MXPA06009652A - Azabicyclo (3.1.0) hexane derivatives useful as modulators of dopamine d3 receptors - Google Patents

Abstract

The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein G is selected from a group consisting of:phenyl, pyridyl, benzothiazolyl, indazolyl;p is an integer ranging from 0 to 5;R1 is independently selected from a group consisting of:halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl;or corresponds to a group R5;R2 is hydrogen or C1-4alkyl;R3 is C1-4alkyl;R4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or a 8- to 11-membered bicyclic group, any of which groups is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of:halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl;R5 is a moiety selected from the group consisting of:isoxazolyl, -CH2-N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2-pyrrolidinonyl, and such a group is optionally substituted by one or two substituents selected from:halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl;and when R1 is chlorine and p is 1, such R1 is not present in the ortho position with respect to the linking bond to the rest of the molecule;and when R1 corresponds to R5, p is 1;processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D3 receptors, e.g. to treat drug dependency or as antipsychotic agents.

Description

AZABICICLO DERIVATIVES (3.1.0) HEXANO USEFUL AS MODULATORS OF THE DOPAMINE D3 RECEPTORS DESCRIPTIVE MEMORY Compounds The present invention relates to novel compounds, processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their uses in therapy, as modulators of dopamine D3 receptors. WO 2002/40471 (SmithKine Beecham) describes certain benzazepine compounds having activity in the dopamine D3 receptor. A new class of compounds has been found which has affinity for dopamine receptors, in particular the dopamine D3 receptor. These compounds have potential in the treatment of conditions wherein the modulation, especially antagonism / inhibition, of the D3 receptor is beneficial, for example to link drug dependence or as antipsychotic agents. The present invention provides a compound of formula (I) or a salt thereof: wherein • G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; • p is an integer that has a range of 0 to 5; • Ri is independently selected from the group consisting of: halogen, hydroxy, cyano, C? - alkyl, C haloalkyl, C? - alkoxy, C 1-4 haloalkoxy, C? -4 alkanoyl; or corresponds to a group R5; • R2 is hydrogen or C? - alkyl; • R3 is C? -4 alkyl; • R4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or an 8- or 11-membered bicyclic group, any of said groups being optionally substituted by 1, 2, 3 or 4 selected substituents from the group consisting of: halogen, cyano, C-alkyl, C-4-haloalkoxy, C 1-4 -alkanoyl; • R5 is a portion selected from the group consisting of: isoxazolyl, -CH2-N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2-pyrrolidinonyl, and said group is optionally substituted by one or two substituents selected from: halogen, cyano, C? -4 alkyl, C? -4 haloalkyl, C? - alkoxy, C? - alkanoyl; and when Ri is chloro and p is 1, said Ri is not present in the ortho position with respect to the binding link to the rest of the molecule; and when Ri corresponds to R5, p is 1. Due to the presence of the fused cyclopropane compounds of formula (I) it is believed that they have a "cis" arrangement of the substituents (both groups associated with the bicyclic ring system are in the same face of this bicyclic ring system). In another embodiment of the present invention there are provided the compounds of formula (I) 'which comprise the compounds of formula (I) which have a "cis" arrangement, represented by the bold highlighting of the bonds wherein G, p, Ri, R2, R3, R4, and R5 are defined as mentioned above for the compounds of formula (I). It will be appreciated that the compounds of formula (I) 'possess at least two chiral centers, ie in position 1 and 5 in the 3-azabicyclo [3.1.0] hexane portion of the molecule. Due to the fixed cis arrangement, the compounds can exist in two stereoisomers which are enantiomers with respect to the chiral centers in the cyclopropane. It will also be appreciated, in common with most biologically active molecules, that the level of biological activity may vary between the individual stereoisomers of a given molecule. The scope of the invention is intended to include all individual stereoisomers (diastereomers and enantiomers) and all mixtures thereof, including but not limited to racemic mixtures, which demonstrates appropriate biological activity with reference to the methods described herein. invention. In the compounds of formula (I) 'there are at least two chiral centers, which are located in the cyclopropane portion, as illustrated below (the bold highlighting of the bonds means the "cis" configuration): when G is a 2-pyridyl derivative the configuration becomes (1R, 5R) due to the different naming priorities of Cahn-Ingold-Prelog. In a further embodiment of the present invention there are provided compounds of formula (IA) which correspond to the stereochemical isomers of the compounds of formula (I) ', enriched in the configuration (1S, 5R) or (1R, 5R) wherein G, p, R1, R, R3, R, and R5 are defined as mentioned above for the compounds of formula (I) 'or a pharmaceutically acceptable salt thereof. It is intended in the context of the present invention that the stereochemical isomers enriched in the (1S, 5R) or (1R, 5R) configuration of the formula (IA) correspond in at least 90% e mode. and. In another embodiment, the isomers correspond to at least 95% e. and. In another embodiment the isomers correspond to at least 99% e. and. In another embodiment of the present invention, the stereochemically isomeric enriched in the configuration (1 R.5S) is provided: • 5- [5- (. {3 - [(1 R, 5S) -1 - (4-Methoxyphenyl)) -3-azabicyclo [3.1.0] hex-3-yl] propyl.} Thio) -4-methyl-4H-1, 2,4-triazol-3-yl] -2-methylquinoline, enantiomer 2; • 5- [5- ( { 3 - [(1 R, 5S) -1- (4-Bromophenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl.} T or) -4-methyl-4H-1, 2,4-triazol-3-yl] -2-methylquinoline, enantiomer 1; • 5- [5- ( {3 - [(1 R, 5S) -1- (4-tert-Buylphenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl.} ThioV4- methyl-4H-1,2,4-triazol-3-yl-1-methyl-quinoline, enantiomer 1: (1 R, 5S) -3- (3 { [4-Methyl-5- ( 4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] t, o.] Propyl) -1- [3- (nifluoromethyl) phenyl] - 3-azabicyclo [3.1.0] hexane, enantiomer 2; (1 R, 5S) -1- (3-chlorophenyl) -5-methyl-3- (3 { [4-methyl-5- ( 4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] t, o.}. Propyl) -3-azabicyclo [3.1.0] hexane , enaniomer 2; • 1- [5 - [(1 R, 5S) -3- (3 { [4-Metyl-5- (4-methyl-1,3-oxazol-5-yl) -4H -1, 2,4-yol-3-yl] thio.] - propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2- (me yloxy) phenyl] -1-propanone , enaniomer 2; • 2-Meily-5 - [(1 R, 5S) -3- (3 { [4-meityl-5- (4-methyl-1,3-oxazol-5-yl) - 4H-1, 2,4-lriazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.0] hex-1-yl] -1,3-benzoylazole, enantiomer 2, or a pharmaceutically acceptable salt thereof The term "5 or 6 membered heteroaromatic group" refers to a group 5 or 6 membered monocyclic heterocyclic ring containing 1, 2, 3 or 4 heteroatoms, for example from 1 to 3 heteroatoms, selected from O, N and S. When the group contains 2-4 helero-atoms, one can be selected from O, N and S and the remaining heteroatoms may be N. Examples of 5- and 6-membered heteroaromatic groups include pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, isoiazolyl, isozolyl, furyl, thienyl, thiadiazolyl, pyridyl. , triazolyl, triazinyl, pyridazinyl, pyrimidinyl and pyrazinyl.

The term "C1- alkyl" refers to an alkyl group having from one to four carbon atoms, in all isomeric forms, such as me yl, ethyl, propyl, isopropyl, buyl, isobutyl, sec-butyl and ter- buíilo. The term "n-C 1 alkyl-" refers to unbranched alkyls as defined above. The term "C? -4 alkoxy" refers to a straight or branched chain alkoxy (or "alkyloxy") group having one to four carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy , sec-butoxy and ér-butoxy. The term "halogen" and its abbreviation "halo" refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I). Where the term "halo" is used before another group, this indicates that the group is replaced by one, two or more halogen atoms. For example, "haloalkyl of C? -4" refers to groups such as trifluoromethyl, bromoethyl, trifluoropropyl, and other groups derived from C? -4 alkyl groups as defined above; and the term "haloalkoxy of C? -4" refers to such groups as írifluoro methoxy, bromoethoxy, írifluoropropoxy, and other groups derived from C alco alkoxy groups as defined above. The term "bicyclic group of 8 to 11 members" refers to a bicyclic ring system containing a toal of 8, 9, 10 or 11 carbon atoms, where 1, 2, 3 or 4 or 5 of the carbon atoms are optionally replaced by a heteroatom independently selected from O, S and N. The term includes bicyclic systems where both rings are aromatic, as well as bicyclic ring systems where one of the rings is partially or completely saíurado. Examples of 8 to 11 membered bicyclic groups wherein both rings are aromatic include indenyl, naphthyl and azulenyl. Examples of bicyclic groups of 8 to 11 members that have 1, 2, 3, 4 or 5 hepheno-areomers, in which both rings are aromatic, include: 6H-lieno [2,3-b] pyrrolyl, imidazo [2,1 -b] [1,3] fiazolyl, imidazo [5,1-b] [1, 3] aiazolyl, [1, 3] thiazolo [3,2-b] [1, 2,4] triazolyl, indolyl, isoindolyl , indazolyl, benzimidazolyl for example benzimidazol-2-yl, benzoxazolyl for example benzoxazol-2-yl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzothienyl, benzofuranyl, naphthyridinyl, quinolyl, quinoxalinyl, quinazolinyl, cinnolinyl and isoquinolyl. Examples of 8 to 11 membered bicyclic groups having 1, 2, 3, 4 or 5 heteroatoms, in which one of the rings is partially or completely saturated include dihydrobenzofuranyl, indanyl, tetrahydronaphthyl, indolinyl, isoindolinyl, terahydroisoquinolinyl, iorahydroquinolyl, benzoxazinyl and benzoazepinyl. The term "heterocyclyl" refers to a monocyclic group of 5 or 6 members or a bicyclic group of 8 to 11 members wherein 1, 2, 3, 4 or 5 of the carbon atoms are replaced by a hetero independently selected from of O, S and N and which is partially or completely saíurado. Examples of "heyerocyclyl" which are fully saturated 5 or 6 membered monocyclic rings include pyrrolidinyl, imidazolidinyl, pyrazolidinyl, isothiazolyl, thiazolyl, tetrahydrofuranyl, dioxolanyl, piperidinyl, piperazinyl, morpholinyl.thiomorpholinyl, idrohydrothienyl, dioxanyl, tetrahydro-2H-pyranyl and dithianil. Examples of "heterocyclyl" groups which are partially saturated 5 or 6 membered monocyclic rings include oxazolinyl, isoaxazolinyl, im'dazolinyl, pyrazolinyl, 1,2,3,6-terahydropyridyl and 3,6-dihydro-2H-pyranyl. Examples of "heterocyclyl" groups which are fully saturated 8- or 11-membered bicyclic rings include decahydroquinolinyl, ociahydro-2H-1,4-benzoxazinyl and ociahydro-1 H-cyclopenia- [b] pyridinyl. Examples of "heyerocyclyl" groups which are partially saturated 8 to 11 membered bicyclic rings include 2,3-dihydro-1 H-indolyl, 1, 2,3,4-teirahydroquinolinyl, 1, 2,3,4-teirahydroisoquinolinyl and 2,3,4,5-tetrahydro-1 H-3-benzazepinyl. Any of these groups can be bound to the rest of the molecule in any suitable position. As used in the present invention, the term "salt" refers to any salt of a compound according to the present invention prepared from an inorganic or organic acid or base, quaternary ammonium salts and internally formed salts. The physiologically acceptable salts are particularly suitable for medical applications due to their higher aqueous solubility relative to the parent compounds. Said salts must clearly have a physiologically acceptable anion or cation. Suitably the physiologically acceptable salts of the compounds of the present invention include acid addition salts formed with inorganic acids such as hydrochloric, hydrobromic, hydroiodic, phosphoric, metaphosphoric, nitric and sulfuric acids, and with organic acids, such as tartaric, acetic , trifluoroacetic, citric, malic, lactic, fumaric, benzoic, formic, propionic, glycolic, gluconic, maleic, succinic, camforsulfuric, isothionic, mucic, gentisic, isonicotinic, saccharic, glucuronic, furobic, glutamic, ascorbic, anthranilic, salicylic, phenylacetic, mandelic, embonic (pamico), methanesulfonic, ethanesulfonic, panlogenic, stearic, sulfinyl, alginic, galacturonic and arylsulfonic, for example benzenesulfonic and p-toluenesulfonic, acids; basic addition salts formed with alkali metals and alkaline toric metals and organic bases such as N, N-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumain (N-methylglucamine), lysine and procaine; and internally formed salts. Salts having a non-physiologically acceptable anion or cation are within the scope of the invention are useful intermediates for the preparation of physiologically acceptable salts and / or for use in non-therapeutic actions, for example, in vitro situations. In one embodiment, Ri is halogen, cyano, acetyl, trifluoromethyl, trifluoromethyloxy. In one embodiment, R2 is hydrogen. In other embodiment R2 is C 1 - alkyl (for example methyl). In one embodiment, R 5 is a group selected from: isoxazolyl, 2-pyrrolidinonyl, 1,1-dioxido-2-isothiazolidinyl which is optionally substituted by one or two sustiluyeníes selected from: halogen, cyano, C-alkyl ? -2 (for example methyl), haloalkyl of C? -2 (for example trifluoromethyl), C? -2 alkoxy (for example methoxy), C? -3 alkanoyl (for example acetyl). Suitably Ri is bromine, fluoro, trifluoromethoxy, cyano, hydroxy, chloro, methoxy, tert-butyl, trifluoromethyl. Suitably, R 5 is isoxazolyl, 2-pyrrolidinonyl, -CH 2 -N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, 2-thienyl, 2-pyridyl, 2-thiazolyl. In one embodiment, p is 1 or 2. In another embodiment p is 0. In one embodiment, R4 may be optionally substituted phenyl (for example phenyl, 4-trifluoromethyl-phenyl, 3,4-difluorophenyl), an optionally substituted bicyclic group such as quinolinyl (for example 2-methylquinoline, 8-fluoro-2-methylquinoline), an optionally substituted pyranyl (for example 4-tetrahydro-2H-pyranyl), an optionally substituted pyridinyl (for example 3-methyl-2-pyridinyl, 2-methyl-3-pyridinyl, 3-pyridinyl, 2-methyl-6-trifluoromethyl-3-pyridinyl), an optionally substituted pyrazolyl (for example 5-chloro-1-methyl-1 H-pyrazole-4) -yl, 1-methylene-3-ylfluoromethyl-1 H-pyrazol-4-yl, 1,5-dimethyl-1 H-pyrazol-4-yl), an optionally substituted pyrimidyl (e.g. 5-pyrimidinyl), an optionally substituted pyridazinyl (for example 4-pyridazinyl), an optionally substituted pyrazinyl (for example 5-methyl-2-pyrazinyl), an optionally substituted furanyl (for example 3-methyl-2-furanyl, 2,5-dimethyl-3-furani) or, an optionally substituted thienyl (for example 5-chloro-2-thienyl), an optionally substituted oxazolyl (for example 4-methyl-1,3-oxazol-5-yl, 2 methyl-5-trifluoromethyl-1,3-oxazol-4-yl), an optionally substituted isoxazolyl (for example 3-methyl-5-isoxazolyl), an optionally substituted thiazolyl (for example 2,4-dimethyl-1,3) -thiazol-5-yl), an optionally substituted triazolyl (for example 1-methyl-1 H-1,2,3-f-riazol-4-yl). In one embodiment, R3 is methyl. In one embodiment, a compound of formula (IB) or a salt thereof is provided, wherein Ri, p, R3 and R4 are as defined for formula (I): In the formula (IB), in one embodiment, R3 is methyl. R may be phenyl, heterocyclyl, a 5 or 6 membered heteroaromatic group or a 9 to 11 membered bicyclic group, any of which is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, hydroxy, oxo, cyano, nitro, C? - alkyl, fluoroalkyl of CM, C? _4 alkoxy, C? -4 fluoroalkoxy, C? - alkanoyl; and when Ri is chlorine and p is 1, such that R is not present in the ortho position with respect to the binding link to the rest of the molecule. Examples of R include an optionally substituted phenyl (e.g., phenyl, 4-trifluoromethylphenyl, 3,4-difluorophenyl), an optionally substituted bicyclic group such as quinolinyl (e.g. 2-methylquinoline, 8-fluoro-2-methylene). noline), an optionally substituted pyranyl (for example 4-tetrahydro-2H-pyranyl), an optionally substituted pyridinyl (for example 3-methyl-2-pyridinyl, 2-methyl-3-pyridinyl, 3-pyridinyl, 2-methyl- 6-trifluoromethyl-3-pyridinyl), an optionally substituted pyrazolyl (for example 5-chloro-1-methyl-1H-pyrazol-4-yl, 1-methyl-3-frifluoromethyl-1 H-pyrazol-4-yl, 1 , 5-dimethyl-1 H-pyrazolyl-4-yl), an optionally substituted pyrimidyl (e.g. 5-pyrimidinyl), an optionally substituted pyridazinyl (e.g. 4-pyridazinyl), an optionally substituted pyrazinyl (e.g. 5-methyl) -2-pyrazinyl), an optionally substituted furanyl (for example 3-methyl-2-furanyl, 2,5-dimethyl-3-furanyl), an optionally substituted thienyl or (for example 5-chloro-2-thienyl), an optionally substituted oxazolyl (for example 4-methyl-1,3-oxazol-5-yl, 2-methyl-5-trifluoromethyl-1,3-oxazole-4-) ilo), an optionally substituted soxazolyl (for example 3-methyl-5-isoxazolyl), an optionally substituted thiazolyl (for example 2,4-dimethyl-1,3-thiazol-5-yl), an optionally substituted triazolyl (per Example 1-methyl-1 H-1,2,3-triazol-4-yl). In another embodiment, a compound of formula (IC) or salt thereof is provided, wherein Ri, p, R3 and R are as defined for formula (I): In formula (10), in one embodiment, R3 is methyl. R 4 can be phenyl, heterocyclyl, a 5 or 6 membered heteroaromatic group or a 9 to 11 membered bicyclic group, any of which is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, hydroxy, oxo, cyano, nitro, C? - alkyl, fluoroalkyl of C. C alkoxy C? -4 fluoroalkoxy, C? -4 alkanoyl; and when Ri is chloro and p is 1, the Ri is not present in the ortho position with respect to the binding link to the rest of the molecule. Examples of R include those previously defined for compounds (IB). In another embodiment, a compound of formula (ID) or salt thereof is provided, wherein Ri, p, R3 and R4 are as defined for formula (I): In the formula (ID), in one embodiment, R3 is methyl. R 4 can be phenyl, heterocyclyl, a 5 or 6 membered heteroaromatic group or a 9 to 11 membered bicyclic group, any of which is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, hydroxy, oxo, cyano, nitro, alkyl of CM, fluoroalkyl of C? -, alkoxy of C? -4, fluoroalkoxy of C1-4, alkanoyl of C1-; and when Ri is chlorine and p is 1, said Ri is not present in the ortho position with respect to the binding link to the rest of the molecule. Examples of R4 include those previously defined for compounds (IB). In another embodiment, a compound of formula (IE) or salt thereof is provided, wherein G is 2-pyridyl or 3-pyridyl and Ri, p, R3 and R4 are as defined for formula (I): In the formula (IE), in one embodiment, G corresponds to 2-pyridyl (compounds (IE1)) and in another embodiment to 3-pyridyl (compounds (IE2)), as illustrated below: In the formulas (IE), (lE ^ and (IE2), in one embodiment, R3 is methyl, R can be phenyl, heterocyclyl, a 5- or 6-membered heteroaromatic group or a 9 to 11-membered bicyclic group, either which is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, hydroxy, oxo, cyano, nitro, CM alkyl, C? - fluoroalkyl, C1-4 alkoxy, fluoroalkoxy of C? -4, C? -4 alkanoyl; and when Ri is chlorine and p is 1, said Ri is not present in the ortho position with respect to the binding link to the rest of the molecule. Examples of R4 include those previously defined for compounds (IB). In another embodiment, a compound of formula (IF) or salt thereof is provided, wherein Ri, p, R3 and R are as defined for formula (I): In the formula (IF), in one embodiment, R3 is methyl. R may be phenyl, heterocyclyl, a 5- or 6-membered heleroaromatic group or a 9 to 11-membered bicyclic group, any of which is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, hydroxy, oxo, cyano, nylro, C? -4 alkyl, C? - fluoroalkyl, C 1-4 alkoxy, fluoroalkoxy of CM, C? -4 alkanoyl; and when Ri is chlorine and p is 1, said Ri is not present in the ortho position with respect to the binding link to the rest of the molecule. Examples of R include those previously defined for compounds (IB). The strategy for the determination of the absolute configuration of the compounds of the present invention comprises as a first step the preparation of chiral intermediate, (1S, 5R) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. 0] hexane, (preparation 18), by the use of (S) - (+) acetyl mandelic acid as an agent for resolution. The absolute configuration of a series of compounds similar to this chiral intermediate is known in the literature, see J. Med Chem 1981, 24 (5), 481-90. For some compounds described in the reference absolute configuration is provided by X-ray analysis in particular crystal.

Among these, 1- (3,4-dichlorophenyl) -3-azabicyclo [3.1.0] hexane was described. The absolute configuration of the optical isomers of the compounds of the present invention was assigned using comparative VCD (vibrational circular dichroism) and OR (optical rotation) analyzes. The configuration of (1S, 5R) -1- (3,4-dichlorophenyl) -3-azabicyclo [3.1.0] hexane was assigned by comparing its experimental VCD spectrum and the specific rotation of the calculated initial derived data was observed for (1S, 5R) -1- (3,4-dichlorophenyl) -3-azabicyclo [3.1.0] hexane (see preparation 48) as the reference sample. Assignment of the absolute configuration of the title compound was confirmed by a particular crystal X-ray structure obtained from a crystal of (1S, 5R) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1 .0] hexane, (S) - (+) - mandelic acid salt. Both the analysis based on the known configuration of (S) - (+) - mandelic acid and the analysis based on the effects of anomalous dispersion confirmed the assignment of the title compound as (1S, 5R) -1- [4- (trifluoromethyl) ) phenyl] -3-azabicyclo [3.1.Ojhexane. For those compounds which were subjected to detailed analysis (VCD, or were included in the experimental details), a common tendency was recognized between the absolute configuration of the 3-azabicyclo [3.1.0] hexane portion and the binding activity measured in the D3 dopamine receptor for each pair of enantiomers. For the remainder of the compounds of the present invention, wherein the stereoisomers were evaluated separately, the absolute configuration was assigned based on a reasonable assumption by a person skilled in the art, for example the absolute configuration was then assigned based on the activity of measured union in the dopamine D3 receptor for both enanfiómeros and the comparison with the daíos of those compounds which were submitted to detailed analysis.

Chiral molecules exhibit vibrational circular dichroism (VCD). Vibrational circular dichroism (VCD) is the differential interaction of a chiral molecule with circularly polarized infrared radiation left and right during vibrational excitation. The VCD spectrum of a chiral molecule is dependent on its three-dimensional structure. More importantly, the VCD spectrum of a chiral molecule is a sesitive function of its absolute configuration and, in the case of flexible molecules, its conformation. Therefore, in principle, VCD allows the determination of the structure of a chiral molecule. The VCD spectra were initially measured in the 1970s. Subsequently, the instrumentation for VCD has developed greatly in a spectral range and in its sensitivity. Currently, VCD spectra of liquids and solutions can be measured over most of the fundamental infrared (IR) spectral range (v >; 650 cm-1) with a high sensitivity at an acceptable resolution (1-5 cm-1) using both instrumentation for dispersive VCD and VCD instrumentation for Fourier transformation (FT). Very recently, commercial instrumentation of FT VCD has been made available, greatly improving the accessibility of the VCD spectra. The use of VCD as a reliable method for determining the absolute configuration of chiral molecules has been well established at present (see for example Shah RD, et al., Curr Opin Drug Disc Dev 2001; 4: 764-774; Freedman TB , et al., Helv Chim Acta 2002; 85: 1160-1165; Dyatkin AB, et al. Chirality 2002; 14: 215-219; Solladie-Cavallo A, Balaz M et al., Tetrahedron Assym 2001; 12: 2605-2611; Ñafie LA, et al. Circular dichroism, principies and applications, 2nd ed. New York: John Wiley & Sons; 2000. p 97-131; Ñafie LA, et al. in: Yan B, Gremlish H-U, editors. Infrared and Raman spectroscopy of biological materials. New York: Marcel Dekker, 2001. p 15-54; Polavarapu PL, et al., J Anal Chem 2000; 366: 727-734; Stephens PJ, et al., Chirality 2000; 12: 172-179; Solladie-Cavallo A, et al., Eur J Org Chem 2002: 1788-1796). The method covers the comparison of the observed IR and VCD specimens with spectral calculations for a specific configuration and provides information about the absolute configuration as well as the conformation of the solution. Given an experimental spectrum of a chiral molecule whose absolute configuration and / or conformation are unknown and must be determined, the general procedure is as follows: 1) all possible structures are defined; 2) the spectra of these structures are predicted; and 3) the predicted spectra were compared with respect to the experimental spectrum. The correct structure will produce a spectrum in accordance with the experiment; incorrect structures will produce spectra at odds with the experiment. The VCD spectra are always measured simultaneously with vibrational unpolarized absorption spectra ("infrared (IR) spectra") and the two vibrational spectra together provide more information than the VCD spectrum alone. In addition, vibrational unpolarized absorption spectra were automatically predicted simul- taneously with the VCD spectra. For the initial assignments, the VCD and unpolarized IR spectra were calculated using the software package Gaussian 98. When the chiral organic molecules are synthesized (or, if natural products are isolated) their optical rotations are routinely measured at a frequency or in a small number of discrete frequencies in the ultraviolet spectral region near the visible region. More commonly, the specific rotation is measured at a frequency, that of the sodium line D, [CC] D. The frequencies used lie below the threshold for electronic absorption, for example, they are in the "transparent" spectral region. The optical rotation is a reflection of the enantiomeric excess (ee) of the sample and the absolute configuration (AC) of the predominant enantiomer. When the optic royation at a given frequency for 100% of ee is available, the optic rotation measured at the same frequency allows the ee of the sample to be determined. The determination of the ee is the predominant application of the discrete frequency, optic rotations in the transparent spectral region. In principle, the AC of the predominant enanlimer can also be determined, if unknown. However, the determination of the AC from the optical rotation requires an algorithm which reliably predicts the optical rotations of known CA molecules and numerous methodologies have been proposed to predict the discrete frequency, optical rotations in the transparent spectral region (Eliel EL, Wilen SH, Stereochemistry of organic compounds, New York: John Wiley &Sons, 1994. Chapter 13). Very recently, the developments at the beginning of the functional density theory (DFT) have radically improved the accuracy of the calculation of optical rotation. As a result, for the first time it has been possible to obtain ACs from the rotation optic in a ruíinaria way. For the OR start assignments, the Dalton Quantum Chemistry program was used. Additional embodiments of the present invention are compounds of formula (IB) ', (IC)', (ID) ', and (IF)' which, respectively, correspond to the stereospecific isomers of the compounds of formula (IB), (IC), (ID) and (IF) as defined above enriched in the configuration (1S.5R). The compounds of formula (IE) 'correspond to the stereospecific isomers of the compounds of formula (IE) as defined above, enriched in the configuration (1 R.5R) or (1R, 5S) depending on the presence of a ring 2-pyridine. In one embodiment, a stereospecific isomer enriched in the (1S, 5R) configuration of formula (IB) 'or a salt thereof is provided, wherein Ri, p, R3 and R4 are as defined for formula (I): In formula (IB) ', in one embodiment, R3 is methyl. R may be phenyl, heterocyclyl, a 5- or 6-membered heteroaromatic group or a 9 to 11-membered bicyclic group, any of which is optionally substituted by 1, 2, 3 or 4 subsitutes selected from the group consisting of: halogen, hydroxy, oxo, cyano, nitro, C -4 alkyl, fluoroalkyl of C? -4, alkoxy of C -4, fluoroalkoxy of C -4, alkanoyl of C? -4; and when Ri is chloro and p is 1, said Ri is not present in the ortho position with respect to the binding link to the rest of the molecule. Examples of R include optionally substituted phenyl (for example phenyl, 4-trifluoromethyl-phenyl, 3,4-difluorophenyl), an optionally substituted bicyclic group such as quinolinyl (e.g. 2-methylenequinoline, 8-fluoro-2-methylquinoline), an optionally substituted pyranyl (for example 4-hydro-2-pyranyl), an optionally substituted pyridinyl (for example 3-methyl-2-pyridinyl, 2-methyl-3-pyridinyl, 3-pyridinyl, 2-methyl-6 trifluoromethyl-3-pyrridinyl), an optionally substituted pyrazolyl (for example 5-chloro-1-methyl-1 H-pyrazol-4-yl, 1-methyl-3-trifluoromethyl-1 H-pyrazol-4-yl, 1 , 5-dimethyl-1 H -pyrazol-4-ylo), an optionally substituted pyrimidyl (e.g. 5-pyrimidinyl), an optionally substituted pyridazinyl (e.g. 4-pyridazinyl), an optionally substituted pyrazinyl (e.g. 5-methyl) -2-pyrazinyl), an optionally substituted furanyl (for example 3-meityl-2-furanyl, 2,5-dimethyl-3-furanyl), an optionally substituted fluid (for example 5-chloro-2-lienyl), an optionally substituted oxazolyl (for example 4-methyl-1,3-oxazol-5-yl, 2-methyl-5-trifluoromethyl-1,3-oxazole-4-) ilo), an optionally substituted isoxazolyl (for example 3-methyl-5-isoxazolyl), an optionally substituted iazolyl (for example 2,4-dimethyl-1,3-thiazol-5-yl), an optionally substituted triazolyl ( for example 1-methyl-1 H-1, 2,3-triazol-4-yl). In another embodiment, a stereospecific isomer enriched in the (1S, 5R) configuration of formula (IC) 1 or a salt thereof is provided, wherein Ri, p, R3 and R are as defined for formula (I) : In the formula (IC), in one embodiment, R3 is methyl. R may be phenyl, heterocyclyl, a 5 or 6 membered heteroaromatic group or a 9 to 11 membered bicyclic group, any of which is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, hydroxy, oxo, cyano, nickel, C? -4 alquilo alkyl, C? - fluoroalkyl, C? -4 alco alkoxy, fluoroalkoxy of CM, C? -4 alca alkanoyl; and when Ri is chlorine and p is 1, said Ri is not present in the ortho position with respect to the binding link to the rest of the molecule. Examples of R include those previously defined for compounds (IB) '.

