Title of Invention	3,4-DIHYDRO-1H-ISOQUINOLOIN-2-YL-DERIVATIVES
Abstract	This invention relates to novel compounds of formula I wherein the variable groups are as defined in the claims or a pharmaceutically acceptable acid addition salt thereof. The compounds of the invention are NK2 antagonists. ._-

Full Text

Field of the Invention The compounds of the present invention belong to a novel class of 3,4-dihydro-lH-isoquinolin-2-yl-derivatives having affinity for the neurokinin 2 (NK2) receptor. The compounds are NK2-anlagonists and are useful in, the treatment of those diseases where an NK2-Teceptor is implicated like asthma and a CNS-disease, These novel 3,4-dihydra-lH-isoquinoUn-2-yl-derivatives are capable of penetrating the blood brain barrier and therefore useful in treating a variety of CNS diseases. Background oftbe invention Three tachykim'ns, Substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) are widely distributed throughout the peripheral and central nervous systems. The biological effects of these neuropeptides are carried out via binding to their preferred receptors, NKl, NK2 and NK3 (Guard, S. and Watson, S. P. Neurochem. Int. 1991, 18, 149). Substance P displays highest affinity for the NKl receptors, whereas NKA and NKB bind preferentially io NK2 and NK3 receptors, respectively. The seleclivities of the endogenous ligands for their respective receptors are not absolute (reviewed in Regoli, D. et at. Pharmacol. Rev. 1994, 46, No. 4, 551 plus Bremer, A. A. et al. Eur J Pharmacol 2001, 423, 143). The three receptor subtypes belong to the G-protein-coupled receptor super family and have been cloned in various species including mice, rats and humans (Giardina, G. A. M. et al. Drugs of the Future 1997, 22, 1235 and references herein). Activation of the tachykinin receptors influences a broad array of biological actions, including pain transmission, vasodilation, smooth muscle contraction, secretion of saliva, bronchoconstriction, activation of the immune system (inflammatory pain), neurogenic inflammation and neurotransmission (Patacchini, R. et Maggi, C. A. Eur J Pharmacol 2001, 429, 13; Longmore, J. et al. Ca/t J Physiol Pharmacol 1997, 75, 612; Giardina, G. A. M. et al. Drugs of the Future 1997, 22, 1235 and references herein). Expression of NK2 receptors in human is somewhat controversial. The receptor is generally expressed in low amounts in CNS, and autoradiographic studies have failed to show NK2 receptors in the human brain. A recent reverse transcription-polymerase chain reaction (RT-PCR) study, however, has revealed a detectable expression of NK2 receptor mRNA in various human brain regions including caudate nucleus, putamen, hippocampus, substantia nigra and cerebral cortex (Bensaid, M et al. Neurosci Lett 2001, 303,25). Up-regulation of the preprotachykinin (PPT) genes and mRNAs for the neurokinin receptors occurs both in animal models of disease (Fischer, A. et &IJ Clin Invest 1996, 98, 22S4) and in human diseases, such as asthma(Adcock, I. M. etal. JMo/Sndocnno 1993, il,\). NK antagonists have been and are under investigations for the treatment of a vast amount of both CNS related and peripheral diseases, A number of pre-cUnical studies have been performed to assess the involvement of NK] and NK2 receptors mediation and modulation of diseases related to anxiety and/or depression (Griebel, G. Et al. Psycopharmacology, 2001, 158, 24!; Walsh, D. M. et al. Psychopharmacology 1995, !21, 186; Rupniak, N. M. et al. Neuropharmacology 2000, 39, 1413; Rupniak, N. M. et Kramer, M.S. TiPS 1999, 20, 485;; Giardina, G. A. M. et al. Drugs of the Future 1997, 22,1235, and references in these). These studies indicate that NK2 antagonists will be useful in treating or preventing a variety of brain disorders including depression, manic depression, bipolar disorder, dysthymia, mixed anxiety depression, generalised anxiety disorder, social anxiety disorder, panic anxiety disorder, post traumatic stress disorder, obsessive compulsive disorder, acute stress disorder, phobia, pre-menstrual dysphoric disorder, psychosis, and Huntington's disease as well as Parkinson's disease, adjustment disorders, pain, emesis, migraine, epilepsia, obesity, asthma and cerebrovascular disease. However, peripheral diseases such as inflammation, inflammatory bowel disease, hypertension, arthritis, cardiovascular diseases, neuritis, neuralgia, urticaria, incontinence, gastrointestinal diseases, influenza, allergy, pulmonary allergy and carcinoma / tumural growth may also be addressed by NK2 antagonists. US 3,994,891 discloses tetrahydroisoquinolines of the general formula wherein R is hydrogen or methyl, and G is NH or CH2. The dihydroxy compounds are described as effective vasodilators, whereas the dimelhoxy compounds are intermediates in the manufacture of the dihydroxy compounds. Hence, there is a desire for novel compounds that are antagonists at the NK2 receptor. Summary of the Invention The objective of the present invention is to provide compounds that are antagonists at the NK2 receptor. A further objective of the present invention is to provide compounds with such activities which have improved solubility, metabolic stability and/or bioavailability compared to prior art compounds. Accordingly, the present invention relates to novel compounds of formula I wherein R' is a group RC0-, RCS-, RS02-, R0C0-, RSC0- or RC0-CR'1R'1- wherein R is C1.i2-alkyl, Ca-e-alkenyl, Cj-fi-alkyny!, Cj-g-cycloalfcyl, Cj-g-cycloalkyl-Cuj-atkyl, aryl, aryl-C|.6-aIkyl, heteroaryl, heteroaryl-CM-alkyl, tetrahydropyranyl, 1,2,3,4-tctrahydronaphtalenyi, or 4H-benzo[l,3]dioxinyl optionally substituted with halogen wherein each of said Ci1-alkyl, aryl, heteroaryl and Cj1-cycloalkyl groups independently are unsubstttuted or substituted with one or more substltuents selected from the group comprising halogen, C1-g-alkyl, C|1-alkoxy, aryl-C1-6-alkoxy, Cj1-alkylsulfanyl, aryl and aryloxy wherein said aryl and aryloxy independently are unsubstituted or substituted with one or more halogen, and R'1 and R'1 indqjendently are hydrogen or C1-s-alkyl; or R' is a group R'1R'1NCO-, R'1R'1NCS-, wherein R' and R' are independently hydrogen, C1-c-alkyi, Ca-g-alkenyl, Cz-e-alkynyl, Cs1g-cycioalkyl, Cs-s-cycloalkyl-Ci1-alkyl, aryl or aryl-C]1-alky!, wherein each of said Ci1-alkyl, aryl and Cj-s-cycloalkyl groups independently are unsubstituted or substituted with one or more substituents selected from the group comprising halogen, Ci1-alkyl and Ci1-alkoxy, or R' and R'1 together with the N-atom to which they are linked, form a pyrrolidinyi, piperidinyl or pcrhydroazepinyl group; R1 is selected from hydrogen, trifluoromethyl and C1-e-alkyl; R1-R', TC\ R', R1' and R are independently selected from hydrogen, halogen, cyano, nitro, C1-6-alkyI, Ca1-alkenyl, Ca-s-alkynyl, Cj-s-cycloalkyl, Cj-g-cycloalkyl-Ci1-alkyl, amino, C|1s-alkylamino, di-(C|.a-aikyl)amino, C1.6-alkylcarbonyl, aminocarbonyl, C|-6-atkylaminocarbonyl, di-{C1.6-alkyl)aminocarbonyl, C1-6-alkoxy, C1-g-alkyhhio, hydroxy, trifluoromethyl, trifluoromethylsulfonyl and CM-alkylsulfonyl; m is 2-6; R' is benzyl, benzoyl, 2,3-dihydrobenzofuranyl or mono- or bicyclic aryl or heteroaryl wherein each benzyl, benzoyl, aryl or heteroaryl optionally is substituted with one or more substituents selected from halogen, cyano, nitro, Ci1-alkyl, Cz-e-alkenyl, C2-6-alkyny!, Cj-g-cycloalkyl, Cj1-cycloalkyl-Ci1-alkyl, amino, Ci1-alkylamino, di-(C1.6-aIkyI)amino, C|.6-alkylcarboiiyl, aminocarbonyl, CM-alkylaminocarbonyI, di-(Ci1-alkyl)aminocarbonyI, Ci1-alkoxy, C1-G-alkylthio. hydroxy, trifluoromethyl, difluoromethyl, fluoromethyl and trifluoromethylsu 1 fonyl; wherein R' is selected from hydrogen, halogen, cyano, nitre, d-c-alkyl, C2-6-alkenyI, Cj-G-alkyny], Cj-s-cycloalkyl, Cj-g-cycIoalkyl-Ci1-alkyl, amino, C1-s-alkylamino, di- (C1 (C1.6-aUcyI)aminocarbony!, C|-1-alkoxy, Ci1-alkylthio, hydroxy, trifluoromethyl, difluoromethyl, fluoromethyl, trifluoromethylsulfonyl, a group -NR1VOR1' wherein R' is hydrogen or Cj-6-alkyl and R1' is C|1-alkyi, a group -COOR' wherein R' is hydrogen or C|.6-alkyl, or a group -CONRR' wherein R and R'1 independently are selected from hydrogen and C1-6-alkyl or R'1 and R' together with the nitrogen to which Ihey are attached form a piperidinyl, piperazinyl or morpholinyl, wherein said piperidinyl, piperazinyl and mOTpholinyl is unsubstituted or substituted with a C|.6-alkyl; or R' and R' together with the carbon to which they are attached form a cyclic structure selected from the group comprising: X, Y, and Z are independeatly chosen &om O; NR; CR1R1; S(0)„ and a bond; wherein R'1 is selected from hydrogen, Ci1i-alkyl, C2-6-aIkenyl, C2-6-alkynyl, Cs1g-cycloaikyl, Cj-g-cycloalkyl-Ci1-alkyl, trifluoromethyl,acyl, thioacyl and trifluoromethylsulfonyl, or R is a group R1°S02-, R11OCO- or R11SCO- wherein R1 U Ci1-alkyl, C2.6-alkenyl, C2-5-alkynyl, C1-s-cycloaikyl, C31-cycloalkyl-C1.fi-alkyl or aryl, or R is a group R1'RNCO- or R1'R11NCS-, wherein R1' and R are independently hydrogen, C,-6-a!kyl, C2-6-alkenyl, C2-6-alkynyl, Ca-s-cycloalkyl, Gj-s-cycloalkyl-C1-e-alkyl, or aryl, wherein said aryl is unsubstituted or substituted with one or more substituents selected from C1-e-alkyI or halogen; or R1' and R11 together with the N-atom to which they are linked, form a pyrrolidinyl, piperidinyl or perhydroazepinyl group; R1' and R1 are independently selected from hydrogen, halogen, cyano, nitro, C1-e-alkyl, Cz1-alkenyl, Cj-e-alkynyl, Cs-g-cycloaikyl, Cj1-cycloalkyl-C1-e-alkyl, aryl, heieroaryl, wherein said aryl is unsubstituted or substituted with one or more substituents selected from C|.6-alkyl or halogen, amino, Ci1-alkylamino, a group NR11R11 wherein R'1 and R1' are independently selected from C1-e-alkyl Ci1-alkylcarbonyl, aminocarbonyl, C|-6-alkylaminocarbonyl, di-(C|1-alkyl)aminocarbonyI, C1-o-alkoxy, C|.G-alkylthio, hydroxy, trifluoromethyl, trifluoromethylsulfonyl and Ci1-alkylsulfonyl or R11and R11 together with the N-atom to which they are linked, form a pyrrolidinyl, piperidinyl, perhydroazepinyl or morpholinyl group, or R11 and R1 together is oxo; and n is 0, 1 or 2; provided that no more than one of X, Y and Z may be a bond, and provided that two adjacent groups X, Y or Z may not at the same time be selected from O and S; and A', A1, A1 and A are independently selected from N and CR11 wherein R11 is hydrogen, halogen, cyano, nitro, C1-e-alkyl, d-fi-alkenyl, C21-atkynyl, Cs-g-cycloalkyl, Cs-g-cycloalkyl- Cu-aikyl, C|-6-alkylcarbonyl, aminocarbonyl, C|.6-alkylaminocarbonyI, di- (C|.6-aIkyl)aminocarbonyl, C1-a-alkoxy, C|1-alkylthio, hydroxy, trifluoromethyl, difluoromethyi, fluoromethyl, trifluoromethylsulfonyl C1-g-alkylsulfonyl amino or a group NR11R1' wherein R1 and R1' are independently selected from hydrogen and C|.6-alkyl or R1 and R1' together with the N-atom to which they are linked, form a pyrrolidinyl, piperidinyl, perhydroazepinyl or morpholinyl group; provided that only one of A' , A1, A' and A1 may be N; and the dotted line emanating from Q is a bond when Q is C, and no bond when Q is CR or N; or a pharmaceutically acceptable acid addition salt thereof. Detailed Description of the lovention The C,.(2-a]kyi groups defined for R are preferably selected from Cj.,o-a]kyl, more preferred C1-g-alkyl, and most preferred Cj1-atkyl. In one embodiment, the present invention relates to such compwunds wherein Q is CR, and R and R' together with the carbon to which they are attached form a bicyclic structure: wherein Q' is the carbon shared with the piperidine rii1, so that said bicyclic structure together with said piperidine ring form a spiro structure; and X, Y and Z are independently chosen from O; NR'1 CRR1' and S(0)n wherein R is selected from hydrogen, Cl.e-aikyl, C1-s-alkcnyi, C2-6'aIkynyl, Cs-s-cycloalkyl, , C3.8-cycloalkyl-C|.6-alky], trifluoromethyl, acyl, thioacyl and trifluoromethylsulfonyl, or R is a group R1S02-, R11OCO- or R11SCO- wherein R1 is C,.6-alkyl, Cj-o-alkenyl, Ci1-alkynyi, C].g-cycJoa3Jcy}, Cj-g-cycloafkyl-C1-s-alkyl or aryl, or R is a group R1'R1NCO-, R'RNCS-, wherein R1' and R11 are independently hydrogen, C|-6-alkyl, C2-6alkenyl, C:.6-alkynyl, Cj-g-cycloalkyl, C1.e-cycloalkyl-Ci1-alkyl or aryl, wherein said aryl is unsubstituted or substituted with one or more substituents selected from C|.6-alkyl or halogen; or R1' and R11 together with the N-atom to which they are linked, form a pyrrolidinyl, piperidinyl or perhydroazepinyl group; R11 and R11 are independently selected from hydrogen, halogen, cyano, nilro, C1-s-alkyl, C2.6-alkenyl, C2-6-alkynyl, Cj-g-cycloalkyl, C3.8-cycloalkyI-C|.6-alkyi, aryl, heteroaryl, wherein said aryl is unsubstituted or substituted with one or more substituents selected from C1.6-alkyl or halogen, amino, C1.fi-alkylamino, a group NRR wherein R1' and R11 are independently selected from Ci1g-alkyt or R and R11 together with the N-atom to which Ihey are linked, form a pyrrolidinyl, piperidinyl, perhydroazepinyl or morpholinyl group, C|.6-alkylcarbonyl, aminocarbonyl, C]-6-alkylaminocarbonyl, di-{C|-6-a!kyl)aniinocarbony], C1-«-alkoxy, Ci1-alkyithio, hydroxy, trifluoromethyl, trifluoromethylsulfonyl, Mid C|-6-alkyIsulfonyl or R11 and R11 together is oxo; and n is 0,1 or 2; and a bond; provided that no more than one of X, Y and Z may be a bond, and provided that two adjacent groups X, Y or Z may not at the same time be selected from O and S; and A', A1, A1 and A1 are independently selected from N and CR1' wherein R1' is hydrogen, halogen, cyano, nitro, Ci1-alkyl, C1-e-alkenyl, C21-alkynyI, C3.g-cycloalkyl, Cs-g-cycloalkyl- C1-e-alkyl, amino, a group NR1*R1' wherein R11and R1' are independently selected from hydrogen and C|-6-alkyi or R1* and R1'together with the N-atom to which they are linked, form a pyrrolidinyl, piperidinyl. perhydroazepinyl or morpholinyl group, C|.6-alkylcarbonyI, arainocarbonyl, C|.6-alkylaminocarbonyl, di-{C1.6-alkyl)aminocarbonyl, C1-e-alkoxy, C|1-alkylthio, hydroxy, trifluoromethyl, difluoromethyl, fluoromethyl, trifluoromethylsulfonyl or Ci1-alkylsulfonyl; provided that only one of A', A', A1 and A* may be N. In a preferred embodiment, the present invention relates to such compounds wherein X, Y and Z are selected fixim one of the combinations: X is oxygen, Y is a bond and Z is CR"R"; X is CR"R", V is a bond and Z is oxygen; X is NR'1 Y is a bond and Z is CR"R1', X is CR"R1*, Y is a bond and Z is NR'1 X is CO, Y is a bond and Z is NR'1 X is SO2, Y is a bond and Z is NR'1; X is SO, Y is a bond and Z is NR'1 X is CR"R", Y is a bond and Z is S; X is CR"R1\ Y is a bond and Z is SO; X is CR"R", Y is a bond and Z is SO2; wherein R" is hydrogen, acetyl or methykulfonyl and R11 and R11 are independently selected from hydrogen, methyl, isobutyl, cyclohexyl and 4-fluorophenyl. In another preferred embodiment, the present invention relates to such compounds wherein -X-Y-Z- together form a group selected from: -O-CR1'R"-, -CR1R1"-©-, -NR'-CR"R"-, -CR11R"-NR'\ -CO-NR"-, -SOJ-NR'*-, -SO-NR'1-. -CR"R"-S-, -CR"R"-SO-, -CR11R1'-S02-; wherein R" is hydrogen, acetyl or methylsulfonyl tyl and R11 and R11 are independently selected from hydrogen, methyl, isobutyl, cyclohexyl and 4-fluorophenyl, In another preferred embodiment, the present invention relates to such compounds wherein A1 is N or CR" wherein R" is halogen, cyano, nitro, a group NR"R" wherein R1'and R11 are independently selected from hydrogen and Ci1-alkyl or R1* and R11 together with the N-atom to which they are linked, form a pyrrolidinyl, piperidinyl, pcrhydroazepinyl or morpholinyl group, Ci1-alkylcarbonyl, aminocarbonyl, C1-s-alkylaminocarbonyl, di-{C1.6-alkyl)aininocarbonyl, C1-6-aIkoxy, hydroxy, trifluoromethyl, difluoromethyl, fluoromethyl, trifluoromethylsulfonyl or Ci1-alfcylsulfonyl. In another preferred embodiment, the present invention relates to such compounds wherein A', A , A1 and A1 are independently selected from CR1' wherein R 1 is as defined above. In a more preferred embodiment, the present invention relates to such compounds wherein bicyclic structure described above is selected from the group comprising: wherein Q' is the carbon shared with the piperidine ring, so that said cyclic structure together with said piperidine ring form a spire structure In yet another embodiment, the present invention relates to such compounds wherein R' is benzyl, benzoyl, 2,3-dihydrobenzofUran-7-yi or mono- or bicyclic aryi or heteroaryl wherein each benzyl, benzoyl, aryl or heteroaryl optionally is substituted with one or more substituents selected from halogen, cyano, nitro, C1-e-alkyl, Cj-e-allcenyl, Cj1-alkynyl, Cs-g-cycloalkyl, Cs-g-cycloalkyl-C1-c-alkyl, amino, C1.6-alkylamino, di-(Cu6-a!kyI)amino, C|1-alkylcarbonyl, aminocarbonyl, C1.6-alkyIaminocarbonyl, di-(C1.6-aIkyl)aminocarbonyI, C1-s-alkoxy, Ci1-alkylthio, hydroxy, trifluoromethyl, difluorotnethyl, fluororaethyl and trifluoromethylsulfbnyl. In yet another embodiment, the present invention relates to such compounds wherein R' is 2,3-dihydrobenzofijran-7-yI, benzy! or benzoyl wherein said benzyl or benzoyl is unsubstituted or substituted with ons or more halogens in the phenyl groups, or R' is mono-or bicyclic aryl or heteroaryl selected from the group comprising phenyl, indolyl, pyridyl, thiophenyl and benzisoxazolyl, wherein each aryi or heteroaryl optionally is substituted with one or more substituents selected from halogen, cyano, nitro, C1-s-alkyl, C2.