance Imaging (l\/iRI), and Computed Axial X-ray Tomography (CAT), or combinations thereof.
Methods of Preparation
The chemical compounds of the invention may 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 may readily be prepared by conventional methods from commercially available chemicals.
Also one compound of the invention can be converiied to another compound of the Invention using conventional methods.
The end products of the reactions described herein may be Isolated by conventional techniques, e.g. by extraction, crystallisation, distillation, chromatography, etc.

Biological Activity
Compounds of the Invention may be tested for their ability to Inhibit reuptalte of the monoamines dopamine, noradrenaline and serotonin in synaptosomes eg such as lescribed in WO 97/30997. Based on the balanced activity observed In these tests he compound of the invention Is considered useful for the treatment the treatment, )revention or alleviation of a disease or a disorder or a condition of a mammal, includ-ng a human, which disease, disorder or condition is responsive to inhibition of nonoamlne neurotransmitter re-uptake in the central nervous system.
In a special embodiment, the compounds of the Invention are considered useful or the treatment, prevention or alleviation of: mood disorder, depression, atypical lepresslon, major depressive disorder, dysthymic disorder, bipolar disorder, bipolar I lisorder, bipolar II disorder, cyclothymic disorder, mood disorder due to a general ledical condition, substance-induced mood disorder, pseudodementia, Ganser's yndrome, obsessive compulsive disorder, panic disorder, panic disorder without goraphobia, panic disorder with agoraphobia, agoraphobia without history of panic isorder, panic attack, memory deficits, memory loss, attention deficit hyperactivity isorder, obesity, anxiety, generalized anxiety disorder, eating disorder, Parkinson's isease, parkinsonism, dementia, dementia of ageing, senile dementia, Alzheimer's isease, acquired immunodeficiency syndrome dementia complex, memory ysfunction In ageing, specific phobia, social phobia, post-traumatic stress disorder, cute stress disorder, drug addiction, drug misuse, cocaine abuse, nicotine abuse, )bacco abuse, alcohol addiction, alcoholism, pain, chronic pain, inflammatory pain, europathic pan, migraine pain, tension-type headache, chronic tension-type eadache, pain associated with depression, fibromyalgia, arthritis, osteoarthritis, leumatoid arthritis, back pain, cancer pain, irritable bowel pain, irritable bowel /ndrome, post-operative pain, post-stroke pain, drug-induced neuropathy, diabetic suropathy, sympathetically-maintained pain, trigeminal neuralgia, dental pain, lyofacial pain, phantom-limb pain, bulimia, premenstrual syndrome, late luteal phase yndrome, post-traumatic syndrome, chronic fatigue syndrome, urinary incontinence, ress incontinence, urge incontinence, nocturnal incontinence, sexual dysfunction, 'emature ejaculation, erectile difficulty, erectile dysfunction, eating disorders, lorexla nervosa, sleep disorders, autism, mutism, triohotiiiomania, narcolepsy, post-roke depression, stroke-induced brain damage, stroke-induced neuronal damage or ilies de la Tourettes disease. In a preferred embodiment, the compounds are )nsidered useful for the treatment, prevention or alleviation of depression.
It is at present contemplated that a suitable dosage of the active jarmaceutical Ingredient (API) is within the range of from about 0.1 to about 1000 mg 'I per day, more preferred of from about 10 to about 500 mg API per day, most eferred of from about 30 to about 100 mg API per day, dependent, however, upon