In another embodiment, a stereospecific isomer enriched in the (1S, 5R) configuration of formula (ID) 'or a salt thereof is provided, wherein Ri, p, R3 and R are as defined for formula (I): In the formula (ID) ', in one embodiment, R3 is methyl. R may be phenyl, heterocyclyl, a 5 or 6 membered heteroaromatic group or a 9 to 11 membered bicyclic group, any of which is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, hydroxy, oxo, cyano, nitro, C -4 alkyl, C1-4 fluoroalkyl, C? -4 alkoxy, C? -4 flu fluoroalkoxy, C1- alkanoyl; and when Ri is chlorine and p is 1, said Ri is not present in the ortho position with respect to the binding link to the rest of the molecule. Examples of R include those previously defined for compounds (IB) '. In another embodiment, a stereospecific isomer enriched in the configuration (1S, 5R) or in the configuration (1R.5R) of the formula (IE) 'or a salt thereof is provided, wherein G is 2-pyridyl or 3- pyridyl and Ri, p, R3 and R4 are as defined for formula (I): In formula (IE) ', in one embodiment, G corresponds to 2-pyridyl (compounds (IE1)') and in another embodiment to 3-pyridyl (compounds (IE2) '), as illustrated below: wj i? rjim The configuration will then change depending on the type of pyridine ring, as mentioned above. In the formulas (IE) ', (IE1)' and (IE2) ', in one modality, R3 is melil. R 4 can be phenyl, heterocyclyl, a 5- or 6-membered heteroaromatic group or a 9 to 11-membered bicyclic group, any of which is optionally substituted by 1, 2, 3 or 4 subsitutes selected from the group consisting of: halogen, hydroxy, oxo, cyano, nickel, alkyl of CM, fluoroalkyl of C? -4, alkoxy of C? -4, fluoroalkoxy of C? -4, alkanoyl of C? -4; and when Ri is chlorine and p is 1, said Ri is not present in the ortho position with respect to the binding link to the rest of the molecule. Examples of R include those previously defined for compounds (IB) '.

In another embodiment, a stereochemically isomer enriched in the (1S, 5R) configuration of formula (IF) 'or a salt thereof is provided, wherein Ri, p, R3 and R4 are as defined for formula (I): In the formula (IF) ', in one embodiment, R3 is methyl. R 4 may be phenyl, heterocyclyl, a 5 or 6 membered heteroaromatic group or a 9 to 11 membered bicyclic group, any of which is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, hydroxy, oxo, cyano, nitro, C? -4 alkyl, C? -4 fluoroalkyl, C? -4 alkoxy, C1-4 fluoroalkoxy, C? -4 alkanoyl; and when Ri is chloro and p is 1, said R is not present in the ortho position with respect to the bond binding to the molecule resi. Examples of R include those previously defined for compounds (IB) '. Some of the compounds of the invention can form acid addition salts with one or more equivalents of the acid. The present invention includes within its scope all possible stoichiometric and non-stoichiometric forms. Acceptable pharmaceutical salts can also be prepared from other salts, including other pharmaceutically acceptable salts, of the compound of formula (I) using conventional methods.

Those skilled in the art of organic chemistry will appreciate that many organic compounds can form complexes with solvents in which they are reacted or from which they precipitate or crystallize. These complexes are also known as "solvates". For example, a complex with water is known as a "hydrate". The solvaíos of the compound of the invention are within the scope of the invention. The compounds of formula (I) can be easily isolated in association with solvent molecules by crystallization or evaporation of an appropriate solvent to produce the corresponding solvates. In addition, prodrugs are also included within the context of this invention. As used in the present invention, the term "prodrug" means a compound which is converted from the body, for example by hydrolysis in the blood, to its active form having medicinal effects. Pharmaceutically acceptable prodrugs are described in T. Higuchi and V. Stella, Prodrugs as Novel Delivery Systems, Vol. 14 of the ACS Symposium Series, Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press , 1987, and in D. Fleisher, S. Ramón and H. Barbra "Improved oral drug delivery: solubility limitations overeóme by íhe use of prodrugs", Advanced Drug Delivery Reviews (1996) 19 (2) 115-130, each of which are incorporated within the present invention as a reference. Prodrugs are any covalently bonded vehicles that release a compound of structure (I) in vivo when said prodrug is administered to a patient. The prodrugs are generally prepared by modifying the functional groups so that the modification is cleaved, either by direct manipulation or in vivo, yielding the parent compound. Prodrugs include, for example, compounds of this invention wherein the hydroxy, amine or sulfhydryl groups are attached to any group which, when administered to a patient, is cleaved to form the hydroxy, amine or sulfhydryl groups. Thus, representative examples of prodrugs include (but are not limited to) acetate, formate and benzoate functional groups derived alcohol, sulfhydryl and amine of the compounds of structure (I). In addition, in the case of a carboxylic acid (-COOH), esters, such as methyl esters, ethyl esters, and the like can be employed. The esters can be false as they are and / or can be hydrolysable under living conditions in the human body. Suitable pharmaceutically acceptable in vivo hydrolysable ester groups include those that readily degrade in the human body to leave the parent acid or its salt. In addition, some of the crystalline forms of the structure (I) compounds may exist as polymorphs, which are included in the present invention. Those skilled in the art will appreciate that in the preparation of the compound of the invention or a solvate thereof it may be necessary and / or desirable to protect one or more sensitive groups in the molecule to prevent undesirable side reactions. Suitable protecting groups for use in accordance with the present invention are well known to those skilled in the art and can be used in conventional manner. See, for example, "Protective groups in organic synthesis" by T. W. Greene and P. G. M. Wuts (John Wiley & amp; amp; amp;; sons 1991) or "Protecting Groups" by P. J. Kocienski (Georg Thieme Verlag 1994). Examples of suitable amino protecting groups include acyl-type protecting groups (for example formyl, trifluoroacetyl, acetyl), aromatic urethane-type protecting groups (for example benzyloxycarbonyl (Cbz) and substituted Cbz), aliphatic urethane protecting groups (for example 9-fluorenylmethoxycarbonyl ( Fmoc), t-butyloxycarbonyl (Boc), sopropyloxycarbonyl, cyclohexyloxycarbonyl) and alkyl type proviral groups (for example benzyl, triyl, chlorotryl). Examples of suitable amino protecting groups can include for example alkyl silyl groups, such as trimethylsilyl or tert-butyldimethylsilyl; alkyl ethers such as teirahydropyranyl or tert-butyl; or esters such as acetate. When a specific enantiomer of a compound of general formula (I) is required, it can be obtained for example by solving a corresponding enantiomeric mixture of a compound of formula (I) using conventional methods. Therefore, the required enaniomer can be obtained from the racemic compound of formula (I) by using a chiral HPLC method. The present invention also includes isotopically labeled compounds, which are identical to those mentioned in formula (I) and following, but due to the fact that one or more atoms are replaced by an atom having an atomic mass or different mass number to the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into the compounds of the invention and pharmaceutically acceptable salts thereof include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, iodine, and chlorine, such as 2H, 3H , 11C, 13C, 14C, 15N, 170, 1dO, 31P, 32p 35o 18p 36. 123I and 125? The compounds of the present invention and pharmaceutically acceptable salts of said compounds containing the aforementioned isotopes and / or other isotopes of other atoms are within the scope of the present invention. The isotopically-labeled compounds of the present invention, for example those in which radioactive isotopes such as 3H, 14C are incorporated, are useful in tissue distribution assays of the drug and / or the substrate. Tritiated isotopes, for example, 3H, and carbon-14, for example, 14C, are particularly preferred for their ease of preparation and detection. Isotopes 11C and 18F are particularly useful in PET (positron emission tomography), and 125L isotopes are particularly useful in SPECT (computed tomography of particular photon emission), all are used in brain imaging. In addition, substitution with heavier isotopes such as deuterium, for example, 2H, can produce certain therapeutic disadvantages due to a greater metabolic stability, for example increased in vivo half-life or reduced dose requirements and, therefore, may be preferred. in some circumstances. The isotopically-labeled compounds of formula I and the following of this invention are generally prepared by carrying out the procedures described in the schemes and / or the examples below, by replacing an easily available isotopically labeled reagent with a non-isotopically reactive agent. marked. Certain groups / subsitutes included in the present invention may be present as isomers. The present invention includes within its scope all those isomers, including racemates, enantiomers, tauomers and mixtures thereof. Certain heteroaryl amino groups included in the compounds of formula (I) may exist in one or more tautomeric forms. The present invention includes within its scope all those tautomeric forms, including mixtures. In one embodiment of the present invention, compounds with a molecular weight of 800 or less are provided. In another embodiment, compounds having a molecular weight of 600 or less are provided. Generally, and without being limited thereto, said compounds may have greater oral bioavailability, and sometimes greater solubility and / or penetration to the brain. The molecular weight in the present invention refers to that of an unsolvated free base compound, excluding any molecular weight contained by the additional salts, solvent molecules (e.g. water), molecular moieties of the excised prodrug in vivo, etc.