&-alkenyl, C1.6-alkynyl, C3.8-cycloalky!, Cs-s-cycloalkyl-Ci1-alkyl, amino, Ci1-alkylamino, di-(Cj1-alkyOamino, C|.6-alkylcarbonyl, aminocarbonyl, C)1-alkylaminocarbonyi, di-CCl-o'alkyl)aminocarbonyl, C1-g-alkoxy, C|1i-alkylthio, hydroxy, trifiuoromethyi, difluoromethyl, fluoromethyl and trifluoromethylsulfonyl. In a preferred embodiment, the present invention relates to such compounds wherein said mono- or bicyclic aryl or heteroaryl is selected from the group comprising phenyl, indol- 3-yl and benzisoxazot-3-yl wherein said phenyl, indo!-3-yl or benzisoxazol-3-yl oprionally is substituted with one or more substituents selected from halogen, cyano, nitro, Ci1-alkyl, C2-6-alkenyl, Ci1-alkynyl. Cs-g-cycloalkyl, Cj-g-cycIoalkyl-Ci1-alky], amino, C|1-aikylamino, di-(C1-6-alkyl)amino, C|.6-alkylcarbonyl, aminocarbonyl, C1-6-alkylaminocarbonyl, di-(CI-e-alkyl)aminocarbonyl, C1-6-alkoxy, Ci1-alkylthio, hydroxy, trifluoromethyl, difluoromethyl, fluoromethyl and trifluoromethylsulfonyl. In an even more preferred embodiment, the present invention relates to such compounds wherein said optional substituents are selected from the group comprising halogen, phenyl and methyl. In yet another embodiment, the present invention relates to such compounds wherein Q is CR"* wherein R'° is selected from hydrogen, C1.6-alkylcari)onyl, hydroxy, a group -NR1COR" wherein R'° is hydrogen or C1.6-alkyl and R1' is Ci1-alkyl, a group -COOR'1 wherein R"1 is C1-e-alky!, or a group -CONR"R'1 wherein R" and R'* together with the nitrogen to which they are attached form a piperidinyl, piperazinyl or morpholinyl, wherein said piperidinyl, piperazinyl and morpholinyl are unsubstituted or substituted with a C,1-alkyl. In a preferred embodiment, the present invention relates to such compounds wherein R'" is selected from hydrogen, acetyl, hydroxy, a group -NR'1COR1' wherein R1° is hydrogen and R1' is methyl, a group -COOR'* wherein R'1 is ethyl, or a group -CONR'1R'1 wherein R'1 and R'1 together with the nitrogen to which they are attached fonn a piperidinyl or a 4-methylpiperazinyl. In another preferred embodiment, the present invention relates to such compounds wherein m is 2,3 or 4, more preferred m is 2, In yet another embodiment, the present invention relates to such compounds wherein R' is a group R"C0-, R"0C0- wherein R" is Cj-a-alkyl, Cj-a-cydoalkyl, Cs-g-cycloaikyl-C|1-alkyi, phenyi, phenyi-C1-6-alkyt, pyridyl, furanyi, benzo[l,2,5]oxadiazolyl, quinoxalinyl, bcnzo[b]thiophenyl or naphthalenyl wherein each of said Cj.a-alkyl, phenyl, pyridyl and furanyl groups independently are unsubstituted or substituted with one or more subsiiluenls selected from the group comprising haJogen, C1-6-alky], C(.(i-aIkoxy, phenyl and phenoxy wherein said phenyl and phenoxy independently are unsubstituted or substituted with one halogen; or R' is a group R'*R'*NC0-, wherein R'" and R" are independently hydrogen, C1.6-alkyl, aryl, or aryl-Cj-fi-alkyl, wherein each of said Ci1-alkyl and aryl groups independently are unsubstituted or substituted with one substituent selected from the group comprising halogen and C1-e-alkoxy. In yet another embodiment, the present invention relates to such compounds v/herein R1 is hydrogen. In yet another embodiment, the present invention relates to such compounds wherein R-* is hydrogen. In yet another embodiment, the present invention relates to such compounds wherein ft' is hydrogen or methoxy. In yet another embodiment, the present invention relates to such compounds wherein ft* is hydrogen or methoxy. In yet another embodiment, the present invention relates to such compounds wherein ft1 is hydrogen. In yet another embodiment, the present invention relates to such compounds wherein R'° and R1** is hydrogen. In yet another embodiment, the present invention relates to such compounds wherein R*' and R1' is hydrogen. Preferred compounds of the invention are compounds number 1-209 as disclosed in the experimental section as well as the compounds in the following list: l-(l-{2-[4-(5-Fluoro-y//-tndol-3-yl)-piperidin-l-yl]-ethyl}-5-chloro-3,4-dihydro- ///-isoquinolin-2-yl)-l-C4-fluoro-phenyl)methanone, l-cyclopentyl-l-(l-{2-[4-C5-fluoro-7H-indol-3-yt)-piperidin-l-yl]-ethy!}-5-chloro- 3,4-dihydro-V//-isoquinolin-2-yl)methanone, l-cyclopentyl-l-(l-{2-[6-fluorospiro[isobenzoftiran-U3H),4'-piperidine-r-yI]-ethyl}- 5-ch!oro-3,4-dihydro-///1-isoquinolin-2-yl)methanone, l-(4-fluorophenyl)-i-(I-{2-[6-fluorospiro[isoben2oftiran-l(3H),4'-piperidine-r-yl]-ethyl}- 5-ch]oro-3,4-dihydro-7/f-isoquinolin-2-yl)methanone, ]-cyclopentyl-l-(l-{2-[6-trifluoromethylspiro[isobenzofiiran-l(3H),4'-piperidine-r-yI]- ethyI)-5-chIoro-3,4-dJhydro-//Aisoqu!noiin-2-yI)methanone, !-(4-fluorophenyl)-l-(l-(2-[6-trifluoromethylspiro[isobenzofurati-l(3H),4'-piperidine- i'-yO-ethyl>-5-chloro-3,4-dihydro-i//-isoquinolin-2-yl)methanone, N-[ 1 -{2-[2-(l -cyclopentyl-methanoyl)-1,2,3,4-tetrahydro-isoquinoiin-1 -yl]-ethyl) - 4-(3-fluorophenyI)-piperidin-4-y]lacetainide, Af-[l-{2-[2-(l-(4.fluorophenyl)-methanoyl)-l.2,3,4-tetrahydro-isoqumolin-l-yl]-ethyI}- 4-(3-fluorophenyl)-piperidin-4-yl]acetamide, jV-[I-{2-[2-(I-cycIopentyI-niethanoyI)-I,2,3,4-te(rahydro-isoquinoliii-I-yI]-ethyl}- 4-phenylpiperidin-4-yl]acetamide, W-[l-{2-[2-(I-(4-fluorophenyl)-iiiethanoyl)-l,2,3,4-tetrahydro-isoquinoIiii-l-yl]-ethyi)- 4-phenylpiperidin-4-yl]acetaiiiide, i-cyclopentyi-l-{l-[l-acetyl-spiro[2,3-dihydro-///-indol-3,4'-piperidm-r-yl]ethyn- 5-chloro-3,4-dihydro-7//-isoquinolin-2-yl}methanone, l-(4-f]uorophenyl)-l-{l-[l-acctyI-spiro[2,3-dihydro-///-indo!-3,4'-piperidin-r-yl]ethyl]- 5 -chloro- 3,4-di hydro- /ff-isoquinoIin-2-yl} methanone, ]-cyclopentyI-l-{l-[l-acetyl-spiro[2,3-dihydro-5-fluoro ///-indol-3,4'-piperidin-r-yI]- ethy]]-5-chioro-3,4-d!hydrf>-y//'-isoqiiinolin-2-yI} methanone, ]-(4-fluorophenyl)-l-{l-[l-acetyl-spiro[2,3-dihydro-5-fluoro-7H-indol-3,4'-piperidin-r-yl]- ethyl]-5-ch]oro-3,4-di hydro-/H-isoquinolm-2-yI} methanone, l-cyclopentyl-l-(1-{2-[4-(3-trifluoromethyIphenyl)-piperidin-l-yI]-ethyl}-5-chIoro' 3,4-dihydro-7//-isoquinoUn-2-yl)methaiione, I-(4-f1uorophenyl)-l-{l-{2-[4-(3-trif]iioromethylphenyl)-piperidin-l-yl]-ethyl)-5-chlorO- 3,4-dihydro-7H-iEoquinolin-2-yl)melhanone, l-(l-{2-[4-(6-fIuorobenzo[dJisoxazol-3-yI)-piperidin-f-yl]-rfhyl}-5-chloro-3,4-dihydro-///- isoquino]in-2-yl)-l-(4-fluoropheny!)methanone, l-(l-(2-[4-{6-fluorobenzo[d]isoxazol-3-yl)-piperidin-l-yl]-ethyl}-5-chloro-3,4-dihydro-i//- isoquinolin-2-yI)-l-(cyclopenty))niethaiione, l-(4-fluorophenyl)-l-(l-{2-[5,6-difluorospiro[benzofuran-l(3H),4'-piperidine-i'-yl]-ethyl}- 5-chloro-3,4-dihydro-///-isoquin,oiin-2-yl)-raethanone, !-(4-fluoropheny!)-l-({2-[6-fluorospiro[benzofuran-l(3H),4'-piperidine-l'-yl]-ethyl}- 5-ch(om-3,4-dihydro-///-isoquinolin-2-yOmethanone, l-cyclopenty!-l-(l-{2-[S,6-difluorospiro[benzofuran-l(3H),4'-piperidine-r-yl]-ethyl}- 5-chloro-3,4-dihydro-y//-isoquinoiin-2-yl)-methanone, l-cyclopentyI-l-((2-[6-fluorospirop5enzofuran-l(3H),4'-piperidine-r-yl]-ethyl}- 5-chloro-3,4-dihydro-7//-isoquinolin-2-yl)[nethanone, 1 -(1 - {2-[4-(5-fluoro-y//-indol-3-yl)-piperidin-1 -yi]-ethyi} -3,4-dihydro-5-fluoro- /i/-isoquinolin-2-yl)-l-(4-fluoro-phenyl)methanone, l-cycIopentyM-(l-{2-[4-(5-fluoro-/H-indo!-3-yI)-piperidin-f-yI]-ethyl}-3,4-dihydro- 5-fluoro-///-isoquinolin-2-y])methanotie, l-cyclopentyi-l-(l-{2-[6-fliiorospiro[isobenzofuran-l(3H),4'-piperidine-i'-yl]-ethyl}- 3,4-dihydro-5-fluoro-///-isoquinolin-2-yl)methanone, l-(4-fluorophenyl)-l-(l-{2-[6-fluorospiro[isobenzofuran-l(3H),4'-piperidine-r-yl]-ethyl}- 3,4-dihydro-5-fluoro-/7/-isoquinolin-2-yl)inelhanone, l-cyclopentyM-(l-{2-[6-trifluoromethylspiro[isobenzofiiran-lC3H),4'-piperidine-r-yl]- ethyf}-3,4-dihydro-5-nuoro-///-isoquinolin-2-yI)methanone, l-{4-fluorophenyI)-I-(I-{2-[6-trifluoromethy[spiro[isobenzofuran-l(3H),4'-piperidine- r-yl]ethyl}-3,4-dihydro-5-fluoro-i//-isoquinolin-2-yl)methanone, A/-[l-{2-[2-(l-cyclopentyl-methanoyl)-l,2,3,4-tetrahydro-isoqijinolin-l-yl]-efhyl)- 4-(3-fluorophenyl)-piperidin-4-yl]acetamide, 71/-[l-{2-[2-(l-(4-fluorophenyI)-mcthanoy])-l,2,3,4-teirahydro-isoquinolin-l-yI]-ethyl}- 4-(3-fluorophenyl)-piperidin-4-y]]acetamide, W-[]-{2-[2-(l-cyc!opentyl-methanoyl)-l,2,3,4-tetrahydro-isoqumolin-l-yI]-ethyI}- 4-phenylpiperidin-4-yl]acetamide, A'-[l-{2-[2-(l-(4-fluorophenyI)-methanoyl)-l,2,3,4-tetrahydro-isoquinoiin-l-yl]-ethyl)- 4-phenylpiperidin-4-yl]acetainide, I-cyclopentyl-l-{l-[l-acetyl-spiro[2,3-dihydro-yH1indo!-3,4'-piperidm-r-yl]ethyl]- 3,4-dihydro-5-fluoro-7//-isoquinoIin-2-yI}methanone, I-(4-fluorophenyi)-l-{l-[l-acetyl-spiro[2,3-dihydro-/jy-indol-3,4'-piperidin-r-yl]ethyl]- 3,4-dihydro-5-fluoro-7//-isoquinolin-2-yl}methanone, l-cyclopentyl-l-{l-[l-acetyl-spiro[2,3-dihydro-5-fluoro ///-indol-3,4'-piperidin-r-yl]- e thy 1 j-3,4-d ihydro-5 -fluoro- ///-isoquinolin-2-y 1} methanone, l-(4-fluorophenyl)-l-{l-[l-acetyl-spiro[2,3-dihydro-5-fluoro-7//-mdol-3,4'-piperidm-r-y!]- ethyl]-3,4-dihydro-5-fluoro-y//-isoquinolin-2-yl}methanone. I-cyclopentyl-l-(I-{2-[4-(3-trifluoroniethylphenyl)-pjperidin-l-yI]-eIhyl}-3,4-dihydro- 5-fluoro-///-isoquinolin-2-y])methanone, l-(4-fluorophenyI)-l-(l-{2-[4-(3-trifluoromethylphenyl)-piperidin-l-yl]-ethyI}-3,4-dihydro- 5'fluoro-y//-isoquinolin-2-yl)methanone, I-(l-{2-[4-(6-fluorobenzo[d]isoxazol-3-yI)-piperidm-l-yI]-ethyl}-3.4-dihydro-5-fluoro- ///-isoqumolin-2-yl)-1 -(4-fIuorophenyl)niethanone, lT(l-{2-[4-(6-fluorobenzo[d]isoxazo]-3-yl)-piperidm-l-yi]-ethyl}-3,4-dihydro-5-fluoro- 7/f-isoquinolin-2-yl)-l-(cyclopentyl)methanone, l-(4-fluorophenyl)-I-(l-(2-[5,6-difluorospiro[benzofiiran-l(3H),4'-piperidine-r-yl]-ethyl}- 3,4-dihydro-5-fluoro-i//-isoquinolin-2-yl)-methanone, l-(4-fluorophenyl)-l-({2-[6-fluorospiro[ben2ofuran-l(3H),4'-pipcridine-r-yl]-ethyl}- 3,4-dihydro-5-fluoro-///-isoquinolin-2-yl)tnethanone, i-cyclopentyl-l-(I-{2-[5,6-difluorospiro[benzofuraii-l(3H),4'-piperidine-r-yl]-ethyl}- 3,4-dihydro-5-ftuoro-y//-isoquinolin-2-yl)-methanone, l-cyclopentyl-l-({2-[6-fIuorospiro[benzoftiran-l{3H),4'-piperidine-r-yl]-ethyl}- 3,4-dihydro-5-fluoro-/W-isoquinolin-2-yl)metlianone, l-(l-{2-[4-(5-fluoro-///-indol-3-yl)-piperidm-l-yl]-eIhyl}-5,6-dichloro-3,4-dihydro- y//-isoquinoIin-2-yl)-l-{4-fluoro-phenyi)methanone, l-cyclopentyI-l-(l-{2-[4-(5-fluoro-///-indol-3-yl)-piperidin-l-yl]-ethyl}-5,6-dichloro- 3,4-dihydro-y//-isoquirioIin-2-yl)niethanotie, I-cyclopenty!-l-(t-{2-[6-fluorospiro[isobenzofuran-!(3H),4'-piperidine-r-yl}-ethyl)- 5,6-dichloro-3,4-dihydro-JH-isoquinolin-2-yl)methanone, l-(4-fluorophenyl)-l-(I-{2-[6-fluorospiro[isobenzofiiraji-l(3H),4'-piperidine-r-y!]-ethyl}- 5,6-dichloro-3,4-dihydro-y//-isoquinoIiii-2-yl)tnethanone, l-cyciopentyI-l-(l-{2-[6-trifluoromethylspiro[isobenzofuran-l(3H),4'-piperidine-r-yl]- ethyl}-5,6-dich]oro-3,4-dihydro-y/1-isoquinolin-2-yl)methanone, l-(4-fluorophenyl)-l-(l-{2-[6-trifluoromeIhylspiro[isobenzofiiran-l(3H),4'-piperidine- r-yl]ethyI}-5,6-dichloro-3,4-dihydro-7//-isoquino!in-2-yI)methanone, N-[ 1 - {2-[2-( 1 -cyclopentyl-methanoyl)-1,2,3,4-tetrahydro-isoquiiiolin-l -yl]-ethyl} - 4-(3-fluorophenyl)-piperidin-4-yl]acetaniide, A'-[ 1' {2-[2-{ 1 -(4-f]uorophenyl)-inethanoyI)-1,2,3,4-tetrahydro-isoquinolin-l -yl]-ethyl} - 4-(3-fluorophenyl)-piperidin-4-yl]acetamide, /»/-[l-{2-[2-(l-cyclopentyl-methanoyl)-l,2,3,4-tetrahydro-isoquinolin-l-yl]-ethyl}- 4-phenylpiperidin-4-yI]acetamide, Ar.[I.{2-[2-(l-(4-fluorophenyI)-mcthanoyl)-l,2,3,4-tetrahydro-isoquinolm-l-yl]-cthyl}- 4-phenyIpiperidin-4-yl]acetainid6, l'Cyclopentyi-l-{l-[l-acetyl-spiro[2,3-dihydro-///-indol-3,4'-piperidin-r-yi]ethyl]- 5,6-dichloro-3,4-dihydro-y1-isoqumolm-2-yl}methanone, 1 '(4-fluorophenyl)-1 - {I -[l-acety]-spiro[2,3-dihydro-i/1-indol-3,4'-piperidin-1 '-yljethyl]- 5,6-d!chloro-3,4-dihydro-/1-isoquinolin-2-y!}niethanone, i-cyclopentyl-I-{l-[l-acetyl-spiro[2,3-dihydro-5-fluoroy/f-indol-3,4'-piperidin-r-yl]- ethyi]-5,6-dichloro-3,4-dihydro-7//-isoquinoHn-2-yI}raethanone, 1 -(4-fluorophenyl)-1- (1 -[ l-acetyl-spiro[2,3-dihydro-5-fluoro-///-indol-3,4'-piperidin-1 '-yl]- ethyl]-5,6-dichloro-3,4-dihydro-/W-isoqulnolin-2-yl}niethaiione, l-cycIopentyl-l-(I-{2-[4-{3-trif!uoromethylphenyI)-piperidin-l-yl]-ethyI}-5,6-dichloro- 3,4-dihydro-7//-isoquinolin-2-yl)methanone, I -(4-fIuorophenyl)-1 -(1 - {2-[4-(3-trifluoromethylphenyl)-piperidin-I -y!]-ethyl} - 5,6-dichIoro-3,4-dihydro-//f-isoqumoIin-2-yI)melhanone, l-{l-{2-[4-(6-fluorobenzo[d]isoxazol-3-yl)-piperidin-l-yl]-ethy]}-5,6-dichloro-3,4-dihydro- ///"-isoquinoltn-2-yl)-l-(4-fluorophenyl)methanone, ]-(l-{2-[4-(6-fluorobenzo[d3isoxazol-3-yl)-piperidin-l-yl}-elhyl}-5,6-dichIoro-3,4-dihydro- y//-isoquinolin-2-yl)-]-(cyclopenIyl)methanone, l-(4-fluorophenyl)-l-(l-{2-[5,6-difluorospiro[betizoftiran-l(3H),4'-piperidme-r-y!]-ethyl}- 5,6-dichloro-3,4-dihydro-/W-isoquinolin-2-yl)-methanone, 1 -(4-fiuorophenyl)-1 -({2-[6-fluorospiro[benzofiiran-I (3H),4'-piperidine-r-yl]-ethyl} • 5,6-dichIoro-3,4-dihydro-//1-isoquinotin-2-yl)methanone, l-cyciopentyi-l-(l-{2-[5,6-difluorospiro[benzofi!ran-l(3H),4'-piperidine-r-yl]-ethyI}- 5,6-dichloro-3,4-d ihydro-///-isoquiiiolin-2-yI)-methanone, l"Cyclopentyl-l-({2-f6-fluorospiro[benzofuran-l(3H),4'-piperidine-r-yl]-ethyl}- 5,6'dichloro-3,4-dihydro-///-isoquinolin-2-yl)methanone, l-(l-{2-[4-(5-fluoro-y//-indol-3-yl)-piperidin-l-yIl-ethyl}-5,6-difluoro-3,4-dihydro- 7/f-isoquinolin-2-yl)-1 -(4-fluoro-phenyl)methanone, l-cyctopenty!-l-(i-{2-[4-(5-fluoro-/H-indol-3-y!)-piperidin-l-yl]-ethyl)-5,6-difluoro- 3,4-dihydro-y//-isoquiiiolin-2-yl)methanone, l-cyclopentyl-]-(!-{2-[6-fluorospiro[isobenzofuraii-l(3H),4'-piperidine-r-yI]-ethyi}- 5,6-difluoro-3,4-dihydro-7//-isoquinolin-2-yl)methanone, l-(4-fluoropheny!)-I-(l-{2-l6-fluorospiro[isoben2ofuran-l(3H),4'-piperidine-r-yl]-ethyl}- 5,6-difluoro-3,4-dihydro-7//-isoquinoIin-2-yI)methanone, l-cyclopentyl-I-(l-{2-[6-trifluoromethylspiro[isobenzofuran-l(3H),4'-pipcridine-r-yI]- ethyl}-5,6-difluoro-3,4-dihydro-/1-isoquinolin-2-yl)methanone, l-(4-fluorophenyl)-I-(l-{2-[6-trifluoromethyIspiro[isobenzofijran-l(3H),4'-piperidine- r-yl]elhyl}-5,6-difluoro-3,4-dihydro-7W-isoquinolin-2-yl)methaDone, A'[l-{2-[2-(l-cyclopentyl-methanoyl)-i,2,3,4-tetrahydro-isoquino]in-l-yl]-ethyl}- 4-(3-fluorophenyl)-piperidin-4-yl]acetamide, A1-[l-{2-[2-(I-(4-fluoroph6nyI)-raethajioyl)-l,2,3,4-tetrahydro-isoquiiiolin-l-yI]-ethyl}- 4-(3-fluorophenyl)-pjperidin-4-yI]acetamide, N-[ 1 - {2-[2-(I -cyclopeiityl-methanoyl)-1,2,3,4-tetrahydro-isoquinoHn-1 -yl]-ethyl}- 4-phenylpiperidin-4-yI]acetamide, Af-[l-{2-[2-(l-(4-fluorophenyl)-niethanoyl)-l,2,3,4-tetrahydro-isoquinolin-l-yI]-ethyl}- 4-phenylpiperidin~4-yl]acetamide, l-cyclopentyl-l-{l-[l-acetyl-spiro[2,3-dihydro-7/f-indoI-3,4'piperidin-r-yl]ethyl}- 5,6-difluoro-3,4-dihydro-y//-isoqumo!in-2-yl}niethanoiie, l-(4-fluorophenyl)-l-{l-[l-acetyl-spiro[2,3-dihydro-///-indol-3,4'-piperidin-r-yi]ethyl]- 5,6-difluoro-3,4-dihydro-J//-isoquinolin-2-yl}methanone, l-cyc!opentyl-l-{I-[l-acetyl-spiro[2,3-dihydro-S-fluoro ///-indol-3,4'-piperidin-r-yi]- ethyi]-5,6-dif]uoro-3,4-dihydro-//7-isoquino]in-2-yI}methanone, 1 -(4-fluorophenyl)-1 - {1 -[ I -acetyl-spiro[2,3-dihydro-5-fluoro-///-indol-3,4'-piperidin-1 '-yl]- elhyl]-5,6-difluoro-3,4-dihydro-7//-isoquinoIin-2-yl}methanone, l-cyciopentyl-I-(I-{2-[4-{3-trifluoromelhy!phenyl)-piperidin-l-yI]-ethyl}-5,6-difluoro- 3,4-dihydro-///-isoquinolin-2-yl)niethanone, 1 -(4-fluoropheiiyl)-1 -(1 - {2-[4-(3-trifluoromethylphenyl)-piperidin-1 -yl]-ethyl}- 5,6-dif]uoro-3,4-dihydro-/H-isoquinolin-2-y])methanone, l-{l-{2-[4-(6-fluorobenzo[d]isoxazol-3-yl)-piperidin-l-yl]-ethyI}-5,6-difluoro-3,4-dihydro- ///-isoqu!nolin-2-yl)-l-(4-fluorophenyl)methanone, l-(l-{2-[4-(6-fluorobenzo[d]isoxazol-3-yi)-piperiditi-l-yl]-elliyl}-5,6-difluoro-3,4-dihydro- 7//-isoquinotin-2-yl)-l-(cyclopentyl)methanone, \-(4-fluorophenyl)'l-(l-1.2-[5,6-difluoiospiio[benzoftiran-l(3H),4'-piperidine-V-yll-ethyl}-5,6-difluoro-3,4-dihydro-y//1-isoquinoIin-2-yl)-methanone, i-(4-fluoi:ophenyl)-l-({2-[6-fluoroapirolben2oftiran-l(3H),4'-piperidine-r-y!]