the exact mode of administration, the form in which it is administered, the indication considered, the subject and in particular the body weight of the subject involved, and further the preference and experience of the physician or veterinarian in charge. Preferred compounds of the invention show a biological activity in the sub-micromolar and micromoiar range, i.e. of from below 1 to about 100 ^M.
Pharmaceutical Compositions
In another aspect the Invention provides novel phamnaceutical compositions comprising a therapeutically effective amount of the chemical compound of the invention.
While a chemical compound of the invention for use in therapy may be administered In the form of the raw chemical compound, it Is preferred to introduce the active ingredient, optionally in the form of a physiologically acceptable salt, in a pharmaceutical composition together with one or more adjuvants, excipients, can-Jers, buffers, diluents, and/or other customary pharmaceutical auxiliaries.
in a prefenred embodiment, the invention provides pharmaceutical compositions comprising the chemical compound of the invention, or a pharmaceutlcaliy acceptable salt or derivative thereof, together with one or more pharmaceutlcaliy acceptable carriers therefore, and, optionally, other therapeutic and/or prophylactic ingredients, know and used in the art. The carrier(s) must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not harmful to the recipient thereof.
Pharmaceutical compositions of the invention may be those suitable for oral, rectal, bronchial, nasal, pulmonal, topical (including buccal and sub-lingual), tnansdemnal, vaginal or parenteral (including cutaneous, subcutaneous, intramuscular, intraperitoneal, intrave¬nous, intraarterial. Intracerabnal, intraocular injection or infusion) administnation, or those in a form suitable for administration by inhalation or Insufflation, including powders and liquid aerosol administration, or by sustained release systems. Suitable examples of sustained release systems include semipemneable matrices of solid hydrophobic polymers contain¬ing the compound of the invention, which matrices may be in form of shaped articles, e.g. films or microcapsules.
The chemical compound of the inventbn, together with a conventional adjuvant, :;arrier, or diluent, may thus be placed Into the fomi of phamiaceutical compositions and jnit dosages thereof. Such forms Include solids, and in pariicuiar tablets, filled capsules, 3owder and pellet forms, and liquids, in particular aqueous or non-aqueous solutions, suspensions, emulsions, elixirs, and capsules filled with the same, all for oral use, sup-jositories for rectal administration, and sterile Injectable solutions for parenteral use. Such jhannaceutical compositions and unit dosage forms thereof may comprise conventional igredients 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 ingredient commensurate with the Intended daily dosage range to be employed.
1
The chemical compound of the present invention can be administered In a wide va¬riety of oral and parenteral dosage forms, it will be obvious to those skilled in the art that the following dosage forms may comprise, as the active component, either a chemical compound of the invention or a phanmaoeutically acceptable salt of a chemical compound of the invention.
For preparing pharmaceutical compositions firom a chemical compound of the pre¬sent invention, pharmaceutically acceptable earners can be either solid or liquid. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersibie granules. A solid earner can be one or more subslances which may also act as diluents, flavouring agents, solubilizers. lubricants, suspending agents, binders, preserva-b'ves, tablet disintegrating agents, or an encapsulating material.
In powders, the earner is a finely divided solid, which is in a mixture with the finely divided active component.
In tablets, the active component is mixed with the carrier having the necessary binding capacity in suitable propori:lons and compacted In the shape and size desired.
The powders and tablets preferably contain from five or ten to about seventy per-[;entcf the active compound. Suitable caniers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylceliulose, sodium carisoxymethylceliulose, a low melting wax, cocoa butter, and the like. The term 'preparation" is intended to include the formulation of the active compound with encapsu-ating material as canler providing a capsule In which the active component, with or with-3ut caniers, is surrounded by a carrier, which is thus in association with it. Similariy, ca¬chets and lozenges are Included. Tablets, powders, capsules, pills, cachets, and lozenges :»n be used as solid forms suitable for oral administration.
For preparing suppositories, a low melting wax, such as a mixture of fatty acid glyc-}ride or cocoa butter, is first melted and the active component is dispersed homogene-)usly therein, as by stinring. The molten homogenous mixture is then poured into conven-ent sized moulds, allowed to cool, and thereby to solidify.
Compositions suitable tor vaginal administration may be presented as pessaries, ampons, creams, gels, pastes, foams or sprays containing in addition to the active ingre-iient such caniers as are known in tiie art to be appropriate.
Liquid preparations include solutions, suspensions, and emulsions, for example, i/ater or water-propylene glycol solutions. For example, parenteral injection liquid prepara-lons can be fonmulated as solutions in aqueous polyethylene glycol solution.
The chemical compound according to the present invention may thus be fomnulated 3r parenteral administration (e.g. by Injection, for example bolus injection or continuous ifusion) and may be presented in unit dose fomn in ampoules, pre-filled syringes, small

volume infusion or in multi-dose containers with an added preservative. The compositions may talce such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulation agents such as suspending, stabilising and/or dispersing agents. Alternatively, the active ingredient may be in powder form, obtained by aseptic iso¬lation of sterile solid or by lyophiiization from solution, for constitution with a suitable vehi¬cle, e.g. sterile, pyrogen-free water, before use.
Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavours, stabilising and thicl Aqueous suspensions suitable for oral use can be made by dispersing the finely di¬vided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, or other well l Also included are solid form preparations, intended for conversion shortly before use to liquid form preparations lor oral administration. Such liquid forms include solutions, suspensions, and emulsions. In addition to the active component such preparations may comprise colorants, flavours, stabilisers, buflisrs, artificial and natural sweeteners, dis-persants, thiclceners, solubilizing agents, and the lil For topical administration to the epidermis the chemical compound of the invention may be formulated as ointments, creams or lotions, or as a transdermal patch. Ointments and creams may, for example, be formulated with an aqueous or oily base with the addi¬tion of suitable thicl Compositions suitable for topical administration in the mouth include lozenges comprising the active agent In a flavoured base, usually sucrose and acada or tragacanth; pastilles comprising the active ingredient in an inert base such as gelatin and glycerine or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier.
Solutions or suspensions are applied directiy to tiie nasal cavity by conventional means, for example with a dropper, pipette or spray. The compositions may be provided in single or multi-dose fonn.
Administration to tiie respiratory tract may also be achieved by means of an aerosol formulation In which Une active Ingredient is provided in a pressurised pacl
Alternatively the active ingredients may be provided In the form of a dry powder, for example a powder mix of the compound in a suitable powder base such as lactose, starch, starch derivatives such as hydroxypropylmethyl cellulose and polyvinylpyrrolidone (PVP). Conveniently the powder carrier will form a gel in the nasal cavity. The powder composi¬tion may be presented in unit dose form for example in capsules or cartridges of, e.g., gelatin, or blister packs from which the powder may be administered by means of an in¬haler.
In compositions intended for administration to the respiratory tract, including intra¬nasal compositions, the compound will generally have a small particle size for example of the order of 5 microns or less. Such a particle size may be obtained by means known in the art, for example by micronization.
When desired, compositions adapted to give sustained release of the active ingre¬dient 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 ac¬tive component. The unit dosage form can be a packaged preparation, the package con¬taining discrete quantities of preparation, such as packaged tablets, capsules, and pow¬ders in vials or ampoules. Also, the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or It can be the appropriate number of any of these in packaged form.
Tablets or capsules for oral administration and liquids for intravenous administra-tkMi and continuous infusion are preferred compositions.
Further details on techniques for formulation and administration may be found in the latest edition of Remington's Pharmaceutical Sciences (l\/laack Publishing Co., Easton, PA).
A therapeutically effective dose refers to that amount of active ingredient, which ameliorates the symptoms or condition. Therapeutic efficacy and toxiclly, e.g. EDeo and LDso, may be detenmlned by standard pharmacological procedures in cell cultures or ex¬perimental animals. The dose ratio between therapeutic and toxic effects is the tiierapeutic index and may be expressed by the ratio LD50/ED50. Phamiaceutlcal compositions exhibit¬ing large therapeutic indexes are preferred.
The dose administered must of course be carefully adjusted to tiie age, weight and condition of the Individual being treated, as well as the route of administration, dosage form and regimen, and tiie result desired, and tiie exact dosage should of course be de¬termined by the practitioner.
The actual dosage depend on the nature and severity of the disease being treated, and Is within the discretion of the physician, and may be varied by titration of the dosage to the particular circumstances of this invention to produce tiie desired therapeutic effect. However, it is presently contemplated that pharmaceutical Mmpositi'ons containing of from about 0.1 to about 500 mg of active ingredient per