In general, the compounds or salts of the invention are to be included as excluded from those compounds (if present) which are chemically unusable, either per se or in water, which are clearly unsuitable for pharmaceutical use through all the routes of administration, whether oral, parenteral or otherwise. Said compounds are known to a person skilled in the art. However, the prodrugs or compounds which are stable ex vivo and which are converted in the mammalian body (for example human) to the compounds of the invention are included. Examples of compounds of the present invention include: 5- [5- ( {3 - [(1 R, 5S / 1S, 5R) -1- (4-Methoxyphenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl.} - thio) -4-methyl-4H-1, 2,4-triazol-3-yl] -2-methylquinoline; • 5- [5- ( { 3 - [(1S, 5R) -1- (4-Methoxyphenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl.} Thio) -4- meilyyl-4H-1, 2,4-triazol-3-yl] -2-meitylquinoline, enantiomer 1; • 5- [5- ( {3 - [(1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl. thio) -4-methyl-4H-1, 2) 4-triazol-3-yl] -2-methylquinoline; 5- [5- ( { 3 - [(1S, 5R) -1- (4-Bromophenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl.} T or) -4 -met.l-4H-1, 2,4-triazol-3-yl] -2-methylquinoline, enantiomer 2; 2-Methyl-5- [4-methyl-5- (. {3 - [(1 R, 5S / 1 S, 5R) -1-phenyl-3-azabicyclo [3.1.0] hex-3-yl] propyl.} thio) -4H-1, 2,4-triazol-3-yl] quinoline; • 2-Methyl-5- [4-methyl-5- (. {3 - [(1S, 5R) -1-phenyl-3-azabicyclo [3.1.0] hex-3-yl] propyl} thio ) -4H-1, 2,4-triazol-3-yl] quinoline, enaniomer 2: • 5- [5- (. {3 - [(1 R.5S / 1 S, 5R) -1 - (3 , 4-Dichlorophenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl} thio) -4-methyl-4H-1, 2,4-triazol-3-yl] -2-methylquinoline; • 5- [5- ( { 3 - [(1S, 5R) -1- (3,4-Dichlorophenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl} thio) - 4-methyl-4H-1, 2,4-triazol-3-yl] -2-methylquinoline, enantiomer 1; 5- [5- ( { 3 - [(1 R.5S / 1 S, 5R) -1 - (4-tert-butylphenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl, thio) -4-methyl-4H-1, 2,4-triazol-3-yl] -2-methylenequinoline; • 5- [5- ( { 3 - [(1S, 5R) -1- (4-ér-butylphenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl}. 4-meityl-4H-1, 2,4-triazol-3-yl] -2-meityl-quinoline, enaniomer 2; • 4 - [(1 R.5S / 1 S, 5R) -3- (3- { [4-Mephyl-5- (2-meyylquinolin-5-yl) -4H-1, 2,4-Iriazole -3-yl] io.}. Propyl) -3-azabicyclo [3.1.0] hex-1-phenylbenzonitrile; • 4 - [(1 R.5S / 1 S, 5R) -3- (3- { [4-Methyl-5- (2-methylquinolin-5-yl) -4H-1, 2,4-triazole -3-yl] thio.}. Propyl) -3-azabicyclo [3.1.0] hex-1-yl] phenol; (1 R, 5S / 1S, 5R) -3- (3 { [4-methyl-5- (4-methyl-3,3-oxazole-5-ii) -4H-1, 2.4- Iriazol-3-yl] -ioio}. propyl) -1-phenyl-3-azabicyclo [3.1.0] hexane; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { (4-methyl-5- (4-mephyl-1,3-oxazol-5-yl) - 4H-1, 2,4-triazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- (4-Bromophenyl) -3- (3- { [4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] -ioio}. Propyl) -3-azabicyclo [ 3.1.Oxhexane, enantiomer 1; • (1 R, 5S / 1 S, 5R) -1- (4-tert-butylphenyl) -3- (3 { [4-methyl-5- (4-methyl) 1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1.Ohexane; • (1 R.5S / 1 S, 5R) -1 - (3,4-Dichlorophenyl) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazole-5 -yl) - 4H-1, 2,4-triazol-3-yl] thio.] propyl) -3-azabicyclo [3.1.Ohexane; • (1S, 5R) -1 - (3,4-Dichlorophenyl) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazole-5-yl) - 4H-1, 2,4-triazol-3-yljio.} Propyl) -3-azabicyclo [3.1.Oxhexane, enantiomer 2; • (1 R, 5S / 1S, 5R) -1- (4-methoxyphenyl) -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- (4-methoxyphenyl) -3- (3 { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylchthio}. Propyl) -3-azabicyclo [3.1.Oxhexane, enantiomer 2; • (1 R, 5S / 1S, 5R) -1- [4- (5-methyl-3-isoxazole) phenyl] -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -3- (3 { [4-Meityl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-triazole-3- il] thio.) propyl) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazole-3 -yl] thio.}. propyl) -1- [4- (trifluoromethyl) phenylj-3-azabicyclo [3.1. Ojhexano; • (1 R, 5S / 1 S, 5R) -1 - [2-Fluoro-4- (trifluoromethyl) phenyl] -3- (3 { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylchthio}. Propyl) -3-azabicyclo [3.1.Ojhexane; (1 R.5S / 1 S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2.4 -triazo! -3-yl] thio) propyl) -1- [3- (trifluoromethyl) phenylj-3-azabicyclo [3.1.Ojhexane; • (1 R.5S / 1 S, 5R) -1 - [4-Fluoro-3- (trifluoromethyl) phenyl] -3- (3 { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylchthio}. Propyl) -3-azabicyclo [3.1.Ojhexane; 1 - . 1 - [5 - [(1 S.5R / 1 R, 5S) -3- (3 { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H -1, 2,4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.0] hex-1-ylj-2- (methyloxy) phenyl-ketanone; • 1- [5 - [(1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2, 4-triazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2- (methoxyl) phenyl] ethanone, enantiomer 1; (1S, 5R / 1R, 5S) -1 - (4-chlorophenyl) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1- (4-chlorophenyl) -3- (3 { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.Ojhexane, enantiomer 1; (1S.5R / 1 R, 5S) -1- (4-chlorophenyl) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) - 4H-1, 2,4-triazol-3-ylchthio}. Propyl) -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1- (4-chlorophenyl) -3- (3 { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.Ohexane, enantiomer 1; • (1S, 5R / 1R, 5S) -1- (3-chlorophenyl) -5-methyl-3- (3 { [4-meityl-5- (4-methyl-1,3-oxazole- 5-yl) -4H-1, 2,4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1- (3-chlorophenyl) -5-methyl-3- (3 { [4-methyl-5- (4-meityl-1,3-oxazoI-5-yl) -4H -1, 2, 4-triazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1. Ojhexane, enantiomer 1; • (1S, 5R / 1R, 5S) -1- (3-Fluorophenyl) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-Iriazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1 - (3-Fluorophenyl) -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1 , 2,4-triazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1.Ojhexane, enantiomer 1; (1S, 5R / 1R, 5S) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4- triazol-3-yl] lio.] propyl) -1- [3- (methyloxy) phenylj-3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-meityl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazole-3- ilthio.) propyl) -1- [3- (methyloxy) phenyl] -3-azabicyclo [3.1. Ojhexane, enantiomer 1; • (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (1-tetrahydro-2H-pyran-4-yl) -4H-1, 2,4- triazol-3-yl] -ioio}. propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- [4- (trifluoromethyl) phenylj-4H-1, 2,4-triazole- 3-yl.} .io) propyl] -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (3-pyridinyl) -4H-1, 2,4-lriazol-3-yljio} - propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [5- (3,4-difluorophenyl) -4-methyl-4H-1, 2,4-triazole-3- Fig. 1) .propyl) -3-azabicyclo [3.1.Ojhexane; • 5- [5- ( {3 - [(1S, 5R / 1R, 5S) -1- (4-chlorophenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl. thio) - 4-methyl-4H-1, 2,4-triazol-3-yl] -2-methylquinoline; • 5- [5- ( { 3 - [(1S, 5R / 1R, 5S) -1- (4-chlorophenyl) -3-azabicyclo [3.1.Ojhex-3-il1propil > tio) -4- methyl-4H-1, 2,4-triazol-3-p-2-methylquinoline, enantiomer 1: (1S, 5R / 1R, 5S) -3- (3 { [4-Methyl-5 - (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.} Propyl) -1-. { 4 - [(trifluoromethyl) oxy] phenyl} -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazole-3- iljt¡o.}. -propl) -1-. { 4 - [(trifluoromethyl) oxy] phenyl} -3-azabicyclo [3.1. Ojhexane, enantiomer 1 (1S, 5R / 1R, 5S) -3- (3 { [4-Methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1 , 2,4-triazol-3-yl] -thio.}. Propyl) -1- [2-meityl-4- (trifluoromethyl) phenyl] -3-azabicicio [3.1.Ojhexane; (1S, 5R / 1R, 5S) -3- (3 { [4-Methyl-5- (terahydro-2H-pyran-4-yl) -4H-1, 2,4-triazole-3 -il] tio.}. propil) -1 -. { 4 - [(ialifluoromethyl) oxy] phenyl} -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -3- (3 { [4-Methyl-5- (tetrahydro-2H-pyran-4-yl) -4H-1, 2,4-triazol-3-yljthio. propyl) -1 -. { 4 - [(trifluoromethyl) oxy-phenyl} -3-azabicyclo [3.1.Ojhexane, enantiomer 2; • (1 R, 5S / 1S, 5R) -1- (3-Bromophenyl) -3- (3 { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylchthio.] Propyl) -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -3- (1-Methyl-3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4- triazol-3-yl] thio.} propyl) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (1 -Methyl-3 { [4-meityl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4- iriazole-3-yljido.) propyl) -1- [4- (n-fluoromethyl) phenyl-3-azabicyclo [3.1.O-hexane, diastereoisomer 1; (1S, 5R) -3- (1-Methyl-3 { [4-methyl-5- (4-meiyl-1,3-oxazol-5-yl) -4H-1, 2,4-tr Azol-3-yljiui.} Propyl) -1- [4- (trifluoromethyl) phenyj-3-azabicyclo [3.1. Ojhexane, diastereoisomer 2; • (1 R, 5 S / 1 S, 5 R) -1 - [2-Fluoro-5- (ír-fluoromethyl) phenyl] -3- (3 { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-iriazole-3-yl) jtio} propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1- [2-Fluoro-5- (trifluoromethyl) phenyl] -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl ) -4H-1, 2,4-triazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.Ohexane, enaniomer 2; 1 - [4 - [(1 R.5S / 1 S, 5R) -3- (3 { [4-Methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H -1, 2,4-triazol-3-yljio.} Propyl) -3-azabicyclo [3.1.0jhex-1-ylj-2- (methyloxy) phenylyenanone; 1 - [4 - [(1 R.5S / 1 S, 5R) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H -1, 2,4-triazol-3-ylthio.} Propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2- (methoxy) phenyl] -1-propanone; • (1 R, 5S / 1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2.4 -triazol-3-ylchthio.} propyl) -1 - [2- (trifluoromethyl) phenylj-3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1 - [2-Fluoro-4- (trifluoromethyl) phenylj-3- (3 { [4-methyl-5- (4-methyl-1,3-oxazole-5- il) -4H-1, 2,4-triazol-3-yl] thio.} propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -3- (3 { [4-Meityl-5- (2-methyl-3-pyridinyl) -4H-1, 2,4-iriazol-3-yl] thio. propi) -1- [4- (trifluoromethyl) phenylj-3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-Meityl-5- (4-pyridazinyl) -4H-1, 2,4-pyridin-3-yl], propyl) -1- [4- (O-fluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -3- (3 { [5- (1, 5-Dimethyl-1 H -pyrazol-4-yl) -4-meityl-4H-1, 2,4-triazole- 3-yl] io.}. Propyl) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -3- (3 { [4-Met.l-5- (5-pyrimidinyl) -4H-1, 2,4-idriazol-3-yljio.}. Propyl) - 1- [4- (O-fluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-Methyl-5- (3-methyl-2-furan-1) -4H-1, 2,4-triazol-3-yl] thio} propyl) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -3- (3 { [4-Methyl-5- (6-methyl-3-pyridinyl) -4H-1, 2,4-triazol-3-yl] thio} propyl) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [5- (2,4-Dimethyl-1,3-thiazol-5-yl) -4-methyl-4H-1, 2,4-triazole- 3-ylthio.) Propyl) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -3- (3 { [4-Methyl-5- (5-methyl-2-pyridinyl) -4H-1, 2,4-triazol-3-yljthio. propyl) -1- [4- (frifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-Methyl-5- (tetrahydro-2H-pyran-4-yl) -4H-1, 2,4-lriazol-3-yl] ion} propyl) -1- [4- (l-trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; 2-Methyl-6-. { 4-meityl-5 - [(3- {(1 S, 5R) -1 - [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.0] hex-3-yl} propyl) thio ] -4H-1, 2,4-triazol-3-yl} quinoline; 8-Fluoro-2-methyl-5-. { 4-methyl-5 - [(3 { (1S, 5R) -1- [4- (trifluoromethyl) phenii] -3-azabicyclo [3.1.0jhex-3-yl.] Propyl) thio] -4H -1, 2,4-triazol-3-yl} quinoline; 2-Methyl-5-. { 4-methyl-5 - [(3- {(1S, 5R) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.0] hex-3-yl} propi) thio] -4H-1, 2,4-triazol-3-yl} quinoline; (1S, 5R) -1 - [2-Fluoro-4- (trifluoromethyl) phenyl] -3- (3 { [4-methyl-5- (2-methyl-3-pyridinyl) -4H -1, 2,4-Iriazol-3-yl] lio.] Propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1 - [2-Fluoro-4- (trifluoromethyl) phenyl] -3- (3 { [4-methyl-5- (4-pyridazinyl) -4H-1, 2, 4 -triazol-3-ylchthio.} propyl) -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1- [2-Fluoro-4- (trifluoromethyl) phenylj-3- (3 { [4-methyl-5- (5-pyrimidinyl) -4H-1, 2.4 -yriazol-3-yl] lio.] propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [5- (2,4-Dimethyl-1, 3-fiazol-5-yl) -4-methyl-4H-1, 2,4-triazole-3 -yl] thio.} propyl) -1- [2-fluoro-4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- [2-Fluoro-4- (trifluoromethyl) phenylj-3- (3 { [4-methyl-5- (5-methy1-2-pyrazinyl) -4H-1, 2 , 4-triazol-3-yljlio.}. Propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1 - [2-Fluoro-4- (trifluoromethyl) phenyl] -3- [3- (. {4-methyl-5- [4- (trifluoromethyl) phenylj-4H-1 , 2,4-triazol-3-yl.} Lio) propylj-3-azabicyclo [3.1.Ojhexane; 1 -. { 4 - [(1 R, 5S / 1 S, 5R) -3- (3 { [4-Methyl-5- (2-meityl-5-quinolinyl) -4H-1, 2,4-triazole- 3-yl] io.}. Propyl) -3-azabicyclo [3.1.0] hex-1-yl] phenyl} -2-pyrrolidinone; • 5-. { 5 - [(3- { (1 R, 5S / 1S, 5R) -1- [4- (1, 1-Dioxido-2-isothiazolidinyl) phenylj-3-azabicyclo- [3.1.0] hex-3-yl.} propyl) ioj-4-methyl-4H-1, 2,4-iazol-3-yl} -2-methylquinoline; (1 R, 5S / 1S, 5R) -1- [3-Fluoro-4- (trifluoromethyl) phenylj-5-methyl-3- (3 { [4-meityl-5- (4-methyl-1 , 3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.Ohexane; 1- (2- (Methyloxy) -5-. {(1 R, 5S / 1S, 5R) -3- [3- (. {4-meityl-5- [4- (trifluoromethyl) phenyl] -4H -1, 2,4-triazol-3-yl.}., Iio) propyl] -3-azabicyclo [3.1.Ojhex-1-yl.] Phenyl) einone; • 1 - [5 - [(1 R, 5S / 1 S, 5R) -3- (3 { [5- (3,4-Difluorophenyl) -4-methyl-4H-1, 2,4- Nazol-3-yljthio., propyl) -3-azabicyclo [3.1.0jhex-1-yl] -2- (methyloxy) phenyl-ketanone; • 1-. { 2- (Meilyox) -5 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-methyl-5- (3-pyridinyl) -4H-1, 2, 4-Iriazol-3-yljyl.} Propyl) -3-azabicyclo [3.1.0jhex-1-ylphenyl} ethanone; 1 - [5 - [(1 R.5S / 1 S, 5R) -3- (3 { [4-Meyyl-5- (2-methyl-5-quinolinyl) -4H-1, 2.4 -Iriazol-3-yl] -ioio}. propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2- (methyloxy) phenyl-ketanone; • 1-. { 2- (Methyloxy) -5 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-methyl-5- (tetrahydro-2H-pyran-4-yl) -4H-1 , 2,4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.0] hex-1-ylphenyl} ethanone; 1 - (2-hydroxy-5-. {(1 R.5S / 1 S, 5R) -3- [3- (. {4-methyl-5- [4- (trifluoromethyl) phenyl] -4H- 1, 2,4-triazol-3-yl.} Thio) propyl] -3-azabicyclo [3.1.Ojhex-1-yl.] Phenyl) ethanone; 1-. { 5 - [(1 R, 5S / 1S, 5R) -3- (3 { [5- (3,4-Difluorophenyl) -4-methyl-4H-1, 2,4-triazol-3-yljthio .}. propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2-hydroxyphenyl} ethanone; 1 -. { 2-hydroxy-5 - [(1 R.5S / 1 S, 5R) -3- (3 { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) - 4H-1, 2,4-triazol-3-yl] thio} propyl) -3-azabicyclo [3.1.Ohex-1-yl] phenyl} ethanone; 1-. { 2-hydroxy-5 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-methyl-5- (2-methyl-5-quinolinyl) -4H-1, 2,4-triazol-3-ylthio} propyl) -3-azabicyclo [3.1.0] hex-1-ylphenyl} ethanone; • 1- [5 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1,3-oxazole-5-I) - 4H-1, 2,4-triazol-3-ylchthio}. Propyl) -3-azabicyclo [3.1.0jhex-1-ylj-2-tmethyloxy) phenyl] -1-propanone; • 1 - [5 - [(1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2 , 4-Iriazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1.0jhex-1-yl] -2- (methyloxy) phenyl] -1-propanone enaniomer 1; • 2-Meityl-5 - [(1 R, 5S / 1 S, 5R) -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-lriazol-3-ylchthio.] Propyl) -3-azabicyclo [3.1.0] hex-1-ylj-1,3-benzothiazole; • 2-Meityl-5 - [(1S, 5R) -3- (3 { [4-meityl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-lriazol-3-ylchthio.] Propyl) -3-azabicyclo [3.1.0] hex-1-ylj-1,3-benzoiazole, enantiomer 1; • 2-Methyl-6 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-meityl-5- (4-methyl-1,3-oxazol-5-yl) - 4H-1, 2,4-yriazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1.Ohex-1-ylj-1,3-benzothiazole; • 1-Meityl-5 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) - 4H-1, 2,4-triazole-3-yl] -propyl) -3-azabicyclo [3.1.0] hex-1-ylj-1 H-indazole; • 1-Methyl-5 - [(1S, 5R) -3- (3 { [4-meityl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2 , 4-lriazol-3-yl] thio.) Propyl) -3-azabicyclo [3.1.0] hex-1-ylj-1 H-indazole, enantiomer 1; (1 R.5S / 1 S, 5R) -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2.4 -yriazole-3-glycol.} propyl) -1- [6- (urea) -3-pyridinyl] -3-azabicyclo [3.1.Ohexane; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (2-methyl-3-pyridinyl) -4H-1, 2,4-triazol-3-ylchthio}. Propyl) -3-azabicyclo [3.1.Ojhexane; • (1 R.5S / 1 S, 5R) -1 - (4-Bromophenyl) -3- (3 { [4-methyl-5- (4-pyridazinyl) -4H-1, 2,4- triazol-3-yl] thio.} propyl) -3-azabicyclo [3.1.Ojhexane; (1 R.5S / 1 S, 5R) -1 - (4-Bromophenyl) -3- (3 { [5- (5-chloro-1-methyl-1 Hp -razol-4-yl) - 4-methyl-4H-1, 2,4-triazole-3-ylthio}. Propyl) -3-azabicyclo [3.1. Ojhexano; • (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (1-methyl-1 H-1, 2,3-triazole -4-yl) -4H-1, 2,4-triazole-3-ylthio}. Propyl) -3-azabicyclo [3.1.Ojhexane; • (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [5- (1, 5-dimethyl-1 H-pyrazole- -l) -4- methyl-4H-1, 2,4-Iriazol-3-yl] thio.] propyl) -3-azabicyclo [3.1. Ojhexano; • (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (5-pyrimidn-1) -4H -1, 2,4-triazol-3-ylchthio.] Propyl) -3-azabicyclo [3.1.Ojhexane; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- [3- (. {4-methyl-5- [1-methyl-3- (trifluoromethyl) -1 H-pyrazole- 4-yl] -4H-1, 2,4-triazol-3-yl.} Thio) propyl] -3-azabicyclo [3.1. Ojhexano; (1 R.5S / 1 S, 5R) -1 - (4-Bromophenyl) -3- (3 { [4-methyl-5- (3-methyl-2-furanyl) -4H-1, 2 , 4-Iriazol-3-yl] io.}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (3-methyl-5-isoxazolyl) -4H-1, 2, 4-Iriazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1. Ojhexano; • (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (6-meityl-3-pyridinyl) -4H-1, 2 , 4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.Ojhexane; • (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (1-methyl-1 H -pyrazole-5-yl) -4H-1, 2,4-triazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1. Ojhexano; (1 R.5S / 1 S, 5R) -1 - (4-Bromophenyl) -3- (3 { [4-methyl-5- (5-meityl-3-pyridinyl) -4H-1, 2 , 4-triazol-3-ylchthio}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- [3- (. {4-meti) -5- [2-meityl-5- (trifluoromethyl) -1, 3- oxazol-4-yl] -4H-1, 2,4-iazol-3-yl} io) propyl] -3-azabicyclo [3.1.Ojhexane; (1 R.5S / 1 S, 5R) -1 - (4-Bromophenyl) -3- (3 { [4-methyl-5- (3-meityl-2-pyridinyl) -4H-1, 2 , 4-triazol-3-yljioi}. Propyl) -3-azabicyclo [3.1.Ojhexane; • (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [5- (2,4-dimethyl-1,3-yiazol-5-yl) -4 -methyl-4H-1,2,4-triazol-3-yl] thio.] propyl) -3-azabicyclo [3.1. Ojhexano; • (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [5- (2,5-dimethyl-3-furanyl) -4-meityl-4H-1 , 2,4-Iriazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { - [5- (5-chloro-2-thyl) -4-methyl-4H-1 , 2,4-triazol-3-yl] thio}. Propyl) -3-azabicyclo [3.1. Ojhexano; • (1 R.5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (3-pyridinyl) -4H-1, 2, 4-triazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.Ojhexane; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- [2-meityl-6- (trifluoromethyl) -3-pyridinyl) ] -4H-1, 2,4-Iriazol-3-yl.} .io) propylj-3-azabicyclo [3.1.Ojhexane. . 5- [5- ( {3 - [(1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3-azabicyclo [3.1.0] hex-3-ylpropyl.] Thio) - 4-methyl-4H-1, 2,4-triazol-3-yl] -1-methyl-3- (trifluoromethyl) -1 H -thieno [2,3-cjpyrazole; 3- (3- { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl-yl}. ) - (1 R, 5R / 1S, 5S) -1- [5- (irifluoromethylal) -2-pyridinyl] -3-azabicyclo [3.1.Ohexane; • 3- (3- { [4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] yl} propyl) - (1 R, 5R) -1- [5- (trifluoromethyl) -2-pyridinyl-3-azabicyclo [3.1. Ojhexano. enantiomer 2; • 3- (3- { [4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] t.o} propyl) - (1 R, 5R / 1S, 5S) -1- [6- (trifluoromethyl) -2-pyridinylj-3-azabicyclo [3.1.Ojhexane; • (1 R, 5S / 1S, 5R) -1- [3-Fluoro-4- (1 H -pyrrol-1-ylmethyl) phenylj-3- (3 { [4-methyl-5- (4 methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.} propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R / 1R, 5S) -3- (3- { [4-Methyl-5- (5-methyl-2-pyrazinyl) -4H-1, 2,4-triazol-3-yl ] .propyl) -1- [6- (trifluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R / 1R, 5S) -3- (3 { [4-Metl-5- (6-meityl-3-pyridinyl) -4H-1, 2,4-triazole-3- ilthio.) propyl) -1 - [6- (trifluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1.Ohexane; (1S.5R / 1R, 5S) -3- (3- { [4-Methyl-5- (2-methyl-3-pyridinyl) -4H-1, 2,4-Iriazol-3-yl ] t ~ o.) propyl) -1- [6- (n-trifluoromethyl) -3-pyridine-3-azabicyclo [3.1. Ojhexano; • (1S, 5R 1 R, 5S) -3- (3 { [4-Methyl-5-phenyl-4H-1, 2,4-triazol-3-yl] thio}. Propyl) -1- [6- (O-fluoromethyl) -3-pyridinyl-3-azabicyclo [3.1.Ojhexane; • (1S.5R / 1R, 5S) -3- (3- { [5- (2,4-Dimethyl-1, 3-yiazol-5-yl) -4-methyl-4H-1, 2,4-triazol-3-yl] thio.) Propyl) -1- [6- (trifluoromethyl) -3-pyridyl] -3-azabicyclo [3.1.Ohexane; • (1S.5R / 1R, 5S) -3- [3- ( { 4-Methyl-5- [4- (trifluoromethyl) phenyl] -4H-1, 2,4-triazole-3- il.) thio) propyl] -1- [6- (trifluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1. Ojhexano; • (1 S.5R / 1 R, 5S) -2-Methyl-5- [3- (3 { [4-methyl-5- (5-methyl-2-pyrazinyl) -4H-1 ^^ - triazole-S-ylthio-Jpropi -S-azabicyclop.l. 0] hex-1-yl-1,3-benzothiazole; • (1 S.5R / 1 R, 5S) -2-Meilyl-5- [3 - (3- { [4-methyl-5- (6-meyyl-3-pyrazinyl) -4H-1, 2,4-triazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1 .0] hex-1-yl-1, 3-benzothiazole; (1S, 5R / 1R, 5S) -2-Methyl-5- (3- (3 - [(4-methyl-5-phenyl- 4H-1, 2,4-triazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.Ohex-1-ylj-1,3-benzothiazole; • (1S.5R / 1R, 5S) -5- [3- (3. {[[5- (2,4-Dimethy-l, 3-yiazyl-5-yl) -4-meityl-4H -1, 2,4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2-methyl-1,3-benzothiazole; • (1 S.5R 1 R, 5S) -2-Methyl-5-. { 3- [3- ( { 4-methyl-5- [4- (trifluoromethyl) phenyl] -4H-1, 2,4-triazol-3-yl.} Thio) propyl] -3- azabicyclo [3.1.Ojhex-1-il} -1, 3-benzothiazole; • (1 R, 5S / 1S, 5R) -1- [3-Fluoro-5- (trifluoromethyl) phenyl] -3-. { [4-methyl-5- (4-methyl-1, 3-oazol-5-yl) -4H-1, 2,4-triazol-3-yljthio} propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1- [3-Fluoro-5- (trifluoromethyl (phenyl) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl ) -4H-1, 2,4-lriazol-3-yljyl}. Propyl) -azabicyclo [3.1.Ojhexane, enaniomer 1; • (1 R, 5S / 1 S, 5R) -1 - [ 2-Fluoro-3- (trifluoromethyl) phenylj-3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4- Iriazol-3-yljioi.) propyl) -azabicyclo [3.1.Ojhexane; (1S, 5R) -1- [2-Fluoro-3- (trifluoromethyl) phenyl] -3- (3 { [4 -methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] lio}. propyl) -azabicyclo [3.1.Ojhexane, enantiomer 2; (1 R, 5S / 1S, 5R) -1- [4- (Methyloxy) -5- (trifluoromethyl) phenyl] -3- (3 { [4-methyl-5- (4-methyl-1 , 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] io.}. Propyl) -azabicyclo [3.1.Ojhexane; • (1 R, 5S / 1S, 5R) -1 - [4- (4-chloro-2-fluorophenyl) -3- (3 { [4-meityl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2, 4-Iriazol-3-ylchthio}. Propyl) -azabicyclo [3.1.Ojhexane; »(1 R.5S / 1 S, 5R) -1 - [3- (2- { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1 , 2,4-triazol-3-yl] thio.} Propyl) -1-. { 3 - [(trifluoromethyl) oxy] phenyl} -3-azabicyclo [3.1.Ojhexane; • (1 R, 5S / 1S, 5R) -1- (2-Chloro-4-methylphenyl) -3- (2 { [4-methyl-5- (4-methyl-1,3-oxazole- 5-yl) -4H-1, 2,4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.Ojhexane; • (1 R, 5S / 1 S, 5R) -1 - [3-chloro-4- (methyloxy) phenylj-3- (2 { [4-methyl-5- (4-methyl-1, 3 oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.} propyl) -3-azabicyclo [3.1.Ojhexane; (1 R, 5S / 1S, 5R) -1- [4- (2,4-Dimethyl-1,3-thiazol-5-yl) phenylj-3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio}. Propyl) -3-azabicyclo [3.1.Ojhexane; (1 R.5S / 1 S, 5R) -3- (3- { [4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2.4 -yriazole-3-yl.). propyl) -1-. { 4- [6- (ír-fluoro-methyl) -2-pyridinyl-phenyl} -3-azabicyclo [3.1.Ojhexane: (1 R, 5S / 1S, 5R) -1- [3- (2,4-dimethyl-1,3-thiazol-5-yl) phenyl] -3- (3- {. [4-Methyl-5- (4-mef-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] yl}. Propyl ) -3-azabicyclo [3.1.Ojhexane; (1 R, 5S / 1 S, 5R) -3- (3 { [4-meityl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2.4 -triazol-3-yl] thio.} propyl) -1- [3- (5-methyl-2-thienyl) phenylj-3-azabicyclo [3.1. Ojhexano; • (1 R, 5S / 1 S, 5R) -1 - [4- (3,5-dimethyl-4-isoxazolyl) phenyl] -3- (3- { [4-methyl-5- (4- methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylthio.} propyl) -3-azabicyclo [3.1.Ohexane; • (1S, 5R) -3- (3- { [5- (2,4-Dimethyl-1, 3-oxazol-5-yl) -4-methyl-4H-1, 2,4-triazole -3-yl] thio.} Propyl) -1- [2-fluoro-4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexane and the acceptable pharmaceutical salts thereof. Examples of compounds of the present invention include the following, which are obtained by means of the methods of the present invention: • 4 - [(1S, 5R) -3- (3 { [4-Methyl-5- (2-methylquinolin-5-yl) -4H-1, 2,4-triazol-3-yl] thio}. Propyl) -3-azabicyclo [3.1.0] hex-1-yl] benzonitrile; • 4 - [(1S, 5R) -3- (3- { [4-Methyl-5- (2-methylquinolin-5-yl) -4H-1, 2,4-triazol-3-yl] io.}. propyl) -3-azabicyclo [3.1.0] hex-1-ylphenol; • (1S, 5R) -3- (3- { [4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-Iriazole-3 -iljtio.}. propyl) -1-phenyl-3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1- (4-tert-butylphenyl) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazole-5-yl) -4H -1, 2,4-Iriazol-3-yljthio.] Propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- [4- (5-meityl-3-isoxazolyl) phenyl] -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazole -5-yl) -4H-1, 2,4-yriazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -3- (3- { [4-Melyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazole-3- il] thio.) propyl) -1 - [3- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.Ohexane; (1S, 5R) -1- [4-Fluoro-3- (trifluoromethyl) phenylj-3- (3 { [4-methyl-5- (4-methyl-l, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazole-3- ilj-thio.) propyl) -1- [2-methyl-4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1 - (3-Bromophenyl) -3- (3 { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1 , 2,4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1. Ojhexano; • 1- [4 - [(1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2, 4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2- (methyloxy) phenyl-ketanone; • 1 - [4 - [(1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2 , 4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2- (methyloxy) phenyl] -1-propanone; (1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazole-3- ilthio.) propyl) -1- [2- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; 1-. { 4 - [(1S, 5R) -3- (3 { [4-Methyl-5- (2-meityl-5-quinolinyl) -4H-1, 2,4-triazole-3-yl]. propyl) -3-azabicyclo [3.1.0] hex-1-ylphenyl} -2-pyrrolidone; • 5-. { 5 - [(3-. {(1S, 5R) -1- [4- (1, 1-Dioxido-2-isothiazolidinyl) phenylj-3-azabicyclo [3.1.0] hex-3-yl.} propyl) thioj-4-methyl-4H-1, 2,4-triazol-3-yl} -2-methylquinoline; 1- (2- (Methyloxy) -5-. {(1S, 5R) -3- [3- (. {4-methyl-5- [4- (trifluoromethyl) phenylj-4H-1, 2, 4-triazol-3-yl.} Thio) propyl] -3-azabicyclo [3.1.0] hex-1-yl.} Phenyl) ethanone; • 1- [5 - [(1S, 5R) -3- (3 { [5- (3,4-Difluorophenyl) -4-methyl-4H-1, 2,4-triazole-3-l ] thio} propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2- (methyloxy) pheny] ethanone; • 1 -. { 2- (Methyloxy) -5 - [(1S, 5R) -3- (3 { [4-methyl-5- (3-pyridinyl) -4H-1, 2,4-triazol-3-yljthio .}. propyl) -3-azabicyclo [3.1.0jhex-1-yl] phenyl} ethanone; • 1- [5 - [(1S, 5R) -3- (3 { [4-Methyl-5- (2-methyl-5-quinolinyl) -4H-1, 2,4-triazole-3- ilthio., propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2- (methyloxy) phenyl] ethanone; • 1-. { 2- (Methyloxy) -5 - [(1S, 5R) -3- (3 { [4-methyl-5- (tetrahydro-2H-pyran-4-yl) -4H-1, 2,4- triazol-3-yl] lyo.] propyl) -3-azabicyclo [3.1.0jhex-1-ylphenyl} ethanone; • 1 - (2-hydroxy-5-. {(1S, 5R) -3- [3- (. {4-methyl-5- [4- (trifluoromethyl) phenylj-4H-1, 2,4 -triazol-3-yl.} thio) propyl] -3-azabicyclo [3.1.0] hex-1-yl.} phenyl) ethanone; • 1-. { 5 - [(1S, 5R) -3- (3 { [5- (3,4-Difluorophenyl) -4-methyl-4H-1, 2,4-triazol-3-yl] thio.} propyl) -3-azabicyclo [3.1.0jhex-1-ylj-2-hydroxyphenyl} ethanone; • 1-. { 2-hydroxy-5 - [(1S, 5R) -3- (3 { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2, 4-triazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.0] hex-1-ylphenyl} ethanone; " 1-. { 2-hydroxy-5 - [(1 S, 5R) -3- (3 { [4-methyl-5- (2-methyl-5-quinolinyl) -4H-1, 2,4-iriazole -3-yljiio.) Propyl) -3-azabicyclo [3.1.0] hex-1-yl] phenyl} ethanone; • 2-Meityl-6 - [(1S, 5R) -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylthio.} Propyl) -3-azabicyclo [3.1.0] hex-1-yl-1,3-benzothiazole; (1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yljthio .}. propyl) -1- [6- (trifluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (2-methyl-3-pyridinyl) -4H-1, 2,4- triazol-3-ylchthio} propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (4-pyridazinyl) -4H-1, 2,4-triazole-3- il] thio.] propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [5- (5-chloro-1-methyl-1 H -pyrazol-4-yl) -4-methyl- 4H-1, 2,4-Iriazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.Ohexane; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (1-mephyl-1 H-1, 2,3-triazol-4-yl) - 4H-1, 2,4-Iriazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.Ohexane; • (1S, 5R) -1 - (4-Bromophenyl) -3- (3 { [5- (1, 5-dimethyl-1 H -pyrazol-4-yl) -4-meityl-4H- 1, 2,4-triazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1 - (4-Bromophenyl) -3- (3 { [4-methyl-5- (5-pyrimidinyl) -4H-1, 2,4-Iriazol-3-yljio .}. propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- (4-Bromophenyl) -3- [3-. { [4-methyl-5- [1-meityl-3- (trifluoromethyl) -1 H -pyrazol-4-yl] -4H-1, 2,4-iazol-3-yl} tio) propyl] -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-Methyl-5- (3-methyl-2-furanyl) -4H-1, 2,4-triazole- 3-yljyl.} Propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1 - (4-Bromophenyl) -3- (3 { [4-methyl-5- (3-meyyl-5-isoxazolyl) -4H-1, 2,4-triazole -3-yljthio.) Propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (6-methyl-3-pyridinyl) -4H-1, 2,4-triazole- 3-yl] tio .. propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (1-meyyl-1 H -pyrazol-5-yl) -4H-1, 2 , 4-triazol-3-yl] io.}. Propyl) -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (5-mephyl-3-pyridinyl) -4H-1, 2,4- triazole-3-yljido.) propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- (4-Bromophenyl) -3- [3-. { [4-methyl-5- [2-meityl-5- (trifluoromethyl) -1,3-oxazol-4-ylj-4H-1, 2,4-triazol-3-yl} thio) propyl-3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1 - (4-Bromophenyl) -3- (3 { [4-methyl-5- (3-methyl-2-pyridinyl) -4H-1, 2,4-triazole -3-yl] thio.) Propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1 - (4-Bromophenyl) -3- (3 { [5- (2,4-dimethyl-1,3-thiazol-5-yl) -4-meityl-4H -1, 2,4-triazol-3-ylchthio.} Propyl) -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [5- (2,5-dimethyl-3-furanyl) -4-methyl-4H-1, 2,4- triazol-3-yl] io.}. propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- (4-Bromophenyl) -3- (3 { - [5- (5-chloro-2-thienyl) -4-methyl-4H-1, 2,4-lriazole -3-yl] io.}. Propyl) -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1 - (4-Bromophenyl) -3- (3 { [4-eyl-5- (3-pyridinyl) -4H-1, 2,4-triazol-3-yljio .}. propyl) -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1 - (4-Bromophenyl) -3- [3- (. {4-methyl-5- [2-meityl-6- (trifluoromethyl) -3-pyridinyl] -4H -1, 2,4-triazol-3-yl.} Thio) propylj-3-azabicyclo [3.1.Ojhexane. • 5- [5- ( { 3 - [(1S, 5R) -1- (4-Bromophenyl) -3-azabicyclo [3.1.OJhex-3-ylpropyl.] Io) -4-meityl-4H- 1, 2,4-triazol-3-yl] -1-methyl-3- (trifluoromethyl) -1 H -thieno [2,3-cjpyrazole; • 3- (3- { [4-methyl-5- (4-methyl-1,3-oxazole-5-ii) -4H-1, 2,4-triazol-3-yl] thio. propyl) - (1R, 5R) -1- [6- (trifluoromethyl) -2-pyridinyl] -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1 - [3-Fluoro-4- (1 H -pyrrol-1-ylmethyl) phenylj-3- (3 { [4-methyl-5- (4-methyl-1 , 3-oxazole-5-yl) -4H-1, 2,4-lriazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -3- (3 { [4-Methyl-5- (5-meityl-2-pyrazinyl) -4H-1, 2,4-yriazol-3-yl] lio. propyl) -1- [6- (n-fluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -3- (3 { [4-Methyl-5- (6-methyl-3-pyridinyl) -4H-1, 2,4-triazol-3-yljt}. propyl) -1- [6- (trifluoromethyl) -3-pyridinyl-3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -3- (3 { [4-Methyl-5- (2-methyl-3-pyridinyl) -4H-1, 2,4-triazol-3-ylthio.} Propyl ) -1- [6- (trifluoromethyl) -3-pyridinyl-3-azabicyclo [3.1. Ojhexano; • (1 S, 5R) -3-. { 3 - [(4-Met.l-5-phenyl-4H-1, 2,4-triazol-3-yl) -iojpropyl} -1- [6- (trifluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -3- (3- {[[5- (2,4-D-methyl-1,3-thiazol-5-yl) -4-methyl-4H-1, 2,4-Iriazol-3-yl-phenyl}. Propyl) -1 - [6- (n-fluoromethyl) -3-pyridinyl-3-azabicyclo [3.1.O-hexane; • (1S, 5R) -3- [3- ( { 4-Methyl-5- [4- (trifluoromethyl) phenyl] -4H-1, 2,4-triazole-3-yl. propyl] -1- [6- (1-fluoromethyl) -3-pyridinyl-3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -2-Methyl-5- [3- (3 { [4-meityl-5- (5-methyl-2-pyrazinyl) -4H-1, 2,4- Iriazol-3-ylthio}. propyl) -3-azabicyclo [3.1.0] hex-1-yl] -1,3-benzoyiazole; • (1S, 5R) -2-Met.l-5- [3- (3 { [4-methyl-5- (6-methyl-3-pyridinyl) -4H-1, 2, 4-triazole-3-ylthio.} Propyl) -3-azabicyclo [3.1.0Jhex-1-yl] -1,3-benzothiazole; (1S, 5R) -2-Methyl-5- (3. {3 - [(4-methyl-5-phenyl-4H-1, 2,4-triazol-3-yl) thio] propyl.} .3-azabicyclo [3.1.0] hex-1-yl) -1, 3-benzoiazole; • (1S, 5R) -5- [3- (3 { [5- (2,4-Dimethyl-1, 3-thiazol-5-yl) -4-mephyl-4H-1, 2, 4-triazol-3-ylchthio}. Propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2-methyl-1,3-benzothiazole; • (1 S.5R / 1 R, 5S) -2-Methyl-5-. { 3- [3- ( { 4-me? Il-5- [4- (trifluoromethyl) phenylj- 4H-1, 2,4-triazol-3-yl.}. Iio) propyl] -3-azabicyclo [ 3.1.0Jhex-1-il} -1, 3-benzothiazole; • (1S, 5R) -1 - [4- (4-Chloro-2-fluorophenyl] -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazole-5 -yl) - 4H-1, 2,4-triazol-3-yl] io.}. propyl) -azabicyclo [3.1.Ojhexane; (1S, 5R) -1- [3- (2- { [4 -Meityl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-t-riazol-3-yl] thio.} Propyl) -1 -. 3 - [(trifluoromethyl) oxy] phenyl] -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1- (2-chloro-4-methylphenyl) -3- (2- { [4- methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylthio}. propyl) -3-azabicyclo [3.1.Ohexane; • (1S, 5R) -1- [3-chloro-4- (methyloxy) phenyl] -3- (2 { [4-methyl-5- (4-methyl-1,3-oxazole-5- il) -4H-1, 2,4-triazol-3-ylthio.} propyl) -3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1- [4- (2,4-Dimethyl-1, 3-yiazol-5-yl) phenyl] -3- (3 { [4-methyl-5- (4- methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.} propyl) -3-azabicyclo [3.1.Ohexane; • (1S, 5R) -3- (3- { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-iriazole-3 -l] lio.} Propil) -1-. { 4- [6- (N-fluoromethyl) -2-pyridinyl] phenyl} -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -1- [3- (2,4-dimethyl-1,3-thiazol-5-yl) phenylJ-3- (3 { [4-methyl-5- (4-methyl) -1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylthio}. Propyl) -3-azabicyclo [3.1.Ohexane; • (1S, 5R) -3- (3- { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazole-3- ilthio.) propyl) -1- [3- (5-methyl-2-thienyl) phenylj-3-azabicyclo [3.1. Ojhexano; • (1S, 5R) -1 - [4- (3,5-dimethyl-4-isoxazolyl) phenyl] -3- (3 { [4-methyl-5- (4-methyl-1 , 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylthio}. Propyl) -3-azabicyclo [3.1.Ojhexane; • (1S, 5R) -3- (3- { [5- (2,4-Dimethyl-1, 3-oxazol-5-yl) -4-methyl-4H-1, 2,4-triazole -3-ylthio.) Propyl) -1- [2-fluoro-4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexane and the acceptable pharmaceutical salts thereof. The present invention also provides a process for the preparation of a compound of formula (I) or a salt thereof as defined above. The process of the present invention for the preparation of the compounds of formula (I) in which G is phenyl derivative, comprises the steps of: (a) reacting a compound of formula (II): wherein Ri and p are as defined for formula (I), with a compound of formula (III): wherein R2, R3 and R4 are as defined for formula (I) and X is a residual group, or (b) for a compound of formula (I) wherein p is 1 or 2, by reacting a compound of formula (IV): wherein Ri, R2, R3, and R are as defined for formula (I), p is 0 or 1 and Y is halogen, a perfluoroalkylsulfonyloxy group (for example trifluoromethylsulfonyloxy), or Y is a group M selected from a boron derivative (for example a function of the boronic acid B (OH) 2) or a metal function such as trialkylstannyl (for example SnBu3), zinc halide or magnesium halide; with a compound R1-Y1, wherein Y1 is halogen when Y is a group M; or when Y is halogen or a perfluoroalkylsulfonyloxy group Y1 is a group M as defined above or hydrogen that can be activated by a suitable base (for example Cs2C03) in the presence of a suitable transition metal (for example Pd)iN. ; "residual group" is as understood by an expert chemist, for example a group which can be displaced by nucleophile in for example a SN2, SN1 or SNAr type reaction; and subsequently optionally for procedure (a) or procedure (b): (i) remove any prolector group (s); and / or (ii) forming a salt; and / or (iii) converting a compound of formula (I) or a salt thereof to another compound of formula (I) or a salt thereof. Process (a) can be carried out using conventional methods for the formation of a tertiary amine. The residual group X can be halogen such as chlorine. Alternatively X may be a suifonyloxy group such as C 1 -sulfonyloxy alkyl (for example methanesulfonyloxy), C 4 -sulfonyloxy alkyl or C 4 -sulfonyloxy haloalkyl (for example trifluoromethanesulfonyloxy); or arylsulfonyloxy wherein the aryl is optionally substituted with phenyl, a 5- or 6-membered heteroaromatic group optionally substituted, or an optionally substituted bicyclic group, for example optionally substituted phenyl, wherein in each case the optional substituents are one or more alkyl groups of C? -2; for example para-toluenesulfonyloxy. When X is a halogen the reaction can be carried out using a base such as carbonate of poasium in the presence of an iodide source such as sodium iodide in a solvent such as N, N-dimethylformamide at a suitable temperature, for example 60 ° C. The compounds of formula (II) can be prepared by methods well known in the art (for example J. Med. Chem. 1981, 24, 481-490). For typical conditions see Preparations 1-6 and 15-18 below. The interconversion of Ri groups can be affected by methodology well known in the art (for example demethylation of a methoxy group resulting in a hydroxy group using a suitable Lewis acid reagent such as boron tribromide in an inert solvent such as dichloromean). Preparations 7-11 below provide further examples of such inverse conversions in the presence of a suitable protecting group for the secondary amine, such as N-trifluoroacetyl. The reaction of a compound of formula (IV) with R1-Y1 in accordance with process (b) can be affected in the presence of a transition metal, for example, palladium catalyst such as bis-triphenylphosphinpalladium dichloride, eryrakis-riphenylphosphinpalladium (0) or the complex formed in situ from tris (dibenzylidene ketone) dipalladium (0) and 4,5-bis (diphenylphosphino) -9,9-dimethylxanfen. When M is a function of boronic acid such as B (OH) 2 the reaction can be carried out under basic conditions, for example using aqueous sodium carbonate in a suitable solvent such as dioxane. When M is trialkylsilyl, the reaction can be carried out in an inert solvent, such as xylene or dioxane optionally in the presence of LiCl. When M is a zinc or magnesium halide the reaction can be carried out in an aprotic solvent such as tetrahydrofuran. When M is hydrogen which can be activated by a suitable base (for example Cs2C03) in the presence of a suitable transition metal (for example Pd) the reaction can be carried out in an inert solvent such as dioxane in the presence of a Suitable base such as Cs2C03. Substituent Y can be halogenal as bromine, or a sulfonyloxy group such as trifluoromethylsulfonyloxy; and Y1 can be a group M, fa as hydrogen which can be activated by a suitable base (for example Cs2C03) in the presence of a suitable transition metal (for example Pd). In one aspect of the present invention, a synthetic process is provided for the preparation of the compounds of formula (II). The process can also convenly be carried out for the preparation of compounds of formula (lia), in which the phenyl portion is replaced by pyridine, useful for the preparation of the compounds of formula (IE). This procedure comprises the following steps: wherein: the step (a ') means the diazotization of an aniline (VII) followed by the reaction with the maleimide to produce 3-arylmaleimide (VIII); step (b ') means the cycloropanation of (VIII) to provide the bicyclic imide (IX); step (c ') means reduction of imide (IX) to produce compounds of formula (II). Step (a ') can be carried out using conventional methods for the Meerwein reaction (for example J. Am. Chem. Soc. 1955, 77, 2313 describes the formation of arylmaleimides using this method). Alternatively, in many cases this step is carried out suitably by applying a process wherein to a mixture of maleimide, an appropriate copper (II) salt such as anhydrous CuCI2, and a suitable organonitrite, such as tert-butyl nitrite, in a compatible solvent, such as acetonitrile, is added slowly to a solution of a compound of formula (VII). This is followed by a time that allows reacting as appropriate and proper processing. Preparation 37 exemplifies this procedure. Step (b1) consists of the slow addition of a solution of the purified compound of formula (VIII), or mixtures containing a compound of formula (VIII), dissolved in a suitable solvent such as dimethisulfoxide, to a solution of trimethylsulfoxonium iodide in a suitable solvent such as dimethisulfoxide and a suitable base, such as sodium hydride. This is followed by a time that allows reacting as appropriate and proper processing. Preparation 37 exemplifies this procedure. Step (c ') can be carried out using a suitable reducing agent in a compatible solvent, such as borane in tetrahydrofuran or Red-Al® in toluene at an appropriate temperature, such as for example 65 ° C in the case of borane as the reducing agent. This is followed by proper processing. Preparation 38 exemplifies this procedure. In another aspect of the present invention an alternative synthetic process is provided for the preparation of the compounds of formula (II), or generally of formula (Xlll). This procedure comprises the following steps: (X) (XI) (XI!) (XN) (Xill) wherein: Ri, p and G are as defined for formula (I), R14O is a suitable alkoxy group, PG is an appropriate protecting group and Y can be halogen such as bromine, or a sulfonyloxy group such as trifluoromethylsulfonyloxy and comprises following steps: step (a ") means the coupling reaction of a (2,5-dihydro-1 H-pyrrol-3-yl) boronate (X) with the aromatic halogen or sulfonyloxy derivative (XI); ") means cyclopropanation of (Xll) followed by, if appropriate, deprotection to provide the bicyclic amine (Xlll). Step (a ") can be carried out using conventional methods for Suzuki coupling, for example using tetrakis (triphenylphosphine) palladium (0) as the palladium (0) calalytic source in the presence of cesium fluoride in a solvent suitable as terahydrofuran at a suitable temperature (R? 40) 2B can suitably be 4,4,5,5-teremethyl-1, 3,2-dioxaborolan-2-yl and PG benzyl, which represents a compound of structure (X) as reported in Synletí 2002, 5, 829-831.Preparation 50 exemplifies this procedure Step (b ") consists of a cyclopropanation reaction which is carried out for example using the reagent generated from the trimethisulfoxonium iodide and a suitable base such as sodium hydride, in a compatible solvent, for example dimethyl sulfoxide. Preparation 52 exemplifies this procedure. This is followed by a deprotection reaction as exemplified in preparation 54. A compound of formula (III) can be prepared by reacting a compound of formula (V): wherein R3 and R4 are as defined above in the present invention; with a compound of formula (VI): L (CHR2) (CH2) 2X (VI) wherein X is defined as for formula (I) and L is a residual group, for example, a bromine atom. For typical reaction conditions, see Preparation 13 below. Compounds of formula (I) wherein R-i, R2, R3, R4, G and p are as defined above can be prepared by reacting a compound of formula (XIV): wherein Ri, R2, G and p are as defined for formula (I) and X is a residual group, with a compound of formula (V): wherein R3 and R4 are as defined above in the present invention. For the typical reaction conditions when X is chloro see example 35 or alternatively examples 41-52. A compound of formula (XIV) wherein Ri, G and p are as defined for formula (I), X is a residual group and R 2 is H (hydrogen) can be prepared by alkylation of a compound of formula (Xlll) in the presence of a suitable base such as a tertiary amine, for example diisopropylethylamine, with a propyl derivative carrying two residual groups preferably of differential reactivity at positions 1 and 3, for example 1-bromo-3-chloropropane. Typical reaction conditions for this transformation are given in preparation 40. A compound of formula (XIV) wherein R1; G and p are as defined for formula (I), X is a residual group and R 2 is C 4 -4 alkyl can be prepared by the reaction between a beta-hydroxy ketone, for example 4-hydroxy-2-butanone if R2 is methyl, with a compound of formula (Xlll) in the presence of a suitable borohydride ester such as NaBH (OAc) 3, followed by conversion of the hydroxyl group to a residual group by methods known to the person skilled in the art, for example by the action of the chloralionyl chloride. The typical reaction conditions for these transformations are given in Preparations 19 and 20. The interconversion reactions between the compounds of formula (I) and salts thereof can be carried out using methods well known in the art. Examples include: (i) the conversion of one or more Ri from alkoxy (eg methoxy) to hydroxy, (ii) the conversion of one or more of Ri from hydroxy to sulfonyloxy, such as alkylsulfonyloxy or haloalkylsulfonyloxy , for example methanesulfonyloxy or alkylsulfonyloxy or trifluoromethanesulfonyloxy, (ii) the conversion of one or more Ri from halogen or perfluoroalkylsulfonyloxy to cyano; and optionally subsequently forming a salt of formula (I). It has been found that the compounds of formula (I) exhibit affinity for dopamine receptors, in particular the D3 receptor, and are expected to be useful in the tracing of disease states which require the modulation of said receptors, as conditions psychoic Said affinity is typically calculated from the IC50 as the concentration of a compound necessary to displace 50% of the radiolabeled ligand from the receptor, and is reported as a "Ki" value calculated by the following equation:? ? . - IC; 50. / K D wherein L = radioligand and KD = affinity of the radioligand for the receptor (Cheng and Prusoff, Biochem Pharmacol 22: 3099, 1973). In the context of the present invention pKi (which corresponds to the Ki antilogarithm) is used in place of Ki and the compounds of the present invention typically show a pKi greater than 7. In one aspect the present invention provides compounds of formula (I) having a pKi comprising between 7 and 8. In another aspect the present invention provides compounds of formula (I) having a pKi comprising between 8 and 9. In a further aspect the present invention provides compounds of formula (I) which they have a pKi greater than 9. It has also been found that many of the compounds of formula (I) have a higher affinity for the dopamine D3 receptors than for the D2 receptors. It is generally believed that the therapeutic effect of currently available antipsychotic agents (neuroleptics) is exerted via blocking of D2 receptors; however, it is also thought that this mechanism is responsible for the undesirable extrapyramidal side effects (eps) associated with many neuroleptic agents. It has been suggested that blocking the newly characterized dopamine D3 receptor can result in beneficial antipsychotic activity without significant eps, (see for example Sokoloff et al, Nature, 1990; 347: 146-151; and Schwartz et al, Clinical Neuropharmacology, Vol 16, No. 4, 295-314, 1993). In one embodiment, the compounds of the present invention are provided which have a higher affinity (for example:> 10x or> 100x greater) for the dopamine D3 receptors than for the dopamine D2 receptors (said affinity can be measure using standard methodology for example using cloned dopamine receptors - see in the present invention). Suitably said compounds can be used as selective modulators of D3 receptors. From the location of the D3 receptors, it could also be considered that the compounds could also have utility for the treatment of substance abuse where it has been suggested that the D3 receptors are involved (for example see Levani, 1997, Pharmacol Rev., 49, 231-252). Examples of such substance abuse include alcohol, cocaine, heroin and nicotine abuse. Other conditions which may be irradiated by the compounds include dyskinetic disorders such as Parkinson's disease, neuroleptic-induced parkinsonism, and tardive dyskinesia; depression; anxiety, cognitive impairment include memory disorders such as Alzheimer's disease, eating disorders, sexual dysfunction, sleep disorders, emesis, movement disorders, obsessive-compulsive disorders, amnesia, aggression, autism, vertigo, dementia, rhythm disorders circadian and gastric motility disorders for example IBS. The compounds of formula (I) can be used for the treatment of all aspects of drug dependence including withdrawal symptoms from the abuse of drugs such as alcohol, cocaine, opiates, nicotine, benzodiazepines and inhibition of tolerance induced by drugs. opioids In addition, the compounds of formula (I) and the acceptable pharmaceutical salts and solvates thereof can be used to reduce craving and will therefore be useful in the travail of drug craving. The craving for drugs can be defined as the incentive motivation to self-administer a psychoactive substance that was previously consumed. Three main factors are involved in the development and maintenance of drug craving: (1) dysphoric states during drug abstinence can function as active reinforcers that lead to craving; (2) the environmental stimuli associated with the effects of the drugs may become progressively more powerful (sensitization) in the control of drug seeking or drug craving, and (3) a cognition (memory) of the drug's ability to promote pleasurable effects and alleviate a dysphoric state during abstinence. The craving for drugs may be related to the difficulty that individuals have in withdrawing from drug abuse and therefore contributes significantly to the development and maintenance of a drug dependency.