-ethyIJ- 5,6-difluoro-3,4-dihydro-y//-isoquinolin-2-yl)methanone, l-cycIopet\tyl-l-(l-{2-[5,6-difluoTOSpiio[benzofutan-l(3H),4'-piperidme-l'-yIl-ethyl)- 5,6-dif]uoro-3,4-dihydro-y//-isoquinolin-2-yl)-methanone, and l-cyclopentyH-({2-t6-fliK)rospiro[benzQfuran-l(3H),4'-piperidine-r-y[l-eUiyl}- 5,6 -difluoro-3,4-dihydro-///'-isoquinol in-2-yl)methanone. The compounds of the invention are NK2 receptors antagonists having a human NK; binding affinity (IC50) of 5 \iM or less, tj1ically of 1 nM or less, preferably of 200 nM or less, more preferred of 50 nM or less and most preferred of 10 nM or less. Accordingly, the compounds of the invention are considered useful in treating a variety of CNS diseases such as depression, manic depression, bipolar disorder, dysthymia, mixed anxiety depression, generalised anxiety disorder, social anxiety disorder, panic anxiety disorder, post traumatic stress disorder, obsessive compulsive disorder, acute stress disorder, phobia, pre-menstnial dysphoric disorder, psychosis and Huntington's disease as well as Parkinson's dementia, adjustment disorders, pain, emesis, migraine, epilepsia, obesity and cerebrovascular disease. In particular, the compounds of the invention are considered useful in the treatment of depression, manic depression, bipolar disorder, dysthymia, mixed anxiety depression, generalised anxiety disorder, social anxiety disorder, panic anxiety disorder, post traumatic stress disorder, obsessive compulsive disorder, acute stress disorder, phobia, pre-menstruai dysphoric disorder and psychosis. Thus, in another aspect, the present invention provides a pharmaceutical composition comprising at least one compound of fonnula I as defined above or a pharmaceutical ly acceptable acid addition salt thereof in a therapeutically effective amount and in combination with one or more phannaceutically acceptable carriers or diluents. In a further aspect, the present invention provides the use of a compound of formula I as defined above or an acid addition salt thereof for the manufacture of a pharmaceutical preparation for the treatment of the above mentioned disorders. The compounds of the general formula I may exist as optical isomers thereof and such optical isomers are also embraced by the invention. Throughout the specification and claims, reference to specific compounds refers to the racemates unless otherwise indicated. The term C1-e-alkyl refers to a branched or unbranched alkyi group having from one to six carbon atoms inclusive, such as methyl, ethyl, l-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methyl-2-propyl, and 2-methyl-l-propyl. The terms C|1-alky!, Ct.io-alkyI and C1-i2-atkyl, respectively, refer similarly to branched or unbranched alkyl group having from one to eight, ten or twelve carbon atoms inclusive, respectively. Similarly, Cz-e-alkenyl and Cj-e-alkynyl, respectively, designate such groups having from two to six carbon atoms, including one double bond and one triple bond, respectively, such as ethenyl, propenyl, butenyl, ethynyl, propyny! and butynyl. The term Cj-g-cycloalkyl designates a monocyclic or bicyclic carbocycle having three to eight C-aloms, such as cyclopropyl, cyclopentyl, cyclohexyl, etc. Halogen means fluoro, chloro, bromo or iodo. As used herein, the term acyl refers to a formyl, Ci1s-alkylcarbonyl, arylcarbonyl, aryl-C|,fi-alkylcarbonyl, Cs-s-cycloalkylcaibonyl or a Cj-B-cycloalkyl-Ci1-alkyl-carbonyl group, and the term thioacyl is the corresponding acyl group, in which the carbonyl group is replaced with a thiocarbonyl group. The terms C|.6-alkoxy, Cj-g-cycloalkyl-C1-e-alkyl, Ci1i-alkylsulfonyl, C1-o-aikylamino, C1-ralkyicarbonyl, and the like, designate such groups in which the C|-6-alkyI and the Cj.g-cycloalky] group are as defined above. The term aryl refers to a carbocyciic aromatic 1up, such as phenyl or naphthyl, in particular phenyl. The term heteroaryl refers to 5-membered monocyclic rings such as l//-tetrazolyl, 3i:f-l,2,3-oxathiazolyl, 3H-l,2,4-oxathiazolyi, 3/f-i,2,5-oxathiazolyl, 1,3,2-oxalhiazolyl, 1,3,4-oxathiazolyl, 1,4,2-oxalhiazolyl, 3//-1,2,4-dioxazolyl, 1.3,2-dioxazolyl, 1,4,2-dioxazoIyl, 3//-I,2,3-dithiazolyl, 3//-J ,2,4-dithiazolyl, 1,3,2-dithiazolyl, l,4,2-dithiazo]yl, 1,2,3-oxadiazolyI, l,2,4-oxadia2olyl, 1,2,5-oxadiazolyl, l,3v4-oxadiazolyl, 1,2,3-thiadiazoiyl, t,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, l,3,4-thiadia2olyl, lH-l,2,3-triazolyl, l/f-l1,4-triazolyl, isoxazolyl, oxazolyl, isothiazolyl, thiazolyl, 11-imidazoIyi, I/1-pyrazolyl, l//-pyrrolyl, fiiranyl, thienyl, 11-pentazoIe; 6-membered monocyclic rings such as 11,3-oxathiazinyl, l1,4-oxathia2inyl, 1,2,5-oxathiazinyi, 4//-l,3,5-oxathiazinyl, 1,4,2-oxathiazinyl, 1,4,3-oxathiazinyl, 1,2,3-dioxazinyl, 1,2,4-dioxa2inyl, AH- X ,3,2-dioxazinyl, 4//-1,3,5-dioxazinyl, 1,4,2-dioxazinyl, 2H-1.5,2-dioxazinyl, 1,2,3-dithiazinyl, 1,2,4-dithiazinyl, 47/-l,3.2-dithiazinyl, AH- ] ,3,5-dithiazinyl, 1,4,2-dithiazinyI, 2H-1,5,2-dithiazinyl, 2//- 1,2,3-oxadiazinyl, 2//-l,2,4-oxadiazinyl, 2//-l,2.S-oxadiazinyl, 2//-i,2,6-oxadiazinyl, 2//-l,3,4-oxadiazinyl, 2W-l,3,5-oxadiazinyl, 2H-l,2,3-ttiiadiazinyl, 2H-l,2,4-thiadiazinyl, 2//-l,2,5-Uiiadiazinyl, 2//-l,2,6-thiadiazinyI, 2/r-l,3,4-thiadiazinyl, 2/i'-I,3,5-thiadiazinyl, 1,2,3-triazinyl, I,2,4-tria2inyl. 1,3,5-triazinyl, 21-1,2-oxazinyl, 2//~l,3-oxazinyl, 2//-1,4-oxazinyl, 2//-i,2-thiazinyl, 2//-l,3-thiazinyl, 2//-l,4-thiazinyl, pyrazinyl, pyridazinyl, pyrimidyl, pyridyl, 2//-pyranyI, 21-thiinyl; and to bicyclic rings such as 3/1-1,2,3-benzoxathiazolyl, 1,3,2-bsnzodioxazolyt, 3/f-l,2,3-beiizodUhiazo\yl, 1,3,2-benzodithiazolyl, bcnzfurazanyl, 1,2,3-benzoxadiazolyI, 1,2,3-benzothiacliazolyl, 2,1,3-benzolhiadiazolyl, W-benzotriazolyl, 1,2-benzisoxazolyl, 2,1-bBnzisoxazoly!, benzoxazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzothiazolyl, l//-benzimidazolyl, I//-indazolyl, 3//-l,2-benzoxathioIyl, 1,3-benzoxathiolyl, 3J¥-2,l-benzoxathiolyl, 3/f-l,2-benzodioxo[yl, 1,3-benzodioxolyl 3/f-l,2-benzodithiolyl, l,3-ben2odithiolyl, lH-in6olyl, 2H-isoindolyl, benzofiiranyl, isobenzoftiranyi, l-benzothienyl, 2-beniMthienyl, l//-2,l-benzoxazinyl, l/f-2,3-benzoxazinyl, 2//-I,2-benzoxazinyl, 2//-l,3-benzoxazinyi, , 2ff-l,4-benzoxazinyl, 2H-3,l-benzoxazinyl, I//-2,l-benzothiazinyl, l//-2,3-benzothiazinyl, 2//-l,2-benzothiazinyl, 2//-l,3-benzothiazinyl, 2//-l,4-benzothiaziny!, 2H-3,l-benzothiazinyl, cinnoUny), phtalazinyl, quinazoUnyl, quinoxalinyl, isoquinolyl. quinolyl, l//-2-benzopyranyl, 2/f-l-benzopyranyi, l//-2-benzothiopyranyl or 2//-l-benzothiopyranyl. The acid addition salts of the compounds of the invention are pharmaceutically accqjtable salts formed with non-toxic acids. Exemplary of such organic salts are those with maleic, fumaric, benzoic, ascorbic, succinic, oxalic, bis-methylenesalicylic, methanesulfonic, ethanedisulfonic, acetic, propionic, tartaric, salicylic, citric, gluconic, lactic, malic, raandeiic, cinnamic, citraconic, aspartic, stearic, palmitic, itaconic, glycolic, p-aminobenzoic, glutamic, benzenesulfonic and theophylline acetic acids, as well as the 8-halotheophyllines, for example S-bromotheophylline. Exemplary of such inorganic salts are those with hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric and nitric acids. The phamiaceutical compositions of this invention, or those which are manufactured in accordance with this invention, may be administered by any suitable route, for example orally in the form of tablets, capsules, powders, symps, etc., or parenteraiiy in the form of solutions for injection. For preparing such compositions, methods well known in the art may be used, and any pharmaceutically acceptable carriers, diluents, excipients or other additives normally used in the art may be used. Conveniently, the compounds of the invention arc administered in unit dosage form containingsaid compounds in an amount of about 0.01 to 100 mg. The total daily dose is usually in the range of about 0.05 - 500 mg, and most preferably about 0.1 to 50 mg of the active compound of the invention. The compounds of the invention may be prepared as follows: 1) Alkylating a piperazine, piperidine or tetrahydropyridine of formula III with an alkylating derivative of fomiula 11: (III) wherein R'-R' and Q are as previously defined and L is a leaving group such as e.g. halogen, mesylate or tosylate; 2) Reductive alkylation of an amine of formula III with a reagent of formula IV: (IV) tl") .1 nS wherein R'-R'"' and Q arc as previously defined and E is an aldehyde or an activated carboxylic acid; 3) Acylating an amine of formula V by the use of a carboxylic acid and a coupling reagent, an activated ester, an acid chloride, an isocyanate, carbamoyl chloride or by a two-step procedure by treatment with phosgene followed by addition of an amine: wherein R -R and Q are as previously defined, whereupon the compound of formula I is isolated as the free base or a pharmaceutically acceptable acid addition salt thereof. The alkylation according to method 1) is conveniently performed in an organic solvent such as a suitably boiling alcohol or ketone, preferably in the presence of an organic or inorganic base (potassium carbonate, diisopropylethylamitie or triethylamine) at reflux temperature. Alternatively, the alkylation can be performed at a fixed temperature, which is different froni the boiling point, in one of the above-mentioned solvents or in dimethyl formamide (DMF), dimethylsulfoxide (DMSO), or N-methylpyrTOlidin-2-one (NMP), preferably in the piesence of a base. The alkylating agents of formula II can be prepared by methods analogues to those described in the ex.amples or can be synthesised by applying methods described in standard works such as Houben-Weyl, Methoden der organischen Chemie {Methods of Organic Chemistry), Georg-Thieme-Verlag, Stuttgart; Organic Reactions, John Wiley & Sons, Inc. New York, namely under reaction conditions such as those which are known and suitable for such reactions. The amines of formula III are either commercially available or have been described in the literature or can be prepared by methods analogues to those described in the literature e.g. Marxer et al. / Org. Chem. 1975, 40, 1427, by Parham ef al. J. Org. Chem. 1976, 41, 2628 and by Bauer et al. / Med Chem. 1976, /9, 1315, Maligres et al. Tetrahedron 1997, 53, 10983, and by Cheng et al. Tei. Lett. 1997, 38, 1497, Chen, Meng-Hsin; Abraham, John A. Tetrahedron Lett. 1996, 31, 5233-5234 and Slade, P.D. el al. J. Med. Chem. 1998, 4\, 1218-1235, or can be synthesised by methods described in standard works such as Houben-Weyl, Methoden der organischen Chemie (Methods of Organic Chemistry), Georg-Thieme-Verlag, Stuttgart; Organic Reactions, John Wiley & Sons, Inc. New York, namely under reaction conditions such as those which are known and suitable for such reactions. The reductive alkylation according to method 2) is perfonned by standard literature methods or as described in standard works such as Houben-Weyl, Methoden der organischen Chemie (Methods of Organic Chemistry), Georg-Thieme-Verlag, Stuttgart; Organic Reactions, John Wiley & Sons, Inc. New York, namely under reaction conditions such as those which are known and suitable for such reactions. The reaction can be performed in two steps, e.g. coupling of amines of fonnulalll with a reagent of formula IV by standard methods via the carboxylic acid chloride, activated esters or by the use of carboxylic acids in combination with a coupling reagents such as e.g. dicyclohexyl carbodiimide, followed by reduction of the resulting amide with lithium aluminium hydride or alane. The carboxylic acids of formula IV are either commercially available or can be prepared by methods analogues to those described in the literature (e.g. Tet. Lett. 37,1996, pp. 5453-5456; Tet Lett. 35,1994, pp. 6567-6570; J. Med. Chem. 25,1982, pp, 1235-1240; Synthesis 1987, pp. 474-477). The acylation according to method 3) is conveniently performed by standard methods via the carboxylic acid chloride, activated esters or by the use of carboxylic acids in combination with coupling reagents such a* e.g. dicyclohexyl carbodiimide. When the acylating reagent is carbamoyl chlorides or isocyanates, the sujylation produces urea derivatives. The urea derivatives can also be prepared by a two-step procedure consisting of treatment with phosgene followed by addition of an amine. The intermediate compounds of formula V are prepared as described in methods 1) and 2), wherein R1-R1, Q, L and E are as previously defined, and R' is a protection group. This protection group may be chosen from those protection group generally used for protection of amino groups. Those skilled in the art will know to select q)propriate protection groups and how to protect and deprotect the amines with these protection groups. Experimental Section Melting points were determined on a BUchi SMP-20 apparatus and are uncorrected. Analytical LC-MS data were obtained on a PE Sciex API 150EX instrument equipped with lonSpray source and Shimadzu LC-8A/SLC-10A LC system. The LC conditions (C18 column 4.6 x 30 mm with a particle size of 3.5 jim) were linear gradient elution with water/acetonitrile/trifluoroacetic acid (90:10:0.05) to water/acetonitrile/trifluoroacetic acid (10:90:0.03) in 4 min al 2 mL/min. Purity was determined by integration of the UV trace (254 nm). The retention times, Ri, are expressed in minutes. Mass spectra were obtained by an alternating scan method to give molecular weight information. The molecular ion, MH+, was obtained at low orifice voltage (5'20V) and fragmentation at high orifice voltage (100-200V). Preparative LC-MS-separation was performed on the same instrument. The LC conditions (CIS column 20 x 50 mm with a particle size of 5 urn) were linear gradient elution with water/acetonitrile/trifluoroacetic acid (80:20:0.05) to water/acetonitrile/trifluoroacetic acid (5:95:0.03) in 7 min at 22.7 mL/min. Fraction collection was performed by split-flow MS detection. ' H NMR spectra were recorded at 500.13 MHz on a Bruker Avance DRX500 instrument or at 250.13 MHz on a Bruker AC 250 instrument, Deulerated chloroform (99.8%D) or dimethyl sulfoxide (99.9%D) were used as solvents. TMS was used as internal reference standard. Chemical shift values are expressed in ppm-values. The following abbreviations are used for multiplicity of >MR signals: s-singlet, d=doublet, t=triplet, q=quartet, qui1quintet, h=heptet, dd=double doublet, dt=double triplet, dq=double quartet, tt=triplet of triplets, m=mu!tiplet. NMR signals corresponding to acidic protons are generally omitted. For column chromatography silica gel of type Kieselge! 60, 230-400 mesh ASTM was used. For ion-exchange chromatography (SCX, I g, Varian Mega Bond Elut®, Chrompack cat. No. 220776) was used. Prior use of the SCX-columns was pre-conditioned with 10% solution of acetic acid in methanol (3 mL). Preparation of intermediates AlkylatiDg reagents of the formula II 1. (RS)-I-{2-Bromo-eihy()-5,4- The following compound was prepared in a similar vi'ay: (RS)-i-(2-Bromo-ethyI)-6,7-dimethoxy-3,4-dihydro-///-isoquinoline-2-carboxyIic acid- lert'buXyl ester Piperidines of the formula III The piperidine-derivatives of formula III, wherein X is oxygen, Z is CR1"*, Y is a bond, A', A1 and A* are CH, A1 is CR", i.e. spiro[isobenzofiiran-l(JH),4'-piperidines] are prepared according to the methods described by Marxer et al. J. Org. Chem. 1975, 40, 1427, by Parham et al J. Org. Chem, 1976, ■?!, 2628 and by Bauer et al. /. Med. Chem. 1976,19, 1315, The following compounds were prepared in a similar way; 6-Fluorospiro[isoben2X>furan-!(JH),4'-piperidine], 6-trifluoromelhylsp)ro[isobenzofiiran-l(iH),4'-piperidinej, 6-fluoro-3-methylspiro[isobenzofuran-l(iH),4'-piperidine], 6-trif!uoromethyl-3-methylspiro[isobenzofuran-l(JH),4'-piperidine], 5-methyIspiro[isobenzofuran-l(5H),4'-piperidine], 6-fluoro-3-isobutylspiro[isobenzoiuran-l{5H),4'-piperidine], 6-fli!oro-3-cyclohexylspiro[isobenzofurjin-l (5H),4'-piperidine] and 6-fluoro-3-(4-fluorophenyl)spiro[isobenzofiiran-l(5H),4'-piperidine] The piperidine-derivatives of formula III, wherein X is CR'R , Z is NR , Y is a bond, A', A1 and A"* areCH, A1 is CR" and R" is fluoro or trifluoromethyl, are prepared according to the methods described by Maligres et al. Tetrahedron 1997, 53, 109S3, and by Cheng et al. Tet.Lell. 1997,38, 1497, The following compound was prepared in a similar way: 1 -Acety !-5 -fluoro-spiro[2,3 -dihydro- /H-indol -3,4'-piperidine]. The piperidine-derivatives of forniula III, wherein the X is CR'R"*, Z is oxygen, Y is a bond, A', A1 and A1 are CH, A1 is CR", i.e. 2,3-dihydro-spiro(ben2ofuran-3,4'-piperidines), are prepared according to the methods described by Chen. Meng-Hsin; Abraham, John A. Tetrahedron Lett. 1996, 57, 5233-5234 and Slade,P.D. et al. 7. Med. Chem. 1998,11, 1218- 1235. The following compounds were prepared in a similar way: 2,3-Dihydro-5-fiuorospiro[benzofuran-3,4'-piperidine] and 2,3-dihydro-5,6-difluorospiro[ben2ofuran-3,4'-pipcridine] The substituents R1 -R' ' are introduced by applying suitably substituted starting compounds to methods analogous to the above mentioned. Amines of the formula V An amine of formula V was prepared by the following procedure: A mixture of an amine of formula III (1 mmol), (RS)-l-(2-Bromo-ethyl)-3,4-dihydro-7//-isoquinoline-2-carboxylic acid-(ert-butyl ester (1.3 mmol) and potassium carbonate (1.3 mmol) in acetonitrile (20 raL) were heated to 85 °C for 6 h. The mixture was cooled to room temperature and evaporated in vacuo to give an yellow oily residue. The product was redissolved in dichloromethane (10 mL) and anisole (0.26 mL) and trifluoroacetic acid (10 mL) were added and the mixture stirred at room temperature for 90 min. The mixture was evaporated in vacuo. The product was either purified by chromatography or used directly in the next step without purification. The following compounds were purified by chromatography before fiirther use: (RS)- 1 - {2-[4-{5-Fluoro-J//-indol-3-yI)-piperidin-1 -yl]-ethy!