individual dose, preferably of from about 1 to about 100 mg, most preferred of from about 1 to about 10 mg, are suitable for therapeutic treatments.
The active Ingredient may be administered in one or several doses per day. A satisfactory result can, in certain instances, be obtained at a dosage as low as 0.1 jxg/kg i.v. and 1 |ig/kg p.o. The upper limit of the dosage range is presently considered to be about 10 mg/kg i.v. and 100 mg/kg p.o. Preferred ranges are from about 0.1 p,g/kg to about 10 mg/kg/day I.v., and from about 1 |.ig/kg to about 100 mg/kg/day p.o.
Methods of Therapy
in another aspect the invention provides a method for the treatment, prevention or alleviation of a disease or a disorder or a condition of a living animal body, including a human, which disease, disorder or condition Is responsive to Inhibition of monoamine neurotransmitter re-uptake in the central nervous system, and which method comprises administering to such a living animal body, including a human, In need thereof an effective amount of a chemical compound of the invention.
11 is at present contemplated that suitable dosage ranges are 0.1 to 1000 milligrams daily, 10-500 milligrams daily, and especially 30-100 milligrams daily, dependent as usual upon the exact mode of administration, form in which administered, the Indication toward which the administration is directed, the subject Involved and the body weight of the subject Involved, and further the preference and axperience of the physician or veterinarian in charge.
EXAMPLES
The invention Is further Illustrated with reference to the following examples, which are not intended to be in anyway limiting to the scope of the Invention as claimed.
General: Ail reactions Involving air sensitive reagents or Intermediates were lerformed under nitrogen and in anhydrous solvents. Magnesium sulphate was used IS drying agent In the workup-procedures and solvents were evaporated under re¬duced pressure.
Method A
)ndo-3-(3,4,5-Trichloroth!open-2-yloxy)-8-nnethyl-8-azabicyclo[3.2.1]octane umaric acid salt
V mixture of tetrachlorothiophene (5.48 g, 24.69 mmol), troplne (enrfo-8-methyl-8-izabicycio[3.2.1]octan-3-ol) (3.48 g, 24.69 mmol), potasslum-terf-butoxide (4.16 g,

37.04 mmol), 18-crown-6-ether (6.53 g, 24.69 mmol) and DI\/IF (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 addition of a diethyl ether and methanol mixture (9:1) saturated with fumaric acid. l\/lp 200.4-206.4°C.
encfo-3-(3,4-Dichlorothlopen-2-ylox/)-8-methyl-8-azabicyclo[3.2.1]octane
Was prepared according to method A from 2,3,4-trichlorothiophene and tropine {endo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol) isolated as the free base and oil.
exo-3-(3,4,5-Trichlorothiopen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane hydrochloric acid salt
Was prepared according to method A from tetratrichlorothiophene and pseudo-tropine (©xo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol). Mp 249-250'C.
exo-3-(1,2-Benzol8othiazol' Was prepared according to method A from 3-chloro-1,2-benzoisothiazole and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol). Mp 259.4-261.2°C.
ejro-3-(5-Bromothlazol-2-yloxy)-8-methyl>8-azabicyclo[3.2.1]octane
Was prepared according to method A from 2,5-dibromothiazole and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1loctan-3-ol). Isolated as the free base. Mp 104-106°C.
exo-3-(Benzothlazol-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octanefun(iarfcacid salt
Was prepared according to method A from 2-chlorobenzothiazole and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.11octan-3-ol). Mp 160-162°C.
exo-3-(6-Chlorobenzothlazol-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt
i/Vas prepared according to method A from 2,6-dichlorobenzothiazole and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-oi). Mp 163-164.5°C.

0jco-3-(Quinoxalin-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt
Was 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.
I exo-3-(QuiaoIin-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method A from 2-chloroquinoline and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2,1]octan-3-ol). iVIp 192.5-195°C.
exO'^-(Benzoxazol-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt
\ Was prepared according to method A from 2-chlorobenzoxazole and pseudo-tropine (exo-8-methyl-8-azablcyclo[3.2.1]octan-3-oi). Mp 141-144°C.
exo-3-(6-Ciiloro-pyridazin-3-yloxy}-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid aait
I Was prepared according to method A from 3,6-dichloropyridazine and pseudo-tropine (exo-8-methyl-8-azablcyclo[3.2.1]octan-3-ol). Mp 181-183°C.
e)ro-3-(5-Ciiioro-pyridin-2-yloxy)>^-methyl-8-azabicycio[3.2.1]octane fumaric acid salt
Was prepared according to method A from 2,5-dichioropyridine and pseudo-tropine (exo-8-methyl-8-azab!cycio[3.2.1]oclan-3-ol). Mp 214-216°C.
euro-3-(isoquinolin-1-yioxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method A from 1-chloroisoquinoline and pseudo-tropine ^ (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol). Mp 180-181.5°C.
exo-3-(6-Cliloropyridin-2-yioxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid sait
Was 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-Bromopyrldin-2-yloxy)-8-methyl-8-azablcyclo[3.2.1]octane fumaric acid salt
Was prepared according to method A from 2,5-dibromopyrldine and pseudo-tropine (exo-8-methyl-8-azablcyclo[3.2.1]octan-3-ol). Mp 213-215°C.
€!)ro-3-(8-Bromopyridin-2-yioxy)-8-methyl-8-azabicyelo[3.2.1]octane fumaric acid salt
Was prepared according to method A from 2,6-dibromopyrldlne and pseudo-tropine (exo-8-methyl-8-azablcyclo[3.2.1]octan-3-ol). Mp 198-200°C.