The compounds of formula (I) are of potential use as antipsychotic agents for example in the treatment of schizophrenia, schizoaffective disorders, psychotic depression, mania, paranoid disorders and hallucinations. In addition, these may have utility as adjunctive therapy in Parkinson's disease, particularly with compounds such as L-DOPA and possibly dopaminergic agonis, to reduce the side effects experienced with these treatments in long-term use (for example see Schwartz et al. , Brain Res. Reviews, 1998, 26, 236-242). Within the context of the present invention, the terms describing the indications used in the present invention are classified in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, published by the American Psychiatric Association (DSM-IV) and / or the International Classification of Diseases, 10th Edition (ICD-10). The various subtypes of the disorders mentioned in the present invention are contemplated as part of the present invention. The numbers in brackets after the diseases listed below refer to the classification code in DSM-IV. Within the context of the present invention, the term "psychotic disorder" includes: Schizophrenia, including the subtypes of the paranoid type (295.30), disorganized type (295.10), cayatonic type (295.20), undifferentiated lipo (295.90) and residual type ( 295.60); schizophreniform disorder (295.40); esq uizoaf ective disorder (295.70) including bipolar and depressive type subtypes; hallucinations disorder (297.1) including erotomanic type subtypes, large lipo, jealous type, persecutory type, somatic type, mixed type and unspecified type; brief psychic transorbital (298.8); shared psychophysical ego (297.3); psychotic disorder due to a general medical condition including hallucinatory and hallucinatory subtypes; psychotic trasforno induced by suspensions including the hallucinatory subtypes (293.81) and with hallucinations (293.82); and psychogenic disorder not otherwise specified (298.9). Within the context of the present invention, the term "transaction related to subsidies" includes: Substance-related disorders including substance use disorders such as substance dependence, craving for subsidies and abuse of subsidies; substance-induced disorders such as substance poisoning, substance withdrawal, substance induced delirium, substance-induced persistent dementia, substance-induced persistent amnestic disorder, substance-induced psychotic disorder, substance-induced disorder, anxiety-induced anxiety disorder substances, substance-induced sexual dysfunction, substance-induced sleep disorder and persistent hallucinogenic perception disorder (retrospective); alcohol-related disorders such as alcohol dependence (303.90), alcohol abuse (305.00), alcohol intoxication (303.00), alcohol withdrawal (291.81), delirium from alcohol intoxication, alcohol withdrawal delirium, persistent induced dementia for alcohol, alcohol-induced persistent amnestic disorder, alcohol-induced psychotic disorder, alcohol-induced mood disorder, alcohol-induced anxiety disorder, alcohol-induced sexual dysfunction, alcohol-induced sleep disorder, and alcohol-related disorder not otherwise specified another way (291.9); disorders related to amphetamines (or amphetamine-like) such as amphetamine dependence (304.40), amphetamine abuse (305.70), amphetamine poisoning (292.89), amphetamine abstinence (292.0), delirium from amphetamine intoxication, psychotic disorder induced by amphetamines, amphetamine-induced disorder, amphetamine-induced anxiety disorder, amphetamine-induced sexual dysfunction, amphetamine-induced sleep disorder, and amphetamine-related disorder not otherwise specified (292.9); caffeine-related disorders such as caffeine intoxication (305.90), caffeine-induced anxiety disorder, caffeine-induced sleep disorder, and caffeine-related disorder not otherwise specified (292.9); Cannabis-related conditions such as Cannabis dependence (304.30), Cannabis abuse (305.20), Cannabis poisoning (292.89), Cannabis intoxication delirium, Cannabis-induced psychogenic disorder, Cannabis-induced anxiety disorder and related disorder with Cannabis not otherwise specified (292.9); cocaine-related disorders such as cocaine dependence (304.20), cocaine abuse (305.60), cocaine poisoning (292.89), cocaine abstinence (292.0), delirium from cocaine poisoning, cocaine-induced psychotic disorder, cocaine disorder cocaine-induced character, cocaine-induced anxiety disorder, cocaine-induced sexual dysfunction, cocaine-induced sleep disorder, and cocaine-related disorder not otherwise specified (292.9); hallucinogen-related disorders such as hallucinogen dependence (304.50), hallucinogen abuse (305.30), hallucinogen intoxication (292.89), persistent hallucinogen perception disorder (retrospective) (292.89), delirium from hallucinogen intoxication, psychotic disorder induced by hallucinogen, hallucinogen-induced character disorder, hallucinogen-induced anxiety disorder, and hallucinogen-related disorder not otherwise specified (292.9); inhalant-related disorders such as inhalant dependence (304.60), inhalant abuse (305.90), inhalant poisoning (292.89), delirium from inhalant poisoning, persistent inhalant-induced dementia, inhalant-induced psychotic disorder, character-induced disorder inhalants, transients of inhalant-induced anxiety and inhalant-related disorders not otherwise specified (292.9); Nicotine-related conditions such as nicotine dependence (305.1), nicotine withdrawal (292.0), and nicoine-related disorders not otherwise specified (292.9); transitions related to opioids such as opioid dependence (304.00), opioid abuse (305.50), opioid poisoning (292.89), opioid withdrawal (292.0), delirium due to opioid poisoning, opioid-induced psychotic disorder, induced mood transient for opioids, opioid-induced sexual dysfunction, opioid-induced sleep transorbital and cocktail-related uranium not otherwise specified (292.9); disorders related to Phencyclidine (or similar to Phencyclidine) such as dependence to Phencyclidine (304.60), abuse of Phencyclidine (305.90), intoxication with Phencyclidine (292.89), delirium from intoxication with Phencyclidine, psychotic disorder induced by Phencyclidine, character disorder induced by Phencyclidine, Phencyclidine-induced anxiety disorder and Phencyclidine-related disorder not otherwise specified (292.9); disorders related to sedatives, hypnotics, or anxiolytics such as dependence on sedatives, hypnotics, or anxiolytics (304.10), abuse of sedatives, hypnotics, or anxiolytics (305.40), intoxication with sedatives, hypnotics, or anxiolytics (292.89), abstention of sedatives , hypnotics, or anxiolytics (292.0), delirium due to intoxication with sedanis, hypnotics, or anxiolytics, delirium due to withdrawal of sedans, hypnotics, or anxiolytics, persistent dementia due to sedatives, hypnotics, or anxiolytics, persistent amnesic transience by sedanies, hypnotics, or Anxiolytics, psychogenic disorder induced by sedatives, hypnotics, or anxiolytics, character rearrangement induced by sedanis, hypnotics, or anxiolytics, senescence induced anxiety hypnotic, hypnotic, or anxiolytic, sexual dysfunction induced by sedatives, hypnotics, or anxiolytics, sleep induced by sedatives, hypnotics, or anxiolytics and disorder related to sedatives, hypnotics, or anxiolytics not otherwise specified (292.9); disorder related to polysubstances as a dependence of polysubstances (304.80); and other disorders related to suspensions (or with unknown elements) such as anabolic steroids, nitrate inhalants and nitrous oxide. Therefore in a further aspect the present invention provides a method for the traceability of a condition for which the modulation (especially anomagonism / inhibition) of dopamine receptors (especially dopamine D3 receptors) is beneficial, which comprises administration to a mammal (e.g., human) that needs therefrom an effective amount of a compound of formula (I) or a pharmaceutically (eg, physiologically) acceptable salt thereof. Such conditions in particular include psychosis / psychic conditions such as schizophrenia, and substance abuse. The invention also provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the transport of a condition in a mammal for which the modulation (especially antagonism / inhibition) of dopamine receptors (especially dopamine D3 receptors) is beneficial. The invention also provides a compound of formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of a condition in a mammal for which the modulation (especially antagonism / inhibition) of dopamine receptors (especially dopamine D3 receptors) ) is beneficial. In one embodiment, antagonisms of D3 according to the present invention are used in the treatment of psychosis. Such as schizophrenia or in the treatment of substance abuse. Therefore, a further aspect of the invention provides a method for the processing of a psychotic condition (eg, schizophrenia) or substance abuse which comprises administration to a mammal (eg, human) that needs a quantity of the same. effective of a compound of formula (I) as defined in the present invention or a pharmaceutically acceptable salt thereof. Also provided is the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of a psychotic condition (eg, schizophrenia) or substance abuse in a mammal. A compound of formula (I) or a pharmaceutically acceptable salt thereof is also provided for use in the treatment of a psychotic condition (e.g., schizophrenia) or substance abuse in a mammal. A compound of formula (I) or a pharmaceutically acceptable salt thereof is also provided for use as an active therapeutic substance in a mammal, for example for use in the treatment of any of the conditions described in the present invention.

"Treatment" includes prophylaxis, where it is appropriate for the relevant condition (s). For use in medicine, the compounds of the present invention are usually administered as a standard pharmaceutical composition. The present invention therefore provides in a further aspect a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically (eg, physiologically) acceptable salt thereof and a pharmaceutically (eg, physiologically) acceptable carrier. The pharmaceutical composition can be for use in the treatment of any of the conditions described in the present invention. The compounds of formula (I) can be administered by any convenient method, for example by oral, parenteral (for example intravenous), buccal, sublingual, nasal, rectal or transdermal administration and the pharmaceutical compositions adapted accordingly. The compounds of formula (I) and their pharmaceutically acceptable salts which are active when provided orally can be formulated as liquids or solids, for example syrups, suspensions or emulsions, tablets, capsules and tablets. Generally a liquid formulation consists of a suspension or solution of the compound or a pharmaceutically acceptable salt in a suitable liquid carrier (s) for example an aqueous solvent such as water, ethanol or glycerin, or a non-aqueous solvent, such as polyethylene glycol or an oil . The formulation may also contain an agent for suspension, preservative, flavoring agent or colorant. A composition can be prepared in the form of a tablet using any suitable pharmaceutically suitable carrier (s) routinely used for the preparation of extruded formulations. Examples of such carriers include magnesium stearate, starch, lactose, sucrose and cellulose. A composition can be prepared in the form of a capsule by using fluidal procedures for encapsulation. For example, concentrates containing the active ingredient can be prepared using standard vehicles and then used to fill a hard gelatin capsule; alternatively, a dispersion or suspension can be prepared using any suitable pharmaceutical carrier (s), for example aqueous gums, celluloses, silicates or oils and then the dispersion or suspension is used to fill a soft gelatin capsule. The parenteral parenteral compositions consist of a solution or suspension of the compound or a pharmaceutically acceptable salt in a sterile aqueous carrier or parenterally acceptable oil, for example polyethylene glycol, polyvinyl pyrrolidone, lecithin, arachis oil or sesame oil. Alternatively, the solution can be lyophilized and then reconstituted with a suitable solvent just prior to administration. Compositions for nasal administration can be conveniently formulated as aerosols, drops, gels and powders. Aerosol formulations typically comprise a solution or fine suspension of the active substance in a pharmaceutically acceptable aqueous or non-aqueous solvenie and are usually present in particular amounts or in multiple doses in sterile form in a sealed container, which can take the form of a cartridge or filler for use with an atomizer device. Alternatively, the sealed container may be a unitary dispersing device such as a particular dose nasal inhaler or an aerosol dispenser fitted with a metering valve which is intended for the application of the contents of the container at an angle. Where the dosage form comprises an aerosol dispenser, it will contain a propellant which may be a compressed gas such as compressed air or an organic propellant such as a fluorochlorohydrocarbon. The aerosol dosage forms can also take the form of a pump-atomizer. Compositions suitable for buccal or sublingual administration include tablets, tablets and lozenges, wherein the active ingredient is formulated with a carrier such as sugar and acacia, tragacanth, or gelatin and glycerin. Compositions for rectal administration are conveniently in the form of suppositories containing a conventional suppository base such as cocoa butter. Compositions suitable for transdermal administration include ointments, gels and patches.

In one embodiment, the composition is in the form of a unit dose such as a tablet, capsule or ampule. Each dose unit for oral administration contains for example from 1 to 250 mg (and for parenteral administration they contain for example from 0.1 to 25 mg) of a compound of the formula (I) or a pharmaceutically acceptable salt thereof calculated as the free base . The pharmaceutically acceptable compounds of the invention will normally be administered in a daily dose regimen (for an adult patient) of, for example, an oral dose of enriched 1 mg and 500 mg, for example 10 mg and 400 mg, for example enimer. 10 and 250 mg or an intravenous, subcutaneous, or intramuscular dose of between 0.1 mg and 100 mg, for example between 0.1 mg and 50 mg, for example between 1 and 25 mg of the compound of the formula (I) or a pharmaceutically acceptable salt of the same calculated as the free base, the compound is administered 1 to 4 times per day. Suitably the compounds will be administered for a period of continuous therapy, for example for a week or more.

Biological test methods The functional potency and intrinsic activity of the compounds of this invention can be measured by the following proximity scintillation assay GTp? S (GTp? S-SPA). The cells used in the study are Chinese hamster ovary (CHO) cells.

Cell line CHO_D2 CHO_D3 The membranes of the cells were prepared as follows. The cell concentrates were resuspended in 10 volumes of 50 mM HEPES, 1 mM EDTA pH 7.4, using KOH. The next day the proteases were added to the pH regulator just before providing the pH regulator for homogenization. Leupeptin 10"6 M (Sigma L2884) -5000 x storage solution = 5 mg / ml pH regulator 25 ug / ml Bacitracin (Sigma B0125) -1000 x storage solution = 25 mg / ml pH regulator PMSF 1 mM-1000 x storage solution = 17 mg / ml in 100% ethanol Pepstain A 2x10"6 M-1000 x storage solution = 2 mM in 100% DMSO. The cells were homogenized by 2 x 15 second applications in a 1 liter Glass Waring blender inside a bell for class 2 biologic products. The resulting suspension was centrifuged at 500 g for 20 minutes (Beckman T21 centrifuge: 1550 rpm). The supernatant was removed with a 25 ml pipette, aliquoted into pre-cooled centrifuge tubes and centrifuged at 48,000 g to concentrate the membrane fragments (Beckman T1270: 23,000 rpm for 30 minutes). The final concentrate at 48,000 g was resuspended in a pH regulator for homogenization, (4 x the volume of original cell concentrate). The concentrate at 48,000 g was resuspended by vortexing for 5 seconds and homogenizing in a Dounce homogenizer 10-15 times. The preparation was dispensed into aliquots of appropriate size (200-1000 ul) in polypropylene tubes and stored at -80 ° C. Proiein content in the membrane preparations is evaluated with the Bradford protein assay. The final top concentration of the test drug is 3 uM in the assay and serial dilution curves of 11 points 1: 4 are performed in 100% DMSO using a Biomek FX. The drug test at 1% of the total assay volume (TAV) was added to a 384 well solid assay blank plate. 50% of TAV of the pre-coupled membranes (for 90 minutes at 4 ° C), 5 ug / well, and beds for proximity scintillation test on polystyrene with wheat germ agglutinin (RPNQ0260, Amersham), 0.25 mg / well, in 20 mM HEPES pH 7.4, 100 mM NaCl, 10 mM MgCl 2, 60 ug / ml saponin and 30 pM GDP are added. The third addition was a 20% addition of TAV of any pH regulator, (agonist format) or EC8o concentration of the final agonist assay, Quinelorano, prepared in a pH regulator for assay (antagonism format). The assay was initiated by the addition of 29% TAV of final GTPI [35S] 0.38 nM (37 MBq / ml, 1160 Ci / millimoles, Amersham). After all additions, the test plates were centrifuged for 1 minute at 1,000 rpm. The test plates are counted in a Viewlux, filter 613/55, for 5 minutes, between 2-6 hours after the final addition. The effect of the test drug on the baseline generates an EC50 value by means of an iterative least squares curve fitting program, expressed in the table as pEC50 (for example -logEC50). The relationship between the maximum effect of the test drug and the maximum effect of the total agonist, Quinelorano, generates the value of intrinsic activity (IA) (for example IA = 1 total agonist, IA <; 1 partial agonist). The fpKi values of the test drug are calculated from the IC 50 generated by the experiment in "antagonist format", using the Cheng & Prusoff: fKi = C50 / 1 + ([Aj / ECdo) where: [A] is the concentration of the 5-HT agonist in the assay and EC50 is the 5-HT EC50 value obtained in the same experiment. fpKi is defined as -logfKi. The compounds of the invention listed above have pKi values within the range of 7.0-10.5 in the dopamine D3 receptor. The results of pKi alone are estimated to be accurate to approximately ± 0.3-0.5. The compounds of the invention listed above have a selectivity on D2 greater than 30.

EXAMPLES The invention is further illustrated by the following non-limiting examples. Preparations 1 to 5 were carried out in analogy to the synthetic route described in J. Med. Chem. 1981, 24, 481-490. All temperatures refer to C. Infrared spectra were measured in FT-lR apparatus. The compounds were analyzed by means of direct infusion of the sample dissolved in acetoniiril within a mass spectrum operated in a posifive ionization mode by electro-spraying (ES +). The proton magnetic resonance spectra (1H-NMR) were recorded at 400 MHz, the chemical changes are reported in ppm of low field (d) from Me4Si, are used as infernal standards, and are assigned as singlet (s) , broad singles (bs), doublets (d), doubles doublets (dd), tripleies (í), quartets (q) or multiplets (m). The experimental spectra of vibrational circular dichroism (VCD) were measured using a Chiral I DRTM VCD spectrometer operating at the frequency interval of 2000-800 cm-1. The spectra were measured at room temperature (23 ° C) using a sealed transmission cell with barium fluoride windows and a route length of 100 microns. (The registration times varied from 60 to 120 minutes per isomer). Sample solutions were typically prepared by dissolving 10 milligrams of each enantiomer in 100 micolollins of deutero-chloroform (CDCl3). For start assignments, unpolarized VCD and IR spectra were calculated using Gaussian 98 software package.1. Optical rotations were measured using a polarimeter (Perkin Elmer Model 241) operating at 589 nm (sodium source) ). The measurements were made using a microcell of 1 decimeter thermostated at 23 ° C. The concentrations were typically 10 mg / ml (c = 0.01). For the start assignments, the Dalton Quantum chemistry program was used. Column chromatography was carried out on silica gel (Merck AG Darmstaadt, Germany). The following abbreviations were used in the text: NBS = N-bromosuccinimide, Vitride = "Red-Al®", HOBt = 1-hydroxybenzotriazole EtOAc = ethyl acetate, Et 0 = diethyl ether, DMF = N, N'-dimethylformamide, MeOH = methanol, TFA = trifluoroacetic acid, tetrahydrofuran = terahydrofuran, IPA = isopropanol, TEA = triethylamine, DCC = 1,3-dicyclohexylcarbodiimide, SCX = strong cation exchanger, Tic refers to thin-layer chromatography on silica plates, and dried refers to a dried solution over anhydrous sodium sulfate, r. t. (RT) refers to ambient temperature, Rí = retention time, DMSO = dimethyl sulfoxide.

PREPARATION 1 Methyl bromine (4-methoxyphenyl) acetate To a mixture of methyl-4-methoxyphenylacetamide of (20 g, 0.11 mol) and NBS (0.11 mol) in CCI4 (0.2 I) was added 3 drops of 48% HBr and this mixture was heated to reflux for 8 hours. The cooled solution was filtered through a pad of silica gel and the filtrate was evaporated in vacuo to yield 29 g of the title compound as a light yellow oil, which was used in the subsequent step without further purification. NMR (1H, CDCl 3): d 7.3 (d, 2H), 6.8 (d, 2H), 5.1 (s, 1 H), 3.8 (s, 3H), 3.5 (s, 3H).