} -1,2,3,4-tetrahydro-isoquinoline {RS)-l-{2-[6-fIuorospiro[isobenzofuran-l(3H),4'-piperidine-r-yll-ethyI}-1,2,3,4-tetTahydroisoquiiioUnc Enantiomeric forms of Amines of the formula V Enantiomer 1 and enantiomer 2 of N-{4-(3-Fluoro-phenyl)-}-[2-(l,2.3.4'tetrahydro-isoquinohn-}-yl)~ethyl}-piperidin-4-yl}acetamide Racemic N-(4-(3-flaoro-phenyl)-l-[2-(l,2,3,4-tetrahydro-isoquinolin-l-yl)-ethyl]-piperidin-4-yI}acetaniide was subjected to resolution by chiral HPLC using a Gilson SF3 supercritical fluid chromatography system equipped with chiratcelOD columns (4.6 mm x 25 cm for analytical and 10 mm x 25 cm for preparative runs). The particle size in the columns was 10 |im. A solution of the racemic compound N-{4-(3-fluoro-phenyI)-l-[2-(l,2,3,4-letrahydro-isoquinolin-l-yl)-ethyl]-piperidin-4-yl)acetamide (1 g) in methanol (1 mL) was injected in 40 fiL portions on a preparative column. The column was eluted with carbondioxide -modifier (75:25). The modifier was 2-propanol with diethylamine (0.5%) and trifluoracetic acid (0.5%.). The flow was 18.9 mL/min at 20 Mpa. Fraction collection was triggered by UV-detection (210 nM). The fractions containing the separate products were pooled and evaporated in vacuo which gave the enantiomers. The first eluted enantiomer is called Enantiomer 1 and the second eluted is called Enantiomer 2 of N-{4-(3-fluoro-phenyI)-I-[2-(l,2,3,4-tetrahydro-isoquinolin-i-yl)-ethyl]-piperidin-4-yl}acetamide. The enantiomers were measured by HPLC to have an enantiomeric excess higher than 95%, The following enantiomers were prepared in a similar way: Enantiomer 1 and enantiomer 2 of N'{4~(phenyl)'l-[2'(1,2,3,4'tetrahydrO'isoquinoUn-I~yl)-etkyl]-piperidin-4-yl}acetamide Examples Preparaliqn of the compounds of the inventioo The compounds of the present invention were prepared by one of two general methods: Method A: Alkylating a piperidine of formula III with an alkylating derivative of formula II: A mixture of a piperidine of formula III (1 mmol), (RS)-l-(2-Bromo-ethyl)-3,4-dihydro-///-isoquinoline-2-carboxylic acid-iert-butyl ester (1.3 mmol) and potassium carbonate (].3 mmol) in acelonitrile (20 mL) were heated to 85 °C for 6 h. The mixture was cooled to room temperature and evaporated in vacuo. The product was purified by chromatography either on silicagel using as eluent elhylacetate/triethylamine (99:1) or by purified by HPLC. Fractions containing the product were pooled and evaporated in vacuo. Method B: Acylating an amine of formula V by the use of a carboxylic acid and a coupling reagent, an activated ester, an acid cliloride or an isocyanate: An amine of formula V (prepared as described above; 1 mmol) and triethylamine (5 mmoi) were dissolved in anhydrous acetonitrile (10 mL). An appropriately substituted acid chioride (5 mmol) was added and the reaction mixture stirred at room temperature for 30 min. Methanol (0.5 mL) was added to the reaction mixture followed by evaporation in vacuo. The product was purified by chromalography either on silicagel using ethyiacetate/lriethylamine (99:1) as eluent or by HPLC. Fractions containing the product were pooled and evaporated in vacuo and characterised by HPLC-UV-ELSD-MS. The measured HPLC-retention time, the measured molecular mass and UV- and ELSD-purities are shown in table 1. The following compounds were made by the methods indicated In table I. Analytical data are shown in tabic \. Compound 1. i-(l-{2-[4-(5-FIuoro-///-indoI-3-yI)-piperidin-l-yI]-ethyl}-3,4-dihydro-7//-isoquinotin-2-yI)-1 -(4-fluoro-phenyl)methanone 2. l-Cyclopentyl-l-(l-{2-[4-(5-fluoro-;ff-indol-3-yl)-piperidin-l-yl]-ethyl}-3,4-dihydro-J'//-isoquinolin-2-yl)methanone 3. l-{2-[4-(5-Fluoro-///-indol-3-yi)-piperidin-l-yl]-ethyl}-3,4-dihydro-///-isoquinoiine-2-carboxylic acid phenethyl-ainide 4. l-(l-{2-[4-(5-Fluoro-///-!ndol'3-yl)-piperidin-l-yl]-ethyl}-3,4-dihydro-/H-isoquinolin-2-yl)-l-phenylmethanQne 5. l-(l-{2-[4-(5-Fluoro-;W-indol'3-yl)-piperidin-l-yl]-ethyi}-3,4-dihydro-;//-isoquinolin-2-yl)-I-(2-fIuoro-phenyl)methanone 6. l-(!-{2-[4-(5-FIuoro-///-indol-3-yl)-piperidin-l-yl]-ethyl}-3,4-dihydro-71-isoquinolin-2-yl)-3 -phenyl-propan-1 -one 7. I-(2-[4-(5-Fluoro-/H-indol-3-yl)-piperidin-l-yl]-ethyl}-3,4-dihydro--/i/-isoquinoline-2-carboxylic acid (3-chloro-propyI)amide 8. l-{2-[4-(5-Fiuoro-;H-indol-3-yl)-piperidin-l-yl]-ethyl}-3,4-dihydro-;//-isoquinohne-2-carboxy!ic acid (2-methoxy-phenyl)amide 9. l-{2-[4-(5-Fluoro-y//-indoI-3-yl)-piperidin-l-yl]-ethyl}-3,4-dihydro-///-isoquinoIine-2-carboxyIic acid tert-butyl ester 10. 3-Chloro-I-(]-{2-[4-(5-f]uoro-7//-indol-3-yl)-piperidin-l-yl]-ethyl}-3,4-dihydro-/1-isoquinolin-2-yl)-2,2-dimethyl-propan-l-one 12. l-Cyclopentyl-l-(l-{2-[6-fluorospiro[isobenzofuran-l(3H),4'-piperidine-l'-yl]-ethyl}-3,4-dihydro-V//-isoquinolin-2-yI)methanone 13. 1 -[2-(4-Chloro-phenoxy)-pyridin-3-yl]-l -{1 - {2-[6-fluorospiro[isobenzofuran-l(3H),4'-piperidine-l'-yl]-ethyl}-3,4-dihydro-7//-isoquinolin-2-yi)methanone 14.1 - {2-[6-Fluorospiro[isobenzofuran-1 (3H),4'-piperidine-l '-yl]-ethy 1} -3,4-dihydro-7/f-isoquinoliRe-2-carboxylic acid tert-butyl ester 15. ]-(l-{2-[6-Fluorospiro[isobenzofuran-l(3H),4'-piperidine-l'-yl]-ethyI}-3,4-dihydro-/H-isoquinolin-2-y!)-l-phenylmethanone 16. l-(I-{2-[6-Fluorospiro[isobenzofi]rMi-l(3H,),4'-piperidine-l'-yl]-ethyl}-3,4-dihydro-//f-isoquinolin-2-y])-l-p-tolylmethanone 17. l-(l-{2-[6-Fluorospiro[isobenzofliran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-y1-isoquinolin-2-yl)-l-(2-methoxy-phenyl)methanone 18. l-Cycloheptyl-l-(l-{2-[6-fiuorospiro[isobenzofiiran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-///-isoquinolin-2-yl)niethanone 19. l-(2-Fluoro-phenyI)-l-(l-{2-[6-fluorospiro[isobenzofiiran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-///-isoquinoliii-2-yl)methanone 20. 1 -(2-Chloro-phenyl)-1 -(1- {2-[6-fluorospiro[isobenzofuraii-l (3H),4'-piperidine-1 '-yl]-ethyl)-3,4-dihydro-///-isoquinoliti-2-yl)methanone 21. l-(4-Fluoro-phenyI)-l-(l-{2-[6-fluorospiro[isobenzofuran-l{3H),4'-pjperidine-r-yl]-ethyl)-3,4-dihydro-///-isoquinolin-2-y!)methanone 22. 1 -(4-Chloro-phenyL)-1 -(1 - {2-[6-fiuorospirotisobenzofiiran-l {3H),4'-piperidine-1 '-yl]-ethyl}-3,4-dihydro-///-isoquinoIin-2-yl)methanone 23. l-{2-[6-Fluorospiro[isobenzofiiran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-///-isoquinoline-2-carboxylic acid phenethyl amide 24. l-{l-{2-[6-Fuorospiro[isobenzofUran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-///-isoquinolin-2-yl)-l-(4-methoxy-pheny!)methanone 25. l-(t-{2-[6-FIuorospiro[isobenzoftiran-l(3H),4'-piperidine-I'-yI]-ethy!)-3,4-dihydro-///-isoquinolin-2-yI)-3-phenyl-propan-l-one 26. 2-EUvyl-l-(l-{2-[6-fluo1osp1ro[isobenzoftlran-U3H),4'-piperidine-l■-yl]-ethy\}-3,4-dihydro-i1-isoqui1olin-2-yl)■butan-I-o1e 27. l-{l-{2-[6-Fiuorospiro[isobenzofiiran-l(3H),4'-.piperidine-I'-yl]-ethyl}-3,4-dihydro-/1-isoquinoIin-2-yl)-1 -{3-methoxy-phenyl)methanone 28. l-(l-{2-[6-Fluorospiro[isobenzofuran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-7W-isoquinolin-2-yI)-2-ph6nyielhanone 29. 3-Cyclohexyl-l-(l-{2-[6-fluo1ospiro[isobenzofuran-l(3H),4'-piperidme-1-yl]-ethyl}-3,4-dihydro-J H-isoquinoUn-2-yl)1ropan-l -one 30. 2-{4-Fluoro-phenyl)-l-{l-{2-[6-fluoroapiro[isobenzoftiran-l{3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-iH-isoiiuinolin-2-yl)ethanone 31. l-(2-[6-Fluorospiro[isobenzoftiran-l(3H),4'-piperidine-r-yl]-cthyi}-3,4-dihydro-///-isoquinoUne-2-carboxylic acid (3,4-dichloro-phenyl)amide 32. 1 -Cyc!opropyl-l -(1 - {2-[6-fluorospiro[isobenzofuran- l(3H),4'-piperidine-r-yl]-ethy[} -3,4-dihydro-77/-isoquinoiiii-2-yl)methanone 33. l-Cl-{2-[6-Fluorospiro[isobenzofuran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-i//"isoquinolin-2-yl)-l-pyridin-3-yI-methanone 34. l-[5-(4-Chloro-phenyl)-2-inethyI-furan-3-y!]-l-(l-{2-[6-fluorospiro[isoben2ofuran-H3H),4'-pip6ridiiie-l'-y!l-ethyl}-3,4-dihydro-i/{-isoqumolin-2-yI)methanone 35-2-(4-Chloro-phenyl)-l-(l-{2-[6-fluorospiro[isobenzofiirati-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-///-isoquinoUn-2-yl)ethanotie 36. l-{]-{2-[6-Fluorospira[iaoben2»furan-l(3H),4'-piperidine-l'-yl]-ethyl}-3,4-dihydro-///-isoquinolin-2-yl)-2-niethyi-propan-l-one 37. l-{2-[6-Fluorospiro[isobenzofuran-l(3H),4'-piperidine-r-yi]-ethyl}-3,4-dihydro-7/y-isoquinoline-2-cart)oxylic acid (2-ethyl-phenyl)amide 38.W-[l-{2-[2-(l-Cycloheptyl-methanoyl)-i,2,3,4-tetrahydro-isoquinolin-l-yl]-ethyl>- 4-(3-fluorophenyl)-piperidin-4-yl]acetamide 39. l-Cyctopentyt-I-{l-{2-[6-fluoro-3-methylspiro[isobenzofijran-l(3H),4'-piperidin- r-yl]]-ethyl}-3,4-dihydro-y1-isoquinoli!i-2-yl)methanone 40.1 -CycloheptyI-1 - {1 -[ 1 -acetyl-sp!ro[2,3-dihydro-J//-indol-3,4'-piperidin~r-yI]ethyl]- 3,4-dihydro-///-isoquinoIin-2-yI}methanone 41.N-(l-{2-[2-{l-Cycloheptyl-methanoyl)-l,2,3,4-tetrahydro-isoquinolin-I-yl]-ethyl}- 4-phenylpiperidin-4-yl)acetamide 42. l-Cycloheptyl-I-(l-{2-[6-fluorospiro[isobenzofurai)-l(3H),4'-piperidine-r-yl]-ethyI}-3,4-dihydro-6,7-dimethoxy-7J^-isoquinolin-2-yl)methanotie 43. l-(4-Fluorophenyl)-l-(]-{2-[6-fluoro-3-methylspiro[isobenzofuran-l(3H),4'-piperidine-r-yl]-elhyl}-3,4-dihydro-7ff-isoquinolin-2-y!)methatione 44. l-Cycloheplyl-l-(l-{2-t5-fluoro-l-methansulfonyl-spiro[2,3-dihydro-//^-mdol-3,4'-piperidin-r-yl]-ethyl}-3,4-dihydro-y//-isoquinolin-2-yl)methanone 45. I-(l-{2-[2-(!-Cycloheptyl-methanoyi)-l,2,3,4-tetrahydro-isoquinolin-I-y!]-ethyl}-4-phenyl-piperidin-4-yI)-i-pjperidin-l-ylmethanone 46. l-(4-Fluorophenyl)-l-(l-{2-[5-fluoro-l-methansulfonyl-spiro[2,3-dihydro-y//-indol-3,4'-piperidin-r-yl]-ethyl}-3,4-dihydro-y//-isoquinolin-2-yl)nielhanone 47. l-Cycloheptyl-l"(l-{2-t4-(2-methyJ-;//-indol-3-yl>piperidin-l-yI]-ethyl}-3,4-dihydro-y//-isoquino]in-2-yl)methaiione 48. l-Cycloheptyl-l-(l-{2-[4-(3-trifluoroniethyl-phenyI)-piperidin-l-yl]-ethyI)-3,4-dihydro-///-isoquinolin-2-yl)inefhanone 49. ]-CycIopentyl-l-(l-{2-[6-fluoro-3-methylspiro[isobenzofuran-l(3H),4'-piperidinc-r-yl]-ethyl}-3,4-dihydro-6,7-dimethoxy-///-isoquino]!n-2-yl)rnethajione 50. l-Cyclopentyt-l-{l-[spiro[2,3-dihydro-W-indol-3,4'-piperidin-r-yl]ethyl]-3,4-dihydro-V//-isoquinoIin-2-yl}niethanone 51. l-Cyclopentyl-l-(l-{2-[5-fluoro-l-methansulfonyl-spiro[2,3-dihydro-///-indol-3,4'piperidin-r-yl]-ethy]}-3,4-dihydro-7W-isoquinolin-2-yl)methanone 52. l-(4-Fluoroplienyl)-l-{l-{2-[6-fluoro-3-niethylsp!ro[isobenzo{uran-l(3H},4'-piperidine-r-yl]-ethyl}-3,4-dihydro-6,7-dimethoxy-///-isoquinoIm-2-yl)methanone 53. l-(2-Fliiorophenyl)-l-(]-{2-[6-fluorospiro[isoben2ofuran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-y7/-isoquinolm-2-yl)methajione 54. l-Cycloheptyl-l-(l-{2-[spiro[isobenzoRiran-l(3H),4'-piperidine-l'-yi]-ethyl}-3,4-dihydro-///-isoquinolin-2-yI)methanone 55. 1 -Cycioheptyl-1 -(1 - {2-[6-fluoro-3-methylspiro[isobenzoiliran-1 (3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-6,7-dimethoxy-///-jsoquinolin-2-y]}nicthanone 56. ]-(l-{2-[4-(4-Chloro-phenyl)-piperidin-l-yl]-ethyl}-3,4-dihydro-lH-isoquinolin-2-yl)-1 -cycloheptylmethanone 57. 1 -Cyclopentyl-1 -(1 - {2-[5-isopropyIspiro[isoben2ofuran-l (3H),4'-piperidine-1 '-yl]-ethyi)-3.4-dihydro-///-isoquinolin-2-yl)methaiione 58. N-[ 1 -{2-[2-(l-Cyclopentyl-methanoyl)-!,2,3,4-telrahydro-isoquinolin-]-yl]-ethyl}-4-(3-fluorophenyl)-piperidin-4-yl]acetamide 59. I-Cycloheptyl-l-{l-[2-(4-phenylpiperidin-l-yl)-ethyl]-3,4-dihydro-lH-isoquinolm-2-yl) methanone 60. l-Cycloheptyl-l-(l-{2-[6-fluoro-3-methylspiro[isobenzofuran-I(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-7//-isoqumo]in-2-y!)m«hanone 61. l-Cyclopeiilyl-l-(l-{2-[4-(3-trifluoromethylphenyi)piperidin-l-yl]-ethyl}-3,4-dihydro-1 //-isoquinolin-2-yl)methanone 62. l-CyclopentyI-l-(l-{2-[6-fluorospiro[isobenzoftiran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-6,7-dimethoxy- y//-isoquinolin-2-yI)methanone 63. l-(4-FIuoropbenyI)-l-(I-{2-[6-ftuorospiro[isobenzofiiran-l(3H),4'-pif>eridine-r-yl]-ethyl}-3,4-dihydro-6,7-dimcthoxy-i/^-isoqiiinolin-2-yI)methanone 64. l-(l-{2-[4-(6*Fluorobenzo[d]isoxazol-3-yl)-piperidin-I-yl]-efhyl}-3,4-dihydfo-/H-isoquiiiolin-2-yl)-l-(4-fluorophenyl)methanone 65. l-[;i-(2-{2-[l-(4-Fluorophenyl)-raethanoyi]-l,2,3,4-tetrahydro-isoquinolin-l-yi}-ethyl)-4-phenylpiperidin-4-yl]-l-piperidin-l-yl-mcthanone 66. l-Cydopentyl-I-(l-{2-[4-(3-fIuoro-phenyl)-piperidm-l-yl]-ethyl}-3,4-dihydro-l//-isoquinolin-2-yI)niethanone 67. 8-{2-[2-(l-CycioheptyI-methanoyl)-I,2,3,4-tetrahydro-isoquinoiiii-l-yl]-ethyI}-1 -phenyl-1,3,8-triaza-spiro[4.5]decan-4-one 68. l-Cyclohep£yi-I-(l-{2-[6-trifluoromediylspiro[isoben2ofuran-l(3H),4'-piperidine-r-yl]-ethy!}-3,4-dihydro-6,7-dimethoxy-;/^-isoquinolin-2-yi)methanone 69. l-[l-(2-{2-[l-(2-Fluoro-phenyi)-methanoyl]-l,2,3,4-tetrahydro-isoquinolin-l-yl}-ethyl)-4-phenyl-piperidin-4-yI]-1 -(4-melbyl-pipera2in-l -yl)methanone 70. l-{2-[2-(l-Cycloheptyl-melhanoyl)-l,2,3,4-tetrahydro-isoquinolin-I-yl]-ethyl}-4-phenyl-piperidine-4-carboxylic acid ethyl ester 71. l-(l-{2-[2-(l-Cycloheptyl-methEmoyi)-l,2,3,4-tetrjdiydro-isoquinQUn-l-yl]-ethyl)-4-phenyt-piperidin-4-yi)-ethanonc 72. l-Cyclopentyl-i-(l-{2-[6-trifluoromethylspiro[isobenzofiiran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-6,7-dimethoxy-;//-isoquinolin-2-yl)methanone 73. l-CycIopentyl-l-Cl-{2-[4-(2-metbyM//-mdol-3-yI)-piperidin-l-yl]-ethyli-3,4-dihydro-1//-isoq uinoUn-2-yI)methanone 74. l-(I-{2-[2-(l-Cyctopentyl-methanoy])-1.2,3,4-tetrahydro-isoquinolin-l-y]]-ethyl}-4-pheiiyl-piperidin-4-y])ethanone 75. l-(4-Fluorophenyl)-l-(l-{2-[6-lrifluoromethylspiro[isobenzoftiran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-6,7-dimethoxy-y//-isoquinolin-2-yl)melhanone 76. l-(l-{2-[4-(4-Chloro-phenyl)-piperidin-l-y\]-elhyl>-3,4-dihydro-l//-isoquinolm-2-yl)-1-(4-fluoro-pheny Omethanone 77. l-(l-{2-[2-(l-Cycloheptyl-methanoyl)-l,2,3,4-telrahydro-isoquinolin-l-yl]-ethyl}-piperidin-4-yI)-l-(4-fluoro-phenyl)methanone 78.1 -(1 - {2-[2-( 1 -Cyc!oheptyl-methanoyl)-6,7-dimethoxy-l ,2,3,4-tetrahydro-isoquinolm-l-y!]-ethyl}-4-phenyl-piperidin-4-yl)-l~(4-methyi-piperazin-l-yl)methanone 79. i-(1 -{2-[4-(4-Chloro-phenyl)-piperidin-l-yl]-ethy])-3,4-dihydro-l//-isoquinoIin-2-yI)-1 -cyclopentylmethanonc 80. 1 -(4-FIuoro-phenyl)-1 -(1 - {2-[4-(3-trifluororaethyl-phenyl)-piperidin-1 -yl]-ethyl} -3,4-dthydro-l//-isoquinoHn-2-yl)meth2none 81.1-{4-Fluorophenyl)-l-{l-{2-[piro[isobenzofuran-l(3H),4'-piperidine-r-yt]-ethyi}-3,4-dihydro-///-isoquinolin-2-yl)methajione 82. l-Cyclopentyl-l-(I-{2-[4-fluorospiro[isoben2ofuran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-//^-isoquinolin-2-yl)methanone 83. l-(2-Fluorophenyl)-l-(i-{2-[6-fluoro-3-niethyIspiro[isobenzofuran-I(3H),4'-piperidine-]'-yl]-ethyl}-3,4-dihydro-6,7-dimethoxy-7H-isoquinolin-2-yl)methano!ie 84. N-[4-(3-Fiuoro-phenyl)-l-(2-{2-[I-(4-f]uoro-phenyl)-methanoyl]-l,2,3,4-telrahydrO' isoquinolin-)-yl}-ethyl)-piperidin-4-yl]-acetamide 85. I-(2-Fluoropheiiyl)-!-{l-[spiro[2,3-dihydro-//f-indoi-3,4'-piperidin-l'-yl]ethyi]-3,4-dihydro-/H-isoquinolin-2-yl}me(hanone 86. l-Cycloheptyl-l-(l-{2-[5'fluoro-I-niethansu!fonyI-spiro[2,3-dihydro-///-indot-3,4'-piperidin-r-yl]-ethyl}-3,4-dihydro-6,7-dimethoxy-///-isoquinolin-2-yl)methanone 87. l-( I - {2-[2-( l-Cycloheptyl-methanoyI)-6,7-diniethoxy-l ,2,3.4-tetrahydro-isoquinoiin-l-yl]-ethyl}-4-phenyl-piperidin-4-yI)-l-piperidin-l-ylmethanone 88. l-{l-[2-(4-Benzyl-piperidin-l-yl)-ethyl]-3,4-dihydro-;i/-isoquinoUn-2-yi}-1 -cycloheptylmethanooe 89. l-(2-Fluorophenyl)-l-{I-{2-[6-trifluoromethylspiro[isobenzofuran-l{3H),4'-piperidine-r-yl]-elhyl}-3,4-dihydro-6,7-dimethoxy-///-isoquinolin-2-yl)methanone 90. l-(l-{2-[(Chloro-trifluoromethyl-phenyl)-hydroxy-piperidin-I-yl]-ethyl}-6,7-dimethoxy-3,4-dihydro-l//-isoquinoUn-2-yl)-l-cycloheptylmethanone 91. l-(l-{2-[4-(4-Chloro-phenyi)-4-hydroxy-piperidin-l-yl]-ethyl}-6.7-diinethoxy-3,4-dihydro-i/]'-isoquinolin-2-yl)-I-cycloheptylmelhanone 92. 1-Cycloheptyl-1 -(1 - {2-[4-(2-isopropoxy-phenyl)-piperidin-l -yl]-ethyl} -3,4-dihydro-1//-isoqui nolin-2-y I)raethanone 93. l-(l-{2-[4-(7-Chloro-77/-indoI-3-yl)-piperidin-l-yl]-ethyl}-3,4-dihydro-y//-isoquinolin-2-yl)-l -cyclopentylmcthanone 94. i-Cyclopentyl-l-(i-{2-[4-(2,3-dihydro-benzofuran-7-yI)-piperidin-I-yl]-ethyl)-3,4-dihydro-l//-isoquinolin-2-yl)methanone 95.1-(l-{2-[4-(2,3-Dihydro-ben2ofuran-7-yI)-piperidm-]-yl]-ethyl)-3,4-dihydro-lf?-isoquinolin-2-yl)-l-(4-fluoro-phenyl)methanone 96. N-[l-{2-[2-(l-Cycioheptyl-methanoyl)-6,7-dimelhoxy-l,2,3,4-t^ahydro-isoquinolin-l-yl]-ethyl}-4-{3-fluoro-phenyi)-piperidin-4-yl]-acetamide 97. l-{4-FIuoro-phenyl>l-{l-[2-(4-phenyl-piperidin-l-yl)-ethyl]-3,4-dihydro-7//-isoquinolin-2-yl}methanone 98. l-(l-{2-[4-{6-Chloro-///-mdol-3-yl)-piperidin-l-yl]-ethyl}-3,4-dihydro-J//-isoquinotin-2-yl)-l-(4-fluoro-phetiyl)tnethanone 99. I-(4-F!uorO'phenyl)-l-(l-(2-[4-(3-fluoro-phenyl)-piperidin-l-yl]-ethyl}-3,4-dihydro-I//-isoquinoltn-2-yl)melhanone 100.1-Cycloheptyl-l-{l-[spiro[2,3-dihydro-;//-iridol-3,4'-piperidin-l'-yl]ethyl]- 3,4-dihydro-6,7-dimethoxy-///-isoquinolin-2-yl}niethanoiie 101.N-(l-{2-[2-(l-Cyclopentyl-methanoyI)-l,2,3,4-tetrahydro-isoqumolin-l-yn-elhyl}' 4-phenyl-piperidiii-4-yi)acetamide 102.1-(l-{2-[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-pipcridin-I-yl]-ethyl}-3,4-dihydro- IH-isoquinoliii-2-yl)-l-(2-fluoro-phenyl)methanone 103.1 -cycloheptyl-1 -(1- {2-[spiro[isoben2o(uran-l (3H),4'-piperidine-I '-yl]-ethyl} - 3,4-dihydro-6,7-dimethoxy-y/r-isoquinoIm-2-yl)melhanone 104.I-{2-[2-(l-Cyclopentyl-methanoyl)-l,2,3,4-tetrahydro-isoquinoIm-l-yl]-ethyl}- 4-pheiiyl-piperidine-4-caiboxylic acid ethyl ester 105.1-(l-{2-[4-(4-Djmethylainino-phenyl)-piperidin-I-yI]-ethyl)-3,4-dihydro- yH-isoquinolin-2-yl)-l-(4-fluoro-phenyl)methanone 106.1-Cyclopentyi-l-(l-{2-[4-(4-isopropyl-phenyl)-piperidin-I-yl]~ethyl}-3,4-dihydro- yH-isoquiTioUn-2-yl)methanone 107.1-[l-(2-{2-[l-(4-Fluoro-phenyl)-methanoyl]-l,2,3,4-tetrahydro-isoquinolin-l-yl}- ethyl)-4-phenyl-pipcridin-4-yl]ethanone 108.1-[!-(2-{2-[l-(2-FIuoro-phenyl)-methaiioyl]-l,2,3,4-tetrahydro-isoquinolin-l-y!}- ethyl)-4-phenyi-piperidin-4-y!]ethanone I09.1-[l-(2-{2-[l-(2-Fluoro-phenyl>niethanoyl]-l,2,3,4-tetrahydro-isoquinolm-l-yl}- ethyl)-4-phenyl-piperidin-4-yl]-1 -piperidin-1 -yl-methanone 110.1-Cyclopentyl-I-{l-[2-(4-phenyl-piperidin-l-yl)-cthyJ]-3,4-dihydro-l//-isoquinoIin- 2-yl}methanone llI.I-(2-Ftuorophenyl)-l-(l-{2-[6-fiuorospiro[isobenzofuran-l(3H),4'-piperidinc-r-yl]- ethyl)-3,4-dihydro-6,7-dimethoxy-///-isoquinoiin-2-yl)methanone 112.1-{4-Fluoro-phenyI)-l-(l-{2-[5.6-difluorospiro[benzoftiran-l(3H),4'-piperidine-r-yl]- ethyl} -3,4-dihydra-l H-isoquinolin-2-yI)-methanone 113.I-(4-Fluorophenyl)-l-({2-[6-fluorospiro[benzofuraii-l{3H),4'-piperidine-r-yl]~ethyl}- 3,4-dihydro-lH-isoquinoiin-2-yI)methanone 114. 