exo-3-(5-Bromopyrimidin-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octanefumaric acid salt
Was prepared according to method A from 5-bromo-2-chioropyrimidine and pseudo-tropine (©xo-8-methyl-8-azabicycloI3.2.1]octan-3-oi). Mp 198-200°C.
exo-3-(Quinazolin-2-yloxy)-8-methyl-B-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method A from 2-chloroquinazoline and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol). Mp 209-211°C.
exo-3-(5-Trifluoromethylpyridln-2-yloxy)-8-methy[-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method A from 2-chloro-5-trifluoromethyIpyridlne and pseudo-tropine (exo-8-m0thyl-8-azabicyclo[3.2.1]octan-3-ol). IVIp 190-191.5 "C.
exo-3-(3,4,5-Tribromothlophen-2-yloxy}-8-methyl-8-azabicyclo[3.2.1]octane hydrochloric acid salt
Was prepared according to method A from tetrabromothiophene and pseudo-tropine (©xo-8-methyl-8-azabicyclo[3.2.1]octan-3-oI). I^p 223.3-223.9 °C.
exo-3-(4-Bromothiophen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane hydrochloric acid salt
Was prepared from exo-3-(3,4,5-Tribromothiophen-2-yioxy)-8-methyl-8-azabicyclo [3.2.1]octane by stirring with 5 eq of zincpowder in concentrated acetic acid at 75 °C for 15 h. Worlcup procedure was performed according to method A. IVIp 222.1 °C.
endo-3-(3-Bromo-5-chloro-thiophen-2-yloxy)-8-methyl-B-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method A from 3-bromo-2,5-dichiorothiophene and tropine (enQfo-8-methyl-8-azabicyclo[3.2.1]octan-3-oi) IWp 171 -173 "C.
end'o-3-(4-Bromo-5-chloro-th!ophen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method A from 3-bromo-2,5-dichlorothiophene and tropine (e/7do-8-methyl-8-azabicyclo[3.2.1]octan-3-ol) Mp 136 -139 °C.

Method B
e/}cro-3-(3,4,5-Trichlorothiopen-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane
A mixture of ©/7c/o-3-(3,4,54richlorothlophen-2-yloxy)-8-methyl-8-f azabicyclo[3.2.1]octane (0.50 g, 1.53 mmol), 1-chloroethyl chloroformate (1.27 ml, 11.5 mmol) and toluene (20 ml) was stirred at reflux for 15 h. Water (10 ml) was added and the was stin-ed at reflux for 3.5 h. The mixture was evaporated. Sodium methoxide in methanol (5 mi, 1 M) and silica gel 60 (2 g) was added and was followed by evaporation. Chromatography, of the crude mixture, on silica gel with \ dichloromethane, methanol and cone, ammonia (89:10:1) gave the title compound in quantitative yield as free base and oil.
exo-3-(2,3-D!chlorophenoxy)-8-H-8-azablcyclo[3.2.1]octane
Was prepared according to method B. Isolated as the free base. Mp 62.3-65.4°C.
ejro-3-(3,4-Dichlorophenoxy)-8-H-8-azabicyclo[3.2.1]octane hydrochloric acid salt
Was prepared according to method B. Mp 160.1°C.
ejro-3-(3,4,5-Trichlorothiophen-2-yloxy)-8-H-8-«zabicyclo[3.2.1]octane hydrochloric acid salt
Was prepared according to method B. Mp 255-256°C.
axo-3-(3-Ctiloro-4-fluorophenoxy)-8-H-8-azabicyclo[3.2.1]octanefumaricacid salt
Was prepared according to method B. Mp 151-154°C.
ex'o-3-(3-Chloro-phenoxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method B. Mp 195-196°C.
exo-3-(4-Ctiloro-3-fiuorophsnoxy)-8-H-8-azabicyclo[3.2.1]octane
Was prepared according to method B. Isolated as free base and oil.
exo-3-(4-Chloro-phenoxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method B. Mp 188-188.5°C.
exo-^-(2-Chioro-3-trifluoromethyl-phenoxy)-8-iHI-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method B. Mp 190-193°C.

e)ro-3-(Fluoren-9-one-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane
Was prepared according to method B. Isolated as the free base. Mp 242.8 - 256.3°C.
exo-3-(1,2-Benzoisothiazol-3-yloxy)-8-H-8-azabicyclo[3.2.1]octane hydrochloric acid salt
Was prepared according to method B from 3-chloro-1,2-benzoisothiazolG and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol). Mp252.5'C.
exo-3-(3,4-Dichlorophenylthio)-8-methyl-8-azablcycIo[3.2.1]octanefumaricacid salt
Was prepared according to method B. Mp 194-196°C.
en Was prepared according to method B from. Mp 287°C.
ajro-3-(4-Chioro-3-trifluoromethylphenoxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method B. Mp 215-217°C.
ejro-3-(2-Dibenzofuranyloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 217-221°C.
exo-3-(1-Naphthyloxy)-8-H-8-azablcycloI3.2.1loctane fumaric acid salt
i/Vas prepared according to method B. Mp 223-224°C.
Bxo-3-(2-Naphthyloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt
\Nas prepared according to method B. Mp 202-204°C.
exo-3-(3-Chloro-4-cyanophenoxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt
Nas prepared according to method B. Mp 176.3-178.9°C.
axo-3-(4-Chloro-3-methylphenoxy}-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method B. Mp 192.5-194.5°C.
»ro-3-(4-Chloronaphthalen-1-yloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid talt
Vas prepared according to method B. Mp 226-227°C.