PREPARATION 2 Dimethyl-1- (4-methoxyphenyl) -1,2-cyclopropanedicarboxylate To a stirred paste with stirring of NaH (4.4 g, 60% in mineral oil) in anhydrous Et20 (0.3 I) was added methanol (10.3 mL) followed by a solution of bromine ester obtained in preparation 1, methyl bromine (4). -methyloxyphenyl) acetate (29 g) in methyl acrylate (19.8 mL) (for the examples starting from a derivative, phenylacetate derived from ethanol and ethyl acrylate, respectively) and methanol (3 mL) were used at 0 ° C, for 30 minutes. The mixture was stirred at 25 ° C for 24 hours and then unreacted NaH was decomposed with 3 mL methanol. Water (75 mL) was added, the organic phase was separated, dried over Na2SO4 and filtered. The volatile elements were evaporated in vacuo to yield 31.5 g of the title compound as an oil, which was used in the subsequent step without further purification. NMR (1H, CDCl 3): d 7.3 (d, 2H), 6.8 (d, 2H), 3.77 (s, 3H), 3.73 (s, 3H), 3.64 (s, 3H), 2.18 (dd, 1 H) , 2.05 (dd, 1 H), 1.46 (dd, 1 H). MS (m / z): 265.4 [MHJ +. PREPARATION 3 1- (4-Methoxyphenyl) -1,2-cyclopropanedicarboxylic acid A mixture of diester obtained in preparation 2 (31.5 g) and KOH (13.5 g) in 1: 1 EtOH: H20 (240 mL) was heated to reflux for 6 hours and then concentrated to half the original volume. The aqueous solution was extracted with Et20, cooled on ice, and then made acidic with 25 mL of 12 N HCl. The product in white crystals was collected by filtration and dried under vacuum to yield 12.8 of the title compound (general yield from meityl bromo (4-methioxyphenyl) acetamide: 50%). NMR (1H, DMSO): d 12.5 (bs, 2H), 7.25 (d, 2H), 6.85 (d, 2H), 3.7 (s, 3H), 2.0 (dd, 1 H), 1.85 (dd, 1 H) ), 1.38 (dd, 1 H). MS (m / z): 235.0 [M-H] 0 PREPARATION 4 (1 R, 5S / 1S, 5R) -1-F4- (Methoxy) phenin-3-azabicyclo3.1.01hexane-2,4-dione A mixture of 12.8 g of the diacid obtained in preparation 3 and 6. 5 g of urea in 300 mL of m-xylene was heated to reflux for 8 hours and then concentrated to dryness in vacuo. The crude product was purified by column chromatography (AcOEt: cyclohexane = 1 (?): 10 to 4: 6) to yield 5.5 g of the title compound (y = 46%). MS (m / z): 218.1 [MHJ0 PREPARATION 5 (1R, 5S / 1S, 5R) -1-r4- (Methoxy) phenin-3-a2abicyclor3.1.01hexane To a stirred pass of 5.5 g of the measurement obtained in Preparation 4 in 170 mL of toluene were added 45 mL of Vifride (3.4 M in toluene) under N2. This solution was stirred at reflux for 2 hours. To the cooled solution was carefully added aqueous NaOH (10 M, 40 mL) and the organic layer was washed with two portions of water and dried over Na 2 SO. This solution was filtered, and the filtrate was evaporated in vacuo to yield 4.8 g of the title compound (y = 100%).

NMR (1H, CDCl 3): d 7.10 (d, 2H), 6.82 (d, 2H), 3.77 (s, 3H), 3.35-2. 98 (m, 4H), 2.58 (dd, 1 H), 0.87 (dd, 1 H), 0.78 (dd, 1 H), NH not observed. MS (m / z): 190.1 [MHJ0 PREPARATION 6 (1R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3-azabicyclo3.1.01hexane To 20 mL of 1 M-tetrahydrofuran BH3, stirred at 0 ° C under N2, a solution of 1.32 g (5 mmol) of (1 R, 5 S / 1 S, 5 R) -1- (4-bromophenyl) was added slowly. ) -3-azabicyclo [3.1.0] hexane-2,4-dione, prepared in analogy to preparation 4, in 20 mL of dry tetrahydrofuran. This solution was stirred at ambient temperature for 15 minutes and then heated in a steam bath for 1 hour. Then the solution was cooled in a bath with ice, 2.5 mL of 6 M HCl was added carefully, and the solvent was removed in vacuo. The residual material was combined with 12.5 mL of 5 M NaOH and the mixture was extracted with ether. The ether extract was washed twice with water, dried over Na 2 SO and filtered to yield 1.19 g of the title compound (y = 100%). NMR (1H, CDCl 3): d 7.35 (d, 2H), 7.02 (d, 2H), 3.25-2.96 (m, 4H), 1.63 (dd, 1 H), 1.55 (dd, 1 H), 1.30 (dd) , 1 H), NH not observed. MS (m / z): 238.1 [MH] +, 1 Br.

PREPARATION 7 (1R.5S / 1S, 5R) - 4-r3- (Trifluoroacetyl) -3-azabicyclo3.1.01hex-1-illbenzonitrile Trifluoroacetic anhydride (0.21 mL) was added to a solution of 4- [3-azabicyclo [3.1.0] hex-1-yl] benzonyryl (280 mg, prepared in analogy to the method described in Preparation 5), and triethylamine (0.25 mL) in dichloromethane (15 mL) at 0 ° C. The reaction mixture was allowed to warm to room temperature for 2 hours, then washed with saturated NaHCO 3, the organic layer was dried and evaporated to yield 269 mg of the title compound. MS (m / z): 281.2 [MHJ0 PREPARATION 8 (1R, 5S / 1S, 5R) - 4-r3- (Trifluoroacetyl) -3-azabicyclo3.1.0lhex-1- Ubenzaldehyde A mixture of 4- [3- (trifluoroacetyl) -azabicyclo [3.1.0] hex-1-yl-benzonitrile (283 mg), Ni-AI alloy (450 mg), formic acid (3.9 mL) and water (1.1 mL) it was stirred at 80 ° C for 3 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was extracted with ethyl acetate and the organic phase was washed with NaHCO 3, dried over NaSO 4 and evaporated in vacuo to yield 195 mg of the compound of the product as a yellow-colored oil. MS (m / z): 284.2 [MH] +.

PREPARATION 9 (1 R.5S / 1 S, 5R) -4-r3- (Trifluoroacetyl) -3-azabicyclo3.1.0 * lhex-1 - illbenzaldehyde oxime To a solution of 4- [3- (trifluoroacetyl) -3-azabicyclo [3.1.0Jhex-1-yl-benzaldehyde (195 mg) in 5 mL of pyridine was added hydroxylamine hydrochloride (57.5 mg) and the mixture was stirred for 3 hours to temperaíura ambienie. The solvent was evaporated, the crude product was dissolved in ethyl acetate and the organic phase was washed with 10% aqueous Na 2 CO 3 and brine, dried over Na 2 SO 4 and evaporated in vacuo to yield 225 mg of the title compound as an oil. yellow. MS (m / z): 299.2 [MH] +.

PREPARATION 10 Chloride of (1R, 5S / 1S, 5R) -4-r3- (Trifluoroacetyl) -3-azabicyclo3.1.01hex-1-inN-hydroxybenzenecarboximidoyl To a solution of 4- [3- (trifluoroacetyl) - (3-azabicyclo [3.1.0Jhex-1-yl] benzaldehyde oxime (0.69 mmol) in 3.5 mL of dimethylformamide was added portion by portion N-chlorosuccinimide (97 mg) at 0 ° C. After stirring for 1.5 hours at 40 ° C the solvent was evaporated. The crude product was dissolved in diethyl ether / dichloromethane (4/1) and the organic phase was washed with water, dried over Na 2 SO 4 and concentrated in vacuo to yield 243 mg of the title compound as a brown oil.

PREPARATION 11 (1R.5S / 1S.5R) -1-r4- (5-Methyl-3-isoxazolyl) phenin-3- (trifluoroacetin-3-azabiciclof3.1.Olhexane To a solution of 4- [3- (trifluoroacetyl) -3-azabicyclo [3.1.0Jhex-1-yl] -N-hydroxybenzenecarboximidoyl chloride (0.69 mmol) in 6 mL of chloroform triethylamine (0.24 mL) and 2 was added. -chlorine propene (0.29 mL) and the reaction was stirred for 18 hours at ambient temperature. The solution was washed with water, dried over Na 2 SO 4 and the volatile elements were evaporated in vacuo. The crude product was purified by column chromatography (AcOEt: cyclohexane = 1: 10 to 4: 6) to yield 180 mg of the title compound. MS (m / z): 337.2 [MHJ0 PREPARATION 12 (1R, 5S / 1S, 5R) -1-r4- (5-Methyl-3-isoxazolyl) phen-3-azabicyclo3.1.01hexane A mixture of 1- [4- (5-methy1-3-isoxazolyl) phenyl] -3- (trifluoroacetyl) -3-azabicyclo [3.1. Ojhexane (0.54 mmol) and K2CO3 (296 mg) in methanol (5 mL) and water (5 mL) were stirred for 4 hours at 50 ° C. The solvent was evaporated in vacuo and the product was treated with 1/1 dichloromethane / isopropanol and filtered. The filtrate was dried over Na2SO and the volatile elements were evaporated in vacuo to yield 105 mg of the title compound (y = 81%). MS (m / z): 241.2 [MH] 0 PREPARATION 13 5-. { 5 - [(3-chloropropyl) thio-1-4-methyl-4H-1,2,4-triazol-3-yl > -2-methylquinoline To 4-methyl-5- (2-methyl-5-quinolinyl) -2,4-dihydro-3H-1, 2,4-triazole-3-thione (3.6 g, prepared in analogy to the method described in WO 200240471) in elanol (60 mL) containing 1-bromo-3-chloropropane (2.0 mL), stirring sodium hydride (0.60 g, 60% in petroleum) was carefully added. The mixture was heated to reflux for 45 minutes. The volatile elements were evaporated in vacuo and the residue was subjected to column chromatography (EtOAc-acetylene gradient). The material thus obtained was precipitated by heating with hot EOAc (20 mL) by the addition of peiroleum ether (40-60, 50 mL), cooled and collected by filtration to provide the title compound as colorless crystals (2.1 g). ). NMR (1H, CDCl 3): d 8.18 (d, 1 H), 8.12 (d, 1 H), 7.76 (t, 1 H), 7.55 (d, 1 H), 7.30 (d, 1 H), 3.75 (t, 2H), 3.50 (t, 2H), 3.40 (s, 3H), 2.76 (s, 3H), 2.37 (m, 2H).

PREPARATION 14 3-r (3-chloropropyl) thio > 4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1,2,4-triazole cr V N / Eile-2-chloroacetoacety (1 wt (weight), 1 equivalent, 1000 g) was aged with formamide (0.68 volumes, about 2.8 equivalents) and the resulting solution was heated to 120 ° C. After 5 hours the mixture was allowed to cool to room temperature and allowed to age under nitrogen overnight. The mixture was treated with NaOH (3 M, 6 volumes, moderately exothermic reaction) and stirred at room temperature for 4 hours. Ethyl acetic acid (6 volumes) was added and the phases were allowed to separate. The organic layer was discarded while the aqueous layer it was acidified with concentrated aqueous HCl (32%) to pH 2 (about 2.0 volumes). A precipitate began to form. The suspension was treated with AcOEt (8 volumes) and agitated vigorously until the mass of the precipitate dissolved. The aqueous phase was further extracted with AcOEt twice (6 volumes each) and the combined organic layers were distilled to decrease the volume (again a low volume suspension was observed). Freshly prepared AcOEt (8 volumes) was added and the mixture evaporated to dry. The collected solid was placed in the oven at 40 ° C overnight under reduced pressure to produce 4-methyl-1 acid., 3-oxazole-5-carboxylic acid (498 g, 64.5%). This material (498 g, 1 wt (weight)) was dissolved in dry tetrahydrofuran (5 volumes), under nitrogen, cooled to 0 ° C. DCC (1.62 wt (weight), 1 equivalent) was added portion by portion followed by HOBt (1.07 wt (weight), 1 equivalent). The mixture was heated to 252 ° C and stirred for 30 minutes. Then 4-Methyl-3-iosemicarbazide (0.83 wt (weight), 1 equivalent) was added and the mixture was further agitated for 2 hours at 25 + 2 ° C. The mixture was filtered and the concentrate was washed with freshly prepared telrahydrofuran (1 volume) and d on the filter for a few hours. The concentrate was suspended in 1 M aqueous NaOH (13 volumes) and heated at 70 ° C for 30 minutes. After this time, the mixture was cooled to 25 ± 2 ° C and a solid was removed by filtration. The concentrate was washed with 1 M aqueous NaOH (10 volumes). The combined mother liquors were cooled to 0 ° C and acidified to about pH 5 with HCl (aqueous, 16%; NOTE: keep the temperature while HCl is added below + 10 ° C). The suspended product was isolated by filtration by washing with water (2x3 volumes). The concentrate was dried at 40 ° C for 18 hours under high vacuum to obtain 4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -2,4-dihydro-3H-1, 2, 4-triazole-3-thione (respectively a tautomeric form thereof, 290 g, 37%). NaOEt (21% solution in EtOH, 2.08 volumes, 1.1 equivalents) was added to EOH (20 volumes) under nitrogen atmosphere. 4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -2,4-dihydro-3H-1, 2,4-triazole-3-thione (respectively a tautomeric form thereof; 290 g, 1 wt (weight)) was added in one portion and the resulting mixture was stirred at 25 ± 2 ° C until a clear solution was obtained. Then 1-bromo-3-chloropropane (0.54 volumes, 1.1 equivalents) was added and the solution was stirred at 40 ° C for 24 hours then cooled to 25 ° C. After filtration, water (20 volumes) was added and the ethanolic phase was removed by vacuum distillation (initial temperature ~ 40 ° C). The mixture was extracted with EtOAc (41 volumes). The aqueous layer was removed and the organic phase was evaporated to dryness. Dichloromethane (4 volumes) was added. The organic solution was purified through a short column of silica gel (18 wt (weight) of silica), eluting with EtOAc (200 volumes) to yield the title compound as a solid foam (267.64 g, 66%). NMR (1H, CDCl 3): d 7.90 (s, 1 H), 3.70 (s, 5H), 3.40 (t, 2H), 2.52 (s, 3H), 2.30 (m, 2H).

PREPARATION 15 3-r4- (Trifluoromethyl) phenyl '| -1H-pyrrole-2,5-dione A mixture of hydrochloric acid (37%, 285 mL) and water (190 mL) was added to 4- (trifluoromethyl) aniline (150 g, 116 mL) at ambient temperature with vigorous stirring and the formed precipitate was allowed to stir by 30 additional minutes The temperature was reduced to 0 ° C and sodium nitrite (70.6 g) in 180 mL of dropwise water was added to the suspension under stirring. At the end of the diazoization, a light yellow solution was obtained. Maleimide (180 g) in acetone (1.1 I) was added dropwise at 0 ° C and then the pH of the solution was adjusted to 3-3.5 by the addition of sodium acetate. Copper (II) chloride (18.8 g) was added to the vigorously stirred mixture. After a few minutes a gas began to develop (conspicuous foam formation). The reaction mixture was allowed to stir at 0 ° C for 1 hour and overnight at room temperature. The acetone was removed in vacuo, the residue was filtered and dried overnight under vacuum to yield the title compound (155 g) as a light brown solid (y = 63%). MS (m / z): 242.2 [MHJ +.

PREPARATION 16 (1R.5S / 1S, 5R) -1-r4- (Trifluoromethylphenin-3-azabicyclo3.1.01hexane-2,4-dione Sodium hydroxide (40 g) was added in small portions to an agitated solution of iodide of dimethyl sulfoxide (219 g) in DMSO (anhydrous, 2 I). The resulting mixture was allowed to stir at ambient temperature for 1.5 hours. 3- [4- (Trifluoromethyl) phenyl] -1H-pyrrole-2,5-dione (preparation 15, 120 g) was dissolved in DMSO (anhydrous, 0. 5 I) then added dropwise and the The resulting mixture was allowed to agligate at room temperature for 20 minutes. The temperature was then reduced to 0 ° C and NH 4 Cl (saturated aqueous solution, 2 L) was slowly added, followed by Et 20 (1 L). After separation of the two phases, the aqueous layer was extracted repeatedly with Et20 (3 x 1 I). The combined organic layers were washed with brine (2 x 1 L) and then dried over Na 2 SO. Evaporation of the solvent produced a light brown solid which was suspended in 1 l of dichloromethane and 1 l of cyclohexane. The mixture was allowed to stir at room temperature for 45 minutes and then filtered to yield the title compound (116 g) as a white solid (y = 71%). MS (m / z): 256.1 [MHJ +.

PREPARATION 17 (1R.5S / 1S, 5R) -1-r4- (Trifluoromethyl) phenin-3-azabicyclo3.1.01hexane Borane (1 M in tetrahydrofuran, 1.4 I) was charged into a 5 I reactor under N2 and cooled to 0 ° C. (1 R, 5S / 1S, 5R) -1- [4- (Trifluoromethyl) phenyl] -3-azabicyclo [3.1.0Jhexane-2,4-dione (preparation 16, 101 g) was dissolved in tetrahydrofuran (anhydrous, 1 I) was then added dropwise with vigorous stirring while the temperature was constantly kept below 5 ° C and the evolution of the gas was monitored. At the end of the addition the resulting mixture was allowed to stir at 0 ° C for 1 hour and then at room temperature overnight. Then the mixture was cooled to 0 ° C and methanol (200 mL) was added carefully followed by hydrochloric acid (6 M solution, 0.8 I) monitoring the evolution of the gas. Then the tetrahydrofuran was removed in vacuo, the residue was cooled to 0 ° C and sodium hydroxide (5 M solution) was added until pH 9-10 was reached. The aqueous layer was extracted with E20 (3 x 1 L). Removal of the solvent in vacuo afforded the title compound (140 g) as a colorless oil. MS (m / z): 228.1 [MHJ +.

PREPARATION 18 (1S.5R) -1-r4- (Trifluoromethyl) phenin-3-azabicyclo3.1.01hexane (S) - (+) - Mandelic acid (94 g) was added in portions to a stirred solution of (1 R, 5S / 1S, 5R) -1- [4- (trifluoromethyl) phenylJ-3-azabicyclo [3.1 . Ojhexane (preparation 17, 140 g) in 1.4 I of tetrahydrofuran. The resulting mixture was stirred at room temperature for 2 hours until a white precipitate formed. Then the mixture was heated to a reflux temperature, stirred for 45 minutes and then cooled slowly to room temperature. The white solid was collected by filtration and dried in vacuo. This material was recrystallized 4 times from tetrahydrofuran (10 volumes) to yield 32.5 g of a white solid. Then this material was suspended in sodium hydroxide (1 M solution), 400 mL) and in E20 (400 mL) and allowed to stir at ambient temperature until complete dissolution. After separation of the two phases, the aqueous layer was extracted again with Et20 (3 x 250 mL). The combined organic layers were washed with sodium hydroxide (1 M solution, 3 x 200 mL) and then dried over Na 2 SO. Evaporation of the solvent in vacuo afforded the title compound (19 g) as a white solid (y = 37%). The absolute configuration of the optical isomers was assigned using comparative VCD (vibrational circular dichroism) and OR (optical rotation) analyzes. The configuration of the title compound was assigned by comparing its experimental VCD spectrum and observed the specific rotation to the observed data for (1S, 5R) -1- (3,4-dichlorophenyl) -3-azabicyclo [3.1. Ojhexano (see preparation 48) as the reference sample. Assignment of the absolute configuration of the title compound was confirmed by a particular crystal X-ray structure obtained from a crystal of (1S, 5R) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexane, salt of (S) - (+) - mandelic acid. Both, analyzes based on the known configuration of (S) (+) - mandelic acid and on the basis of anomalous dispersion effects confirmed that the assignment of the title compound was (1S, 5R) -1- [4- (trifluoromethyl) ) phenol] -3-azabicyclo [3.1. Ojhexano. NMR (1H, CDCl 3): d 7.51 (d, 2H), 7.25 (d, 2H), 3.20 (d, 1 H), 3.0-3. 1 (m, 3H), 1.69 (m, 1 H), 0.8-1.0 (m, 2H), NH not observed. MS (m / z): 228.1 [MHJ +. Analytical chromatography Column: chiralcel OD 10 um, 250 x 4.6 mm Mobile phase: A: n-hexane; B: Isopropanol + 0.1% Isopropyl amine Gradient: isocratic 2% B Flow rate: 1 mL / minute UV wavelength range: 200-400 nm Analysis time 25 minutes Retention time (minute)% a / a 16.5 0.4 (1 R, 5S) -1- [4- (trifluoromethyl) fenii] -3-azabicyclo [3.1.Ojhexane 21.7 99.6 Compound of the specific epicyclic Royac ion: [a] D = -10 ° (CDCI3, T = 20 ° C, c = 0.004 g / 0.8 mL).

PREPARATION 19 3-f (1S, 5R) -1-r4- (Trifluoromethyl) phen-3-azabicyclic3.1.0lhex-3-yl) -1-butanol To a suspension of (1S, 5R) -1- [4- (trifluoromethyl) phenylJ-3-azabicyclo [3.1. Ojhexane (preparation 18, 100 mg) in teirahydrofuran (1.1 mL), was added 4-hydroxy-2-buyenone (0.66 mmol), acetic acid (0.66 mmol) and NaBH (OAc) 3 (0.88 mmol). The mixture was stirred at room temperature for 2 hours. After the addition of NaOH (1M), the solvent was removed under vacuum, the residue was dissolved in ethyl acetate and the organic layer was washed with H20 and dried over Na2SO4. This solution was concentrated in vacuo to yield 130 mg of the title compound which was used without further purification. MS (m / z): 300 [MHJ +.

PREPARATION 20 (1S.5R) -3- (3-Chloro-1-methylpropyl) -1-r4- (trifluoromethyl) phenan-3-azabicyclo | * 3.1.Olhexane To a solution of 3-. { (1S, 5R) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.0Jhex-3-yl} -1- butanol (preparation 19,130 mg) in chloroform (4 mL), thionyl chloride (0.87 mmol) was added and the mixture was stirred at room temperature for 6 hours. After the addition of NaOH (1M), dichloromethane was added and the organic layer was washed with brine and dried over Na2SO4. The solution was concentrated in vacuo and the unpurified product was purified by flash chromatography (ethyl acetate: cyclohexane = :95) to yield 106 mg of the title compound. MS (m / z): 318 [MH] +.

PREPARATION 21 1 - 5-M1 S.5R / 1 R, 5S) -3-Azabicyclo3.1.01hex-1 -yl) -2- (methyloxy) phenyl > Etanone The title compound was prepared in a yield of 32 mg from 1- [4- (mellyloxy) phenyl] -3- (trifluoroacetyl) -3-azabicyclo [3.1. Ojhexane (94 mg) as described by preparation 34. MS (m / z): 232 [MH] +. CLAR: condition 1, Rí = 3,393 minutes.

PREPARATION 22 (1S.5R 1R, 5S) -1- (4-chlorophenyl) -3-azabicyclo3.1.01hexane The title compound was prepared in a yield of 230 mg from commercially available mephyl-4-chlorophenylacetate (1 g, 5.5 mmol) following the methods described in preparations 1, 2, 3, 4, 6. MS (m / z): 194 [MH] +.

PREPARATION 23 (1S, 5R / 1R, 5S) -1 - (4-Fluorophenyl) -3-azabicyclo3.1.01 hexane The compound of the title was prepared with a yield of 160 mg from commercially available 4-fluorophenylacetate (1 g, 6 mmol) following the methods described in Preparations 1, 2, 3, 4, 6. MS (m / z) ): 178 [MH] +.

PREPARATION 24 (1S.5R / 1R.5S) -1- (3-chlorophenyl) -3-azabicyclo3.1.01hexane The title compound was prepared in a yield of 1.25 g from commercially available 3-chlorophenylacetate (5 g, 27 mmol) following the methods described in preparations 1, 2, 3, 4, 5. MS (m / z) : 194 [MH] +. CLAR: condition 1, Rt = 3,469 minutes.

PREPARATION 25 (1S, 5R / 1R, 5S) -1- (3-Fluorophenin-3-azabicyclo3.1.01hexane The title compound was prepared in a yield of 1.97 g from commercially available meityl 3-fluorophenylacetal (5 g, 29.7 mmol) following the methods described in preparations 1, 2, 3, 4, 5. MS (m / z) : 178 [MHJ +.

PREPARATION 26 (1S.5R / 1R.5S) -1-r3- (Methyloxy) phenan-3-azabicyclo3.1.01hexane The title compound was prepared with a yield of 1.2 g from methyl 3-meioxyphenylaceae (5 g, 27.7 mmol) commercially available following the methods described in preparations 1, 2, 3, 4, 5. MS (m / z) : 190 [MHJ +. CLAR: condition 1, Rt = 3.219 minutes.

PREPARATION 27 (1S, 5R / 1R.5S) -1-r2-MetHl-4- (trifluoromethyl) phenin-3-azabicyclo3.1.01hexane The title compound was prepared in a yield of 71 mg from commercially available 2-meityl-4- (trifluoromethyl) aniline (1 g, 5.7 mmol) following the methods described in Preparations 15, 16, 17. MS (m / z): 242 [MH] +.

PREPARATION 28 Methyl bromine. { 4- | * (trifluoromethyl) oxy-phenyl} acetate Oxalyl chloride (25 mmol) and two drops of DMF at 0 ° C were added to a solution of 4-trifluoromethoxyphenylacetic acid (5 g, 23 mmol) in carbon tetrachloride. After stirring the solution at room temperature for 1 hour, NBS (25 millimoles) and a few drops of 48% HBr were added and the mixture was heated to reflux for 4 hours. The solution was allowed to cool, MeOH (5 mL) was added and the mixture was stirred at room temperature for 1 hour. After filtration through a pad of silica gel, the filtrate was evaporated in vacuo to yield 7.2 g of the title compound as a yellow foam, which was used in the subsequent step without further purification. MS (m / z): 314 [MH] +.

PREPARATION 29 (1S, 5R / 1R.5SÍ-1- (4-r (Trifluoromethyl) oxphenyl) -3-azabicyclo3.1.01hexane The title compound was prepared in a yield of 1.2 g from methyl 3-trifluorominoxyphenylacetate (preparation M, 23 mmol) following the methods described in preparations 2, 3, 4, 5. MS (m / z): 244 [MHJ + . CLAR: condition 1, Rt = 3,942 minutes.

PREPARATION 30 (1S, 5R 1R.5S) -1-r3- (Trifluoromethyl) phenin-3-azabicyclo3.1.01hexane The title compound was prepared in a yield of 1.5 g from commercially available 3-trifluoromethylphenylacetic acid (5 g, 24.5 millimoles), following the methods described in Preparations 28, 2, 3, 4, 5.

MS (m / z): 228 [MHJ +. CLAR: condition 1, Rt = 3,665 minutes.

PREPARATION 31 (1R.5S / 1S.5R) -1- (3-Bromophenyl) -3-azabicyclo3.1.01hexane The title compound was prepared with a yield of 1.6 g from 3-bromophenylacetic acid (5 g, 23.2 mmol) commercially available, following the methods described in preparations 28, 2, 3, 4, 6. MS (m / z) ): 239 [MHJ +. CLAR: condition 1, Rt = 3,528 minutes.

PREPARATION 32 (1S, 5R) -1- (4-Bromophenyl) -3-azabicyclo3.1.01hexane (S) (+) - Acetyl mandelic acid (3.22 g) was added in portions to a stirring solution of (1 R, 5S / 1S, 5R) -1- [4-bromophenyl] -3-azabicyclo [3.1. Ojhexane (preparation 6, 3.96 g) in 80 mL of IPA. The mixture was stirred at room temperature for 2 hours until a white precipitate formed. The mixture was then heated to a reflux temperature, stirred for 45 minutes and then allowed to cool slowly to room temperature. The white solid was collected by filtration and dried in vacuo. This material was recrystallized 4 times from IPA (10 volumes) to yield 2.3 g of a white solid. Then this material was suspended in sodium hydroxide (aqueous solution 1 M, 400 mL) and Et20 (400 mL) and allowed to stir at ambient temperature until complete dissolution. After separation of the two phases, the aqueous layer was exfoliated again with E20 (3 x 250 mL). The combined organic layers were washed with sodium hydroxide (1 M solution, 3 x 200 mL) and then dried over Na 2 SO 4. Evaporation of the vacuum solder produced the compound of the title (1.24 g) as a white solid. The absolute configuration of the optical isomers was assigned as described by preparation 18. The assignment of the absolute configuration of the title compound was confirmed by a particular crystal X-ray structure obtained from a crystal of the acid salt ( 1S, 5R) -1- (4-bromophenyl) -3-azabicyclo [3.1.0] hexane, (S) - (+) - 0-acetyl mandelic. Both, the analyzes based on the known configuration of (S) (+) - acetyl mandelic acid and on the basis of anomalous dispersion effects confirmed that the assignment of the title compound was (1S, 5R) -1- (4-bromophenyl) ) -3-azabicyclo [3.1.Ojhexane.