3,3-Dimethyl-[l-{2-[spiro(5-fluor-benzofuran-2/f-3,4'-piperidine-l'-yl)-]ethyl}-3,4-dihydro-I//'-isoquinoline-2-yI]-butan-l-one 115. Cyclohexyi-[l-{2-[spiro(5-fluor-benzofuran-2H-3,4'-piperidine-l'-yl)-]ethyl)-3,4-dihydro-lH-isoquinoline-2-yI]-methanone 116. Cyclohexyl-(l-{2-[spiro(5-methyl-isobenzofuran-3//-l,4'-piperidine-r-yl)-]ethyl}-3,4-dihydro-l//-isoquino[in-2-yl)-methanone 117. Cyclohexyl-[l-{2-[spiro{benzofiiran-3H-l,4'-piperidine-r-yl)-]eihyl}-3,4-dihydro-lH-isoquinoline-2-yl]-methanone 118. Cyclohexyl-( I- {2-[4-(2-methyM //-indol-3-yl)-ptperidin-1 -yl]-ethyl} -3,4-dihydro-l//-isoquinol!n-2-yl)-methanone 119. N-{I-[2-(2-CyclohexanecarbonyI-l,2,3,4-tetrahydro-isoquinolin-I-yl)-ethyI]-4-phenyl-piperidin-4-yl}-acetaniide 120. 3,3-Dimethyl-l-(l-{2-[4-(3-trifluoromethyl-phenyl)-piperidin-l-yI]-ethyI}-3,4-dihydro-I//-isoquinoIin-2-yl)-butan-l-one 121. Cyclohexyl-{l-{2-[4-(3-trifluoromethyl-phenyl)-piperidin-l-yl]-ethy]}-3,4-dihydro-l//-isoquinolin-2-y])-methanone 122. Cyclohexyl-(l-{2-t4-(4-dimethylamino-phen.yl)-piperidin-l-yl]-ethyl}-3,4-dihydro-1//-isoquinoIm-2-yl)-methanone 123. 3-PhOTyl-[l-{2-[spiro(5-fluor-benzofuran-2H-3,4'-piperidine-l'-yI)-]ethyl}-3,4-dihydro-1 H-i5oquinoline-2-y]]-propanone 124. (l-(2-[4-(4-Chloro-3-trifiuoromethyl-phenyl)-4-hydroxy-piperidin-l-yl]-ethyl}-6,7-4imethoxy-3,4-dihydro-l//-isoquinolin-2-yl)-cyclohexyl-methanone 125. 2-Phenoxy-[l-{2-[spiro(5-fluor-ben2ofuran-2H-3,4'-piperidine-r-yl)-]ethyl}-3,4-dihydro-lH-isoquinoliiie-2-yl]-ellian-l-one 126. Ben2o[l,2,5]oxadiazol-5-yl-(l-{2-[spiro{5-methyl-isobenzoAiran-3H-l,4'-piperidme-r-yl)-]ethyO-3,4-dihydro-IH-isoqiiinoHn-2-yl)-methanone 127. Cyclohexyl-(l-{2-[4-(4-isopropyl-phenyI)-piperidin-l-yI]-ethyl)-3,4-dihydro-1 /^-isoquino Iin-2-yl)-raethanone 128. 2-^Propyl-n-{2-[spiro(5-fluor-benzofuran-2H-3,4'-piperidme-r-yiHethyt}-3,4-dihydro-lH-isoquinolme-2-yl]-pentan'l-one 129. 2,2-Dimethyi-3-chlor-[I-{2-[spiro(5-fluor-benzofijran-2H-3,4'-piperidine-l'-yl>] ethyl}-3,4-diliydro-IH-isoquinoline-2-yl]-propan-l-one 130. CyclohexyI-(l-{2-[4-(2,3-dihydro-betizofuran-7-yl)-piperidin-!-yl]-ethyl}-3,4-dihydro- lf/-isQquinoUn-2-yl)-tnethaaone 131. 3,3-Dimethyl-( 1 - {2-[spiro(5-methyl-isobenzofiiran-3H- l,4'-piperidme-1 '-yi)-]elhyl}-3,4-dihydrO"IH-isoquinolin-2-yl)-butan-l-one 132. Ben2o[l,2,5]oxaiiiazo1-5-yl-(l-{2-[4-(3-trifluoroniethyl-phenyl)-piperidin-l-yl]-ethyt}-3,4-dihydro-l//-isoqumo!in-2-yl)-methatione 133. 2-El!iyl-I-(l-{2-[4-(3-trifluoromethyl-phenyl)-piperidin-l-yl]-ethyI}-3.4-dihydro-l//-isoqiiinolin-2-yl)-butan-l-one 134. 2-Benzyloxy-{l-{2-[spiro(5-inethyl-isobenzofuran-3H-l,4'-piperidine-l'-yl)-]ethyl}-3,4-dihydro-lH-isoquinol!n-2-yl)-ethaii-l-one 135. Benzo[l,2,5]oxadiazol-5-yl-[l-{2-[spiro(5-fluor-benzx)furan-2H-3,4'-piperidine-1 '-yl>-] ethyl}-3,4-dihydro-1 H-isoquinoIine-2-y[]-methanone 136. (l-{2-[4-(4-Chloro-phenyl)-piperidin-l-ylj-ethyl}-3,4-dihydro-l/Msoquinolin-2-yl)-cyciohexyl-methanone 137. i-(l-{2-[4-(4-Chloro-phenyl)-piperidin-l-yl]-ethyI}-3,4-dihydro-lH-isoqumoIin-2-yI)-3,3-dimethyl-butan-I-one 138. 3.5,5-Trimethyl-(l-{2-[spiro(5-fluor-benzofiiran-2H-3,4'-piperidme-r-y])-]ethyl}-3,4-dihydro-lH-isoquino]ine-2-yI]-hexan-!-one 139. 3,5,5-Trimethyl-(l-{2-lspiro(5-methyl-isobenzofuran-3H-l,4"-piperidiiie-r-yl)-]ethyl}-3,4-dihydro-lH-isoquinolin-2-yI)-hexan-l-one 140. 2-Phenoxy-(l-{2-[spiro(5-niethyI-isobenzofiiran-3H-l,4'-piperidine-]'-yl)-]ethyl}-3,4-dihydro-lH-isoquinolin-2-yl)-ethan-l-one 141. (l-(2-[4-(4-Chloro-phenyl)-piperidin-l-yl]-ethyI)-3,4-dihydro-lH-isoqumolin-2-y!)-(2,2-dichloro-cyclopropy])-methanone 142. 2-BenzyIoxy-[l-{2-[spiro(5-iluor-bei]zofuran-2H-3,4'-piperidine-l'-yl)-]ethyl}-3,4-diliydro-lH-isoquinoline-2-yl]~ethan-l-one 143. ]-(l-{2-[4-(4-ChIoro-3-trifluoromethyI-phenyl)-4-hydroxy-piperidin-l-yl]-elhyl}-6,7-dimethoxy-3,4-dihydro-lH-isoquinolin-2-yl)-3,3-dimethyl-butan-l-one 144. I-(l-{2-[4-(2.3-Dihydro-benzofuran-7-yl)-piperidin-i-yl]-ethyl}-3.4-dihydro-1 H-isoquinoIm-2-yt)-3,3-dimethyl-butan-1 -one 145. 3,5,5-Triniethyl-]-(l-{2-[4-(3-trinuoromethyl-phenyl)-piperidin-l-yI]-ethyI}-3,4-dihydro-IH-isoquinolin-2-yI)-hexan-l-one 146. 2,2-Dimethyl-[I-{2-[spiro(5-fluor'benzofuran-2H-3,4'piperidine-r-yl)-]ethyI}-3,4-dihydro-lH-isoquino!ine-2-yl]-propan-l-one 147. 3-CyclohexyI-l-(l-{2-t4-(3-trifluoromethyl-phenyl)-piperidin-l-yl]-ethyl}-3,4-dihydro-1 H-isoquinoiin-2-yl)-propan-1 -one 148. Furan-2-yl-[l-{2-[spiro(5-fluor-benzofuran-2H-3,4'-piperidine'l'-yl>]ethyl}-3,4-dihydro-lH-isoquinoline-2-yl)-methanone 149. N-(4-Phenyl-l-{2-[2-(3,5,5-trimethyl-hexanoyl)-l,2,3,4-tetrahydro-isoquinoIin-i-yl]-et!iyl}-piperidin-4-yl)-acetamide 150. Quinoxalin-2-yi-[l-{2-[spiro(5-fluor-benzofuran-2H-3,4'-piperidine-r-yi)-]ethyl}-3,4-dihydro-lH-Jsoquinoline-2-y!]-methanone 151. 3-CyclohexyI-[l-{2-[spiro(5-fluor-benzofijran-2H-3,4'~piperidine-l'-yl)-]ethyl}-3,4-dihydro-l H-isoquino!!ne-2-yl]-propaii-1 -one 152. Benzo[!,2,5]oxadia2ol-5-yl-(l-(2-(4-(2,3-dihydro-benzofuran-7-yl)-piperidin-I-yl]-ethyl}-3,4-dihydro-lH-isoquinolin-2-yl)-methanone 153. Benzo[l,2,5]oxadiazol-5-yl-(l-(2-[4-(2-methy!-IH-indo!-3-yl)-piperidin-i-yl]-ethyl}-3,4-dihydro-lH-isoquinolin-2-yl)-methanone 154. (Tetrahydro-pyra!i-4-yI)-(l-{2-[4-(3-trifluoromethyI-phenyl)-piperidin-l-yl]-ethyl}-3,4'dihydro-lH-isoquinoiin-2-yl)-methanone 155. 2-Propyl-l-(l-{2-[4-(3-trifluoromeIhyl-phenyl)-piperidin-I-yl]-ethyl}-3,4-dihydro-lH'isoquinolin-2-yl)-pentan-l-one 156. 2-Ethyl-[l-{2-[spiro(5-fiuor-benzofuraii-2H-3,4'-piperidme-l'-yl)-]ethyl}-3,4--dihydro-lH-isoqumoline-2-yiJ-butan-l-one 157. 3-Phenyl-I-(l-{2-[4-(3-trifluorome^yi-pheny!)-piperidin-I-yl]-ethyI}-3,4-dihydro-1 H-isoquiiioIin-2-yI)-propan-1 -one 158. 3,3-Dimethyl-l-{l-{2-[4-(2-methyl-IH-mdol-3-yl)-piperidin-l-yl]-ethyl}-3,4'dihydro-lH-isoquinolin-2-yl)-bulan-l-one 159. (l-(2-[4-(4-Chloro-3-trifluoromethyl-phenyl)-4-hydr(Jxy-piperidin-l-yI]-ethyl}-6,7-dimethoxy-3,4-dihydro-lH-isoquinolin-2-yi)-{2,2-dichloro-cyclopropyi)-methanone 160. l,2,3,4-tetrahydro-naphthaiene-2-y!-(l-{2-[spiro(5-methyl-isobenzofuran-3H-I,4'-piperidine-l'-yl)-]ethyl}-3,4-dihydro-lH~isoquinolin-2-yl)-methanonc 161. (4-MethylsuIfanyl-phenyl)-(l-{2-[4-(3-trifluoromethyl-phenyl)-piperidin-l-yi]-ethyi}-3,4-dihydro-lH-isoquinolin-2-yl)-methanone 162. 3,5,5-Trimethyl-l-(l-{2-[4-(2-methyi-(H-indol-3-yl)-piperidin-l-yl]-ethyl}-3,4-dihydro-lH-isoquinolin-2-yl>hexan-l-one 163. 3-Phenyl-(l-{2-[spiro(5-methyl-isobenzofuran-3H-l,4'-piperidine-r-yI)-]ethyl}-3,4-dihydro-lH-isoquinolin-2-yl)-propan-!-one 164. Furaii-2-yl-(l-{2-[4-(3-trifluoromethyl-pheQyl)-piperidin-l-yi]-ethyl}-3,4-dihydro-1 H-isoq utnolin-2-yl)-methanone 165. 2-Benzyloxy-1-(1 - {2-[4-(2-methyl- i H-indol-3-yI)-piperidin- l-yl]-ethyl} -3,4'dihydro-lH-isoquinolin-2-yl)-elhanone 166. HI- {2-[4-(4-ChIoro-pheny!)-piperidin-1 -yl]-ethyl) -3,4-dihydro-l H-isoquinolin-2-yl)-2-pheiioxy-ethanone 167. Qtiinoxalin-2-yI-(l-{2-[spiro(5-methyl-isobenzo&ran-3H-l,4'-piperidine-y'-yl)-]ethyli-3,4-(iihydro-lH-i3oquinolm-2-yI)-methaiKtoe 168. 2,2-Diinethyl-l-(l-{2-[4-(3-trifluoromethyl-phenyl)-piperidm-l-yI]-ethyl)-3,4-dihydro-IH-!Soquinolin-2"yI)-propan-l-otie 169. (2,2-Dichloro-cyclopropyI)-(l-{2-[4-(3-trifluoromethyI-phenyl)-piperidin-l-yl]-ethyi}-3,4-dihydro-lH-isoquinonn-2-yl)-methanone 170. 4-MethytsuIfanyl-phenyl-(l-{2-[spiro{5-methyl-isobenzofuran-3H-l,4'-piperidine-r-yl)-]ethyl}-3,4-dihydro-lH-isoquinoiin-2-yl)-methanone 171. , (2,2-Dichloro-cyclopropyl)-(I-{2-[4-{2,3-dihydro-beiizofiiran-7-yI)-piperidin-l-yI]-ethyl}-3,4-dihydro-lH-isoquinolin-2-y])-methanotie 172. l-(l-{2-[4-(4-Isopropyl-phenyI)-piperidin-l-yl]-ethyI}-3,4-dihydro-lH-isoqumoliTi-2-yl)-3,5,5-trimethyl-hexan-l-one 173. 2,2-Dichloro-cyclopropyKl-(2-[spiro(isobenzofuran-3H-l,4'-piperidine-r-yl>]ethyl}-3,4-dihydro-lH-isoquinolin-2-yl)-methanone 174. N-(4-PhenyM - {2-f2-(l ,2.3,4-tetrahydro-naphtha)ene-2-carbony])-1,2,3,4-tetrahydro-isoquinolin-l-yl}-elhyl}-piperidin-4-yl)-acetamide 175. Benzo[ 1,2,5]oxadiazol-5-yl-( I- {2-[4-{4-chloro-phenyl)-piperidin-1 -yl]-elhyl} -3,4-dihydro-lH-isoquinolin-2-yl)-methanone 176. N-(I-{2-[2-(3,3-Dimelhyl-butyiyl)-l,2,3,4-tetrahydro-isoquinolin-I-yl]-ethy]}-4-phenyl-piperidm-4-yl)-acetamide 177. 3-ChIoro-2,2-dimethyI-l-(l-{2-[4-(3-trifluoromethyi-phenyl)-piperidin-l-yI]-ethyI}-3,4-dihydro-lH-isoquinolin-2-yI)-propan-l-one 178. Tetrahydro-pyran-4-yl-[l-{2-[spiro(5-fluor-benzofiiran-2H-3,4'-piperidine-r-yl)-3ethyl}-3,4-dihydro-lH-isoquinoline-2-yl]-butan-l-one The following compounds were made as enantiomers by method B starting from Enantiomer Z of the corresponding amines of formula V. Analytical data are shown in table 1. Compound 179. N-(4-(3-Fluoro-phenyl)-1 - {2-{2-(2-methoxy-benzoyl)-1,2,3,4-tetrahydFo-isoquinolin-l-yi]-ethyl}-piperidin-4-yl)acctamide (Enantiomer) 180. N-(4-(3-Fiuoro-plienyl)-l-{2-[2-(2-melhoxy-benzoyl)-l,2,3,4-tetrahydro-isoquinolin-l-yl]-ethyl)-piperidin-4-yl)acetamide (Enantiomer) 181. N-[l-{2-t2-(4-Chloro-ben2oyI)-1.2,3,4-tetrahydro-isoquinoIin-l-yI)-ethyl}-4-(3-fluoro-phenyl)-piperidin-4-yI]~acetamide (Enantiomer) 182. N-[l-{2-[2-(4-Bromo-ben2oyl)-l,2,3,4-tetrahydro-isoquinolin-l-yl]-ethy]}-4-(3-fluoro-phenyl)-piperidin-4-yl]-acetamide (Enantiomer) 183. N-[l-{2-[2-(4-Fluoro-benzoyl)-l,2.3.4-tetrahydro-isoqumolm-Uyl]-ethyl}-4-(3-fluoro-phenyl)-piperidin-4-yI]-acetamide(Enantiomer) 184. N-{4-(3-Fluoro-phenyl)-l-{2-[2-(4-isopropyl-^benzoyI)-I,2,3,4-tetrahydro-isoqumolin-l-y!]-ethyl}-piperidin-4-yl)acetamide(Enantioraer) 185. N-(4-(3-FIuoro-phenyl)-1 - {2-[2-(4-methyl-benzoyl)-l ,2,3,4-tet^ahydro-isoquinolin-l-yl3-ethyl}-piperidin-4-yI)acetamide(Enantiomer) 186. N-[l-{2-[2-(3-Chioro-benzoyl)-l,2,3,4-tetrahydro-isoquinolin-l-y]]'ethyl}-4-(3-fliioro-phenyl)-piperidm-4-ylj-acetamide 187. N41-{2-[2-(2-Bromo-benzoyl)-l,2,3,4-tetrahydro-isoquinolin-l-y]]-ethyl)-4-(3-fiuoro-phenyl)-p'peridin-4-yl]-acetamide(Enantiomer) 188. N-(i-{2-[2-(4-Bromo-benzoyli>l,2,3,4-tetrahydro-isoqumo\in-l-yl]-ethyl>-4-phenyl-piperidin-4-yl)acetatnide(Enantiomer) !89. N-(l-{2-[2-(2,4-Dich!oro-benzoyI)-l,2,3,4-tetrahydro-isoqmnolin-l-yl]-ethyl}-4-phenyl-piperidin-4-yI)acetamide(Enantiomer) 190. N-[l-{2-[2-(2,4-Dichloro-benzoyi)-l,2,3,4-tetrahydro-isoqmnolin-l-yI]-ethyl}-4-(3-fluoro-phenyl)-piperidin-4-y!]-acetamide(Enantiomer) 191. N-[l-{2-[2-(Benzo[I,2,5Joxadia2ole-5-carbonyl)-l,2,3,4-tetrahydro-isoquinolin-l-ylJ-elhy!}-4-(3-fluoro-phenyl)-piperidin-4-yi]-acetaniide(Enantioiner) 192. N-(4-(3-FIuoro-pheny!)-I-{2-[2-(naphthalene-l-carbonyt)-l,2,3,4-tetrahydro-isoquiiiolin-l-yl]-ethyl)-piperidin-4-yl)acetamide(Enantiomer) 193. N-[i-[2-{2-CyclopentanecarbonyI-l,2,3,4-tetrahydro-isoquiiiolin-l-yl)-elhylj-4-(3-fluoro-phenyi)-piperidin-4-yl]-acetamide{Enantiomer) 194. N-(l-{2-[2-(4-Chloro-benzoyl)-1.2,3,4-tetrahydro-isoquinolin-l-yl]-elhyl}-4-phenyl-piperidin-4-yl)acetainide(Enaiitiomer) 195. N-[l-{2-[2-(Benzo[bjthiophene-3-carbonyI)-l,2,3,4-tetrahydro-isoquinolm-l-yl]-ethyl}-4-(3-fluoro-phenyl)-piperidin-4-yI]-acetamide{Enantiomer) 196. N-[l-{2-[2-(6-Fluoro-4H-benzo[l,3]dioxine-8-carbonyl)-1.2,3,4-tetrahydro-isoquinolin-l-yl]-ethyl}-4-(3-fluoro-phenyl)-piperidin-4-yl]acetamide(Enanliomer) 197. N-[i-{2-[2-(3-Brorao-benzoyi)-],2,3,4-tetrahydro-isoquino!in-l-yl]-ethyl}-4-{3-fiuoro-phenyI)-piperidin-4-yI]acetamide(Enantiomer) 198. N-[l-{2-[2-(2-Fiuoro-ben2oyl)-l,2,3,4-tetrahydro-isoquinohn-l-yl]-ethyl}-4-(3-fluoro-phenyl)-piperidm-4-yl]acelamide(Enantiomer) 199. N-(l-{2-[2-(4-Methyl-benzoyl)-l,2,3,4-tetrahydro-isoquinoIiti-]-yI]-ethyl}- 4-phenyI-piperidin-4-yl)acetaraide(Enantioiner) 200. N-11 - {2-[2-{2-Chloro-benzoy])- 1,2,3,4-tetrahydro-isoquinoiin-l -yl]-ethyl} - 4-(3-fluoro-phenyl)-piperidin-4-yl]-acetamide(Enantiomer) 201. N-(4-(3-F]uoro-phenyl)-l-{2-E2-(4-methoxy-benzoyl)-l,2,3,4-tetrahydro- isoquinolin-l-ylj-ethyl}-piperidin-4-yl)acetamide (Enantiomer) 202. N-(l-{2-[2-(3-Chloro-beiizoyl)-l,2,3,4-tctrahydro-isoquinolin-l-yI]-ethyI}-4-phenyl-piperjd!n-4-yI)acetamide (Enantiomer) 203. N-(l-{2-(2-(4-Fluoro-beiizoyl)-l,2,3,4-tetrahydro-isoquinolin-l-yl]-ethyl}-4-phenyl-piperidin-4-yi)acetamide (Enantiomer) 204. N- {1 -[2-(2-CycloheptanecarbonyM .2,3,4-tetrahydro-:soquinolin-1 -yl)-ethyl]-4-pheny!-pjperidin-4-yl}-acetamide (Enantiomer) 205. N-(l-{2-[2-(3-Bromo-benzoyl)-l,2,3,4-tetrahydro-isoquinolin-l-yI]-cthyl}-4-phenyl-piperid!n-4-yl)acetamide (Enantiomer) 206. 2-N-(4-(3-Fluoro-phenyl)-l-{2-[2-(3-methoxy-benzoyl)-l,2,3,4-tetrahydro- isoquinolLn-I-yl]-ethyI}-piperidin-4-yl)acetamide (Enantiomer) 207. N-(4-(3-Fluoro-phenyl)-l-{2-[2-(thiophene-3-carbonyl)-l,2,3,4-tetrahydro- isoquinolin-l-yl]-ethyl}-piperidin-4-yl)acetamide (Enantiomer) 208. N-(4-(3-F]iiorD-phenyI)'l-{2-[2-(4-pyra201-l-yl-ben2oyl)-l,2,3,4-tetrahydro-!soquinolin-l-yl]-ethyl}-piperidin-4-yl)acetamide (Enantiomer) 209. N-(l-{2-[2-(Naphtha!ene-l-carbonyi)-l,2,3,4-tetrahydro-isoquinoltn-l-yl]-ethy!}-4-pheny!-piperidin-4-yl)acetamide (Enantiomer) Table 1. Measured molecular mass (M+H*), measured HPLC-retention time (RT, min) and UV- and ELSD-purities (%) and synthesis method. Pbarmacological Testing The compounds of the invention were tested in a well-recognised and reliable test. The test was as follows: InhibUion of blading of'"l-NKA to human NK2 receptors The compounds of the invention have been found to potently inhibit (he binding of -NKA to the human NK2 receptor. By (his method, the inhibition by drugs of the binding offKA to membranes of human cloned NK2 receptors expressed in CHO-cells is determined in vitro. Briefly, the affinity of the compounds was measured by their ability to displace 'l-NKA, by incubating hNK2 expressing CHO membranes with compound and radioligaed at room temperature for 60 minutes. Incubation was temiinated by rapid filtration through GF/C filters, and filters were counted in a Wallac Trilux Scintillation Counter. The IC50 values for the compounds No. 1-209, exemplified above, was detennined to be 200 nM or less. For the majority of the compounds the IC50 values were 50 nM or less, and for a large group of the compounds the 1C50 values were 10 nM or less. Formulation Examples The pharmaceutical formulations of the invention may be prepared by conventional methods in the art. For example: Tablets may be prepared by mixing the active ingredient with ordinary adjuvants and/or diluents and subsequently compressing the mixture in a conventional tabletting machine. Examples of adjuvants or diluents comprise: Com starch, potato starch, talcum, magnesium stearate, gelatine, lactose, gums, and the like. Any other adjuvants or additives usually used for such purposes such as colourings, flavourings, preservatives etc. may be used provided that they are compatible with the active ingredients. Solutions for injections may be prepared by dissolving the active ingredient and possible additives in a pMi of the solvent for injection, preferably sterile water, adjusting the solution to the desired volume, sterilising the solution and filling it in suitable ampoules or vials. Any suitable additive conventionally used in the art may be added, such as tonicity agents, preservatives, antioxidants, etc. 3) Syrup containing per millilitre: Compound la or lb 25 mg Sorbitol 500 mg Hydroxypropyicellulose 15 mg Glycerol 50 mg Methyl-paraben 1 mg Propyi-paraben 0.1 mg Ethanoi 0.005 mL Flavour 0.05 mg Saccharin sodium 0.5 mg Water ad 1 mL 4) Solution for injection containing per milllitre: Compound la or lb 0.5 mg Sorbitol 5.1 mg Acetic Acid 0.05 mg Saccharin sodium 0,5 rag Water ad 1 mL WE CLAIM: 1. A 3,4-dihydro-IH-isoquinoloin-2-yI-derivative of formula I wherein R' is a group R'1CO-, R.CS-, R'1SO2-, R0C0-, R1SCO- or RCO-CRR- wherein R12 is C1-ij-alky], C2-6-a)kenyl, Cz1-alkynyl, Cs-B-cycloalkyl, C3.g-cyc!oaIkyl-C1.6-alkyl. aryl, aryl-Ci1-alky!, heteroaryl, heteroaryl-Ci1-alkyf, letrahydropyranyl, 1,2,3,4-tetrahydronaphtalenyI, or4H-benzo[l,3]dioxinyI optionally substituted with halogen wherein each of said C|-6-alkyl, aryl, heteroaryl and Ca-s-cycloalkyt groups independently are unsubstjtuted or substituted with one or more substituents selected from the group comprising halogen, C1-is-alkyl, C].6-aIkoxy, aryl-C|-6-aIkoxy, C|-(;~alkylsulfanyl, aryl and aryioxy wherein said aryl and aryloxy independently are unsubstituted or substituted with one or more halogen, and R'1 and R'1 independently are hydrogen or C1-1-alkyl; or R' is a group R'1R'1NCO-, R14R15NCS-. wherein R14 and R'1 are independently hydrogen, Ci1-alkyl, C2-6-alkenyl, Q-6-alkynyl, C3.B-cycloalkyI, C3-8-cycloalkyl-Ci1-alkyl, aryl or aryl-C1.e-alkyI, wherein each of said CM-aH(yl, aryl and C3-g-cycloalkyl groups independently are unsubstituted or substituted with one or more substituents selected from the group comprising halogen, C1-6-alkyl and C|.6-alkoxy, or R14 and R15 1together with the N-atom to which they are linked, form a pyrrolidinyl, piperidinyl or perhydroazepinyl group; R1 is selected from hydrogen, trifluoromethyl and C|-6-aikyl; R3-R6 R2, R2b R15 and R3b are independently selected from hydrogen, halogen, cyano, nitro, C1-6-aIkyl, C21-alkenyl, Cj1-alkynyl, Cj-g-cycloalkyI, C1-g-cycloalkyl-C1-s-alkyl, amino, Cj-e-alkylamino, di-(C11-alkyl)amino, Cus-alkylcarbonyl, aminocarbonyl, C11-alkylaminocaitionyl, di-(C11-alkyl)aminocarbonyl, d1-alkoxy, C|.6-alkylthio, hydroxy, trifluommethyl, trifluoromethylsulfonyl and C11s-alkylsulfonyl; m is 2-6; R1 is benzyl, benzoyl, 2,3-dihydrobenzofuranyl or mono- or bicyclic aryl or heteroaryl wherein each benzyl, benzoyl, aryl or heteroaryl optionally is substituted with one or more substituents selected from halogen, cyano, nitro. C|-6-alkyl, C11-alkenyl, Cj1-alkynyl, Cj-a-cycloalkyl, C3-8-cycloaikyl-C1.6-a!kyl, amino, C11-alkylamino, di-(C11s-alkyl)amino, C1-6-alkylcarbonyl, aminocarbonyl, C11-alkylaminocarbonyl, di-(C11-alkyI)aminocarbonyl, C1-a-alkoxy, Cj1-alkylthio, hydroxy, trifiuoromethyl, difluoromethyl, fluoromethyl and trifluoromethylsulfonyl; Q is C, N or CR'; wherein R'** is selected from hydrogen, halogen, cyano, nitro, C1s-alkyl, C21-alkenyl, C2.6-alkynyl, Cj-g-cycioalkyl, Cs1-cycloaikyl-C1-e-alkyl, amino, C1-G-alkylamino, di- (Cni-alkyl)amino, C|1-a!kylcarbonyl, aminocarbonyl, C[1-alkylaniinocarbonyl, di- (C1.6-atkyl)aminocarbonyl, C1-1-alkoxy, C1-6-alkyIthio, hydroxy, trifiuoromethyl, difluoromethyl, fluoromethyl, trifluoromethylsulfonyl, a group ->fR1'*COR' wherein R1* is hydrogen or C|.6-alky! and R1' is C1-e-alkyl. a group -COOR'* wherein R'* is hydrogen or C|.