ajro-3-(Quinolin-2-yloxy)-8-H-8-azablcyclo[3.2.1]octane fumaric acid salt
Was prepared according to method B. Mp 211 -213°C.
ejro-3-(5-Chloro-pyridin-2-yl)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method B. Mp 196-198°C.
exo-3-(4-Mothoxyphenoxy)-8-H-8-azablcyclo[3.2.1]octane fumaric acid salt
Was prepared according to method B. Mp 137-147°C.
exo-3-(lsoquinoiln-5-yloxy)-8-IHi-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method B. Mp 192-194°C.
axo-3-(6-Bromo-naphthalen-2-yloxy)-8-H-8'azabicyclo[3.2.1]octane hydrochloric acid salt
Was prepared according to method B. Isolated as free base. Mp 270-274°C.
exo-3-(4-Bromo-3-chioro-phanoxy)-8-H-8-azablcyclo[3.2.1]octane fumaric acid salt
Was prepared according to method B. Mp 207-209°C.
ejro-^-(Quinolin-6-yloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric add salt
Was prepared according to method B. Mp 237-239°C.
exo-3-(4-Ti1fluorophenoxy)-8-H-8-azabicyclo[3.2.1]octane hydrochloric acid salt Was prepared according to method B. Mp 178-180°C.
exo-^-(4-Cyanophenoxy)-8-H-8-azablcyclo[3.2.1]octane fumaric acid salt
Was prepared according to method B. Mp 188.9-191.6°C.
exo-3-(Quinolin-8-yloxy)>8-H-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method B. Mp 182-184.5°C.
exo-3-(4-ltflethylphenoxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt Was prepared according to method B. Mp 174-177°C.
exo-3-(&'Chloropyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method B from 2,6-dichloropyridine and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-oi). Mp 202-204°C.
exo-3-(5-Bromopyridin-2-yloxy)-8-l4-8-azabicycio[3.2.1]octane fumaric acid salt
Was prepared according to method B. Mp 216-218°C.

exo-3-(6-Bromopyridin-2-yioxy)-8-H-8'-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to metiiod B. Mp 218-220°C.
exo-3-(lsoqulnolin-1-yloxy)-8-l-l-8-azablcyclo[3.2.1]octane fumaric acid sait
Was prepared according to metiiod B from 1 -cliloroisoqulnoline and pseudo-tropine (exo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol). Mp 215-217°C.
exo-3-(3-Trtfluoromethoxyphenoxy}-8-H-8-azabicycIo[3.2.1]octane
Was prepared according to metiiod B. isoiated as thie free base. i\/lp 185.5-187°C.
exo-3-(4-TrifIuoromethoxyphenoxy}-8-H-8-azabicyclo[3.2.1]octane
Was prepared according to metiiod B. isolated as tlie free base. l\/lp. 192.5-194°C.
«xo-3-(6-IMethoxypyrldin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to metiiod B). l\/ip 200-202°C.
ejro-3-(5-Trifiuoromethylpyridin-2-yioxy)-8-H-8-azabicycio[3.2.1]octane fumaric acid salt
Was prepared according to metiiod B. Mp 196.5-198.5°C.
exo-3-(6-Etlioxypyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to metiiod B. iVIp 192.5-194.5°C.
exo-3-(4-Fluoro-3-trifIuoromethylphBnoxy)-8-H-8-azablcyclo[3.2.1]octane fumaric
acid salt
Was prepared according to metiiod B. Mp 182-185°C.
Method C
eiro-3-(2,3-Dlchlorophenoxy)-8-methyl-B-azabicyclo[3.2.1]octane fumaric acid salt
DIetiiylazodicarboxylate (8.36 ml, 53.1 mmol) was added dropwise at room-temperature to a mixture of tropine (e/7£/o-8-metliyl-8-azablcyclo[3.2.1]octan-3-ol) (5.0 g, 35.4 mmol), 2,3-diciiloropiienoi (6.93 g, 42.5 mmoi), tripiienyipliospliine (13.9 g, 53.1 mmol) and dioxane (55 ml). Tlie mixture was stirred for 40 ii at 100°C. Aqueous sodium iiydroxide (100 ml, 1 M) was added to tiie mixture. Tlie mixture was extracted witii diciilorometliane (2 x 100 mi). Chromatograpiiy on silica gel witii metiianol, diciiloromethane and acetone (1:4:1) gave tiie title compound. Yield 6.22 g, (61%).