NMR (H, CDCl 3): d 7.43 (d, 2 H), 7.09 (d, 2 H), 3.25 (d, 1 H), 3.15 (m, 2 H), 3.06 (d, 1 H), 1.71 (m, 1 H), 0.95 (dd, 1 H), 0. 89 (t, 1 H), NH not observed. MS (m / z): 239 [MHJ +. Analytical chromatography Column: chiralcel OD 5 um, 250 x 4.6 mm Mobile phase: A: n-hexane; B: Isopropanol + 0.1% Isopropyl amine Gradient: isocratic 2% B Flow rate: 1 mL / minute UV wavelength range: 200-400 nm Analysis time 25 minutes Retention time 22.3 minutes, purity > 99% a / a Specific optical rotation: [aJD = -86 ° (CDCI3, T = 20 ° C, c = 0.0053 g / 0.8 mL).

PREPARATION 33 (1R.5S / 1S, 5R) -1-r2- (Trifluoromethyl) phen-3-azabicyclo3.1.01hexane The title compound was prepared in a yield of 53 mg from methyl [2- (trifluoromethyl) phenyl] acetate (944 mg) commercially available following the methods described in preparations 1, 2, 3, 4 and 5.

MS (m / z): 228 [MH] +.

PREPARATION 34 144-1 (1 R, 5S / 1S.5R) -3-Azabicyclo3.1.01hex-1-in-2- (methyloxy) phenylethanone To a mixture of AICI3 (2 equivalents) in 1, 2-dichloroethane (anhydrous, 9 mL) at 0 ° C was added acetyl chloride (1.05 equivalents). The reaction mixture was stirred at 0 ° C for 15 minutes and a solution of 1- [3- (methyloxy) phenyl] -3- (trifluoroacetyl) -3-azabicyclo [3.1. Ojhexane (1.1 g, obtained in analogy to the method described in Preparation 7 from 1- [3- (methyloxy) phenylj-3-azabicyclo [3.1.Ojhexane] in 1,2-dichloroethane (anhydrous, 9 mL). The reaction mixture was stirred at RT for 1.5 hours. HCl (1 M, 4 mL) was added followed by water (20 mL) and the mixture was extracted with dichloromethane. The organic layer was washed with saturated aqueous NaHCO3 and dried over Na2SO4. The solution was filtered and the filtrate was concentrated in vacuo. The crude product was purified by flash chromatography (cyclohexanes: EtOAc 6: 4) to yield 593 mg as a colorless liquid of the protected amine. 143 mg of the protected amine was dissolved in MeOH: H20 (3 mL: 3 mL) and K2C03 (4 equivalents) was added by stirring the mixture at 50 ° C for 2.5 hours. The reaction mixture was extracted with dichloromethane and the organic layer was washed with saturated aqueous NaHCO 3 and dried over Na 2 SO 4. The solution was filtered and the filtrate was concentrated in vacuo to yield the thioule compound as a white solid (88 mg). MS (m / z): 232 [MHJ +. CLAR: conditions 1 analytical column: Supelcosil ABZ + Plus 33 x 4.6 mm, 3 um Mobile phase: A: H2O + 0.1% HCOOH, B: CH3CN Gradient: 0% (B) for 1 minute, 0% (B) to 95% (B) in 5 minutes, 95% (B) for 2 min. Flow rate: 1 mL / minute UV wavelength: 285 nm, bandwidth 130 nm Mass range: 100-1000 amu Ionization: ES + Rt 2,971 minutes PREPARATION 35 1-r4-r (1R, 5S / 1S.5R) -3-Azabicyclo3.1.01hex-1-yl) -2- (methyloxy) phenin-1-propanone The thioule compound was prepared using propionyl chloride in place of acetyl chloride, in a yield of 106 mg from 147 mg of protected amine obtained in 705 mg from 1- [3- (methyloxy) phenyl] -3 - (trifluoroacetyl) -3-azabicyclo [3.1. Ojhexane (1.07 g) as described by preparation 34. MS (m / z): 246 [MHJ +. CLAR: conditions 1 Rt 3.249 min.

PREPARATION 36 1 (1R, 5S / 1S, 5R) - [2-Fiuoro-5- (trífiuorometii) fenip-3-azabicicíof3.1.01hexano The thiful compound was prepared with a yield of 112 mg from 2-fluoro-5- (trifluoromethyl) aniline (1.09 g) following the procedures reported by the preparations 37 and 6. NMR (1H, CDCl 3): d 7.45 ( m, 2H), 7.1 (m, 1 H), 3.2 (m, 2H), 3.05 (m, 2H), 1.7 (m, 1 H), 0.95 (m, 1 H), 0.9 (m, 1 H), NH not observed. MS (m / z): 246 [MH] +.

PREPARATION 37 1 (1R.5S / 1S, 5R) -r2-Fluoro-4- (trifluoromethyl) phenan-3-azabicyclo3.1.01hexano- To a gaseous paste of maleimide (1.7 equivalents), anhydrous CuCI2 (1.2 equivalents) and ter-builyl nitrite (1.5 equivalents) in CH3CN (35 mL) at 0 ° C was added a solution of 2-fluoro-4- (trifluoromethyl) ) aniline (16.3 g) in CH3CN (6.5 mL) dropwise. The reaction mixture was stirred at room temperature for 1 hour and HCl (10%, aqueous, 196 mL) was added. The mixture was extracted with EOAc, the organic layer was washed with saturated aqueous NaCl and dried over Na2SO4. The solution was filtered and the filtrate was concentrated in vacuo. By NMR analysis the unpurified mixture turned out to be a 1: 4 mixture of the arylated maleimide acid chloride adduct (component A) and unreacted maleimide (component B). A solution of DMSO (140 mL) of this unpurified product was added dropwise to a preformed solution of trimethylsulfoxide iodide (2 equivalents with respect to component A plus 2 equivalents with respect to component B) in anhydrous DMSO (412 mL) to which NaH had been added (3 equivalents with respect to component A plus 2 equivalents with respect to component B) portion by portion. The reaction mixture was stirred for 30 minutes and AcOH (2 equivalents) was added followed by water. The reaction mixture was extracted with Et20 and then EtOAc, the combined organic layers were washed with saturated aqueous NaCl and dried over Na2SO4. The solution was filtered and the filtrate was concentrated in vacuo. The obtained crude product was triturated with water and then with cyclohexanes to yield the title compound as a light brown solid (5.98 g). NMR (1H, CDCl 3): 8 7.55-7.3 (m, 3H), 2.8-2.7 (m, 1 H), 2.1 (m, 1 H), 2.0 (m, 1 H), NH not observed. MS (m / z): 274 [MH] +.

PREPARATION 38 (1 R, 5S / 1S, 5R) -1-r2-Fluoro-4- (trifluoromethyl) phenin-3-azabicyclo3.1.01hexane To a solution of (1 R, 5S / 1S, 5R) -1- [2-fluoro-4- (trifluoromethyl) phenylJ-3-azabicyclo- [3.1.0] hexane-2,4-dione (2.6 g) in anhydrous tetrahydrofuran (56 mL), BH3 in tetrahydrofuran (1 M, 4 equivalents) was added at 0 ° C. The reaction mixture was stirred at 65 ° C for 24 hours, cooled to RT and MeOH was added until the evolution of the gas ended. The solvent was removed in vacuo, MeOH (200 mL) was added, p -oluenesulfonic acid (3 equivalents) was added and the reaction mixture was stirred at 65 ° C for 6 hours, the reaction mixture was cooled to ambient temperature and a saturated solution of K2C03 (1.7 equivalents) was added. The mixture was extracted with dichloromethane, the organic layer was washed with saturated aqueous NaCl and dried over Na2SO4. The solution was filtered and the filtrate was concentrated in vacuo to yield the thioule compound as a colorless oil (2.1 g).

NMR (1H, CDCl 3): d 7.2-7.4 (m, 3H), 3.2 (m, 2H), 3.1 (m, 2H), 1.8 (m, 1 H), 0.8 (m, 2H), NH not observed. MS (m / z): 246 [MHJ +.

PREPARATION 39 (1S, 5R) -1-f2-Fluoro-4- (trifluoromethyl ') phenin-3-azabicyclo3.1.01hexane (1 R) 10-Camforsulfonic acid (4.19 g) was added in portions to a stirring solution of (1 R)., 5S / 1S, 5R) -1- [2-fluoro-4- (trifluoromethyl) phenylJ-3-azabicyclo [3.1. Ojhexane (4.4 g) in CH3CN (44 mL). The resulting mixture was stirred at room temperature for 20 minutes until a white precipitate formed. The mixture was then heated to reflux temperature, stirred for 45 minutes and then allowed to cool slowly to room temperature. The white solid was collected by filtration and dried in vacuo. This material was recrystallized 2 times from CH3CN (25 mL per solid g) to yield 1.57 g of a white solid. Then the material was suspended in sodium hydroxide (1 M solution, 1.1 equivalents) and dichloromethane (100 mL) and allowed to stir at room temperature until it was dissolved. After separation of the two phases, the aqueous layer was extracted again with dichloromethane. The combined organic layers were washed with sodium hydroxide and then dried over Na2SO4. Solvent evaporation under vacuum produced the title compound (874 mg) as a colorless liquid. Analytical chromatography Column: chiralcel OD 10 um, 250 x 4.6 mm Mobile phase: A: n-hexane; B: Isopropanol +0.1% Isopropyl amine Gradient: isocratic 2% B Fiow rate: 0.8 mL / minute UV wavelength range: 200-400 nm Analysis Rejection time (minute)% a / a 17.18 > 99.5 (1S, 5R) -1- [2-fluoro-4- (trifluoromethyl) phenylj-3-azabicyclo [3.1. Ojhexano PREPARATION 40 (1S.5R) -3- (3-Chloropropyl) -1-r4- (trifluoromethyl) phenyl-3-azabicyclof3.1.Olhexane To a solution of (1S, 5R) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexane (1.00 g) in dry tetrahydrofuran (5 mL), was added diisopropylethylamine (2.4 mL) and 1-bromo-3-cyanopropane (3.7 mL) and the resulting mixture was heated to reflux for 3 hours. After cooling to room temperature it was diluted with ethyl acetate (30 mL), washed twice with a saturated solution of NH 4 Cl in water (20 mL) and once with a saturated solution of NaHCO 3 in water (20 mL), dried over anhydrous Na 2 SO and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel eluting with 7: 3 cidohexane / EtOAc to yield the title compound as a colorless oil (1.26 g). NMR (1H, CDCl 3): d 7.50 (d, 2H) 7.19 (d, 2H), 3.59 (t, 2H), 3.33 (d, 1 H), 3.09 (d, 1 H), 2.58 (m, 2H) , 2.66 (dd, 1 H), 2.46 (dd, 1 H), 1.92 (m, 2H), 1.74 (m, 1 H), 1, 67 (t, 1 H), 0.81 (dd, 1 H). MS (m / z): 304 [MHJ +.

PREPARATION 41 f1S.5R) -3- (3-Chloropropyl) -1-r2-fluoro-4- (trifluoromethyl) phenan-3-azabicyclo3.1.OJhexane To a solution of (1S, 5R) -1- [2-fluoro-4- (trifiuoromethyl) phenylj-3-azabicyclo [3.1. Ojhexane (300 mg) in dry teirahydrofuran (3 mL), was added diisopropylethylamine (0.65 mL) and 1-bromo-3-chloropropane (1.01 mL) and the resulting mixture was refluxed for 3 hours. After cooling to room temperature it was diluted with ethyl acetamide (15 mL), washed twice with a saturated solution of NH 4 Cl in water (10 mL) and once with a saturated solution of NaHCO 3 in water (10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by chromatography (silica gel) eluting with 6: 4 cidohexane / EtOAc to produce the title compound as a yellow oil (345 mg). NMR (1H, CDCl 3): d 7.24 (d, 2H), 7.16 (1, 1 H), 3.51 (f, 2H), 3.18 (dd, 1 H), 3.03 (d, 1 H), 2.54 (t, 2H), 2.48 (dd, 1 H), 2.37 (d, 1 H), 1.83 (m, 2H), 1.69 (m, 1 H), 1.34 (t, 1 H), 0.70 (dd, 1 H). MS (m / z): 322 [MHJ +.

PREPARATION 42 (1 R.5S / 1 S.5R) -1 -13-Fluoro-4- (trifluoromethylfenin-3-azabiciclof3.1.01hexane The title compound was prepared in 338 mg yield from 3-fluoro-4- (trifluoromethyl) aniline (2 g) following the procedures reported by Preparations 37 and 6. NMR (1H, CDCl 3): d 7.5 (m , 1 H), 6.9 (m, 2H), 3.3-3.0 (m, 4H), 1.7 (m, 1 H), 0.95 (m, 2H), NH not observed. MS (m / z): 246 [MH] +.

PREPARATION 43 (1 R, 5S / 1 S, 5R) -1-l * 4- (Methyloxy) phenin-3- (trifluoroacetyl) -3- azabiciclof3.1.Ojhexane The title compound was prepared in a yield of 1.80 g (95%) as a colorless oil from (1 R, 5S / 1S, 5R) -1- [4- (meioxy) phenylj-3-azabicyclo [3.1. Ojhexane (1.25 g) in analogy to the method described in preparation 7. MS (m / z): 286 [MHJ +.

PREPARATION 44 1-f2- (Methyloxy) -5-r (1R.5S / 1S.5R) -3- (trifluoroacetyl) -3-azabicyclo3.1.01hex-1-illphenyl ethanone v 1- 2-hydroxy-5-r (1R, 5S / 1S, 5R) -3- (trifluoroacetyl) -3- azabiciclof3.1.OIhex-1 -yl "| phenyl.} Ethanone To a suspension of AICI3 (12.6 millimoles) in dry 1,2-dichloroethane (16 mL) at 0 ° C was added acetyl chloride (6.6 mmol) and the mixture was stirred at this temperature for 15 minutes. Then a solution of (1 R, 5S / 1S, 5R) -1- [4- (methyloxy) phenylJ-3- (trifluoroacetyl) -3-azabicyclo [3.1. Ojhexane (1.81 g, 6.3 mmol) in 1,2-dichloroethane (16 mL). The reaction mixture was allowed to stir at 0 ° C for 15 minutes and last the night at room temperature. Then aqueous 1M HCl was added and the mixture was extracted with dichloromethane. The organic phase was washed with 5% NaHCO 3 and water, dried over Na 2 SO and concentrated in vacuo. The two products were separated by flash chromatography (cyclohexane / ethyl acetate 95/5 to 80/20) to yield 965 mg of 1-. { 2- (methyloxy) -5 - [(1 R, 5S / 1S, 5R) -3- (trifluoroacetyl) -3-azabicyclo [3.1.0] hex-1-ylphenyl} eyenone (48%) and 266 mg of 1-. { 2-hydroxy-5 - [(1 R, 5S / 1S, 5R) -3- (trifluoroacetyl) -3-azabicyclo [3.1.0] hex-1-ylphenyl-ketonone (18%) as yellow oils. MS (m / z): 328 [MHJ +, 1-. { 2- (methyloxy) -5 - [(1 R, 5S / 1S, 5R) -3- (trifluoroacetyl) -3-azabicyclo [3.1.0] hex-1-yl] phenyl} eyenona; 312 [M-H] -, 1-. { 2-hydroxy-5 - [(1 R, 5S / 1S, 5R) -3- (trifluoroacetyl) -3-azabicyclo [3.1.0] hex-1-ylphenyl-ketanone.

PREPARATION 45 1-r5-r (1R, 5S / 1S, 5R) -3-Azabicyclo3.1.01hex-1-ill-2- (methyloxy) feninetanone The title compound was prepared with a yield of 624 mg (91%) as a colorless oil from 1-. { 2- (Meilyloxy) -5 - [(1 R, 5S / 1S, 5R) -3- ((trifluoroacetyl) -3-azabicyclo [3.1.0] hex-1-yl] phenyl} ethanone (965 mg) in analogy to the method described in preparation 12.

MS (m / z): 232 [MHJ +.

PREPARATION 46 1-. { 5-r (1R, 5S / 1S, 5R) -3-Azabicyclo3.1.01hex-1-in-2-hydroxyphenyl > Etanone The compound of the tíulo was prepared with yield of 151 mg (82%) as a colorless oil from 1-. { 2-hydroxy-5 - [(1 R, 5S / 1S, 5R) -3- (frifluoroacetyl) -3-azabicyclo [3.1.0] hex-1-ylphenyl} Ethanone (266 mg) in analogy to the method described in Preparation 12. MS (m / z): 216 [M-H] -.

PREPARATION 47 (1S.5R / 1R.5S) -1- (4-Bromophenyl) -3- (3-chloropropyl) -3- azabiciclof3.1.Olhexane To a solution of (1S, 5R / 1R, 5S) -1- (4-bromophenyl) -3-azabicyclo [3.1. Racemic ojhexane (0.12 g) in dry telrahydrofuran (2 mL), diisopropylethylamine (0.22 mL) and 1-bromo-3-chloropropane (0.062 mL) were added and the resulting mixture was heated to reflux for 3 hours. After cooling to room temperature the solveny was removed in vacuo and the resulting unpurified oil was taken up in dichloromethane (10 mL). This solution was then washed twice with a saturated solution of NH 4 Cl in water (5 mL), dried over anhydrous Na 2 SO and concentrated under reduced pressure. The unpurified product was purified by passing the sample through a 2 g silica cartridge (Varian) with an elution gradient of cyclohexane to cyclohexane / EtOAc 7: 3, to yield the title compound as a colorless oil (0.10 g). ). NMR (1H, DMSO): d 7.45 (d, 2H), 7.10 (d, 2H), 3.65 (t, 2H), 3.30 (d, 1 H), 3.00 (d, 1 H), 2.55 (t, 2H) ), 2.45 (m, 1 H), 2.40 (dd, 1 H), 1.85 (m, 2H), 1.80 (m, 1 H), 1.30 (i, 1 H), 0.70 (m, 1 H). MS (m / z): 314, 316, 318 [MH] +.

PREPARATION 48 (1R, 5S / 1S.5R) -1- (3,4-Dichlorophenyl) -3-azabicyclo3.1.01hexane The unpurified title compound was prepared in 0.36 g yield from commercially available methyl 3,4-dichlorophenylacetate (1 g, 4.57 mmol) following the methods described in Preparations 1, 2, 3, 4, 6. The compound of tífulo separated to produce the separated enantiomers by preparative chromatography using a chiralcel chiralcel AD 10um column, 250 x 21 mm, eluent A: n-hexane; B: sopropanol + 0.1% of sopropylamine, isocratic gradient 2% of B, flow rate 7 mL / minute, UV detection at 200-400 nm. The retention times provided were obtained using an analogous HPLC using a chiralcel chiral column AD 5 um, 250 x 4.6 mm, eluent A: n-hexane; B: isopropanol +0.1% Isopropyl amine, gradient isoclastic 2% B, flow rate 1.2 mL / minute, UV detection at 200-400 nm. The enantiomer 1, (1 R, 5S) -1- (3,4-dichiorophenyl) -3-azabicyclo [3.1. Ojhexane was recovered with 20 mg yield as a white solid from the racemate (60 mg). Rl. = 41 minutes. The enantiomer 2, (1S, 5R) -1- (3,4-dichloropheni) -3-azabicyclo [3.1. Ojhexane was recovered with 28 mg yield as a white solid from the racemate (60 mg). Rt. = 43.4 minutes. The absolute configuration of (1S, 5R) -1- (3,4-dichlorophenyl) -3-azabicyclo [3.1. Ojhexano that was assigned using initial VCD analysis and initial OR analysis. Specific optical rotation of (1S, 5R) -1- (3,4-dichlorophenyl) -3-azabicyclo [3.1.Ojhexane: [a] D = -67.9 ° (CDCI3, T = 20 ° C, c = 0.01 g / mL). NMR (1H, CDCl 3): d 7.35 (d, 1 H), 7.27 (s, 1 H), 7.02 (dd, 1 H), 3.25 (d, 1H), 3.13 (bm, 2H), 3.06 (d, 1H), 1.71 (m, 1 H), 0.93 (m, 2H), NH not observed. MS (m / z): 228 [MHJ +, PREPARATION 49 1- (phenylmethyl) -3- (4A5.5-tetramethyl-1,3.2-dioxaborolan-2-yl) -2,5-dihydro-1H-pyrrole Diisopinocamfeilborane was prepared following the procedure reported in J. Org. Chem. 1984, 49, 945-947. 2 - [(1Z) -3-Cyoro-1- (chloromethyl) -1-propen-1-yl] -4,4,5,5-tetramethyl-1,2,2-dioxaborolane (previously described in Telrahedron) was prepared Leit 1993, 34, 4827-4828) following the general procedure reported in Tetrahedron Lett. 1989, 30, 2929, using 1,4-dichloro-2-butyne. The material thus obtained was additionally converted following the procedure reported in Synlett 2002, 5, 829-831. This last procedure was modified so that the isolation of the title product (instead of by distillation) was achieved by extracting a solution of the reaction products without purification in acetonitrile with cyclohexane, to provide the title compound (containing -10 mol% benzylamine) after the evaporation of the volatile elements from the cyclohexane phase.

PREPARATION 50 2-f1- (phenylmethyl) -2,5-dihydro-1 H -pyrrol-3-ip-5- (trifluoromethyl) pyridine To a solution of 2-bromo-5- (trifluoromethyl) pyridine (4.42 mmol) in dry tetrahydrofuran (45 mL) was added 1- (phenylmethyl) -3- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -2,5-dihydro-1 H-pyrrole (3.4 millimoles), tetrakis (triphenylphosphine) palladium (0) (0.196 millimoles) and cesium fluoride (13.2 millimoles) at room temperature. The resulting mixture was stirred at 80 ° C for 1.5 hours. After cooling the solvent was evaporated under reduced pressure and the residue was partitioned between dichloromethane (25 mL) and sodium hydroxide (15 mL, 1 M). The organic phase was evaporated under reduced pressure. The crude product was purified by silica gel column chromatography (AcOEt: cyclohexane = 1: 10 to 4: 6) to yield 0.33 g of the title compound (y = 24%). NMR (1H, CDCl 3): d 9.8 (s, 1H), 7.85 (dd, 1 H), 7.5-7.2 (m, 6H), 6.7 (s, 1 H), 3.95 (m, 2H), 3.9 (s) , 2H), 3.75 (m, 2H). MS (m / z): 305 [MHJ +.

PREPARATION 51 2-ri- (phenylmethyl) -2,5-dihydro-1H-pyrrol-3-yn-6- (trifluoromethyl) pyridine 2- [1- (phenylmethyl) -2,5-dihydro-1H-pyrrol-3-ylJ-6- (trifluoromethyl) pyridine was prepared in analogy to the method described in preparation 50 in 0.56 g (y = 42%) as an oil. NMR (1H, CDCl 3): d 7.7 (t, 1 H), 7.85 (dd, 1 H), 7.4-7.1 (m, 6H), 6.5 (s, 1 H), 3.90 (sb, 2H), 3.8 ( s, 2H), 3.6 (m, 2H). MS (m / z): 305 [MHJ +.

PREPARATION 52 3- (phenylmethyl) -1-f5- (trifluoromethyl) -2-pyridin-3-azabicyclo3.1.01hexane To a slurry of sodium hydride (83 mg) and trimethylsulphoxonium iodide (0.46 g) was added DMSO (anhydrous, 3 mL) to gofa (evolution of gas). The resulting mixture was allowed to run at ambient temperature for 0.5 hours. A solution of 2- [1- (phenylmethyl) -2,5-dihydro-1 H -pyrrol-3-yl] -5- (trifluoromethyl) pyridine (330 mg) in DMSO (anhydrous, 6 mL) was added at room temperature. ambient. After 1 hour a saturated solution of ammonium chloride (4 mL) was added and the mixture was extracted with dichloromethane (2 x 10 mL). The volatile elements from the organic phase were evaporated under reduced pressure, the residue was loaded onto an SCX column and eluted with MeOH followed by MeOH / 0.25M NH3. The methanol / ammonium fractions were concentrated under reduced pressure to yield 0.31. g of the compound of the tíulo (y = 89%). NMR (1H, CDCl 3): d 8.78 (s, 1 H), 8.03 (dd, 1 H), 7.32 (m, 5H), 7.25 (m, 1 H), 3.66 (dd, 2H), 3.25 (d, 1 H), 2.96 (d, 1 H), 2.80 (d, 1 H), 2.46 (sb, 1 H), 2.05 (q, 1 H), 1.58 (m, 1 H), 1.22 (m, 1 H ). MS (m / z): 317 [MHJ +.

PREPARATION 53 3- (phenylmethyl) -1-r6- (trifluoromethyl) -2-pyridinyl '| -3-azabicyclo3.1.01hexane 3- (Phenylmethyl) -1- [6- (trifluoromethyl) -2-pyridinyl] -3-azabicyclo [3.1. Ojhexane in analogy to the method described in preparation 52 (0.46 g, 79%) as an oil. NMR (1 H, CDCl 3): d 7.7 (t, 1 H), 7.4 (d, 1 H), 7.35 (m, 5 H), 7.2 (d, 1 H), 3.7 (s, 2 H), 3.4 (d, 1 H), 3.1 (d, 1 H), 2.85 (d, 1 H), 2.55 (m, 1 H), 2.1 (m, 1 H), 1.7 (m, 1 H), 1.3 (m, 1 H). MS (m / z): 317 [MH] +.

PREPARATION 54 1-f5- (Trifluoromethyl) -2-pyridinin-3-azabicyclo3.1.01hexane 3- (Phenylmethyl) -1 - [5- (trifluoromethyl) -2-pyridinyl] -3-azabicyclo [3.1.0] hexane was dissolved in ethanol (15 mL), hydrochloric acid (3M, 0.76 mL) was added followed , in inert atmosphere, by Pd / C at 10% w / w (120 mg). After 20 hours under a hydrogen atmosphere (1 atmosphere) the mixture was filtered. The solvent was removed under reduced pressure. A saturated sodium bicarbonate solution (10 mL) was added and the mixture was extracted with diethyl ether (2 x 10 mL) to provide the title compound (0.14 g, 81%) after evaporation of the volatile elements. NMR (1H, DMSO-d6): d 8.7 (s, 1 H), 7.8 (d, 1 H), 7.15 (d, 1 H), 3.4-3. 2 (dd, 2H), 3.1 (m, 2H), 2.05 (m, 1 H), 1.4 (m, 1 H), 1.05 (t, 1 H).

PREPARATION 55 2-Fluoro-4-f1- (phenylmetip-2,5-dihydro-1H-pyrrol-3-n-benzonitrile The title compound was prepared in analogy to the method described in preparation 50 in 0.44 g (y = 31%) as an oil. NMR (1H, CDCl 3): d 7.55 (1, 1 H), 7.4-7.2 (m, 5H), 7.2 (d, 1 H), 7.1 (d, 1H), 6.4 (bs, 1 H), 3.9 (s, 2H), 3.8 (m, 2H), 3.75 (m, 2H). MS (m / z): 279 [MH].

PREPARATION 56 2-Fluoro-4-f3- (phenylmethyl) -3-azabicycloF3.1.0lhex-1-inbenzonitrile The title compound was prepared in analogy to the method described in Preparation 52 in 0.39 g (y = 84%) as an oil. NMR (1H, CDCl 3): d 7.41 (t, 1 H), 7.25-7.15 (m, 5H), 6.85-6.8 (dd, 2H), 3.64-3.56 (dd, 2H), 3.19 (dd, 1 H) , 3.01 (dd, 1H), 2.53 (dd, 1H), 2.47 (dd, 1H), 1.73 (q, 1H), 1.67 (m, 1 H), 0.81 (m, 1 H). MS (m / z): 293 [MH] +.

PREPARATION 57 1-r3-Fluoro-4- (1H-pyrrol-1-ylmethyl) phenin-3-azabicyclo3.1.01hexane To a solution of dihydrochloride of. { [4- (3-azabicyclo [3.1.0] hex-1-yl) -2-fluorophenylmethyl} amine in methanol / letterhydrofuran (anhydrous, 1/1, 5 mL), which was prepared in analogy to the method described in Preparation 54 starting from 1.1 mmol of 2-fluoro-4- [3- (phenylmethyl) -3 -zabicyclo [3.1.0] hex-1-yl-benzonitrile and used without further purification, a solution of 2,5-bis (methyloxy) tetrahydrofuran (2.53 mmol), H2SO4 (4.4 mmol) in methanol / hydrofrofuran (anhydrous) was added. , 1/1, 5 mL) was to go for 5 minutes at temperalura ambience. After standing overnight at room temperature, a saturated solution of NaHCO 3 was added slowly, extraction with 2x 15 mL of dichloromethane followed by purification with preparative HPLC provided 14 mg of the title compound as an oil (y = 5%) . NMR (1H, CDCl 3): d 6.88-6.82 (m, 3H), 6.67 (1, 2H), 6.14 (t, 2H), 5.04 (s, 2H), 3.21 (d, 1H), 3.1 (d, 1 H), 3.09 (d, 1 H), 3.01 (d, 1 H), 1.67 (m, 1 H), 0.88 (m, 2H). MS (m / z): 257 [MH] +.