(5-alky!, or a group -CONR'1R'* wherein R'1 and R'1 independently are selected from hydrogen and C1-s-alkyl or R and R'* together with the nitrogen to which they are attached fomi a piperidinyl, piperazinyl or morpholinyl, wherein said piperidinyl, piperazinyl and morpholinyl is unaubstituted or substituted with a C1-6-alkyl; or R9 and R10 together with the carbon to which they axe attached form a cyclic structure selected from the group comprising: wherein Q' is the carbon shared with the piperidine ring, so that said cyclic structure together with said piperidine ring form a spiro structure; and X, Y, and Z are independently chosen from O; NR.'1; CR11R1'; S(0)n and a bond; wherein R'1 is selected from hydrogen, C|-6-alkyl, C1-6-alkenyl, C2-6-alkynyl, Cs-s-cycloalkyl, Cj-g-cycloalkyl-C1-s-alkyl, trifluoromethyl, acyl, thioacyl and trifluoromethylsulfonyl, or R'1 is a group R11'SOj-, R1°OCO- or R1SC0- wherein R1 is C11-alkyl. Cj1-alkcnyl, Cj-e-alkyny], Cj.s-cycloalkyI, Cj-g-cycloalkyl-C1-e-alkyl or aryl, or R is a group R1'R11NCO- or R1'RNCS-, wherein R1' and R are independently hydrogen, C|.6-alkyl, C1.6-alkenyl, Ca-s-alkynyl1 Cj1-cycloalkyl, C1-g-cycloalkyl-C11-alkyl, or aryl, wherein said aryl is unsubstituted or substituted with one or more substituents selected from d-s-alkyl or halogen; or R1' and R11 together with the N-atom to which they are linked, form a pyrrolidinyl, piperidinyl or perhydroazepinyl group; R and R1 are independently selected from hydrogen, halogen, cyano, nitro, C1-6-alkyl, Cj-a-alkenyl, C2-6-alkyny], Cs-g-cycioalkyl, C3.g-cycloalkyi-C1.6-alkyl, aryl, heteroaryl, wherein said aryl is unsubstituted or substituted with one or more substituents selected from C1.6-alkyl or halogen, amino, C|1-alkylamino, a group MTl11R11 wherein R11 and R1'1 are independently selected from C|.6-alkyl C1- oxo; and n is 0, 1 or 2; provided that no more than one of X, Y and Z may be a bond, and provided that two adjacent groups X, Y or Z may not at the same time be selected from O and S; and A', A2, A2 and A are independently selected from N and CR wherein R is hydrogen, halogen, cyano, nitre, C|2-alkyl, Ci2-alkenyl, Cj2-alkynyl, Cj.g-cycloaIkyl, Cs-g-cycloaikyl- C]-(i-alkyl, Ci2-alkylcarbonyl, aminocarbonyl, Ci2s-alkylaminocarbonyl, di- (Ci4-alkyl)aminocarbonyi, C|-6-atkoxy, C].6-alkylthio, hydroxy, trifluoromethyl, difluoromethyl, fluoromethyl, irifiuoromelhylsolfonyi C| the dotted line emanating from Q is a bond when Q is C. and no bond when Q is CR' or N; or a pharmaceutically acceptable acid addition salt thereof. 2. The compound as claimed in claim 1, wherein Q is CR*, and R2 and R' together with the carbon to which they are attached form a bicyclic structure: wherein Q' is the carbon shared with the piperidine ring, so that said bicyclic structure together with said piperidine ring form a spiro struchire; and X, Y and Z are independently chosen ftom O; NR22; CR22R and S(0)n wherein R'2 is selected from hydrogen, CLg-aikyl, Cj2e-alkenyl, Cz-e-alkynyl. Cj-s-cycloalkyI, C3.8-cycloalkyl-Ci.6-aikyl, trifluoromethyl, acyl, thioacyl and irifluoromethyisulfonyl, orR'2 is a group R2'S02-, R22OCO or R2SCO- wherein R2° is Ci-c-allcyl, C2-6-aIkenyl, Cj-e-alkynyl, Cj-g-cycJoalkyl, C3,g-cycloalkyI-C|.6-alkyl, or 2, or R is a group R^'R"NCO-, R^'R^^NCS-, wherein R^' and R" are independently hydrogen, Ci^^alkyl, C2-t.-alkenyI, C2-6-alkynyl, Cj-g-cycloalkyl, Cj-s-cycIoalkyl-Ci-e-alky], or aryl, wherein said aryl is unsubstituted or substituted with one or more substituenls selected from C|js-alkyl or halogen; or R^' and R^^ together with the N-atom to which they are linked, form a pyrrolidinyl, piperidinyl, or perhydroazeyinyl group; R^^ and R^^ are independently selected from hydrogen, halogen, cyano, nitro, Ci^-alkyl, C2^-alk6nyl, C2.6-alkynyl, Cs-g-cycloalkyl, C3^-cycloalkyI-Ci-6-alkyl, aryl, heteroaryl, wherein said aryl is unsubstituted or substituted with one or more substituents selected from C|.6-a]kyl or halogen, amino, C|.6-alkyIamino, a group NR^^R^'^ wherein R^^ and R^^ are independently selected from Ci^-alkyl or R^^ and R^'^ together with the N-atom to which they are linked, form a pyrrolidinyl, piperidinyl, perhydroazepiny], or morpholinyl group, C|^-alkyJcarbonyl, aniinocarijonyl, Cn5-alkyIaminocarbonyl, di-(Ci^-alkyl)aJninocarbonyl, Ci-e-alkoxy, Ci-e-alkylthio, hydroxy, trifluoromethyl, trifluoromethylsulfonyl and C|^-alkylsulfonyl or R^^ and R'* together is oxo; and n is 0, I or 2; and a bond; provided that no more than one of X, Y and Z may be a bond, and provided that two adjacent groups X, Y or Z may not at the same time be selected from O and S; and A , A , A and A are independently selected from N and CR wherein R is hydrogen, halogen, cyano, nitro, Ci-6-aikyl, C2.6-alkenyl, Cj-o-alkyny], Cs^g-cycloalkyl, Cs-g-cycloalkyl-Ci-fi-alkyl, amino, a group NR^^R'^ wherein R^^ and R^' are independently selected from hydrogen and Cj-e-alkyl or R^^and R^^ together with the N-atom to which they are linked, form a pyrrolidinyl, piperidinyl, perhydroazepinyl or morpholinyl group, Ci-o-alkylcarbonyl, aminocarbonyl, Ct-s-alkylaminocarbonyl, di- (C|^-a!kyl)aminocarbonyl, Ci-6-aIkoxy, Ci^-alkylthto, hydroxy, trifluoromethyl, difluoromethyl, fluoromethyl, trifluoromethylsulfonyl orCi^-alkylsulfonyl; provided that only one of A', A^ A^ and A^maybeN. 3. The compound as claimed in claim 1, wherein X, Y and Z are selected from one of the combinations: X is oxygen, Y is a bond and Z is CR"R^; X is CR"R", Y is a bond and 2 is oxygen; X is NR", Y is a bond and Z is CR"R"; X is CR"R'^, Y is a bond and Z is NR'^ X is CO, Y is a bond and Z is NR'^ X is SO;, Y is a bond and Z is NR'^ X is SO, Y is a bond and Z is NR'^ X is CR"R". Y is a bond and Z is S; X is CR"R", Y is a bond and Z is SO; X is CR^^R^*, Y is a bond and Z is SOi; wherein R" is hydrogen, acetyl ot methylsulfonyl and R^^ and R" are independently selected from hydrogen, methyl, isobutyl, cyclohexyl and 4-fluorDphenyl. 4. The compound as claimed in claim 2, wherein -X-Y-Z- together form a group selected fix)m: -0-CR"R"-, -CR"R"-0-. -NR'^-CR^R"-, -CR"R"-NR"-, -CO-NR'^-, -SOj-NR'-. -SO-NR"-. -CR"R^'-S-, -CR'^R"-S0-, -CR^R^-SOJ-; wherein R'^ is hydrogen, acetyl or methylsulfonyl and R^' and R^'* are independently selected from hydrogen, methyl, isobutyl, cyclohexyl and 4-fluorophenyI. 5. The compound as claimed in claims 2 to 4, wherein A is N or CR wherein R" is halogen, cyano, nitro. a group NR^*R^' wherein R^* and R^' are independently selected from hydrogen and C|.6-all(yl oi R^^ and R^^ together with the N-atom to which they are linked, form a pyrfolidinyl, piperidinyl, perhydroazepinyl or morpholinyl group, Cins-alkylcarbonyl, aminocarijonyl, C|^5-alkyIaminocarbonyi, di-(Cv-6-alkyl)aminocaFbonyl, Ci-6-alkoxy, hydroxy, trifluoromethyl, difluororaethyl, fluorornethyl, trifluoromethylsulfonyl, or C|.6-alkyIsulfonyl. 6. The compound as claimed in claims 2 to 5, wherein A', A^, A"' and A"* are independently selected from CR^' wherein R^^ is as defined above. 7. The compound as claimed in claim 2, wherein said bicyclic structure is selected from the group comprising: 8. The compound as claimed in claim 1, wherein R' and R*'^ together with the carbon to which they are attached form a cychc structure selected from the group comprising: 2) wherein Q' is the catbon sh^ed with the piperidine ring, so that said cyclic structure together with said piperidine ring form a spiro structure. 9. The compound as claimed in claim 1, wherein R' is benzyl, benzoyl, 2,3-dihydrobenzofuran-7-yl or mono- or bicyclic aryl or heteroaryl wherein each benzyl, benzoyl, aryl or heteroaryl optionally is substituted with one or more substituents selected from halogen, cyano, nitro, Ci-e-alkyl, Ci.6-alkenyl, C^^-alkynyl, Cj-g-cycloalkyl, Cj-g-cycloalkyl-Ci^-alkyl, amino, Ci-6-alkylai"'no, di-(Ci.6-alkyl)amino, Ci^-alkylcarbonyi, aminocarbonyl, Ci^-alkylaminocarbonyl, di-{CI.6-alky!)aminocarbonyl, Ci-6-alkoxy, Ci-t,-alkylthio, hydroxy, trifluoromethyl, diiluoromethyl, fluoromethyl and trifluoromethylsulfonyl. 10. The compound as claimed In claim 9, wherein R^ is 2,3-dihydrobenzofuran- 7-yl, benzyl or benzoyl wherein said benzyl or benzoyl is unsubslituted or substituted with one or more halogens in the phenyl groups, or R' is mono- or bicyclic aryl or heteroaryl selected from the group comprising phenyl, indolyl, pyridyl, thiophenyl and benzisoxazolyl, wherein each aryl or heteroaryl optionally is substituted with one or more substituents selected from halogen, cyano, nitro, C|.6-alkyl, C2^-alkenyl, Cj.6-alkynyl, C^-g-cycloalkyl, C3.s-cycIoa)kyl-Ci.6-alkyl, amino, Ci-s-alkylamino, di-(Ci-6-alkyl)aniino, Ci-e-alkylcarbony], aminocarbonyl, Ci-o-alkylaminocarbonyl, di-(CI..6-alkyI)aininocarbonyl, C|-6-alkoxy, Ci.6-alkylthio, hydroxy, trifluoromethyl, difluoromethyl, fluoroiiiethyl and trifluoromethylsulfonyl. 11. The compound as claimed in claim 10, wherein said mono-or bicyclic aryl or heteroaryl is selected from the group comprising phenyl, indol-3-yI and benzisoxazol-3-yl wherein said phenyl, indol-3-yl or benzisoxazol-S-yl optionally is substituted with one or more substituents selected from halogen, cyano, nitro, Ci^-aJfcyl, Ci-e-alkenyl, Cj^-alkynyl, Cj-s-cycloalkyl, Cj-g-cycloalkyl-Ci-e-alkyl, amino, C[^s-aikyla^lino, di-(Ci«-alkyI)amino. Ci-6-alkylcari)onyl, Euninocaihonyt, Ci^-alkylaminocarbonyl, di-(C1 .(i-alkyl)aminocarbonyl, Ci_i-alkoxy, Ci -e-alkylthio, hydroxy, trifluoromethyl, difluoromethyl, fluoromethyl and trifluoromethylsulfonyl, 12. The compound as claimed in claim 11, wherein said optional substituents are selected from the group comprising halogen, phenyl and methyl. 13. The compound as claimed in claim 9 to 12, wherein Q is CR"* wherein R'" is selected from hydrogen, Ci-6-alkytcarbonyl, hydroxy, a group -NR^^COR" wherein R^** is hydrogen or Cj-e-alkyl and R^' is Ci-6-alkyl, a group -COOR'" wherein R" is C|.^-alkyl, or a group - 14. The compound as claimed in claim 13, wherein R'° is selected from hydrogen, acetyl, hydrcixy, a group-NR'^'COR'" wherein R^" is hydrogen andR^' is methyl, a group -COOR"" wherein R"^ is ethyl, or a group -CONR"R'* wherein R'^ and R'* together with the nitrogen to which they are attached form a piperidinyl or a 4-methyipiperazinyi. 15. The compound as claimed in claims 1 to 14, wherein m is 2,3 or 4. 16. The compound as claimed in claim 15, wherein m is 2. 17. The compound as claimed in any of claims 1 to 16, wherein R' is a group R"CO-, R"0C0- wherein R" is Ca^-alkyl, Cs-s-cycloalkyI, Cj-s-cycloalkyl-C-e-alkyl, phenyl, phenyl-C|.6-alkyl, pyridyl, furanyl, benzo|;i,2,5]oxadiazolyl, quinoxalinyl, beiizo[b]thiQphenyl or naphthalenyt wherein each of said Cj^-alkyl, phenyl, pyridyl and furanyl groups independently are unsubstituted or substituted with one or more substituents selected from the group comprising halogen, Ci^-alkyl, Ci^-alkoxy, phenyl and phenoxy wherein said phenyl and phenoxy independently are unsubstituted or substituted with one halogen; or R' is a group R'^R'^NCO-, wherein R'"* and R'^ are independently hydrogen, Ci-6-aIkyl, aryl, or aryl-Ci-e-alkyl, wherein each of said Ci-e-alkyl and aryl groups independently are unsubstituted or substituted with one substituent selected from the group comprising halogen and Ci^-aUcoxy. 18. The compound as claimed in claims 1 to 17, wherein R^is hydrogen. 19. The compound as claimed in claims 1 to 18, wherein R^ is hydrogen. 20. The compound as claimed in claims 1 to 19, wherein R* is hydrogen or methoxy. 21. The compound as claimed in claims 1 to 20, wherein R is hydrogen or methoxy. 22. The compound as claimed in claims 1 to 21, wherein R^ is hydrogen. 23. The compound as claimed in claims 1 to 22, wherein R ^ and R is hydrogen. 24. The compound as claimed in claims 1 to 23, wherein R^^ and R^*" is hydrogen. 25. The compound as claimed in claim 1 , wherein it is selected from the group comprising: i -(1 - {2-[4-(5-FIuoro-;//-indoI-3-yl)-piperidin- :-yl]-ethyl} -3,4-dihydro-7//-isoquinohn- 2-yl)-i-(4-fluoro-phenyi)methanone l-CycIopentyl-l-(l-{2-[4-(5-fluoro-///-indol-3-yl)-piperidin-I-yl]-ethyl)-3,4-dihydro- y7/-isoquino]in-2-yl)methanone l-{2-[4-{5-F!uoro-/W-iiKU)l-3-yl)-piperidm4-yn-ethyl}-3,4-c[ihydro-/f/-\soqiiinolme- 2-carboxyUc acid phenethyl-amide l- 2-yI)-l-phenylinethanone l-([-{2-[4-(S-Fluoro-///-mdol-3-yl>-piperidin-l-yl]-eUiyl)-3,4-dihyd!:o-7//-isoqumolm- 2-y[)-l-(2-{liiara-phenyl)methanone l-(l-{2-[4-(5-FluorQ-///-irulol-3-yl)-piperidin-l-yl]-etiiyl}-3,4-dihydro-///-isoqumoUn- 2-yl)-3-pheny(-propan-l-one l-{2-[4-(5-Fluoro-///-indol'3-yl)-piperidm-l-yl]-ethyl}-3,4-dihydro-iH-iscsqiiitK3line- 2-GarboxyUc acid (3-chlQrQ-propyl)amide l-(2-[4-(5-Fluoro-/H^indol-3-yl)-piperidm-l-yi]-ethyll-3,4-dihydro-7f^-tsoquinoiiiie- 2-cari)oxyUc acid (2-methoKy-phenyl)amide l-{2-[4-(5-Fluoro-//i^-indol-3-yl)-piperidi[i-l'yE]-ethyl}-3,4-dihyd[o-///-isoquinoltne- 2-carbQXylic acid tert-butyl ester 3-Chloro-l-(l-(2-[4-(5-fluorQ-/W-indot-3-yl)-piperidin-l-yI]-6thyi}-3,4-dihydto- /H-isQquinoUn-2-y!)-2,2-dimethyl-pTQpan-l-one l-Cyclopenty[-l-(l-{2-[6-fluorQSpito[isobenzofiiran-l(3H),4'-pipei'idine-r-yl]-ethyl}- 3,4-dihydrO'/H-!8oquinolin-2-yl)methanone l-{2-(4-ChlorQ-phenoxy)-pyridin-3-yy-l-(l-{2-[6'fluorospiro[isobenzofiiraii- K3H ),4'-piperidine- I'-y l]-eUiy 1} -3,4-dihydEo-/ //-isoquinoUti-2'y Omethanone 1 - {2-[6- Pluorospiro[isob«^zoftiran- l(3H),4'-piperidine- I'-ylJ-cthyl} -3,4-dihydro- iH-isoquino!ine-2-carboxylic acid tert-buVyl estev l-(l-{2-[6-Fiuoiospiro[isoben2,o{uran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro- / K-isoquinoUn-2-y!)-1 -pheny Imethanone Hl-U-t6-Fliiorospivo[isoben2ofurai\-l(3H),4'-piperidine-r-yll-ethyl}-3,4-dihydro- /H-isoqviinotiii-2-yl>-l-p-to!yimcthanoi\e l-(l-t2-[6-Fluorospiro[i3oben2ofuran-l(3H),4'-piperidine-V-yl]-ethyl}-3,4-dihydro- / H-isoquinolin-2-yl)-1 -(2-methoxy-phenyl)inethsmone l-CycloheptyM-(l-{2-[6-fluoi03piro[JsobenzofuTan-l(3H),4'-piperidine-l'-y!]-ethyl)- 3,4-diliy dio-i H-isoq\imoIin-2-yl)methanone i-(2-Fliioro-phenyl)-l-(1 - {2-[6-fluoiospiro[isobenzoftiran-H3H),4'-piperidine-l'-yi]-ethyii - 3,4-dihydro-i//-isoqusnolin-2-yl)niethanone i-(2-Chloro-phenyl)-l-(^-{2-16"*l"0iospiro[isoben2oftiran-l(3H),4'-piperidme-r--yl]-ethyl)- 3,4-dihydro-/ff-isoquinolin-2-yl)methanone l-(4-Fluoro-phenyl)-I-(l-{2-f6-fluorospiro[isobenzofiiran-I(3H),4'-piperidme-r-yI]-ethyl}- 3,4-dihydro-7H-isoquinolin-2-yOni6thanone l-(4-Chloro-phenyI)-l-(l*{2-[6-fluorospiro[isobenzofuran-I(3H),4'-piperidine-r-yl]-ethyl}- 3,4-dihydro-y//-isoquinolin-2-yl)methanone l-{2-[6-Fluorospiro[isobenzofiiran-l(3H),4'-pip6ridine-]'-yl]-ethyl}-3,4'dihydro- /H-isoqu\noline-2-caTboxyUc acid phenethyi amide l-(l-{2-[6-Fuorospiro[isobenzofuran-l(3H),4'-piperidine-l'-yl]-ethyl}-3,4-dihydro- ^^-isoquino!in-2-yl)-I-{4-methoxy-phenyi)methanone l-(l-{2-J.6-Fluorospiro[isobenzofuran-l(3H),4'-piperidine-r-yl]-etliyl)-3,4-dihydro- y/:/-isoquinolin-2-y!)-3-phenyl-propan-1 -one 2-Ethyl-l-(l-{2-[6-fluorospiroIisobenzofiiran-l(3H),4'-piperidine-l'-yl]-ethyl}-3,4-dihydro- ///■-isoquino]in-2-yl)-butan-l-one [- y//-isoquinolin-2-yl)-l-(3-melhoxy-phenyl)methanone l-(I-{2-[6-Fluorospiro[isobenzofuran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro- /H-isoquinolin-2-yl)-2-phenylethanone 3-CyclohexyI'1-(l-{2-[6-fluorospiro[isobenzofuran-l(3H),4'-piperidine-r-yI]-ethyl}- 3,4-dihydro-7//-isoquinolin-2-yl)-propan-l-one 2'(4-Fluoro-phenyl)-I-{l-{2-[6-f!uorospiroJisobenzofiiran-l(3H),4'-piperidine-r-yl]-ethyl}- 3,4-dihydrQ-///-isoqutnoIin-2-ynetbanone l-{2-[6-Fiuorospiro[isobenzofi]ran-I(3H),4'-piperidine-r-yI]-ethyl}-3,4-dihydro- 7//-isoquinoline-2-carboxyIic acid (3,4-dichloro-phenyl)amide l-Cyclopropyl-l-(l-{2-[6-fluorospiio[isobeii2oftiran-l(3H),4'-pJpeTidme-V-yI]-ethyl}- 3,4-d!hydro-/iY-isoquinolin-2-yl)methanone 1 -{I - {2-[6-FIuorospiro[isoben2oftiran-! {3H),4'-piperidine-1 '-yl]-ethyl} -3.4-dihydro- ///-isoquinolin-2'yi)-l-pyridin-3-y!