The corresponding salt was obtained by addition of a dietliyl ether and methanol mixture (9:1) saturated withfumaric acid. I\1p 171.3-194.7°C.
exO'3-(3,4-Dichlorophenoxy)-B-methyl-8-azablcycio[3.2.1]octanBfuniaricacid salt
Was prepared according to method C. I\4p 225.6°C.
exo-3-(3-Chloro-4-fiuorophenoxy)-8-nnethyl-8-azabicyclo[3.2.1]octane
Was prepared according to method C. Isolated as free base and oil.
ejro-3-(4-Chloro-3-fluorophenoxy)-8-methyl-8-azabicyclo[3.2.1]octane
Was prepared according to method C. Isolated as free base and oil.
exo-3-(2-Chloro-3-4rifluoromethylphenoxy)-8-methyl-8-azabicyc[o[3.2.1]octane
Was prepared according to method C. isolated as free base and oil.
flixo-3-(3-Chloro-phenoxy)-8-m9thyl-8-azabicyclD[3.2.1]octane oxalic acid salt
Was prepared according to method C. i\/lp 208-209°C.
exo-3-(4-Chloro-phenoxy)-8-methyl-8-azabicyclo[3.2.1]octane oxalic acid salt
Was prepared according to method C. Mp 150.5-154.0°C.
ejro-3-(Fiuordn-9-ona-2-yloxy)-8-methyi-8-azabicyclo[3.2.1]octane hydrochloric acid salt
Was prepared according to method C. Mp Decomp.
earo-3-(3,4-DichlorophenyKhio)-8-methyl-8-azabicyclo[3.2.1]octanefumaricacid salt
Was prepared according to method C from 3,4-dichiorothiophenoi. Mp 179-181°C.
sxo-3-(1 -Naphthyloxy)-8-nfiethyl-8-azabicyclo[3.2.1 Joctane
Was prepared according to method C. Isolated as free base. iVIp 72-74°C.
exo-3-(2-Naphthyloxy)-8-niethyl-8-azabicyclo[3.2.1]octane
Was prepared according to method C. isolated as free base. Mp 83-86°C.
exo-3-(4-Chloro-3-trifluoromethylphenoxy)-8-nn8thyl-8-azabicyclc[3.2.1]octane fumaric acid salt
Was prepared according to method C. Mp 172.3-174.2°C.

6xO'-3-(3-Chloro-4-cyanophenoxy)-8-methyl-8-azabicyclo[3.2.1]octanefumaric acid salt
Was prepared according to method C. Mp 191.7-194.3°C.
ajro-3-(2-Dibenzofuranyloxy)-8-methyl-8-azabicyclo[3.2.1]octanefumaricacid salt
Was prepared according to metliod C. l\/lp 199.9-202.0°C.
e)ro-3-(4-ChloronaphthaIen-1-yloxy}-8-methyl-8-azablcyclo[3.2.1]octanefunfiaric acid salt
Was prepared according to metiiod C. ly^p 198-199°C.
exo-3-(4-Ch[oro-3-methylphenoxy)-8-niethyl-8*azabicycio[3.2.1]octanefumaric acid salt
\Nas prepared according to method C. Mp 230-232°C.
sxo-3-(4-Methoxyphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt iA/as prepared according to method C. Mp 164.5-166.5°C.
Bjro-3-(7-Methoxynaphthalen-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt
^as prepared according to method C. Mp 143-145°C.
axo-3-(6-Methoxyiiaphthalen-2-yloxy)-8-methyl-8-azabicyc[o[3.2.1]octane fumaric icid salt
^as prepared according to method C. Mp 78.5-81.5°C.
3XO-3-(4-Bromo-3-chloro-phenoxy)-8-methyl-8-azabicyclo[3.2.1 ]octane fumaric icid salt
Nas prepared according to method C. Mp 218-220°C.
}XO-3-(lsoquinoIin-5-yl)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt
Nas prepared according to method C. Mp 193-196°C.
?xo-3-(6-BromoHnaphthalen-2-yioxy)-8-methyl-8-azabicyc[o[3.2.1]octane fumaric icid salt
Vas prepared according to method C. Mp 227-229°C.
!xo-3-(3-Methoxyphenoxy)-8-mathyl-8-azablcyclo[3.2.1]octane fumaric acid salt
Vas prepared according to method C. Mp 144-147°C.

exo-3-(4-Cyanoph8noxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method C. Mp 177.9-181.9°C.
exo-3-(QuinDlin-6-yloxy)-8-methyl-8*azablcyclo[3.2.1]octane fumaric acid salt
Was prepared according to metliod C. I\4p 221-223°C.
ejro-3-(1,2,3,4-TGtrahydronaphthal8n-6-yloxy)-8-mgthyl-8-azabicycio[3.2.1]octane Fumaric acid salt
Was prepared according to metliod C. Mp 165.9-167.2°C.
B)ro-3-(4-TrlfluoromethyIphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt
i/Vas prepared according to method C. I^p 184.1-186.5°C.
axo-3-(4-IVIetliylpiienoxy]-8-metiiyl-8-azabicycio[3.2.1]octane fumaric acid salt
yVas prepared according to method C. Mp 178-181 °C.
»ro-3-(8-Quinol!nyl)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid saltWas Drepared according to method C. Mp 158-160°C,
»ro-3-(5-lndanyloxy)-8-methyi-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared according to method C. Mp 184.7-185.9°C.
}xo-3-(4-l\/lethoxynaphthalen-1-yIoxy)-8-methyi-8-azabicyclo[3.2.1]octane fumaric icid salt
Vas prepared according to method C. Mp 185-188°C.
ixo-3-(lndol-5-yloxy)-8-metiiyl-8-azabicyclo[3.2.1]octane fumaric acid salt
Vas prepared according to method C. Mp 176.3-178.3°C.
uro-3-(3-Trifluoromethoxyphenoxy)-8-methyI-8'«utabicyclo[3.2.l]octane
Vas prepared according to method C. Isolated as the free base. Oil.
ixo-3-(4-TrifiuoromGthoxyphenoxy)-8-methyl-8'azabicycio[3.2.1]octane
Vas prepared according to method C. isolated as the free base. Oil.
ixo-3-(4-Fiuoro-3-trifluoromethyiphenoxy)-8-methyl-8-azabicyclo[3.2.1]octane umaric acid salt
Vas prepared according to method C. Mp 167-169'C.