PREPARATION 58 (1R.5S / 1S.5R) -3- (3-Chloropropyl) -1-r6- (trifluoromethyl) -3-pyridinyl-3-azabicyclo [3.1.Olhexane The title compound was prepared in 522 mg (84%) yield as a colorless oil from (1 R, 5S / 1S, 5R) -1- [6- (trifluoromethyl) -3-pyridinyl] -3-azabicyclo [ 3.1. Ojhexane (584 mg) in analogy to the method described in preparation 40. NMR (1H, CDCl 3): d 8.47 (s, 1 H), 7.55 (m, 2H), 3.59 (t, 2H), 3.33 (d, 1 H), 3.09 (d, 1 H), 2.6 (m, 3H), 2.52 (dd, 1 H), 1.92 (m, 2H), 1.78 (m, 1 H), 0.85 (m, 1 H), 0.81 (dd, 1 H). MS (m / z): 305 [MH] + PREPARATION 59 5-r (1R, 5S / 1S, 5R) -3- (3-chloropropyl) -3-azabicyclo3.1.01hex-1-n-2-methyl-1,3-benzothiazole The title compound was prepared in 480 mg (84%) yield as a colorless oil from 5 - [(1 R, 5S / 1S, 5R5) -3-azabicyclo [3.1.0] hex-1-yl] - 2-methyl-1,3-benzoiazole (374 mg) in analogy to the method described in preparation 40. NMR (H, CDCl 3): d 7.70 (m, 2H), 7.11 (d, 1H), 3.59 (i, 2H) ), 3.38 (d, 1H), 3.09 (d, 1 H), 2.8 (s, 3H), 2.66 (m, 3H), 2.53 (dd, 1H), 1.95 (m, 2H), 1.74 (m, 1 H), 1, 44 (t, 1 H), 0.83 (dd, 1 H). MS (m / z): 307 [MH] +.

PREPARATION 60 1 (1R, 5S / 1S, 5R) -r3-Fluoro-5- (trifluoromethyl) phenan-3-azabicyclo3.1.01hexane-2,4-dione To a gaseous paste of maleimide (1.8 equivalents), anhydrous CuCI 2 (1.2 equivalents) and urea-nitrile (1.5 equivalents) in CH 3 CN (5 mL) at 0 ° C was added dropwise a solution of 3-fluoro-5 - (Irifluoromethyl) aniline (2.2 g) in CH3CN (4 mL). The reaction mixture was stirred at room temperature for 2 hours and HCl (6 M aqueous, 30 mL) was added. The mixture was extracted with EtOAc, the organic layer was dried over Na2SO4. The solution was filtered and the filtrate was concentrated in vacuo. The filtrate was triturated with water and dried under vacuum. A solution of DMSO (10 mL) of this unpurified product was added dropwise to a preformed solution of trimethylsulfoxonium iodide (2 equivalents) in anhydrous DMSO (20 mL) to which NaH (15 equivalents) portion had been added. to portion. The reaction mixture was stirred for 30 minutes and water was added followed by a saturated solution of NH 4 Cl (up to pH 6.5). The reaction mixture was ex2020 extracted with E20, the combined organic layers were washed with saturated aqueous NaCl and dried over Na2SO4. The solution was filtered and the filtrate was concentrated in vacuo. The obtained crude product was triturated with cyclohexane to yield the title compound as a light green solid (1.02 g). NMR (1H, CDCl 3): d 7.4-7.20 (m, 3H), 2.85-2.75 (m, 1 H), 2.0 (m, 1 H), 1.85 (m, 1 H), NH not observed. MS (m / z): 274 [MHJ +.

PREPARATION 61 (1 R, 5S / 1S.5R) -1-r3-Fluoro-5- (trifluoromethyl) phenan-3-azabicyclo3.1.0l hexane The title compound was prepared in 650 mg yield from (1 R, 5S / 1S, 5R) -1- [3-fluoro-5- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.0] hexane- 2,4-dione following the procedure reported by preparation 38. NMR (1H, CDCl 3): d 7.05-7.40 (m, 3H), 3.1-3.3 (m, 4H), 1.7 (m, 1H), 0.9 (m , 2H), NH not observed. MS (m / z): 246 [MH] +.

PREPARATION 62 (1 R.5S / 1S, 5R) -1-r2-Fluoro-3- (trifluoromethyl) phenan-3-azabicyclo3.1.01hexane The title compound was prepared in yield of 947 mg from 2-fluoro-3- (trifluoromethyl) aniline (3 g) following the procedures reported by preparations 60 and 38. NMR (1H, CDCl 3): d 7.2 (m , 2H), 6.9 (m, 1 H), 3.0-2.7 (m, 4H), 1.6 (m, 1 H), 0.7 (m, 2H); MS (m / z): 246 [MHJ +.

PREPARATION 63 (1R.5S / 1S.5R) -1-r4- (Methyloxy) -5- (trifluoromethyl) phenan-3-azabicyclof3.1. Ojhexano The title compound was prepared in 430 mg yield from 4- (methyloxy) -5- (trifluoromethyl) aniline (2.2 g) following the procedures reported by Preparations 60 and 38. NMR (1H, CDCl 3): d 7.4 -7.3 (m, 2H), 6.9 (m, 1H), 3.9 (s, 3H), 3.2- 3.0 (m, 4H), 1.9 (s, 1 H), 1.65 (m, 1 H), 0.8 (m , 2H). MS (m / z): 258 [MHJ +.

PREPARATION 64 (1R, 5S / 1S, 5R) -1- (4-chloro-2-fluorophenyl) -3-azabicyclo3.1.01hexane The title compound was prepared in 360 mg yield from 4-chloro-2-fluoroaniline (1.87 g) following the procedures reported by preparations 60 and 38. NMR (1H, CDCl 3): d 7.2-7.0 (m , 3H), 3.2-3.0 (m, 4H), 2.0 (s, 1 H), 1.75 (m, 1 H), 0.8 (m, 2H). MS (m / z): 212 [MHJ +.

PREPARATION 65 (1R, 5S / 1S, 5R) -1-. { 3-r (Trifluoromethyl) oxyphenyl > -3-azabicichlor3.1.01hexano The compound of the tíulo was prepared with yield of 600 mg from 3-lrifuoromethyloxy aniline (2.65 g) following the procedures reported by the preparations 60 and 38. RMN (1H, CDCI3): d 7.3-7 (m, 4H), 3.3-3.0 (m, 4H), 1.8 (s, 1H), 1.75 (m, 1 H), 0.95 (m, 2H); MS (m / z): 212 [MH] +.

PREPARATION 66 (1R, 5S / 1S, 5R) -1- (2-Fluoro-4-methylphenyl) -3-azabicyclo3.1.01hexane The title compound was prepared in 148 mg yield from 2-fluoro-4-methyl-aniline (2.18 g) following the procedures reported by Preparations 60 and 38. NMR (1H, CDCl 3): d 7.2 (m , 1 H), 6.85 (m, 2H), 3.2-2.9 (m, 4H), 2.25 (s, 3H), 1.75 (s, 1H), 1.65 (m, 1H), 0.9 (m, 2H); MS (m / z): 192 [MH] +.

PREPARATION 67 (1R.5S / 1S.5R) -1-r3-chloro-4- (methyloxy) phenin-3-azabicyclo3.1.01hexane The title compound was prepared in 60 mg yield from 2-chloro-4-meityl aniline (2.36 g) following the procedures reported by preparations 60 and 38. NMR (1H, CDCl 3): d 7.15-7 (m , 2H), 6.85 (m, 1 H), 3.85 (s, 3H), 3.2-2.9 (m, 4H), 1.8-1.6 (m, 2H), 0.75 (m, 2H); MS (m / z): 224 [MH] +.

PREPARATION 68 (1 R, 5S / 1S, 5R) -1,1 -Dimethylethyl 1- (4-bromophenyl) -3-azabicyclo3.1.01hexane-3-carboxylate To a stirring solution of (1 R, 5S / 1S, 5R) -1- (4-bromopheni!) - 3-azabicyclo [3.1.0] hexane (preparation 6, 1.3 g) in dichloromethane (20 mL) at room temperature environment, triethylamine (0.99 mL) and bis (1, 1-dimethylethyl) dicarbonate were added. Stirring was continued for 6 hours, then the reaction mixture was concentrated under vacuum and the crude product was treated with diethyl ether and water. The organic phase was washed with saturated ammonium chloride solution, dried over sodium sulfate and the solvent was evaporated under vacuum to produce an unpurified product which was purified by chromatography on silica gel (cidohexane / ETOAC 9/1) producing the compound of the tíulo (1.68 g, 91%). MS (m / z): 282.1 [MH-C4H8] +, 1 Br.

PREPARATION 69 (1R, 5S / 1S, 5R) -1,1 -Dimethylethyl 1- | * 4- (4A5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenan-3-azabicyclo3. 1.01hexane-3-carboylate To a stirring solution of (1 R, 5S / 1S, 5R) -1, 1-dimethylethyl 1- (4-bromophenyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate (2 g) in DMF ( 30 mL) at RT, didiboro bis (pinacolato) (2.25 g), potassium acetate (1.75 g) and PdCl2 (dppf) (0.15 g) were subsequently added. The reaction mixture was heated at 85 ° C for 1.5 hours, poured into water and extracted twice with diethyl ether, and the organic phase was washed with brine and dried over sodium sulfate. The solvent was evaporated under vacuum and the crude product was purified by chromatography on silica gel (cyclohexane / ETOAC 9/1) to yield the title compound as a white solid (2.1 g, 92%). MS (m / z): 330.3 [MH -C4H8j +, 1 Br.

PREPARATION 70 (1 R, 5S / 1 S, 5R) -1, 1 -dimethylethyl 1 - (bromophenyl) -3-azabicyclo3.1.OIhexane-3-carboxylate The title compound was prepared in 94% yield as a white solid in analogy to the method described by Preparation 68 starting from (1 R, 5S / 1S, 5R) -1- (3-bromophenyl) - 3-azabicyclo [3.1.0] hexane (7.4 g). MS (m / z): 282.1 [MH-C4H8] +, 1 Br. PREPARATION 71 (1 R, 5S / 1S, 5R) -1,1 -Dimethylethyl 1-r3- (4A5,5-tetramethyl-1,3 , 2-d8oxoborolan-2- l) phenyl-1azabicyclo [3.1.01hexane-3-carboxylate] The title compound was prepared in 84% yield as a white solid in analogy to the method described for preparation 69 starting from (1 R, 5S / 1S, 5R) -1, 1-dimethylethyl 1- ( 3-bromophenyl) -3-azabicyclo [3.1.0 hexahexane-3-carboxylate (2.5 g). MS (m / z): 303.3 [MH-C4H8] +, 1 Br.

PREPARATION 72 (1R.5S / 1S, 5R) -1-r4- (2,4-Dimetii-1,3-thiazol-5-yl) phenin-3-azabicyclo3.1.Olhexane To a solution in agitation of (1 R, 5S / 1S, 5R) -1, 1-dimethyleryl 1- [4- (4,4,5, 5-tetramethyl-1, 3,2-dioxaborolan-2-yl) phenyl] -3-azabicyclo [3.1.0] hexane-3-carboxylate (0.3 g) in tetrahydrofuran (12 mL), at RT and under a nitrogen atmosphere, 5-bromo-2,4-dimethyl-1 was subsequently added , 3-Iiazole (0.22 g), cesium fluoride (0.47 g) and tetrakis- (triphenylphosphine) -palladium (0) (0.06 g). The reaction mixture was heated at 80 ° C for 4 hours and the solvent was evaporated under vacuum. The crude product was treated with diethyl ether and with saturated aqueous solution of ammonium chloride, the organic phase was washed with brine, dried over sodium sulfate and concentrated under vacuum. The crude product was purified by chromatography on silica gel (cyanohexane / ETOAC 8/1). The purified product was then dissolved in CH2Cl2 (10 mL) and trifluoroacetic acid (4 mL) was added. After 2 hours the reaction mixture was treated with solid sodium carbonate and the solvent was evaporated. The residue was treated with water and extracted with CH2Cl2, the organic phase was washed with brine, dried over sodium sulfate and evaporated to yield the title compound (0.1 g, 34%). MS (m / z): 271.2 [MH] +.

PREPARATION 73 (1 R, 5S / 1 S, 5R) -1-f4-r6- (trifluoromethyl) -2-pyridininophenyl-3-azabicyclo [3.1.Olhexane The title compound was prepared in analogy to the method described for preparation 72 (using 2-bromo-6- (trifluoromethyl) pyridine) with a yield of 60% MS (m / z): 305.3 [MH] +.

PREPARATION 74 (1 R, 5S / 1 S, 5R) -1-r4- (3,5-dimethyl-4-isoxazolyl) phenin-3-azabicyclo [3.1.Olhexane To a stirred solution of (1 R, 5S / 1S, 5R) -1, 1-dimethylethyl 1- (4-bromophenyl) -3-azabicyclo [3.1.0] hexane-3-carboxylate (0.37 g) in toluene ( 5 mL) and ethyl alcohol (2 mL), at RT and under a nitrogen atmosphere, there was subsequently added (3,5-dimethyl-4-isoxazolyl) boronic acid (0.25 g), tetrakis- (triphenylphosphine) -palladium (0). ) (0.03 g) and a saturated solution of potassium carbonate (2 mL). The reaction mixture was heated at 88 ° C for 2 hours, and the solvents were evaporated under vacuum. The crude product was treated with diethyl ether and water, the organic phase was washed with brine, dried over sodium sulfate and concentrated in vacuo and extracted twice with ether. The solvent was evaporated and the unpurified product was purified by chromatography on silica gel (cyclohexane / ETOAC 8/1). The recovered product was then dissolved in CH2Cl2 (10 mL) and trifluoroacetic acid (4 mL) was added.

After 3 hours the reaction mixture was treated with solid sodium carbonate and the solvent was evaporated. The residue was treated with water and extracted with CH 2 Cl 2, the organic phase was washed with brine, dried over sodium sulfate and evaporated to yield the title compound (0.12 g, 45%). MS (m / z): 255.2 [MH] +.

PREPARATION 75 (1R.5S / 1S, 5R) -1-r3- (2,4-dimethyl-1,3-thiazol-5-yl) fenin-3-azabiciclof3.1.Olhexane The title compound was prepared in analogy to the method described for preparation 72 using (intermediate 4 1 R, 5S / 1S, 5R) -1, 1-dimethylethyl 1- [3- (4,4,5,5- tetramethyl-1, 3,2-dioxaborolan-2-yl) phenyl] -3-azabicyclo [3.1.0] hexane-3-carboxylate) in 50% yield. MS (m / z): 271.3 [MH] +.

PREPARATION 76 (1R.5S / 1S, 5R) -1-r3- (5-methyl-2-t-enyl) phenan-3-azabicyclo3.1.01hexane The title compound was prepared in analogy to the method described for preparation 72 using (intermediate 4 1 R, 5S / 1S, 5R) -1,1 -dimethylethyl 1 - [3- (4,4,5,5 -tetramethyl-1, 3,2-dioxaborolan-2-yl) phenylJ-3-azabicyclo [3.1.0Jhexane-3-carboxylate] with a yield of 55%. MS (m / z): 256.2 [MHJ +.

PREPARATION 77 5- (2,4-Dimethyl-1,3-oxazol-5-yl) -4-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 2,4-Dimethyl-1,3-oxazole-5-carboxylic acid (0.8 g), N-meitylhydrazinecarboxamide (0.6 g), 1- (3-dimethylaminopropyl) -3-ethyl carbodiimide hydrochloride (1.09 g) were dissolved, HOBt (0.038 g) and eryrylamine (0.86 ml), low nihologen, in dry DMF (15 ml) at room temperature. The mixture was stirred overnight, then the DMF was removed under vacuum. NaOH (0.75 M, 10 ml) was added and the mixture was heated at 80 ° C for 3 hours. The reaction mixture was cooled to 0 ° C and acidified to about pH 5 with HCl (aqueous, 37%). The suspended product was isolated by filtration, washed with water (2x3 ml). The concentrator was dried at room temperature overnight under vacuum to yield the title compound in a 3: 2 mixture with 2,4-dimethyl-1,3-oxazole-5-carboxylic acid as a solid foam (0.68 g, 57% yield). NMR (1H, CDCl 3): d 3.89 (s, 3H), 2.60 (s, 3H), 2.40 (s, 3H), NH / SH not observed.

PREPARATION 78 3-r (3-chloropropyl) thio1-5- (2,4-dimethyl-1,3-oxazol-5-yl) -4-methyl-4H-1,2,4-triazole The mixture of the product from preparation 77 was suspended in EtOH (10 ml). NaOEi (21% solution in EtOH, 1.14 ml) was added followed by 1-bromo-3-chloropropane (0.41 ml), the solution was stirred at 90 ° C for 45 minutes, then cooled to 25 ° C. Acetic acid (0.1 equivalent) was added so that the solvent was removed under vacuum. The solid was purified by column chromatography on silica gel, eluting with cyclohexane / EtOAc to yield the title compound as a solid foam (0.44 g, 54% yield).

NMR (1H, CDCl 3): d 3.70 (t + 5, 5H), 3.35 (t, 2H), 2.50 (s, 3H), 2.4 (s, 3H), 2.30 (m, 2H). MS (m / z): 287 [MH] +.

EXAMPLE 1 5-, 5 - ((3-r (1R, 5S / 1S, 5R) -1- (4-Methoxyphenin-3-azabicyclo-1.01hex-3-propyl) thio) -4-methyl-4H-1 hydrochloride , 2,4-triazol-3-ip-2- metiiquinoíina A mixture of (1R, 5S / 1S, 5R) -1- [4- (methoxy) phenyl] -3-azabicyclo [3.1. Ojhexane (preparation 5, 42 mg), 5-. { 5 - [(3-chloropropyl) thio] -4-methyl-4H-1, 2,4-triazol-3-yl} -2-methylquinoline (0.26 mmol), Na2CO3 (0.44 mmol) and Nal (0.22 mmol) in DMF (anhydrous, 0.4 mL) were heated at 60 ° C for 24 hours. After removal of the solvent under vacuum, the residue was dissolved in ethyl acetate and the organic layer was washed with saturated aqueous NaHCO 3 and dried over Na 2 SO 4. This solution was filtered and the filtrate was concentrated in vacuo. The crude product was purified by instantaneous chromatography (dichloromethane to 10% MeOH in dichloromethane) to yield 65 mg of the free base of the title compound. To a solution of this material in dichloromethane (0.2 mL) was added 0.14 millimoles of HCl (1M in Et20), the solvent was evaporated under vacuum and the material thus obtained was triturated with Et20 to yield 69 mg of the title compound as a slightly hygroscopic solid of white color (59% yield). [The procedure can be adapted in analogy to other combinations of 3-azabicyclo [3.1.0-substituted 1-hexanes and 5 - [(3-chloropropyl) thioj-4-methyl-4H-1, 2,4-triazole 3-subsitutes. An equivalent molar amount of K2C03 can be used to replace Na2C03.J NMR (1H, DMSO): d 10.57 (bs, 1 H), 8.28 (bs, 1 H), 8.2 (d, 1 H), 7.94 (t, 1 H), 7.82 (d, 1 H), 7.56 (d, 1 H), 7.25 (d, 2 H), 6.91 (d, 2 H), 4.01 (dd, 1 H). 3.7 (m, 1 H), 3.74 (s, 3H), 3.6-3.2 (m, 6H), 3.42 (s, 3H), 2.75 (s, 3H), 2.24 (quint, 2H), 2.08 (quint, 1) H), 1.62 / 1.05 (t / t, 2H). MS (m / z): 486.3 [MH] +. Example 1 was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AD-H, 25 x 2.1 cm, eluent C02 containing 20% (ethanol + 0.1% iopropanol), flow rate 25 mL / minute, P 190.1 atmospheres, T35 ° C, UV detection at 220 nm, Handle 1 mL. The retention times provided were obtained using a semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AD-H, 25 x 0.46 cm, eluent C02 containing 20% (ethanol + 0.1% isopropanol), flow rate 2.5 mL / minute, P 190.1 atmospheres, T 35 ° C, UV detection at 220 nm.

The enaniomer 1 was recovered in 15 mg yield as a white solid (y = 27%) from the racemate (60 mg). Rt. = 39.2 minutes. The enantiomer 2 was recovered in 17 mg yield as a white solid (y = 30%) from the racemate (60 mg). Rt. = 43.4 minutes. Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than the enantiomer 2.

EXAMPLE 2 5-r5-3-y Hydrochloride (1R.5S / 1S.5R) -1- (4-Bromophen-3-azabicyclo r3.1.01hex-3-ippropylthio) -4-methyl- 4H-1,2,4-triazole-3-in-2-methylquinoline H-Ct The title compound was prepared in analogy to the method described in Example 1 with a yield of 39 mg as a slightly hygroscopic white solid (y = 40%) from (1 R, 5S / 1S, 5R) -1- (4-bromophenyl) -3-azabicyclo [3.1.Ojhexane (40 mg). NMR (1 H, DMSO): 8 10.28 (bs, 1 H), 8.16 (dd, 2H), 7.89 (dd, 1 H), 7.76 (d, 1 H), 7.55 (d, 2H), 7.49 (d , 1 H), 7.28 (d, 2H), 4.06 (bm, 1 H), 3.77 (bm, 1H), 3.6 (bm, 2H), 3.44 (s, 3H), 3.5-3.2 (bm, 4H), 2.71 (s, 3H), 2.23 (m, 3H), 1.58 / 1.14 (t / m, 2H). MS (m / z): 534.1 [MHJ +, 1 Br. Example 2 was separated to produce the separated enaniomers by semipreparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralcel OJ-H, 25 x 2.1 cm, eluyenie C02 which contains 12% (ethanol + 0.1% of sopropylamine), flow rate 2.5 mL / minute, P 192.8 atmospheres, T 36 ° C, UV detection at 220 nm, Handle 1 mL. The retention times provided were obtained using a semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralcel OJ-H, 25 x 0.46 cm, eluent C02 containing 10% (eneol + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 192.8 atmospheres, T 35 ° C, UV detection at 220 nm. The enaniomer 1 was recovered with yield of 7 mg as a white solid, hydrochloride salt from the racemate (39 mg). Rt. = 56.8 minutes. Purity > 99% a / a UV media. The enaniomer 2 was recovered in 7 mg yield as a white solid, hydrochloride salt from the racemate (39 mg). Rt. = 62.5 minutes. Purity > 99% a / a through UV. The absolute configuration of enantiomer 1 was assigned using the comparative and comparative VCD analyzes or the free base analysis corresponding to 5- [5- (. {3 - [(1 R, 5S) -1- (4-bromopheni ) -3-azabicyclo [3.1.0] hex-3-ylpropyl.} Thio) -4-methyl-4H-1,2,4-idriazol-3-ylJ-2-methylenequinoline. (1S, 5R) -1- (3,4-dichlorophenyl) -3-azabicyclo [3.1. Ojhexano (see preparation 48) that was used as the reference. The absolute configuration of the enantiomer 2 was assigned as described by the enantiomer 1 to be 5- [5- (. {3 - [(1S, 5R) -1- (4-bromophenyl) -3-azabicyclo [3.1. Ojhex-3-yl-propyl.} Thio) -4-methyl-4H-1, 2,4-triazol-3-yl] -2-methylquinoline. Enantiomer 1: specific optic royation of the corresponding free base: [a] D = + 47 ° (CHCI3, T = 20 ° C, c = 0.066 g / mL). Enantiomer 2: specific optical rofación of the corresponding free base: [a] D = -42 ° (CHCI3, T = 20 ° C, c = 0.065 g / mL). Enantiomer 2 showed a fpKi (D3) > 1 log unit greater than enantiomer 1.

EXAMPLE 3 2-Methyl-5-r4-methyl-5-3-r (1R, 5S / 1S.5R) -1-phenyl-3-azabicyclo3.1.0] hex-3-ylpropyl hydrochloride} t¡o) -4H-1,2,4-triazole-3-quinoline The title compound was prepared in analogy to the method described in Example 1 in 74 mg yield as a slightly hygroscopic white solid (y = 59%) from (1 R, 5S / 1S, 5R) -1- phenyl-3-azabicyclo [3.1. Ojhexane (40 mg).

NMR (1 H, DMSO): 6 10.4 (bs, 1 H), 8.3 (bs, 1 H), 8.2 (d, 1 H), 7.9 (1, 1 H), 7.8 (d, 1 H), 7.6 (bd, 1 H), 7.4-7.3 (m, 5H), 4.0-3.5 (m / m, 2H), 3.7-3.45 (m / m, 2H), 3.5-3.3 (m, 7H), 2.73 (s) , 3H), 2.3 (m, 3H), 1.60, 1.1 (1, 2H). MS (m / z): 456.3 [MH] +. Example 3 was separated to produce the separated enaniomers by semi-preparative HPLC using a Chiralcel OD 10 m, 250 x 20 mm chiral column, eluent A: n-hexane; B: isopropanol, isocratic gradient 35% B, flow rate 7 mL / minute, UV detection at 200-400 nm, CD 230 nm. The retention times provided were obtained using an analytical HPLC using a chiral column Chiralcel OD 5 m, 250 x 4.6 mm, eluent A: n-hexane; B: isopropanol, isocrystalline gradient 25% B, flow rate 1 mL / minute, UV detection at 200-400 nm. Enantiomer 1 was recovered in 15 mg yield as a white solid (y = 27%) from the racemate (60 mg). Rt. = 39.2 minutes. The enantiomer 2 was recovered with yield of 17 mg as a white solid (y = 30%) from the racemate (60 mg). Rt. = 43.4 minutes. Enantiomer 2 showed a fpKi (D3) > 1 log unit greater than enantiomer 1.

EXAMPLE 4 Hydrochloride of 5-r5- (. {3- 3 | * (lR, 5S / IS, 5R) -1- (3,4-Dichlorophenyl) -3- azabicyclo3.1.OIhex-3-ippropyl) thio) -4-methyl-4H-1, 2,4-triazol-3-yn-2-methylquinoline The compound of the isolate was prepared in analogy to the method described in Example 1 with 65 mg yield as a slightly hygroscopic white solid (y = 52%) from (1 R, 5S / 1S, 5R) -1- (3,4-dichlorophenyl) -3-azabicyclo [3.1.0] hexane (50 mg). NMR (1H, DMSO): d 10.6 (s, 1 H), 8.32 (bs, 1 H), 8.21 (d, 1 H), 7.96 (d, 1 H), 7.84 (d, 1 H), 7.66 ( d, 1H), 7.61 (d, 1 H), 7.6 (d, 1 H), 7.31 (dd, 1 H), 4.06 (m, 2H), 3.74 (m, 2H), 3.7-3.2 (m, 4H) ), 3.36 (s, 3H), 2.76 (s, 3H), 2.25 (m, 4H), 1.69 (m, 1 H), 1.2 (m, 1 H). MS (m / z): 524.3 [MH] +, 2Cl. Example 4 was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gilson) as described in example 1. Enantiomer 1 was recovered in 19 mg yield as a white solid (y = 36%) a from the racemaio (56 mg). Rí. = 26.9 minutes. The absolute configuration of the enantiomer 1 was assigned using comparative and comparative VCD analyzes or analysis of the corresponding free base to be 5- [5- (. {3 - [(1S, 5R) -1- (3,4- dichlorophenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl} thio) -4-methyl-4H-1, 2,4-iriazol-3-yl] -2-methylquinoline. (1S, 5R) -1 - (3,4-dichlorophenyl) -3-azabicyclo [3.1. Ojhexano (see preparation 48) as the reference. The absolute configuration of enantiomer 2 was assigned as described by enantiomer 1 to be 5- [5- (. {3 - [(IR, 5S) -1- (3,4-dichlorophenyl) -3-azabicyclo [3.1 .0] hex-3-yl] propyl.} Thio) -4-methyl-4H-1, 2,4-triazol-3-yl] -2-methylenequinoline. Enantiomer 1: specific optical rotation of the corresponding free base: [a] D = -38.4 ° (CDCI3, T = 20 ° C, c = 0.010 g / mL). The enantiomer 2 was recovered in 14 mg yield as a white solid (y = 26%) from the racemate (56 mg). Rí. = 31.4 minutiae Enantiomer 2: specific optical radiation of the corresponding free base: [a] D = + 34.4 ° (CDCI3, T = 20 ° C, c = 0.010 g / mL). Enantiomer 1 showed a fpKi (D3) > 0.6 log unit greater than the enantiomer 2.

EXAMPLE 5 Hydrochloride of 5-r5 - ((3-r (1R, 5S / 1S, 5R) -1- (4-tert-butylphenyl) -3-azabicyclo [3.1.0lhex-3-yl] thio) -4- methyl-4H-1,2,4-triazol-3-p-2-methylquinoline The title compound was prepared in analogy to the method described in Example 1 in 38 mg yield as a slightly hygroscopic white solid (y = 51%) from (1R, 5S / 1S, 5R) -1- ( 4-Ier-butylphenyl) -3-azabicyclo [3.1. Ojhexane (29 mg). NMR (1H, DMSO): d 10.16 (bs, 1 H), 8.15 (dd, 2H), 7.89 (t, 1 H), 7.76 (d, 1 H), 7.49 (d, 1 H), 7.36 (d) , 2H), 7.23 (d, 2H), 4.05 (dd, 1 H), 3.77 (dd, 1 H), 3.58 (m, 2H), 3.44 (s, 3H), 2.7 (bm, 4H), 2.34 ( s, 3H), 2.23 (t, 2H), 2.15 (t, 1 H), 1.51 (t, 1 H), 1.27 (s, 9H), 1.14 (m, 1 H). MS (m / z): 512.4 [MHJ +. Example 5 was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gilson) as described in example 1 but applying a pressure of 196 atmospheres instead of 190.1 atmospheres. Enantiomer 1 was recovered with yield of 6.5 mg as a white solid (y = 30%) from the racemate (23 mg). Rt. = 7.0 minutes.