-niethanone i-[5-{4-ChIoro-phenyl)-2-methyl-furan-3-yl]-l-(l-{2-[6-fluorospiro[isobenzofiiran- l(3H),4'piperidine-r-yl]-ethyi)-3,4-dihydro-y/f-isoquinolin-2-yl)methanone 2-(4-Chloro-phenyi)-l-{l-(2-[6-fIuorospiro[isoben2ofiiran-](3H),4'-piperidine-r-yI]-ethyi}- 3,4-dihydro-/H-isoquinoHn-2-yl)ethanoiie I-Cl-{2-[6-Fluorospiro[isobenzofuran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4Miihydn>- 7//-isoqumolin-2-yl)-2-methyl-propan-l-one I-{2-[6-Fluorospiro[isobenzofuran-l(3H),4'-piperidine-]'-yl]-ethyI}-3,4-d!fiydro- 7//-isoquinoline-2-carboxyIic acid (2-elhyJ-phenyl)amide A'-[ 1 - {2-[2-(l -Cycloheptyl-methanoyO-1,2,3,4-tetrahydro-isoquinolin-1 -yl]-ethyl}- 4-(3-fluorophenyl)-piperidin-4-ylJacetamide l-Cyclopenty[-l-(l-{2-[6-fluoro-3-methylspiro[isobenzofiiran-l(3H),4'-piperidin-r-yl]]- ethyl}-3,4-dihydro-y//-isoquinoIin-2-yI)methanone 1 -Cycloheptyl-1 - {1 -f 1 -acetyi-spiro[2,3-dihydro-/jy-indoi-3,4'-piperidin- I'-yljethyl]- 3,4-dihydro-/^-isoquino]in-2-yl)methanone N-(l-{2-[2-(l-CycIoheptyl-methanoyI)-l,2,3,4-tetrahydro-isoquinoiin-l-yl]-ethyl}- 4-phenylpiperidin-4-yI)acetamid6 I -CycloheptyI-1 -(1 - {2-[6-fluorospiroJisobenzofiiran-l{3H),4'-piperidine-1 '-yl]-ethyl}- 3,4-dihydro-6,7-dimethoxy-y//^isoquinolin-2-yl)methanone I-(4-Fluorophenyl)-l-(l-{2-[6-fluoro-3-methylspiro[isobenzofiiran-l(3H),4'-piperidine- r-yi]-etiiyl}-3,4-dihydro-///-isoquino]in-2-yl)methanone l-CycIoheptyl-l-(l-{2-[5-fiuoro-l-niethansiilfonyl-spiro[2,3-dihydro-7//-indol- 3,4'-piperidin-r-yI]-ethyl}-3,4-'i'bydro-///-isoquinolin-2-yl)methanone i-(l-f2-[2-(I-Cyclohqityl-methanoyI)-I,2,3,4-tetrahydro-jsoquinoIin-l-yl]-ethyl)- 4-phenyl-piperidin-4-yl)-l-piperidin-l-ylmethanone l-(4-Fluorophenyl)-l-(l-{2-[5-fluoro-l-mcthansulfonyl-spiro[2,3-dihydro-V//'-indol- 3,4'-piperidin-r-yl3-ethyl)-3,4-dihydro-y//-isoquinolin-2-yl)me(hanone l-Cycioheptyl-l-(l-{2-[4-(2-methyl-///-mdol-3-yl)-piperidin-l-yI]-6lhyl}-3,4-dihydro- ///--isoqumoIin-2-yl)methanone l-Cycloheptyt-l-(l-{2-[4-(3-trifluorornethyl-phenyI)-piperi ///-isoquinolin-2-yl)methanone l-Cyciopentyi-l-(l-{2-[6-fluoro-3'niethyIspiro[isobenzofiiran-l(3H),4'-piperidine-r-yl]- ethyi}-3,4-dihydro-6,7-dimethoxy-i//-isoquinoiin-2-yI)methanone l-Cyclopemyl-l-{l-[spiro[2,3-dihydro-y//-indol-3,4'-piperidin-i'-yl]ethyl]-3,4-dihydro- 7//-isoquinolin-2-yl}methanone l-Cyclopentyl"l-(l-{2-[5-fluoro-I-methansulfonyl-spiro[2,3-dihydro-i//-indoi- 3,4'-p!perid!n-r-yl]-ethyI}-3,4-dihydro-///-isoquinolin-2-yi)mcthanone I-{4-Fiuorophenyl)-I-(l-{2-[6-fluoro-3-methyIspiro[isobenzofiiran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-6,7-dimethoxy-///-isoquino!in-2-yl)methanone l-(2-Fluorophenyl)-l-(l-{2-[6-fiuorospiro[isobenzofuran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-///-isoquinolin-2-yl)methanone l-Cyc!ohepty!-l-(l-{2-[spiro[isobenzoiuran-H3H),4'pipeTidine-l'-yl]-ethyl)-3,4-dihydro-///-isoqu!noIin-2-yl)methanone 1 -Cycloheptyl-1 -(I - {2-[6-fluoro-3-methylspiro[isobenzofuran-l (3H),4'-piperidine- ^-yl]-elhy]}-3,4■diIlyd^o-6,7-dimethoxy-///'-^soquinolin-2-y])methanone l-(I-{2-[4-(4-Chloro-phenyl)-piperidin-I-yl]-ethy!}-3,4-dihydro-lH-isoquinoIin-2-yl)-1 -cycloheplylmethanone l-Cyclopcntyl-I-(l-{2-[5'isopropylspiro[isoben2»fiiran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-dihydro-7//-isoqiiino]in-2-yl)methanone N-[l-{2-[2-(l-Cyclopenty!-methanoyI)-l,2,3,4-tetrahydro-isoquinolin-l-yl)-ethyl}-4-(3-fluorophenyl)-piperidin-4-yiJacetarnide 1 -Cycloheptyl-1 - {1 -[2-(4-phenylpiperidin-l -yl)-ethyl]-3,4-dihydro-l H-isoquinoVin-2-yI)methanone l-CycioheptyH-{l-{2-[6-fluoro-3-methylspiro[isobenzofuran-l{3H),4'-piperidine-r-yl]-ethyI}-3,4- l-Cyclopentyl-l-(l-{2-[4-(3-trif]uoromethylphenyl)piperidin-l-yl]-ethyJ}-3,4-dihydrD-l//-isoquinolin-2-yI)methanone l-Cyclopenty]-l-(l-i2-[6-fluorospiro[isobenzofuran-l(3H),4'-piperidine-r-yl]-ethyl}-3,4-di hydro-6,7-dimethoxy.///-isoq uinolm-2-yl)methanone l-{4-FluorophenyI)-l-(l-{2-[6-fl\iorospiro[isobenzo!uran-I(3H),4'-piperidme-l'-yl]-ethyl}-3,4-dihydro-6,7-dimethoxy-/^-isoquinolin-2'yl)methaiaone l-(l-(2-[4-(6-Fluorobenzo[d]jsoxazoI-3-y1)-piperidin-I-ylJ-ethyl}-3,4-dihydro-///-isoquinolin-2-yl)-l-{4-f(uorophenyi)methanone J-[l-(2'{2-[]-(4-Fluorophenyl)-methanoyi]-l,2,3,4-tetrahydro-isoquinoIin-l-y!}-ethyl)-4-phenyipiperi6in-4-ylVl-piperidin-l-yl-niellianone ]-CycIopentyl-l-(l-{2-[4-(3-fluoro-phenyl)-piperidin-!-yI]-efhyl}-3,4-dihydro-1 H^-isoquinoiin-2-y!)methanone 8- {2-[2-( 1 -Cyclohcptyl-methanoyl)- 1,2,3,4-tetrahydro-isoquinolin-1 -yll-ethyl}-1 -phenyl-1,3,8-triaza-spiro[4.5]decan-4-one l-Cycioh^tyH-(l-{2-[6-trifluQrom«hyl8pito[isQbenzofutan-l(3H),4'-pipcrid\n6-l'-yI]- ethyl} -3,4-dihydro-6,7Hiimethoxy-///-isoquinoUn-2-yl)inethanone l-[l-(2-{2-[l-(2-Ftuoro-phenyl)-ms^anoyI]-l,2,3,4-tetrahydro-isoquinoUn-l-y!}-ethyl)- 4-phenyl-pipeiidin-4-yl]-l-(4-methyl-piperazin-l-yl)methanone l-{2-[2-{l-Cyc!oheptyl-mcthanoyI)-l,2,3,4-tetrahydro-isoquinolm-l-yl]-etliyl)-4-phenyl- piperidine-4-carboKylic acid eAyl ester l-(l-{2-[2-(l-Cyclohq)ty!-niethanoyl)-!,2,3.4-tetrahydro-isoqumolin-l-yl]-eU\yl}- 4-phenyl-p!perid!n-4-yl)-ethanone l-CycIopeiHyl-l-(l-{2-[6-trifluoroniethylsp\ro[isobcnzofuraii-l(3H),4'-piperidme-l'-yl3- ethyl}-3,4-dihydro-6,7-dimethoxy-///-isQquinolin-2-yi)nietl««ione l-CycIopentyl-l-(l'(2-t4- IH-isoquiEioUci-Z-yOmcthanone I-(l-{2-[2-(l-CyclopentyI-methanoyt)-l,2,3,4-tetrj^ydro-isoquinQliii-l-yl]-ethyl}- 4-pheiiyUpiperidin-4-yl)ethaiiQne l-(4-FluoTOphenyl)-l-(l-(2-[6-trifiuoromethylspico[isobenzoturan-l(3H),4'-pipeiidine- r-yl]-ethylj-3,4-dihydro-6,7-dimetKoxy-///-)soquinoUn-2-yl)[nethanone l-(l-{2-[4-(4-CMoio-pheny0-piperidit\-l-yll-ethyl)-3,4-dihydra-lH-iaoquinQUn-2-yI)- i -(4-fluoro-pheny I)methanone l-(l-{2-[2-(l-Cycloheptyl-methanoyl)-l,2,3,4-t«rahydTO-isoquinolm-l-y!]-ethyl}- piperidin-4-y I)-1 -(4-fluoro-pheny l)methatione l-{l-{2-[2-(l-Cycloheptyl-methanoyI)-6,7-dimethoxy-l,2,3,4-tetrahydYO-isoquinoUn~l-yl]- ethyl}-4-f*enyl'piperidin-4-y\)-l-(4-methyl-pipeiaxin-l-yI)methanone l-(l-{2-[4-(4-ChIoro-phenyl)-piperidin-l-yl]-ethyl}-3,4-dihydro-lfl'-isoquJnolin-2-yl)- 1 -cyclopentylmeUianone \-(4-Fiuoro-phenyl)-l-(l-{2-[4-(3-trifluoromethyl-phenyi)-piperidin-l-yll-ethyiJ- 3,4-dihydro-1 H-isoqiiinolin-2-yl)methanone i-(4-Fluorophenyl)-l-(l-{2-[pirolisobenzofuran-l(3H),4'-pipeTidine-l'-yl]-ethyl}- 3,4-dihydto-/H-isoquiiiDlin-2-yi)methanone l-Cyclopentyl-l-(l-(2-[4-fluorospiro[isobenzDfuran-U3H),4'-piperidme-l*-yI3-ethyl}- 3,4-dihydTO-iH-isoquinolin-2-yl)methanone l-(2-Fluoropheny!)-l-(l-{2-[6-fluoro-3-methylspiro[isobenzoftjran-V(3H),4'-piperidine- V-y\l-ethyl}-3,4-dihydro-6,7-dinietVioxy-J/f-isoquinolm-2-yl)methanone N-[4-(3-Fluoro-phenyl)-l-{2-{2-[l-(4-fluoKi-phenyl)-methanoyl3-l,2.3,4-tetrahydro- isoquinolin-I-yl}-ethyl)-piperidin-4-yl]-acetamide I-(2-Fluoropheny])-l-{I-[spiro[2,3-dihydro-///-indol-3,4'-piperidin'l'-yI]ethyl]- 3,4-dihydro-W-isoquinoJin-2-yi}methanone l-Cycloheptyi-l-(l-{2-|;5-fluoro-I-methansulfonyl-spiro[2,3-dihydro-//Aindol- 3,4'-piperidin-r-yl]-ethyI}-3,4-dihydro-6,7-diinethoxy-7//-isoquinolin-2-yl)mcthanone l-(l-{2-[2-(l-CycloheptyI-methanoyl)-6,7-dimethoxy-l,2,3,4-tetrahydro-isoquinolin-l-yl]- ethyl} -4-phenyl-piperidiii-4-yl)-] -piperidin-l -ylmethanone 1' {1 -[2-(4-BenzyI-pipeiidin-l -yl)-ethyi]-3,4-dihydTo-lH-isoquinoiin-2-yJ} - I -cyclohepty Imethanone l-(2-FluoropheiiyI)-I-(l-{2-[6-trifluoromethylspiro[isobenzofiiran-l(3H),4'-pjperidine- r-yl]-ethyI}-3,4-dihydro-6,7-dimethoxy-y^-isoqumolin-2-yl)melhanone l-{l-{2-[(Chloro-trifluoromethyl-phenyl)-hydroxy-piperidin-l-yl3-ethyI}-6,7-dimethoxy- 3,4-dihydro-I//-isoquinolin-2-yI)-l-cycIoheptylmethanone l-(l-{2-[4-(4-ChIoro-phenyl)-4-hydroxy-piperidin-l-yI]-ethyI}-6,7-dimethoxy-3,4-dihydro- l//-isoquinolin-2-y])-l-cyclohepty Imethanone l-Cycloheptyl-l-(l-{2-[4-{2-isopropoxy-phenyl)-piperidin-l-yl]-elhyl}-3,4-dihydro- 1 H-isoquinolin-2"yl)methanone l-(U(2-[4-(7-Chloro-/H-mdol-3-yl)-piperidin-l-yl]-ethyl}-3,4-(iihydro-///4soquttioUn- 2-yl)-1 -cyclopentylmethanone l-Cyclopentyl-]-(l-{2-[4-(2,3-dihydro-benzoiuran-7-yl)-piperidm-I-yl]-ethyI)-3,4-dihydro- I/f-isoquinolin-2-yI)iiethanone l-(I-(2-[4-(2,3-Dihydro-benzofiiran-7-yl)-pjperidin-l-yl]-elhyl}-3,4-dihydro- l//-isoquinolin-2-yl)-l~{4-fluoro-phenyl)methanone N-[ I - {2-[2-( 1 -Cycioheptyi-methanoyl)-6,7-diinethoxy-1,2,3,4-tetrahydro-isoquinolin-1 -yl]- ethyl}-4-(3-fluoro-phenyl)-piperidin-4-yl3-acetainide 1 -(4-Fluoro-pheny\)-l - f l-12-(4-phenyl-piperidin-l -yl)-ethy(]-3,4-d\hydro-iH-isoquinolm- 2-yiJmethanone l-(l-{2"[4-(6-Chloro-///-indo1-3-yl)-piperidin-l-yi]-ethylf-3.4-dihydro- ///-isoquinolin-2-yl)-l-(4-fluoro-phenyI)methanone l-(4-FIuoro-phenyl)-I'(l"{2-[4-(3-fluoro-phenyl)-piperidin-i-ylj-ethyi)-3,4-diiiydro- IH'isoqai nol i n-2-yl)inethanone ]-CycIoheptyl-l-{i-[spiro[2,3-dihydro-V/f-indoI-3,4'-piperidin-r-yl]ethyI]-3,4-4Jhydro- 6,7-dimethoxy-y7?-isoquinolin-2-yl}methanone N-(l-{2-[2-(l-Cyc!opentyl-methanoyl)-l,2,3,4-tetrahydro-isoquinoiin-l-yl]-elhyl}- 4-phenyl-piperidin-4-yl)acetamide l-(l-{2'[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-piperidin-l-yl]-cthyl}-3,4-dihydro- lH-i8oquiiiohn-2-yl>-\-(2-fluoro-phenyI>methanone 1-cycioheptyl-1-(1 - {2-[spiro[isobenzofuran-l (3H),4'-piperi,dine-r-yl]-ethyl}-3,4Mlihydro- 6,7-i3imethoxy-y//-isoquinolin-2-yl)niethanone I-{2-[2-(]-Cyclopentyl-methanoyI)-1.2,3,4-tctrahydro-isoquinoliii-l-yl]-ethyl}-4-phenyl- piperidine-4'-carboxyIic acid ethyl ester l-(l-{2-[4-(4-Dimethylammo-phenyl)-piperidin-l-yI]-ediyI}-3,4-dihydro-//f-isoquinolin- 2-yl)-l-(4-fIuoro-phenyI)methmione l-CycIopentyl-I-(l-{2-[4-(4-isopropyI-phenyl)-piperidin-I-yl]-ethyl}-3,4-dihydro- /f/-isoquino)in-2-yl)methanone l'[l-(2-{2-[l-(4-Flvioro-pheny[)-methMioyll-l,2,3,4-telrahydro-isoquinol!n-l-yl}-ethyt)- 4-ph6iiyl-piperidii\-4-yl]cthanone l-Il-(2-{2-[l-(2-F5uoro-phenyl)-raethanoyl]-l,2,3,4-tetrahydro-isoq«inolin-l-yl}-ethyl)- 4-phenyl-piperidin-4-yl]eIhanone 1 -[ 1 -(2- {2-[ 1 -(2-Pluoro-phenyl)-methanoyl]- 1,2,3,4-tetrahydro-isoqumoIm-l -yl} -ethyl)- 4-phenyI-pip6ridin-4-yl]-1 -piperidin-1 -yl-methanone [ -Cyclopentyi-1 - {I -[2-(4-phenyl-pipertdin-1 -yI)-ethyl]-3,4-dihydro-i//-isoquinolin- 2-yl}melhanone I -(2-FluorophenyI)-1 -(I - {2-[6-fluorospiro[isobenMfiiran-1 (3H),4'-piperidine-1 '-yH-ethy!} - 3,4-dihydco-6,7-dimethoxy-/A'^-isoquinolin-2-yl)methanone l-(4-F!uoro-pUeny!)-!-(\-(2-[5,6-difluorospito[ben2ofurai\-l(3H),4'-piperidine-r-yl]- ety)yli-3,4-dihydro-!H-isoquinolin-2'yl)-methanone l-(4-Fluorophenyl)-l-({2-[6-fluoro^iro[ben2ofuran-U3H),4'-piperidine-r-yl]-ethyl)- 3,4-di hydro-1 H-isoquinoI iii-2-yl)methanone 3,3-DimethyI-[l-{2-[sp!ro(5-fluor-ben2oiuran-2//-3,4'-piperidine-r-yI)-]ethyl}- 3,4-dihydro-l>/-isoqumoiine-2-y]]-butan-l-otie Cyclohexyi-[I-{2-[spiro(5-fluor-ben2ofuran-2H-3,4'-piperidme-I'-yI)-]ethyl}-3,4-dihydro- IH-isoquinoIme-2-yl]-meIhanone CyclohexyH 1' {2-[spiro(5-metliyI-isobenzofliran-3W-1,4'-piperidine-r-yl)-]ethyl}- 3,4-dihydro-l//-isoquinoIin-2-yl)-niethanonc Cyclohexyl-[l-{2-{spiro(benzoftiran-3H-l,4'-piperid!ne-l'-yJ)-] ethyl)-3.4-dihydro- lH-isoquinoline-2-yi]-methanone Cyclohexyl-(l-{2-[4-(2-methyl-li/-indoI-3-yI)-piperidin-l-yt]-ethyl}-3,4-dihydro- 1 H-isciquinolin-2-y i)-methanone N-{l-[2-(2-CycIohexanecarbonyl-l,2,3,4-tctrahydro-isoquinoIin-l-yl)-ethyl]-4-phenyl- piperidin-4-yl} -acetamide 3,3-Dimethy!-l-(l-(2-[4-(3-tri,fluorQmeavy!-pheny!)-piperidin-l-yI]-ethyl}-3,4-dihydro- l//-isoqu!no]in-2-yl)-butan-l-one Cyclohexyl-(l-{2-[4-(3-trifluoromethyl-phenyl)-piperidin-I-yl]-ethyl}-3,4-dihydro- I/r-isoquinoIin-2-yl)-methanone Cyclohexyl-(l-{2-[4-(4-dimethylamino-phenyl)-piperid!ii-I-yIJ-ethyl}-3,4-dihydro- l//-isoquinolin-2-yl)-methanone 3-Phenyl-[l-{2-[spiro(5-fluor-benzoftiran-2H-3,4'-piperidiiie-r-yl)-]ethyI}-3,4-dihydro- lH-isoquinoline-2-ylj-propanone (l-{2-[4-(4-Chloro-3-trinuoromethyl-pheKyl)-4-hydroxy-piperidin-l-y]]'e£hyl}- 6,7-dimethoxy-3,4-dihydro-l//-isoqumolin-2-yl)-cyclohexyI-methanone 2--Phenoxy-[l-{2-[spiro(5-f]uor-beiizofuran-2H-3,4'-piperidine-r-yl)-]ethyl)-3,4-dihydro- lH-isoquinoline-2-yl]-ethan-l-one Benzo[I,2,5]oxadia2oI-5-y]-(l-{2-[spiro(5-methyl-isobenzoftiran-3H-I,4'-piperidine- r-y])-]ethyI}-3,4-dihydro-IH-isoquinolin-2-yl)-methanone Cyclohexyl-(l - 12-[4-(4-isopropyl-phenyl)-piperidin-l -yl]-elhyl) -3,4-dihydTo- ]//-isoquinolin-2-yI)-methanone 2-PropyI-[l-{2-[spiro{5-fiuor-benzofuran-2H-3,4'-piperidine-r-ylHethyl}-3,4-dihydro- lH-isoquinoline-2-ylJ-peiitaii-l-one 2,2-Diniethyl-3-chlor-[;i-{2-[spiro(5-fluor-benzofttran-2H-3,4'-piperidine-r-yl)-]ethyl}- 3,4-dihydro-lH-isoquinoline-2-yl]-propan-]-one Cyclohexyl-(l-{2-[4-(2,3-c!ihydro-benzofuran-7-yI)-piperidin-l-yl]-^hyl}-3,4-dihydro- l//-isoquinolin-2-yl)-methanone 3,3-DiniethyI-(l-{2-[spiro(5-inethyl-isobenzoftiran-3H-l,4'-piperidine-l'-yl)-]ethyI}- 3,4-dihydrQ-1 H-isoquinoUn-2-yi)-butan- 1-one B6nzo[!,2,5]oxadiazoi-5-yl-(l-{2-[4-(3-trifluoromcthyl-phenyI)-piperidin-l-yl]-ethyi}- 3,4-dihydro- lff-iaoquinolm-2-yl)-methanone 2-Ethyl-l-(V-{2-l4-(3-trifluoTOmethyl-f*enyl)-ptp6ridin-l-ylJ-ethyl}-3,4-dihydro- l//-isoquinolin-2-yl)-bman-l-one 2-Benzyioxy-(l-{2-[spiro(5-inethyl-isobenzofiiran-3H-I,4'-piperidine-r-yl)-]ethyl)- 3,4-dihydro-lH-isoquinolm-2-yI)-ethan-l-one Benzo[l,2,5]oxadiazo!-5-yl-[l-{2-|;spiro(5-fluor-ben2oiuran-2H-3,4'-piperidine-]'-yI)]- ethyl)-3,4-dihydro-lH-isoquinoline-2-yI]-nielhanone (l-{2-(4-(4-Chloro-phenyl)-piperidin-l-yll-ethyl}-3,4-dihydro-l//-isoqmnolin-2-yl)- cyclohexyl-methanone l-(l-{2-[4-(4-Chloro-pfaenyi)-piperidiri-l-yl]-etiiyl}-3,4-dihydro-lH-isoquinoliii-2-yi)- 3,3 -dimethyl-butan-1 -one 3.5,5-Trimethyl-[ 1 - t2-[spiro(5-fluor-ben2ofijran-2H-3,4'-piperidine- i '-yl)-] ethyl} - 3,4-dihydro-1 H-isoquinoline-2-yl]-h6xan-1 -one 3,5,5-TrirnethyI-(I-{2-i;spiro(5-niethy^isobenzofliran-3H-l,4'-piperidine-r-yl)-]ethyl}- 3,4-dihydro-lH-isoquinolin-2-yI)-hexan-l-one 2-Phenoxy-(l-{2-[spito(5-methyl-isobeiizofiiran-3H-l,4'-piperidine-r-ylHe(hylJ- 3,4-dihydro-lH'isoqumolm-2-yl)-ethan-l-one (l-{2-[4-(4-Chioro-pheayl)-piperidin-l-yl]-e(hyl}-3,4-dihydro-lH-isoquinolm-2-yl)- (2,2-dichloro-cyclopropyl)-methanone 2-BenzyIoxy-[ 1 -{2-[spiro(5-fluor-benzofuran-2H-3,4'-piperidine-1 '-yl)-] ethyl}- 3,4-dihydro-IH-isoquinoline-2-yl]-ethan-l-one I -(1- {2-[4-(4-Ch!oro-3-trifluoromelhyl-phenyl)-4-hydroxy-piperidin-l -yl]-ethyl} - 6,7-dimethoxy-3,4-dihydro-lH-isoquinolin-2-yl)-3,3-dimethyl-butan-l-one l-(l-{2-[4-(2,3-Dihydro-ben2oftiran-7-yl)-piperidin-l-yl]-elhyl}-3,4-dihydro- IH-isoquinolin-2-yt)-3,3-dimethyl-butan-l-one 3,5,5-TrimethyM-(l-{2-[4-(3-trifIuoromethyI-phenyl}-piperidm-l-yl]-ethyI}-3,4-dihydro- I H-isDquinoliii-2-y!)-hexan-1 -one 2,2-Dimelhyl-[l-{2-Ispiro(5-fluor-benzofi]ran"2H-3.4'-piperidine-r-yI)-]etbyl}- 3,4-dihydro-1 H-isoquinoline-2-yl]-propan-1 -one 3-CyclohexyH-{l-{2-[4-(3-trifluoromethyl-phenyl)-pipecidin-l'yl]-ethylJ-3,4-d!hydro- lH-isoquinoiin-2-yl)-propan-l-one Furan-2-yl-[l'{2-[spiro(5-fluor-benzofuran-2H-3,4'-piperidine-l'-yl>] ethyl}-3,4-dihydro- I H-isoquinoline-2-y!] -methanone N-(4-Phenyl-l-{2-[2-(3,5,5-trimethyl-hexanoyl)-l,2,3,4-tetrahydro-isoquino!in-l-yl]- cthyl)-piperidm-4-yI)-acetamide Qumoxalin-2-y!-[l-{2-[spiro(5-fluor-bcn2ofiiran-2H-3,4'-piperidine-r-yl)-]ethyI}- 3,4-d\hydro-1 H-isoquinoline-2-ylJ-methanORe 3-CyclohexyI-[l-{2-[spiro(5-fluor-benzofiiran-2H-3,4'-piperidine-r-y!)-]ethyi}- 3,4-dihydro-lH-isoquinoUne-2-yl]-propan-l-one Benzo[l,2,5]oxadiazoI-5-yl-(I-{2-[4-(2,3-dihydro-benzofuran-7-yl)-piperidin-l-yl]-ethyl}- 3,4-dihydro-lH-isoquinolin-2-yi)-methanone Benzo[ 1,2,5]oxadiazol-5-yl-( I - {2-[4-(2-methyI-1 H-indol-3-yI)-piperidm-1 -yl]-ethyl} - 3,4-dihydro-lH-isoquinolin-2-yl)-niethanone (Tetrahydro-pyran-4-yO-(l-{2-[4-(3-trifluoroinethyl-pheny])-piperidin-l-yI)-ethyJ}- 3,4-d ihydro-1 H-isoquinolin-2'y!)-methanone 2-Propyl-l'(l-(2-[4-(3-trifluoromethyl-phenyl)-piperidin-l-yll-ethyl}-3,4-dihydro- IH-isoquinolin-2-yl)-pentaii-l-one 2-Ethyi-[l-{2-[spiT0(5-fluor-benzofuraii-2H-3,4'-piperidme-r-yl)-]ethylJ-3,4-dihydro- iH-isoquino)ine-2-yl]-butan-l-one 3-Pheny!-1 -(1 - {2-[4-(3-frifliioromethyI-phenyI)-piperidin-1 -yl]-ethyl} -3,4-dihydro- 1H-isoquinoIin-2-yl)-propan-l-one 3,3-DimelhyM-{l-{2-[4-(2-methyl-IH-indoi-3-yi)-piperidin-l-yI]-ethyI}-3,4-dihydro- I H-isoqutnoIin-2-yI)-butan-l -one (l-{2-[4-(4-Chloro-3-trifluoromethy!-phetiyi)-4-hydroxy-piperidm-I-yI]-ethyl}- 6,7-dimethoxy-3,4-dihydro-lH-isoquinolin-2-yI)-(2,2-dichloro-cyclopropyl)-methanone l,2,3,4-tetrahydro-naphthalen6-2-y]-{l-{2-[spiro(5-methyl-isobenzofiiran- 3H-l,4'-piperidine-l'-yi)-]etyiyl}-3,4-dihydro-lH-isoquii\olin-2-yl)-inethanone (4-Melhyisulfanyi-pheny])-{l-{2-[4-(3-trifluoromethyl-phenyl)-piperidin-l-yl]-ethyl}- 3,4-dihydro-lH-isoquinolin-2-yl)-methanone 3,5,5-Triniethyl-l-(l-{2-[4-(2-methyI-lH-indoi-3-yl)-piperidin-l-yI]-ethyI}-3,4-dihydro- !H-isoquinolin-2-yl)-hexan-l-one 3-Phenyl-(l-{2-Espiro(5-methyI-isoben2ofuran-3H-l,4'-piperidine-r-yl)-]ethyl}- 3,4-dihydro-lH-isoquinolin-2-yl)-propan-l-one Furan-2-yi-(l-{2-[4-(3'Irifluoromethyi-phenyI)-piperidin-!-yl]-ethyl}-3,4-dihydro- IH-isoquinoIin-2-yl)-methanone 2-BenzyIoxy-I-(l-(2-[4-(2-methyl-IH-indol-3-yI)-piperidin-l-yI]-ethyl}-3,4-dihydro- I H-isoquinoIin'2-yl)-ethanone l-(l-{2-(4-(4-ClilorQ-phenyl)-pipe[idin-l-yl]-ethyl}-3,4-dihy 2-phenoxy-ethanone Quinoxalm-2-yI-(l-{2-[spiro(5-meUiyl-isobenzofuran-3H-l,4'-piperidine-l'-yl)-]ethyl)- 3,4-dihydro-iH-isoquinolin-2-yl)-methanone 2,2-DimethyI-l -(1 - {2-[4-(3-trifluoromelhyl-pheny0-piperidin-1 -yl]-ethyl} -3,4-dihydro- lH-isoqumoIin-2-y!)-propan-I-one (2,2-Dichloro-cycloprapyl)-(l-{2-[4-(3-trifluoromethyl-phenyl)-piperidin-I-yl]-ethyl}- 3,4-dihydro- i H-isoquinolin-2-yl)-melhanorie 4-Methylsulfany1-phenyI-Cl-{2-[spiro(5-methyI-isoben2ofuran-3H'l,4'-piperidine- I '-yl))ethyl} -3,4-dihydro-l H-isoquinolin-2-yi)-methaiione (2,2-Dichloro-cyclopropyl)-(l-{2-[4-(2^-dihydro-beii2ofiiran-7-yl)-piperidin-l-yI]-ethyl}- 3,4-dihydro-lH-isoqumolin-2-yl)-methanone l-(l-{2-i4-C4-lsopropyl-pheny\)-piperidm-5-yl]'elhyl)-3,4-dihydro-lH-isoquinolm-2-yl)- 3,5,5-lrimethyl-hexan-l -one 2,2-Dichloro-cyclopropyI-{l-{2-[spiro(isobenzoiuran-3H-I,4'-piperidine-r-yI)-]ethyl}- 3,4-dihydro-lH-isoquinoUn-2-yl)-methanone N-(4-Phenyl-l-{2-[2-(l,2,3,4-tetrahydro-naphthalene-2-carbonyI)-l^,3,4-telrahydro- isoquinolin-l-yij-ethyi}-piperidin-4-yl)-acetamide B6n2o[l,2,5]oxadiazol-5-yl-{I-{2-[4-(4-chloro-pheny!)-piperidin-l-yl]-ethyl}-3,4-dihydro- 1 H-isoquinolin-2-yl)-n]ethanone N-(l-{2-t2-(3,3-Ditnethy!