Method D
endo-3-(3,4-Dichlorophenoxy)-8-methyl-8-azablcyclo[3.2.1]octane fumaric acid salt
A mixture of e/70fo-3-chloro-8-m9thyl-8-azabicyclo[3.2.1]octan (3.9, 24 mmol), (prepared from exo-8-methyl-8-azabicyclo[3.2.1]octan-3-ol and thionylchlorlde at reflux for 3 h), 3,4-dichiorophenol (5.9 g, 36 mmoi), sodium hydride 60% (1.2 g, 36 mmol) and ethanol (30 mi) 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 diethylether (3 x 50 ml). Chromatography, of the crude mixture, on silica gel with dichloromethane, methanol and cone, ammonia (89:10:1) gave the title compound. The corresponding salt was obtained by addition of a diethyl ether and methanol mixture (9:1) saturated with fumaric acid. Yield 0.90 g (9%). Mp 19B.0-207.7'C.
IVIethod E
exo-3-(3,4-Dichlorophenoxy)-8-(2-hydroxyethyl)-8-azablcyclo[3.2.1]octane
\ mixture of ©xo-3-(3,4-Dlchlorophenoxy)-8-H-8-azablcyclo[3.2.1]octane (2.2 g, 8.1 nmol), 2-bromoethanol (0.6 ml, 8.9 mmol), potassium carbonate (1.1 g, 8.1 mmol) and sthanoi (20 mi) was stirred at reflux for 15 h. Aqueous sodium hydroxide (50 mi, 4IVI) A/as added. The mixture was extracted with dichloromethane (3 x 50 ml). Chromatog-■aphy, of the crude mixture, on silica gel with dichloromethane, methanol and cone, ammonia (89:10:1) gave the title compound as free base and oil. Yield 0.40 g (16%).
»ro-3-(3,4-Dlchlorophenoxy)-8-(cyanomethyl)-8-azablcyclo[3.2.1]octane fumaric icid salt
A/as prepared according to method E. Mp 79-82°C.
Mro-3-(3,4-Dichlorophenoxy)-8-(cyclopropylmethyl)-8-azabicyclo[3.2.1]octane umaric acid salt
Vas prepared according to method E. Mp 187-189.5°C.
uro-3-(3,4-Dichlorophenoxy)-8-(allyl)-8-azablcyclo[3.2.1]od:ane fumaric acid salt
Vas prepared according to method E. 202-206'C.

exo-3-(3^-Dichlorophenoxy)-8-(methoxyetliyl}-8-azabicyclo[3.2.1]octanefumaric
acid salt
Was prepared according to method E. Mp 177.8-179.5 "C.
IVIethodF
e]ro-3- A mixture of exo-3-(6-Chloropyridin-2-yioxy)-8-methyi-B-azabicyclo[3.2.1]octane (6.5 g, 25.8 mmol), sodium methoxide (6.5 g, 0.12 mol) and NIVIP (30 mi) was stirred at 1 SO'C for 15 h. Water (300 ml) was added. The mixture was extracted with d 1-ethylether (3 x 150 ml). The con-esponding salt was obtained by addition of a diethyl ether and methanol mixture (9:1) saturated with fumaric acid. Yield 3.0 g (32%). Mp 176-177.5 exo-3-(6-Ethoxypyrldin-2-yloxy)-8-methyl-8-azabicyclo[3.2.1 ]octane fumaric acid
saltWas prepared according to method F, l\/lp 177-179°C.
exo-3-(6-hydroxy-pyridln-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane fumaric acid salt
Was prepared from exo-3-(6-(cls-methylvinyloxy)-pyridin-2-yloxy)-8-methyl-8-azabicyclo[3.2.1]octane by stirring it with concentrated hydrochloric acid at reflux for 0.5 h. Worl Method G
exo-3-(6-Cyano-naphttialen-2-yloxy)-8-mothyl-B-azabicyclo[3.2.1]octane fumaric acid salt
A mixture of exo-3-(6-bromo-napiith-2-yioxy)-8-methyl-8-azablcycio[3.2.1]octane (2.6 g, 7.5 mmol), Zn(CN)2 (2.2 g, 18 mmol), palladacycle (50 mg) and dioxane (30 ml) was stirred at reflux for 70 h. Aqueous sodium hydroxide (50 ml, 1 M) was added to the mixture. The mixture was extracted with dichloromethane (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 addition of a diethyl ether and methanol mixture (9:1) saturated with fumaric acid. Mp 230-232'C.

Method H
exo-(3,4-Dichloro-phenyi)-(8-methyl-B-aza-blcyclo[3i!.1]oct-3-yl)-aminefumaric acid salt
^ mixture of 3,4-dichloroformanllide (0.6 g, 3.17 mmoi), tropine methanesulfonate loiuenesuifonic acid salt (1.24 g, 3.17 mmoi) [S.Archer et ai. JACS 80,4677-4691 [1958], sodium hydride (0.17 g, 6.97 mmoi) and DIVIF (5 mi) was prepared at 0 °C. The nixture was stirred for 15 h at room temperature. Aqueous sodium hydroxide (5 ml, 1 \H) was added to the mixture. The mixture was extracted with dichioromethane (2x5 Til). Chromatography on silica gel with methanol, dichioromethane and aqueous am-■nonia (10: 89:1) gave the title compound. The corresponding salt was obtained by idditlon of a diethyl ether and methanol mixture (9:1) saturated with fumaric add. Kield 23 mg, (2%). Mp 193.5-202.0°C.
)n(/o-(3,4-Dichioro-phanyl)-(8-methyl-8-aza-bicyGio[3.2.1]oct-3-yi)-1brmyiamine umaric acid salt
IVas Isolated from the reaction mixture above according to method I. Yield 32 mg, 3%). Mp 206.3°C.
»xo-(3,4-Dichloro-phenyl)-(8-'nethyl-8-aza-bicyclo[3.2.1]oct-3-yl)-formylamine umaric acid salt
Vas prepared by formylation with concentrated formic acid from exo-(3,4-Dichloro-ihenyl)-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yi)-amine. Workup was performed ac-lording to method I. Mp 150.5-153.0°C.