-bulyryl)-l,2,3,4-tetrahydro-isoqumoUn-l-yl]-ethyl}-4-phenyl- piperidin-4-yi>-acBtaroide 3-Chloro-2,2-dimethy5-l-(l-{2-[4-(3-lrifluoromethyl-phenyl)-piperidin-l-yl]-ethyl>- 3,4-diliydro-lH-isoquinoIin-2-yl)-propan-l-one Tetrahydro-pyran-4-yl-[I-{2-[spiro{5-fluor-beiizoluran-2H-3,4'-piperidine-I'-yI)-]ethyl}- 3,4-dihydro-lH-tsoquinoline-2-yI]-butan-i-one l-(l-{2-[4-(5-Fluoro-//^-indol-3-yl)-piperidin-l-yl]-ethyl}-5-chIorO'3,4"dihydro- /W-isoquinoIin-2-yl)-I-(4-fluoro-phenyl)niethanone, l-Cyclopentyl-l-(l-{2-[4-(5-iluoro-///-indol-3-yl)-piperidin-l-yI]-ethyl}-5-chloro- 3,4-dihydro-y//-isoquino]in-2-yl)methanone, l-CycSopentyS-l"(l-{2-[6-fluOTospiro[isobenzofiiTaii"l(3K),4'-piperidine-i'-yl]-ethyl)- 5-Chloro-3,4-dihydro-/i/-isoquinolm-2-yI)methanone, l-(4-F]uorophenyl)-l-(l-{2-[6-fluorospiro[isobenzofuran-l(3H),4'-piperidine-r-yI]-ethyI}- 5-chioro-3,4-di hydro- / /f-isoquino!in-2-y l)methanone, I-CycIopentyl-I-{l-{2-[6-trifluoroinethy!spiro[i5obenzofiiran-l(3H),4'-piperidine-r-yl]- ethyI}-5-chloro-3,4-dihydro-/W-isoquinolin-2-yl)methanone, l-(4-FIuorophenyl)-l-(l-{2-[6-trifluoromethyfspiro[isobenzoftiran-l(3H),4'-piperidine' r-yi]-ethyI}-5-chIoro-3,4-dihydro-yW'isoquinolin-2-yl)methanone, N-[l- {2-[2-(l -Cyclopentyi-methanoyi)-1,2,3,4-tetrahydro-isoquinolin-1 -y]]-ethyl} - 4-(3-fiuorophenyl)-piperidin-4-y!]acetamide, A'-[l-{2-|;2-(l-(4-Fiuorophenyl)-methanoy!)-l,2,3,4-tetrahydro-is(Kiuinoiin-l-y[]-ethyl>- 4-(3-fIuorophenyl)-piperidin-4-yI]acetamide, A'-[l-{2-[2-Cl-Cyclopentyl-methanoyl)-i,2,3,4-tctrahydro-isoquinolin-I-yI]-ethyI}- 4-pheny!piperidin-4-y]Jacetamide, W-[l-{2-[2-{l-(4-Fluoropheny]>-methanoyl)-l,2,3,4-tetrahydro-isoquinolin-l-yl]-ethyl)- 4-phenyipiperidin-4-yl}acetaniide, l-Cyclopentyl-]-{l-[I-acetyI-spiro[2,3-dihydro-y//-indoI-3,4'-piperidin-r-yl]ethylj- 5-chloro-3,4-dihydro-/H-isoquinolin-2-yl}melhanoiie, I -(4-Fluorophenyl)-1 - {1 -[1 -acetyl-spiro[2,3-dihydro-/^-mdol-3,4'-piperidin-r-yl]ethyl]- 5-chloro-3,4-dihydro-///-isoquinolin-2-yI}methanone, l-Cyclopentyl-l-{l-[l-a(^etyi-spiro[2,3-dihydio-5-fiuoto /H-mdoI-3,4'-piperidin-r-yl]- ethylI-5-chloro-3,4-dihydro-/W-isoquinoiin-2-yl}niethanone, 1 -(4'Fluorophenyl)-1 - {I -[ 1 -acetyl-spiro[2,3-dihydro-5-fIuoro-/^-indol-3,4'-piperidin- l'-yllethyl]-5-ch[oro-3,4-dihydro-/W-isoqumoUn-2-yl}methanone, l-Cyciopentyl-l-(l-{2-[4-(3-trifluoromethylphenyI)-piperidin-l-y!]-elhyl}-5-chIoro- 3,4-d i hydro- //:^-isoqui noIin-2-yl)methanone, l-(4-Fluorophenyl)-l-(l-{2-[4-(3-trifluot:ontethylphenyl)-piperidin-l'yl]-ethyl}-5-chIoro- 3,4-d ihydro- y//-isoquinol in-2-yl)methanone, l-(l-{2-[4-(6-FIuoroben2o[d]isoxazol-3-yl)'piperidin-l-yl]-ethyl}-5-chloro-3,4-dihydro- /i/-isoquinolin-2-yi)'i-(4-fluorophenyl)methanone. t-(l>{2-[4-(6-FI«orobenzo[dlisQxa2ol-3-yl)-piperidm-l-yl]-ethyli-5-cWoro-3,4-dihydro- 7tf-isoquinoiin-2-yI)-1 -{cyclopentyI)methanone, l-(4-Fluorophenyi)-l-{l-{2-[5,6-difluorospiro[benzofiiran-l(3H),4'-piperidine-r'yl]-ethyI}- 5'Chioro-3,4-dihydro-/H-isoquJnoIin-2-yl)-methanone, l-(4-FluorophenyI)-1 -{{2-[6-fluoro5piro[benzofiiran-1 (3H),4'-piperidinc-1 '-ylj-ethyl) - 5-chloro-3,4-dihydro-/W-isoquinolin-2-yl)methanone, l-Cyclopentyl-l- 5-chloro-3,4-dihydro-/JV-isoquinolin-2-yI)-niethanone, I -CyclopentyM -( {2-[6-fluorospiro[benzofuran-l(3H),4'-piperidine-! '-ylj-ethyl) - 5-ch Ior'o-3,4-dihydro-yfl'-isoquinolin-2-yl)methanone, l-(l-{2-[4-(5-Fluoro-//^-indol-3-yI3-piperidin-l-yij-elhy]}-3,4-dihydro-5-fluoro- //f-isoquinolin-2-yl)-!-(4-fluoro-phenyl)methanone, l-Cyclopentyl-l-(l-{2-[4-(5-fluoro-JH-indol-3'yl)-piperidm-l-yi]-ethyI}-3,4-dihydro- 5 - ft uoro- 7 //-isoquina lia-2-y l)methanone, l-CycIopentyI-I-(I-(2-[6-fluorospiro[isobenzofuran'l(3HX4'-piperidine-r-yI]-ethyI}- 3,4-dihydro-5-fiuoro-7//-isoqmnol in-2-y I)methanone, l-(4-Fiuorophenyi)-l-(l-{2-|;6-fluorospiro[isobenzofuran-l(3H),4'-piperidine-r-yl]-6thyl}- 3,4-d!hydro-5-f!uoro-///-isoquinolin-2-yl)methanone, l-Cyclopentyl-l-(l-{2-l6-trifluoromethylspiro[isobenzofuran-l(3H),4'-piperidine-V-yi]- e(hyU-3,4-dihydro-5-fluoro-/H-isoquinolm-2-yl)tnethanone, l-(4-FJuorophenyI)-l-(l-{2-[6-trifluoromethyispiro[isobenzoftiran-l(3H),4'-piperidine- r-yl]elhy!}-3,4-dihydro-5-fluoro-y//-isoquinoliii-2-y!)methanone, N'l 1 - {2-[2-( 1 -Cyclopentyi-methanoy])-1,2,3,4-tetrahydro-isoquinoim-1 -ylj-ethyl} - 4-(3-fIuorophenyl)-piperidiii-4-yl]acetamide, A'-[l-(2-[2-(l-{4-Fluorophenyl)-melh3noyl)-l,2,3,4-telrahydro-isoquinolin-l-yl]-ethyI}- 4-(3-nuorophenyl)-piperidin-4-yl]acetamide, W-[l-{2-[2 4"phenyIpiperidin-4-yl]acetamide. A'-[l-{2-[2-(l-(4-Fluorophenyl)-methanoy!)-l,2,3,4-telrahydro-isoquinolin-l-yl]-ethyl}- 4-plienylpiperidin-4-yl]acelamide, l-Cyclopentyl-l-{l-[l-acetyl-spiro[2,3-dihydro-//f-indoI-3,4'-piperidin-r-yl]ethyl]- 3,4-dihydro-5-fluoro-iH-isoqmnolin-2-yl}methanone, l-(4-FIuorophenyl)-l-{l-[I-acetyl-spiro[2,3-dihydro-7/^-indo]-3,4'-piperidin-r-yl]ethyI]-3,4-dihydro-5-fluoro-///-isoquinolin-2-yl)methanone, l-Cyclopentyl-][-{l-|l-acetyl-spiro[2,3-dihydro-5-fluoro JH-indo]-3,4'-piperidin-l'-yl]-ethyi]-3,4-dihydro-5-fluo^o-/W-isoquinoljn-2-yl)nlethano^e, ]-(4-Fluorophenyi)-l-(l-[l-acetyf-spiro[2,3-dihydro-5-fluoro-///-indoI-3,4'-piperidin-r-yllethyl]-3,4-dihydro-5 -fluoro- / H-isoquinolin -2-y l}methanone, I-Cyclopentyl-I-(l-{2-[4-(3-trifluoromethylphenyl)-piperidiii-l-yl]-ethyl}-3,4-dihydro-5-fluoro-/ff-Jsoquinolin-2-yl)methanone, l-(4-Fluorophenyl)-l-(l-{2-[4-(3-trifluoromethyIphenyl)-piperidin-l-yl]-ethyll-3,4-dihydro-5-fIuoro-//ir-isoquinolin-2-yl)niethanone, l-(l-{2-[4-(6-Fluorobenzo[d]isoxazoI-3-yI)-piperidin-I-yl]-ethyI}-3,4-dihydro-5-fluoro-7//-isociuinolin-2-yt)-l-(4-fluorophenyl)methanone, l-{I-{2-[4-(6-FIuorob6nzo[d]isoxazo!-3-yl)-piperidin-1-yl]-efhyl}-3,4-dihydro-5-fluoro-/H-isoquinoIin-2-yl)-!-(cyclopenty!)methanone, l-(4-Fluoropheny!)-l-(l-{2-I5,6-difluorospiro[beii2ofuran-](3H),4'-piperidine-r-yl]-ethyi}-3,4-dihydro-5-fiuoro-///-isoquinolin-2-yj)-methanone, l-{4-Fluorophenyl)-l-({2-16-fluorospiro[benzoftjran-I(3H),4'-piperidine-r-yI]-eaiyl}-3,4-dihydro-5-fl uoro- ///-isoqu inolin-2-yI)methaiione, l-Cyc!opentyl-l-(l-{2-[5,6-difluorospiro[benzoftiran-l(3H),4'-piperidine-r-yi]-ethyl}-3,4-dihydro-5-fIuoro-i//-isoquinoliii-2-yl)-met}ianone, l-CyclopentyI-l-({2-[6-fluorospiro[benzoftiran-l(3H),4'-piperidine-r-yl]-elhyl}-3,4-dihydro-5-fluoro-7//-isoquinolin-2-yl)methanone, l-(\-{2-[4-(5-Fluoro-J/f-indoI-3-yl)'piperidm-l-yl]-elhyl}-5,6-dichloro-3,4-dihydro-7//-isoquinolin-2-yI)-!-(4-f]uoro-phenyI)methanone, l-Cyclopentyl-i-(I-{2-[4-{5-fluoro-;//-indol-3-yi)-piperidm-l-yl]-ethyl}-5,6-dichloro-3,4'dihydro-///-isoquinolin-2-yi)methanone, l-CyclopeiityI-l-(l-{2-[6-fiuoraspiro[isobenzofiiran-l(3H),4'-ptperidine-r-yi]-ethyl)-5,6-dichloro-3,4-dihydro-7^-isoquinoUn-2-yl)meIhanone, l-(4-FluoTOpheny!)-l-(l-{2-[6-fluorospii:o[isobenzofuran-l(3H),4'-piperidine-l'-yl]-ethylJ-5,6-dichloro-3,4-dihydro-///-isoquinolin-2-yl)niethaione, l-Cyclopentyl-l-(l-{2-[6-trifluoromethylspiro[isaben2ofuran-l(3H),4'-piperidine-r-yl]-ethyl} ~5,6-dichlorQ-3,4-dihydro- ///-isoqumolin-2-yl)methanone. 1 -(4-FIuorophenyl)-1 -(1 - {2-E6-trifluoromethylspiro[isobenzofuran-l (3H),4'-piperidiiie- r-yl]ethyI}-5,6-dichIoro-3,4-dihydro-7//'isoquinolin-2-yl)methanon6, Af-[l-{2-i;2-{l-Cyclopentyi-methanoyl)-l,2,3,4-tetrahydro-tsoquinolin-l-yl]-ethyl}- 4-(3-fluorophenyl)-piperidin-4-yl]acetamide, ?V^[l-{2-[2-(l-(4-Fliiorophetiyl)-methaiioyl)-l,2,3,4-tetrahydra-i60quinolin-l-y!]-^hyI}- 4-(3-fluorophenyl)-piperidin-4-yl]acetam!de, A'-[ I' {2-[2-( 1 -Cyclopentyl-methanoyi)-1,2,3,4-tetrahydro-isoquinolin-1 -yl]-ethyl} - 4-phenyipiperidin-4-yl]acetamide, A^-[l-{2-[2-(l-(4-Fluorophenyl)-methanoyl)-I,2,3,4-tetrahydro-isoquinoIin-l-yi]-ethyl}- 4-phenylpiperjdin-4-yl ]acetamide, l-Cyclopentyl-I-{I-fl-acetyl-spiro[2,3-dihydro-///^-mdol-3,4'-piperidin-l'-yl]ethylj- 5,6-dichloro-3,4-dihydro-y^-isoquinoIin- 2-yif methanone, l-(4-Fluofophenyl)-l-{l-[l-acetyl-spiro(2,3-ditiydro-/H-indol-3,4'-piperidin-r-yl]ethyl]- 5,6-dichloro-3,4-dihydro-i H-isoquinolin-2-yl} methanone, l-Cyclop^ityM-{l-[1-acetyl-spiro[2,3-dihydro-5-fluoro 7H-mdol-3,4'-ptpertdm-l'-yl]- ethyl]-5i6-dichloro-3,4-dihydro-W-isoquinolin-2-yI}niethanone, 1 -(4-FIuorophenyl)' 1 - {1 -[ 1 -acetyi-spiro[2,3-d!hydro-5-fluoro-i^-indol-3,4'-piperidin- r-yI]ethyi]-5,6-dich]oro-3,4-dihydro-y/f-isoquinolin-2-yl} methanone, 1 -Cyclopentyl-1 -(1 - {2-[4-(3-trifluoromethylphenyl)-pip6ridtn-l -ylj-etfiyl) -5,6-dichlDro- 3,4-dihydro-y//-isoquinolin-2-yl)methanone, l-(4-FluorophenyJ)-l-(l-{2-|;4-(3'trif]uoroniethyIphenyI)-piperidin-l-yI]-ethyl}- 5,6-dichloro-3,4-dihydro-///'-isoquinoIin-2-yl)methanone, l-(l-{2-[4-C6-Fluorobwizo[d]isoxazoI-3-yl)-piperidm-1-yl]-ethyi}-5,6-dichloro- 3,4-dihydro-/7/-tsoquinolin-2-yl)-l-(4-fluorophenyl)methanoiie, l-U-{2-[4-(6-Fluorobenzoi;d]isoxazol-3-yI)-piperidin-l-yl]-ethyl}-S,6-dichioro- 3,4-dihydro-///'isoquinoiiti-2-yl)-l-(cyciopentyl)methanone, l-(4-FIuorophenyl)-I-(l-{2-[5,6-difluorospiro[ben2ofuran-l(3H),4'-piperidine-r-yI]-ethyl}- 5,6-dichloro-3,4-dihydro-/^-isoquinolin-2-yl)-methanon6, l-(4-FluorophenyI)-l-{{2-|;6-fluorospiro[benzoftiran-U3H),4'-piperidine-r-yI]-ethyl}- 5,6-dichloro-3,4-dihydro-///-isoquinolin-2-yl)methanone, l-CyclopentyI-l-(l-(2-[5,6-difiuorospiro[benzofuran-I(3H),4"-piperidine-I'-y]l-6thy!)- 5,6-dichloro-3,4-dihydro-y//-iaoqui noHn-2-yI)-methanone, l-Cyclopenlyl-l-({2-[6-fluorospiro[beiizoftiran-l(3H),4'-piperidine-V-yl]-elhyl}-5,6-dichloro-3,4-dihydro-///-isoquinolin-2-yI)methanone, I-(l-{2-[4-(5-FIuoro-yj^-indol-3-yt)-piperidin-l-yl]-ethyl}-5,6-difluoro-3,4-dihydTO-///-isoquinolin-2-yl)-1 -(4-fluoro-phenyl)methanone, !-Cyclopentyl-l-(l-{2-[4-(5-fluoro-/H-inctol-3-yl)-piperidin-l-yl]-ethyl}-S,6-difluoro-3,4-dihydro-y/f-isoquino!in-2-yI)methanone, I-CyclopentyI-I-(l-{2-[6-fluorospiro[isoben2ofuran-I(3H),4'-piperidine-r-yI]-ethyI}-5,6-difI«oro-3,4-dihydro-///-isoquinolin-2-yl)methanone, I-(4-Fluorophenyl)-l-(l-{2-[6-fluorospiro[isobenzofuran-l(3H),4'-piperidine-r-yl]-ethyI}-5,6-difluoro-3,4-dihydro-///^-isoquinolin-2-yI)methanone, l-CycIopentyl-l-(l-{2-[6-trifluoromethyispiro[isobenzofiiran-l(3H),4'-piperidine-r-yl]-ethyl}-5,6-difluoro-3,4-dihydro-i/f-isoqumoiin-2-yl)inethanone, l-(4-FIuorophenyI)-l-(l-{2-[6-lrifluoromelhyispiro[isobenzofuran-l(3H),4'-piperidine-r-yl]ethyl}-5,6-difluoro-3,4-dihydro-//f-isoquinolJ!i-2-yl)methanone, N-[ 1 - {2-[2-(l -Cyclopentyl-methanoyi)-1,2,3,4-tetrahydro-isoquiiioIin-1 -yl]-ethy]} -4-(3-fluocoph«\yt)-pipcridin-4-yl'lacetamide, A/-[I-(2-[2-(l-(4-Fluorophenyl>niethanoyl)-l,2,3,4-tetrahydro-isoquinoHn-]-yI]-ethyl)-4-(3-fluorophenyl)-piperidin-4-yl]acetainide, A'-[l-{2-l2-(l-Cyclopentyl-methanoyl)-l,23,4-tetrahydro-isoquinolin-I-yl]-ethy]}-4-pheny]piperidin-4-yl]acetamide, A'-[l-{2-[2-(I-(4-FIuorophenyl)-methanoyl)-l,2,3,4-l6trahydro-isoquinolin-I-yl]-e(hyl}-4-phenylpiperidin-4-yl]acetamide, 1 -Cyclopenlyl-] -{1 -[1 -acelyl-spiro[2,3-dihydro-JH-i^do^-3,4'-piperidin-^-yl]ethyl]-5,6-diftuoro-3,4-dihyd^o-///-isoquinoli^-2-yI}ltlethanone, l-(4-Fluorophenyl)-l-(141-acetyl-spiro[2,3-dihydro-/H-indol-3,4'-piperidin-r-yl3ethyl]-5,6-difluoro-3,4-dihydro-///-isoquinolin-2-yl}inethanone, i-Cyclopentyl-l-{\-[I-acetyl-spJro[2,3-dihydro-S-{luoFo iH-iiidol-3,4'-piperidiii-1 '-ylj-ethyl]-5.6-difluoro-3,4-dihydro-/^-isoquinolin-2-yl}methanone, I-(4-FluorophenyI)-I-{l-[]-acetyI-spiro[2,3-dihydro-5-fluoro-7//-indoI'3,4'-piperidin-r-yI]ethylj-5,6-difluoro-3,4-dihydro-y//-isoquinofin-2-yi}methanone, l-Cyclop«ityl-l-(I-(2-[4-(3-trifluoroinethylphenyl)-piperidin-l-yl]-ethyl}-5,6-difluoro-3,4-di hydro-///-isoquinolin-2-yl)methanone, l-{4-Fluorophenyl)-l-(l-{2-[4-(3-trifluoromcthylph6nyI)-piperidin-l-yO-etbyl}- S,6-difliioTo-3,4-dihydro-iH-isoquino)in-2-yl)melhanone, l-(l-{2-[4-(6-Fluorobenzo[dl!Soxazo['3-yl)-piperictin-l-yl]-ethyl}-5,6-difluoro-3,4-dihydro- y//-isoqumoIin-2-yI)-l-(4-fluoropheoyl)methanone, i-(l-{2-[4-(6-Fluorobenzo[d]isoxazol-3-yl)-piperidin-l-yl]-ethyl}-S,6-difluoro-3,4-dihydro- ///-isoquinolin-2-yl)-l-(cyclopentyt)meEhanone, l-(4-FIuorophenyl)-l-(I-{2-[5,6-difluorospiro[benzofiiran-l(3H),4'-piperidine-r-ylJ-ethyJ}- 5,6-difluoro-3.4-dihydro-7//-isoqutnoIin-2-yl)-methanone, l-(4-F]uoroph«iyl)-I-({2-[6-fluorospiro[benzofiiran-I(3H),4'-pipcridin6-r-yl]-ethyl}- 5,6-difluoro-3,4-dihydro-JW-i soquinoiin-2-y!)methanone, l-Cyc[opetity[-l-(l-{2-[5,6-difluorospiro[bwi2ofuran-l(3H),4'-piperidine-l'-yI]-ethyl}- 5,6-difluoro-3,4-dihydro-7//-isoquinolin-2-yi)-melhanone, and l-Cyclopenty!-l-({2-[6-fluorospiro[benzofuran-l(3H),4'-piperidine-r-yl]-ethyl}- 5,6-difluoro-3,4-dihydro-///-isoquinolin-2-yI)methanone. or from the group comprising the following enantiomers which are prepared by acylation of Enantiomer 2 of the corresponding amines of formula V, wherein R^-R^ and Q are as defined for formula I; and Enantiomer 2 is the slo^wly eluting of the enantiomer pair by supercritical HPLC at 2QMp3 on a system comprising chiralcelOD columns and an eluent consisting of carbondioxide(75%), 2-propanol(24.75%), diethylamine(0.125%) and trifluoracetic acid{0.125%): N-(4-(3-Fluoro-phenyI)-l-{2-[2-(2-methoxy-benzoyl>l,2,3,4-tetrahydro-isoquinoiin-l-yl]- ethyl}'piperidin-4-yl)acetamide(Enantiomer) N-(4-(3-Fluoro-phenyl)-l-{2-[2-(2-inethoxy-benzoyI)-l,2,3,4-(etrahydro-isoquinolin-l-yl]- ethyl}-piperidin-4-yl)acetamide{Enantiomer) N-[l-{2-[2-(4-Chloro-beiizoyI)-l,2,3,4-tetrahydro-isoquinolin-l-yl]-ethyI}-4-(3-fIuoro- phenyl)-piperidin-4-yl]-a£etamide(E[iantiom«:) N-[l-(2-[2-(4-Bromo-benzoyl)-l,2,3,4-tetrahydro-isoquinolin-l-yl]-ethyI}-4-(3-fluoro- phcnyl)-p!peridin-4-yl]-acetamide(Enantiomer) N-|;i-{2-[2-(4-Fluoro-benzoyl)-l,2,3,4-tetrahydro-isoqiiinolio-I-yl]-ethyl}-4-(3-fluoro- phenyl)-piperidin-4-yl]-acetamide (Enantiomer) N-(4-(3-Fluoro~phenyI)-I-{2-p-(4-isopropyI-benzoyl)-I,2,3,4-tetrahydn>-isoquinolin-l-yl]- ethyl) -piperid!n-4-yl)acetamide (Enantiomer) N-(4-(3-Fluoro-phenyl)-l-{2-[2-{4-methy]-benzoy])-l,2,3,4-tetrahydro-isoquinolin-l-yI]- ethyl}-piperidin-4-yl)acetamide (Enantiomer) N-[l-{2-[2-(3-Chloro-benzoyl)-l,2,3,4-tetrahydro-isoquinoIin-l-yIl-ethyl}-4-(3-fluoro- plienyl)-piperidin-4-y!]-acetamide (Enantiomer) N-[l-{2-|;2-(2-BTomo-benzoyi)-l,2,3,'t-tetrahydro-isoq\iinolii\-l-yl}-ethyl>-4-(3-fluoro- phenyl)-piperidin-4-yl]-acetamide (Enantiomer) N-( I - {2-i2-(4-Bromo-benzoyl}-l ,2,3,4-tetrahydro-isoquinolin-l -yl>ethyl} -4-phenyl- piperidin-4-yl)acetainide (Enantiomer) N-(l-{2-[2-(2.4-Dichloro-benzoyl)-l,2,3,4-tetrahydro-isoquinoIin-l-yI]-ethyl}-4-phenyl- piperidin-4-yl)acetamide (Enantiomer) N-|;i-{2-[2-(2,4-Dichloro-benzoyl)-l,2.3,4-tetrahydro-isoquinolin-l-yl]-cthyl)-4-(3-fluoro- phenyt)-piperidin-4-yl]-acetamide (Enantiomer) N-[l-{2-[2-(Benzo[l,2,5]oxadiazole-5-carbonyl)-I.2,3,44etrahydro-isoquinoiin-l-yl]- ethyl}-4-(3-fiuoro-pheny!)-piperidin-4-yl]-acetamide (Enantiomer) N-(4-(3-Fluoro-phenyl)-l - {2-[2-(naphthalene-1 -carbonyl)-1,2,3,4-tetrahydro-isoquinolin-1- yl]-ethyl} -piperidin-4-yl)acetainide (Enantiomer) N-[l-t2-(2-Cyclopentanecarbonyl-l,2,3,4-tetrahydro-isoqumolin-l-yl)-ethyl]-4-(3-fluoro- phenyl)-piperidin-4-yl]-acetamide (Enantiomer) N-(l-(2-[2-(4-Chloro-benzoyl)-l,2,3,4-tetrahydro-isoquino]in-l-yl]-ethyI}-4-phenyl- piperidin-4-y i)acetam ide (Enantiomer) N-[]-{2-[2-(Benzo[b]thiophene-3-carbonyI)-I,2,3,4-tetrahydro-isoquinolin-l-ylj-ethyl}-4- (3-fluoro-phenyi)-piperidin-4-yl]-acetaiiiide(Enantiomer) N-i;i-{2-[2-(6-Fluoro-4H-ben2o[l,3}dioxine-S-cart)onyl)-l,2,3,4-tetrahydro-isoquinolm-l- yl}-ethyl}-4-(3-fluoro-phenyl>-piperidin-4-yl)acetamide(Enantioiner) N-[i-{2-[2-(3-Brorao-b€i\zoyl)-l,2,3,4-telrahydro-isoquinolm4-yl]-ethyi}-4-(3-fluoro~ phettyt)-piperLditi-4-yl]acetamide(EnanUotn.ef) N-[l-{2-i;2-(2-Fluoro-ben2oyl)-l,2,3,4-tetrahydro-isoquinolin-I-yI]-ethyll-4-(3-fl«oro- phenyI)-piperidin-4-yl]acetaniide(Enantiomer) N-(l-{2-[2-(4-Methyl-ben2oyI)-l,2,3,4-tetrahydro-isoquinoHn-l-yl]-ethyl}-4-phenyl- piperidin-4-yi)acetamide{Enaiitiom6r) N-[l'{2-[2-(2-ChIoro-benzoyI)-l,2,3,4-letrahydro-isoquinolm-l-yl]-ethyI}-4-(3-fluoro- phenyl)-piperidin-4-yl]-acetaniide(Enantiomer) N-(4-(3-Fluoro-phenyI)-1 - {2-E2-{4-methoxy-benzoyl)-l ,2,3,4-tetrahydro-isoquinolin-l -yl]- ethyl) -piperidin-4-yl)acetamide (Enantiomer) N-{l-{2-[2-(3-Chloro-ben2oyl)-l,2,3,4-tetrahydro-isoqijinolin-l-yl]-ethyl}-4-phenyl- piperidin-4-yl)acelamide (Enantiomer) N-(l-{2-[2-(4-FluoTO-benzoyl)-l,2,3,4-tetrahydro-isoquinoUii-l-yl]-^thyl)-4-phenyi- piperidin-4-yl)acetam!de (Enantiomer) N- {I -[2-(2-Cycloheptanecarbonyl-l ,2,3,4-tetrahydro-isoquino!in-l -yl)-ethyll-4-phenyl- piperidin-4-yi}-acetamide (Enantiomer) N-(l-{2-f2-(3-Bromo-benzoyi)-],2,3,4-tetrahydro-isoquinolin-l-yi]-elfayl}-4-phenyl- piperidin-4-yl)acetamide (Enantiomer) 2-N-(4-(3-Fiuoro-phenyl)-l-{2-[2-(3-methoxy-faen2oyl)-l,2,3,4-letrahydro-isoquinolin- 1 -yl]-ethyJ) -piperidin-4-y!)acetaniide (Enantiomer) N-(4-(3-F!uorO'phenyl)-l-{2-[2-(thiophene-3-carbonyi)-I,2,3,4-tetrahydro-isoquinolin- I-yi]-ethyI}-piperid[n-4-yl)acetamide (Enantiomer) N-(4-(3-F|goro-phenyl)-l-{2-[2-(4-pyra2ol-l-yl-benzoyl)-I,2,3,4-tetrahydro-isoquino!in' l-yl]-ethy]}-piperidin-4-yl)aGetamide (Enantiomer) N-(l-{2-[2-(Naphlhalene-l-carbonyl)-!,2,3,4 telrahydro-isoquinoHn-l-yl]-ethy)}-4-phenyl- piperidin-4-yl)acetamide (Enantiomer) 26. A phannaceutical composition comprising a compound of any of claims 1 to 25 in a therapeutically effective amount together with one or more pharmaceutically acceptable carriers or diluents.

Documents:

1546-chenp-2004 abstract-duplicate.pdf

1546-chenp-2004 abstract.jpg

1546-chenp-2004 abstract.pdf

1546-chenp-2004 claims-duplicate.pdf

1546-chenp-2004 claims.pdf

1546-chenp-2004 correspondence-others.pdf

1546-chenp-2004 correspondence-po.pdf

1546-chenp-2004 description (complete)-duplicate.pdf

1546-chenp-2004 description (complete).pdf

1546-chenp-2004 form-1.pdf

1546-chenp-2004 form-18.pdf

1546-chenp-2004 form-26.pdf

1546-chenp-2004 form-3.pdf

1546-chenp-2004 form-5.pdf

1546-chenp-2004 petition.pdf

1546-chenp-2004.rtf