We claim:
1, An 8-aza-bicyclo[3,2,l]octane derivative of the Formula I:

2. The chemical compound as claimed in claim 1, wherein
R represents a phenyl group,

which phenyl group is substituted with one or two substituents independently selected
from the group consisting of:
halo, trifluoromethyl, trifluoromethoxy, cyano and alkoxy.
3. The chemical compound as claimed in claim 1, wherein
R"' represents a pyridyl group,
which pyridyl group is substituted with one or two substituents independently selected
from the group consisting of:
halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy and alkoxy,
4. The chemical compound as claimed in claim 1, wherein
exo-3-(2,3-Dichlorophenoxy)-8-H-8-azabicyclo[3,2,l]octane;
exo-3-(3,4-Dichlorophenoxy)-8-H-8-azabicyclo[3,2,l]octane;
exo-3-(3-Chloro-4-fluorophenoxy)-8-H-8-azabicyclo[3,2,1 ]octane;
ejco-3-(3-Chloro-phenoxy)-8-H-8-azabicyclo[3,2,l]octane;
ejco-3-(4-Chloro-3-fluorophenoxy)-8-H-8-azabicyclo[3,2,l]octane;
ejco-3-(4-Chloro-phenoxy)-8-H-8-azabicyclo[3,2,l]octane;
exo-3-(2-Chloro-3-trifluoromethyl-phenoxy)-8-H-8-azabicyclo[3,2,l]octane;
e«c/o-3-(3,4-Dichlorophenoxy)-8-H-8-azabicyclo[3,2,1 Joctane;
exo-3-(4-Chloro-3-trifluoromethylphenoxy)-8-H-8-azabicyclo[3,2,l]octane;
ejco-3-(3-Chloro-4-cyanophenoxy)-8-H-8-azabicyclo[3,2,l]octane;
ew-3-(4-Chloro-3-methylphenoxy)-8-H-8-azabicyclo[3,2,l]octane;
exo-3-(4-Chloronaphthalen-l-yloxy)-8-H-8-azabicyclo[3,2,l]octane;
exo-3-(5-Chloro-pyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane;
exo-3-(4-Methoxyphenoxy)-8-H-8-azabicyclo[3,2,l]octane;
exo-3-(6-Bromo-naphthalen-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane;
^xo-3-(4-Bromo-3-chloro-phenoxy)-8-H-8-azabicyclo[3,2,1 ]octane;
ejco-3-(4-Cyanophenoxy)-8-H-8-azabicyclo[3,2,1 Joctane;

exo-3-(4-Methylphenoxy)-8-H-8-azabicyclo[3,2,l]octane;
exo-3-(6-Chloropyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane;
exo-3-(5-Bromopyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane;
exo-3-(6-Bromopyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane;
exo-3-(3-TrifIuoromethoxyphenoxy)-8-H-8-azabicyclo[3,2,1 ]octane;
exo-3-(4-Trifluoromethoxyphenoxy)-8-H-8-azabicyclo[3,2,1 ]octane;
eA;o-3-(6-Methoxypyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane;
exo-3-(5-Trifluoromethylpyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane;
ejco-3-(6-Ethoxypyridin-2-yloxy)-8-H-8-azabicyclo[3,2,l]octane;
exo-3-(4-Fluoro-3-trifluoromethylphenoxy)-8-H-8-azabicyclo[3,2,l]octane;
or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt
thereof.
5. A pharmaceutical composition having monoamine neurotransmitter re-uptake inhibitory activity comprising a therapeutically effective amount of a compound as claimed in claim 1, or any of its isomers or any mixture of its isomers, or a pharmaceutically acceptable salt thereof, together with at least one pharmaceutically acceptable carrier, excipient or diluent.

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Patent Number

227197

Indian Patent Application Number

3509/CHENP/2005

PG Journal Number

07/2009

Publication Date

13-Feb-2009

Grant Date

05-Jan-2009

Date of Filing

23-Dec-2005

Name of Patentee

NEUROSEARCH A/S

Applicant Address

93 Pederstrupvej, DK-2750 Ballerup,

Inventors:

#	Inventor's Name	Inventor's Address
1	PETERS, Dan	c/o NeuroSearch A/S, 93 Pederstrupvej, DK-2750 Ballerup,
2	ERIKSEN, Birgitte, L	c/o NeuroSearch A/S, 93 Pederstrupvej, DK-2750 Ballerup,
3	NIELSEN, Elsebet, Ostergaard	c/o NeuroSearch A/S, 93 Pederstrupvej, DK-2750 Ballerup,
4	SCHEEL-KRUGER, Jorgen	c/o NeuroSearch A/S, 93 Pederstrupvej, DK-2750 Ballerup,
5	OLSEN, Gunnar, M	c/o NeuroSearch A/S, 93 Pederstrupvej, DK-2750 Ballerup,

PCT International Classification Number

C07D 451/06

PCT International Application Number

PCT/EP04/51167

PCT International Filing date

2004-06-18

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	PA 2003 01487	2003-10-09	Denmark
2	PA 2003 00939	2003-06-24	Denmark
3	PA 2004 00228	2004-02-13	Denmark