The enaniomer 2 was recovered in 5 mg yield as a white solid (y = 23%) from the racemate (23 mg). Rt. = 7.8 minutes. The enaniomer 2 showed a fpKi (D3) > 0. 9 log unit greater than enanlimer 1.

EXAMPLE 6 4-f Hydrochloride (1R, 5S / 1 S.5R) -3- (3-r4-Methyl-5- (2-methylquinolin-5-ii) -4H-1,2,4-triazole-3-intio .}. propyl) -3-azabicyclo [3.1.01hex-1-inbenzonitrile The title compound was prepared in analogy to the method described in Example 1 with a yield of 19 mg as a slightly hygroscopic white solid (y = 27%) from (1 R, 5S / 1S, 5R) -1- (4-cyanophenyl) -3-azabicyclo [3.1. Ojhexane (25 mg). NMR (1H, DMSO): d 10.45 (bs, 1 H), 8.26 (bd, 1H), 8.17 (d, 1 H), 7.93 (t, 1 H), 7.8 (d / d, 3H), 7.5 ( d, 1 H), 7.46 (d, 2H), 4.09 (d, 1 H), 3.76 (d, 1 H), 3.67 (i, 1 H), 3.6-3.2 (bm, 5H), 3.43 (s, 3H), 2.73 (s, 3H), 2.34 (m, 1 H), 2.25 (quiñi., 2H), 1.71 / 1.22 (dt, 2H).

EXAMPLE 7 4-f Hydrochloride (1R, 5S / 1S, 5R) -3- (3- (r4-Methyl-5- (2-methylquinolin-5-yl) -4H-1,2-triazole-3-intio > propyl) -3-azabiciclof3.1.01hex-1-phenol The title compound was prepared in analogy to the method described in Example 1 with yield of 10 mg as a slightly hygroscopic white solid (y = 11%) from (1R, 5S / 1S, 5R) -1- ( 4-hydroxyphenyl) -3-azabicyclo [3.1. Ojhexane (38 mg). NMR (H, DMSO): d 10.17 (bs, 1 H), 9.4 (s, 1 H), 8.15 (bd, 2H), 7.89 (d, 1 H), 7.75 (d, 1H), 7.48 (d, 1 H), 7.12 (d, 2H), 6.73 (d, 2H), 3.98 (dd, 1 H), 3.74 (m, 1 H), 3.5 (bm, 2H), 3.44 (s, 3H), 3.5- 3.2 (bm, 4H), 2.7 (s, 3H), 2.22 (bquint.2H), 2.03 (m, 1H), 1.46 / 1.03 (dm, 2H). MS (m / z): 486.2 [MHJ +.

EXAMPLE 8 Hydrochloride of d R, 5S / 1 S, 5R) -3- (3- { R4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H- 1,2,4 -triazol-3-iptio) propyl) -1-phenyl-3-azab1ciclof3.1.0 '| hexane H-CI The compound of the tíulo was prepared in analogy to the method described in example 1 with yield of 75 mg as a slightly hygroscopic white solid (y = 70%) from (1 R, 5S / 1S, 5R) -1-phenyl-3-azabicyclo [3.1. Ojhexane (40 mg).

NMR (1H, DMSO): d 10. 46 (bs, 1 H), 8.58 (s, 1 H), 7.4-7.2 (m, 5H), 4.04 (dd, 1 H), 3.73 (m, 1 H), 3.7 (s, 3H), 3.7-3.4 (m, 2H), 3.4-3.2 (m + t, 4H), 2.39 (s, 3H), 2.17 (m, 3H), 1.64, 1.1 (2t, 2H).

EXAMPLE 9 Hydrochloride of d R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3-fr4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H -1,2,4-triazol-3-illthio.} Propyl) -3-azabicyclo [3.1. Ojhexano H-C! The title compound was prepared in analogy to the method described in Example 1 with yield of 24 mg as a slightly hygroscopic white solid (y = 28%) from (1 R, 5S / 1S, 5R) -1- (4-bromophenyl) -3-azabicyclo [3.1. Ojhexane (40 mg). NMR (1H, DMSO): d 10.29 (bs, 1 H), 8. 58 (s, 1 H), 7.55 (dd, 2H), 7. 27 (dd, 2H), 4.03 (dd, 1H), 3.73 (dd, 1H), 3.7 (s, 3H), 3.55 (m, 2H), 3.5-3.2 / 3.28 (m + t, 4H), 2.39 ( s, 3H), 2.19 (m, 3H), 1.59 / 1.12 (2t, 2H). MS (m / z): 474. 1 [MHJ +. Example 9 was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralcel AS-H, 25 x 2.1 cm, eluent C02 containing 11% (ethanol + 0.1% isopropylamine), flow rate 22 mL / minute, P 188.1 atmospheres, T36 ° C, UV detection at 220 nm, Handle 2 mL.

The retention times provided were obtained using semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 0.46 cm, eluent C02 containing 10% (ethanol + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 195 atmospheres, T 35 ° C, UV detection at 220 nm. Enantiomer 1 was recovered in 59 mg yield as a white solid, hydrochloride salt from the racemate (138 mg). Rl. = 22.2 minutes. Purity > 99% a / a by UV The enantiomer 2 was recovered in 50 mg yield as a white solid, hydrochloride salt from the racemate (138 mg). Rí. = 30.8 minutes. Purity > 99% a / a by UV The absolute configuration of enantiomer 1 was assigned using the comparative and comparative VCD analyzes or the corresponding free base analyzes to be (1S, 5R) -1- (4-bromophenyl) -3- ( 3- { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.} Propyl) -3 -azabicyclo [3.1.0] hexane (1 R, 5S) -1- (4-Bromophenyl) -3-azabicyclo [3.1. Ojhexano (compare preparation 32) was used as the reference. The absolute configuration of enantiomer 2 assigned as described by enantiomer 1 to be (1 R, 5S) -1- (4-bromophenyl) -3- (3 { [4-methyl-5- (4- methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazole-3-ylthio}. propyl) -3-azabicyclo [3.1.Ojhexane. Enantiomer 1: specific optical rotation of the corresponding free base: [aJD = -51 ° (CHCI3, T = 20 ° C, c = 0.00913 g / mL). Enantiomer 2: specific optical rotation of the corresponding free base: [a] D = + 27 ° (CHCl3, T = 20 ° C, c = 0.0113 g / mL). Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than the enantiomer 2.

EXAMPLE 10 Hydrochloride of d R, 5S / 1S, 5R) -1 - (4-tert-butylphenyl) -3- (3 { R4-methyl-5- (4-methyl-1,3-oxazole-5 -yl) -4H-1, 2,4-triazol-3-iptio) propyl) -3-azabicyclo3.1.Olhexane p-ci The title compound was prepared in analogy to the method described in Example 1 with a yield of 52 mg as a slightly hygroscopic white solid (y = 57%) from (1 R, 5S / 1S, 5R) -1- (4-yer-butylphenyl) -3-azabicyclo [3.1. Ojhexane (40 mg). NMR (1H, CD3OD): d 8.4 (s, 1 H), 7.42 (d, 2H), 7.28 (d, 2H), 4.11 (d, 1 H), 3.88 (d, 1 H), 3.8 (s, 3H), 3.65 (m, 2H), 3.43 (t, 2H), 3.39 (t, 2H), 2.47 (s, 3H), 2.29 (m, 2H), 2.21 (m, 1 H), 1.44 (m, 1 H), 1.33 (s, 9H), 1.3 (m, 1 H). MS (m / z): 452.3 [MHJ +.

EXAMPLE 11 Hydrochloride of (1R, 5S / 1S, 5R) -1- (3,4-Dichlorophenin-3- (3-f14-methyl-5- (4-methyl-1, 3-oxazol-5-yl) - 4H-1.2n4-triazol-3-intio) propyl) -3-azabicyclo3.1.Olhexane H-CI The title compound was prepared in analogy to the method described in Example 1 with a yield of 35 mg as a slightly hygroscopic white solid (y = 32%) from (1 R, 5 S / 1 S, 5 R) -1 - (3,4-dichlorophenyl) -3-azabicyclo [3.1.0] hexane (50 mg). NMR (1H, DMSO): d 10.11 (vbs, 1 H), 8.58 (s, 1 H), 7.6 (d + d, 2H), 6.29 (dd, 1 H), 4.04 / 3.74 (2dd, 2H), 3.7 (s, 3H), 3.6-3.2 (m, 4H), 3.28 (t, 2H), 2.39 (s, 3H), 2.26 (quiñi, 1 H), 2.15 (quint., 2H), 1.53 / 1.2 ( 2t, 2H). MS (m / z): 464.1 [MHJ +, 2Cl. Example 11 was separated to produce the separated enantiomers by semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 2.1 cm, eluyenie C02 containing 8% (ethanol + 0.1% isopropylamine), flow rate 22 mL / minute, P 190.1 atmospheres, T36 ° C, UV detection at 220 nm, Handle 1 mL. The retention times provided were obtained using a semi-preparative chromalography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 0.46 cm, eluent C02 containing 8% (ethanol + 0.1% isopropylamine), flow rate 2.5 mL / min., P 186.2, syrups, T35 ° C, UV detection at 220 nm. Enantiomer 1 was recovered in 12.5 mg yield as a white solid, hydrochloride salt from the racemate (29 mg). Rt. = 38.0 minutes. Purity 98.6% a / a through UV. The enantiomer 2 was recovered with yield of 12.5 mg as a white solid, hydrochloride salt from the racemate (29 mg). Rí. = 40.8 minutiae Purity 98.6% a / a mediated UV. Enantiomer 1 showed a fpKi (D3) > 0.5 log units greater than the enantiomer 2.

EXAMPLE 12 Hydrochloride of d R, 5S / 1S, 5R) -1- (4-methoxyphenyl) -3- (3-fr4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H -1,2,4-triazol-3-yl 'thio) propyl) -3-azabiciclof3.1.0 hexane p-c? The title compound was prepared in analogy to the method described in Example 1 in 38 mg yield as a slightly hygroscopic white solid (y = 39%) from (1 R, 5S / 1S, 5R) -1- (4-mexoxyphenyl) -3-azabicyclo [3.1. Ojhexane (40 mg). NMR (1H, DMSO): d 10.18 (bs, 1 H), 8.58 (s, 1 H), 7.24 (d, 2H), 6. 91 (d, 2H), 3.97 (dd, 1 H), 3.74 (s, 3H), 3.7 (s, 3H), 3.7 (m, 1 H), 3.6-3.2 (m, 4H), 3.27 (t, 2H), 2.39 (s, 3H), 2.15 (quiñi, 2H), 2.07 (quiñi., 1 H), 1.49 / 1.05 (2í, 2H). MS (m / z): 426.2 [MHJ +. Example 12 was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 2.1 cm, eluent C02 containing 9% (ethanol + 0.1% isopropylamine), flow 22 mL / minute, P 188.1 atmospheres, T36 ° C, UV detection at 220 nm, Handle 1 mL. The retention times provided were obtained using semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 0.46 cm, eluent C02 containing 8% (ethanol + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 186.2 atmospheres, T35 ° C, UV detection at 220 nm. Enantiomer 1 was recovered in 5 mg yield as a white solid, hydrochloride salt from the racemate (30 mg). Rt. = 28.7 minutes. Purity > 99% a / a through UV. The enantiomer 2 was recovered in 12.5 mg yield as a white solid, hydrochloride salt from the racemate (30 mg). Rt. = 36.4 minutes. Purity > 99% a / á by UV. Enantiomer 1 showed an fpKi (D3) > 1 log unit greater than the enantiomer 2.

EXAMPLE 13 (1R, 5S / 1S, 5R) -1-r4- (5-methyl-3-isoxazolyl) phenyl-3- (3-fr4-methyl-5- (4-methyl-1, 3-oxazole) hydrochloride -5-yl) -4H-1, 2,4-triazol-3-yl * | propyl) -3-azabicycloP.I.Olhexane H-Ci The compound of the tíulo was prepared in analogy to the method described in example 1 with yield of 30 mg as a slightly hygroscopic white solid (y = 25%) from (1R, 5S / 1S, 5R) - 1- [4- (5-methyl-3-isoxazolyl) phenylj-3-azabicyclo [3.1. Ojhexane (55 mg). NMR (1H, CD3OD): d 8.37 (s, 1 H), 7.8 (d, 2H), 7.43 (d, 2H), 6.55 (s, 1 H), 4.16 / 3.88 (2d, 2H), 3.78 (s) , 3H), 3.7 (m, 2H), 3.48-3. 4 (2t, 4H), 2.48 (s, 3H), 2.45 (s, 3H), 2.29 (m, 3H), 1.51 / 1.37 (2i, 2H). MS (m / z): 477.2 [MHJ +.

EXAMPLE 14 d S, 5R) -3- (3- { | * 4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4 H-1,2 Atriazol-3-yl ] thio.} propyl) -1-r4- (trifluoromethyl) phenan-3-azabicyclo3.1. Olhexano A mixture of (1S, 5R) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexane (preparation 18, 10.4 g), 3 - [(3-chloropropyl) thio] -4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4- triazole (preparation 14, 15.0 g), K2CO3 (7.5 g) and Nal (8.23 g) in DMF (anhydrous, 100 mL) was heated at 60 ° C for 15 hours. Then the mixture was allowed to cool to room temperature, diluted with Et20 (250 mL) and water (200 mL). After separation of the two phases, the aqueous layer was extracted again with Et20 (2 x 200 mL). The combined organic layers were washed with water (2 x 150 mL) and then dried over Na 2 SO 4. After evaporation of the solvate in vacuo, the unpurified product was purified by insulaneous chromatography (dichloromethane to 10% MeOH in dichloromethane) to yield 16.5 g of a yellow solid. The material thus obtained was triturated with Et20 to provide the thiulo compound (13 g) as a white solid (y = 61%). The assignment of the titre compound configuration is based on two lines of evidence: the fact that it was prepared from (1S, 5R) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.Ojhexane] (of known configuration, see preparation 14) and by comparison of the spectroscopic data obtained for (1S, 5R) -1- [4- (urea) -phenyl] -3-azabicyclo [3.1. Ojhexane: The bands in the VCD spectrum of the title compound are co-occurring with the corresponding bands in the spectrum of (1S, 5R) -1- [4- (trifluoromethyl) phenylJ-3-azabicyclo [3.1.Ojhexane, additionally the sign of the specific rotation is the same for both compounds. NMR (1 H, CDCl 3): d 7.89 (m, 1 H), 7.49 (d, 2 H), 7.18 (d, 2 H), 3.67 (s, 3 H), 3.31 (m, 2 H), 3.30 (d, 1 H) ), 3.09 (d, 1 H), 2.61 (m, 2H), 2.56 (d, 1 H), 2.5 (s, 3H), 2.45 (d, 1H), 1.97 (m, 2H), 1.73 (m, 1 H), 1.47 (i, 1 H), 0.8 (dd, 1 H). MS (m / z): 464 [MH] +.

EXAMPLE 15 dS, 5R) -3- (3- { R4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1.2.4- triazole-3-intio hydrochloride > propyl) -1-r4- (trifluoromethyl) phenin-3-azabicyclo3.1. Olhexano Hydrochloric acid (1 M solution in Et20, 19.4 mL) was added dropwise under N2 to a solution of (1S, 5R) -3- (3 { [4-methyl-5- (4-mephyl-1 , 3-oxazol-5-yl) -4H-1, 2,4-triazoi-3-yl] iio.}. Propyl) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.0] hexane (example 14, 9 g) in Et20 (anhydrous, 135 mL). The resulting suspension was allowed to agill at room temperature for 2 hours. The solid was then filtered, washed with E20 and dried under vacuum overnight to provide the title compound (8.9 g) as a whitish solid (y = 92%). NMR (1H, DMSO): d 10.16 (bs, 1H), 8.58 (s, 1 H), 7.72 (d, 2H), 7.51 (d, 2H), 4.1 (dd, 1 H), 3.78 (dd, 1 H), 3.70 (s, 3H), 3.66 (m, 2H), 3.29 (t, 2H), 2.5 (bm, 2H), 2.39 (s, 3H), 2.33 (quiñi, 2H), 2.19 (m, 1 H), 1.62 / 1.23 (t / i, 2H). MS (m / z): 464 [MH] +.

EXAMPLE 16 Hydrochloride of (1 R.5S / 1 S.5R) -1-r2-Fluoro-4- (trifluoromethylphenyl-3- (3-f4- methyl-5- (4-methylene-1,3-oxazole- 5-yl) -4H-1,2,4-triazole-3-intio> propyl) -3- azabicyclo 31 -hexane A mixture of (1 R, 5S / 1S, 5R) -1- [2-Fluoro-4- (trifluoromethyl) phenylJ-3-azabicyclo- [3.1.0] hexane (preparation 38, 700 mg, 2.8 mmol), - [(3-chloropropyl) lyo] -4-methyl-5- (4-methyl-1), 3-oxazol-5-yl) -4H-1, 2,4-triazole (preparation 14, 3.4 millimoles), Na 2 CO 3 (3.4 mmol) and Nal (3.4 mmol) in DMF (anhydrous, 6 mL) was heated to 60 ° C for 24 hours. After removal of the solvent under vacuum, the residue was dissolved in ethyl acetate and the organic layer was washed with saturated aqueous NaHCO3 and dried over Na2SO4. This solution was filtered and the filtrate was concentrated in vacuo. The crude product was purified by flash chromatography (dichloromethane to 10% MeOH in dichloromethane) to yield 503 mg of the free base of the title compound. NMR (1H, CDCl 3): d 7.89 (s, 1 H), 7.32-7.2 (m, 3H), 3.70 (s, 3H), 3.30 (t, 2H), 3.26 (dd, 1 H), 3.10 (dd) , 1 H), 2.60 (t, 2H), 2.52 (dd, 1 H), 2.51 (s, 3H), 2.43 (dd, 1 H), 1.94 (m, 2H), 1.74 (m, 1 H), 1.40 (t, 1 H), 0.76 (dd, 1 H). MS (m / z): 482.2 [MH] +.

The title compound was obtained as a white solid following the method described by Example 15. NMR (1H, DMSO): 5 10.28 (bs, 1 H), 8.58 (s, 1 H), 7.73 (d, 1) H), 7.6 (m, 2H), 4 / 3.57 (d / m, 2H), 3.79 (d, 1 H), 3.69 (s, 3H), 3.5-3.2 (vbm, 1 H), 3.27 (í, 2H), 2.5 (m, 2H), 2.4 (m, 1H), 2.38 (s, 3H), 2.14 (quint., 2H), 1.62 / 1.16 (2t, 2H). MS (m / z): 481 [MH] +. Example 16 was separated to yield the separated enaniomers by semipreparal HPLC using a Quirai Chiralpak AD 10m, 250 x 21 mm column, eluent A: n-hexane; B: isopropanol + 0.1% isopropyl amine, isocratic gradient 9% B, flow rate 7 mL / minute, UV detection at 200-400 nm. The provided retention times were obtained using an analytical HPLC using a chiral column Chiralpak AD-H 5 um, 250 x 4.6 mm, eluent A: n-hexane; B: isopropanol, isocratic gradient 15% B, flow rate 0.8 mL / minute, UV detection at 200-400 nm. The enantiomer 1 was recovered as a white solid, Rt = 15.4 minutes. The enantiomer 2 was recovered as a white solid, Rt = 16.3 minutes. The enantiomer 2 showed an fpKi (D3) > 1 log unit greater than enantiomer 1.

EXAMPLE 17 Hydrochloride of d R.5S / 1 S.5R) -3- (3- { R4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H- 1.2.4 -triazol-3-illthio> propyl) -1-r3- (trifluoromethylphenol-3-azabicyclo [3.1.Olhexane] H-CI (1 R, 5S / 1S, 5R) -1- [3- (Trifluoromethyl) phenyl] -3-azabicyclo [3.1.0] hexane was prepared in analogy to the method described in Preparations 15, 16 and 17. From This material was composed of a slightly hygroscopic white solid following the method described in Examples 14 and 15. NMR (1H, DMSO): d 10.5 (bs, 1 H), 8.58 (s, 1 H) , 7.7-7.5 (m, 4H), 4.09 (m, 1 H), 3.8-3.2 (m, 8H), 3.29 (l, 2H), 2.39 (s, 3H), 2.3 (m, 1 H), 2.18 (m, 2H), 1.68 (t, 1 H), 1.21 (t, 1 H). MS (m / z): 464 [MH] +. Example 17 was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AD-H, 25 x 0.46 cm, eluent C02 containing 10% (ethanol + 0.1% isopropanol), speed of fiow 2.5 mL / minute, P 176.4 atmospheres, T35 ° C, UV detection at 220 nm, 1 mL handle. The retention times provided were obtained using semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AD-H, 25 x 0.46 cm, eluent C02 containing 10% (ethanol + 0.1% isopropanol), flow rate 22 mL / minute, P 186.2 atmospheres, T36 ° C, UV detection at 220 nm. The enantiomer 1 was recovered as a white solid, Rt = 17.6 minutes. The enantiomer 2 was recovered as a white solid, Rt = 18.4 minutes. Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than the enantiomer 2.

EXAMPLE 18 Hydrochloride of d R.5S / 1S.5R) -1-r4-Fluoro-3- (trifluoromethyl) phenin-3- (3- { R4-methyl-5- (4-methyl-1,3- oxazole-5-yl) -4 H-1.2.4-triazole-3-intio propyl) -3-azabicyclo3.1.01-hexane (1 R, 5S / 1S, 5R) -1- [4-Fluoro-3- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.0] hexane was prepared in analogy to the method described in preparations 15, 16 and 17 From this material the compound of the title was obtained as a slightly hygroscopic solid of white color following the method described by examples 14 and 15.

NMR (1H, DMSO): d 10.2 (bs, 1 H), 8.58 (s, 1H), 7.75 (dm, 1H), 7.72 (m, 1H), 7.53 (1, 1 H), 4.06 (dd, 1 H), 3.74 (dd, 1H), 3.7 (s, 3H), 3.6 (m, 2H), 3.4 (m, 2H), 3.28 (t, 2H), 2.39 (s, 3H), 2.26 (m, 1 H), 2.18 (m, 2H), 1.54 (1, 1 H), 1.22 (dd, 1H). MS (m / z): 481 [MH] +.

EXAMPLE 19 1-r5-r Hydrochloride (1S, 5R / 1R, 5S) -3- (3-fr4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2 , 4-triazole-3-iptio) propyl 3-azabicyclo3.1.01hex-1 -11-2- (methyloxy) phenyl] ethanone The title compound was prepared in analogy to the method described in Example 1 in 25 mg yield as a slightly hygroscopic white solid from (1 R, 5S / 1S, 5R) -1 - [5- (3-azabicyclo [3.1.0] hex-1-yl) -2- (methyloxy) phenyl] ethanone (32 mg). NMR (1H, DMSO): d 10.31 (bs, 1H), 8.58 (s, 1 H), 7.52 (d, 1 H), 7.49 (dd, 1H), 7.16 (d, 1H), 3.98 (dd, 1H) ), 3.89 (s, 3H), 3.7 (m, 4H), 3.6-3.2 (bm, 4H), 3.27 (t, 2H), 2.5 (m, 3H), 2.39 (s, 3H), 2.15 (quiñi, 2H), 2.09 (quint, 1H), 1.54-1.08 (2t, 2H). MS (m / z): 468 [MH] +. Example 19 was separated to produce the separated enaniomers by semi-paraffin chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 2.1 cm, eluent C02 containing 15% (ethanol + 0.1% isopropylamine), flow rate 22 mL / minute, P 192.8 atmospheres, T36 ° C, UV detection at 220 nm, 1 mL handle.

The retention times provided were obtained using semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 0.46 cm, eluyenie C02 which contains 15% (Elanol + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 186.2 atmospheres, T 35 ° C, UV detection at 220 nm. Enantiomer 1 was recovered in 14 mg yield as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 12.5 minutes. Purity > 99% a / a by UV The enantiomer 2 was recovered in 16 mg yield as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 16.8 minutes. Purity > 99% a / a by UV Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than enaniomer 2.

EXAMPLE 20 Hydrochloride of (1S.5R / 1R.5S) -1- (4-chlorophenyl) -3- (3 { R4-methyl-5- (4-methyl-1,3-oxazol-5-yl) - 4H-1,2,4-triazol-3-ylthio.}. Propyl) -3-azabicyclic3.1.Olhexane H-Cl The title compound was prepared in analogy to the method described in Example 1 with a yield of 99 mg as a slightly hygroscopic solid of white color from (1 R, 5S / 1S, 5R) -1- (4- chlorophenyl) -3-azabicyclo [3.1. Ojhexane (58 mg). NMR (1H, DMSO): d 9.93 (bs, 1 H), 8.58 (s, 1H), 7.42 (d, 2H), 7.33 (d, 2H), 4.04 (dd, 1 H), 3.75 (dd, 1 H), 3.7 (s, 3H), 3.5 (m, 2H), 3.3 (bm, 4H), 2.39 (s, 3H), 2.2 (m, 1H), 2.15 (m, 2H), 1.47-1.14 (2t) , 2H). MS (m / z): 431 [MH] +. Example 20 was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 2.1 cm, eluent C02 containing 15% (ethanol + 0.1% isopropylamine), flow rate 22 mL / minute, P 188.1 atmospheres, T 36 ° C, UV detection at 220 nm, Handle 1 mL. The retention times provided were obtained using semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 0.46 cm, eluent C0 containing 5% (ethanol + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 186.2 atmospheres, T35 ° C, UV detection at 220 nm. The enantiomer 1 was recovered in 17 mg yield as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 7.8 minutes. Purity > 99% a / a by UV The enantiomer 2 was recovered in 17 mg yield as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 9.7 minutes. Purity > 99% a / a by UV The absolute configuration of enantiomer 1 was assigned using the comparative and comparative VCD analyzes or the corresponding free base analyzes to be (1S, 5R) -1- (4-chlorophenyl) -3- ( 3- { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl] -iio.} Propyl) -3 -azabicyclo [3.1.0] hexane. 5- [5- ( { 3 - [(1 R, 5S) -1 - (4-Bromophenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl.] Thio) -4- methyl-4H-1, 2,4-triazol-3-yl] -2-methylquinoline (compare example 2) was used as the reference. The absolute configuration of the enantiomer 2 that was assigned as described by the enantiomer 1 to be (1 R, 5S) -1- (4-chlorophenyl) -3- (3 { [4-methyl-5- (4- methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylchthio}. propyl) -3-azabicyclo [3.1.Ojhexane. Enantiomer 1: specific optical rotation of the corresponding free base: [a] D = -25 ° (CHCl3, T = 20 ° C, c = 0.0066 g / mL). Enantiomer 2: specific optical rotation of the corresponding free base: [a] D = + 29 ° (CHCl3, T = 20 ° C, c = 0.0068 g / mL).

Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than the enantiomer 2.

EXAMPLE 21 Hydrochloride of (1S.5R / 1R.5S) -1- (4-Fluorophenyl) - 3- (3- (4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1 , 2,4-triazol-3-yl thio.}. Propyl) -3-azabicyclo | * 3.1. Olhexane H-CI The title compound was prepared in analogy to the method described in Example 1 with a yield of 78 mg as a slightly solid. hygroscopic white starting from (1 R, 5S / 1S, 5R) -1- (4-florophenyl) -3-azabicyclo [3.1.0] hexane (49 mg).

NMR (1H, DMSO): d 10.06 (bs, 1 H), 8.58 (s, 1 H), 7.36 (dd, 2H), 7. 19 (t, 2H), 4.02 (dd, 1 H), 3.74 (dd, 1 H), 3.7 (s, 3H), 3.55 (m, 2H), 3.5-3.2 (bm, 4H), 2.39 (s, 3H), 2.15 (m, 3H), 1.49-1.1 (2t, 2H). MS (m / z): 414 [MH] +.

Example 21 was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 2.1 cm, eluent C02 containing 7% (ethanol + 0.1% isopropylamine), flow rate 22 mL / minute, P 192.8 atmospheres, T36 ° C, UV detection at 220 nm, 1 mL handle. The retention times provided were obtained using semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 0.46 cm, eluyenle C02 containing 6% (ethanol + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 186.2 atmospheres, T 35 ° C, UV detection at 220 nm. The enantiomer 1 was recovered in 14 mg yield as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 26.2 minutes. Purity > 99% a / a by UV The enantiomer 2 was recovered in 16 mg yield as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 32.4 minutes. Purity > 99% a / a by UV Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than the enantiomer 2.

EXAMPLE 22 Hydrochloride of (1S.5R / 1R.5S) -1- (3-chlorophenyl) -5-methyl-3- (3-d4-methyl-5- (4-methyl-1,3-oxazole-5- 0-4H-1, 2,4-triazol-3-iopo) propyl) -3-azabicyclo [3.1.Ojhexane H-CI The title compound was prepared in analogy to the method described in Example 1 with yield of 184 mg as a slightly hygroscopic white solid from (1R, 5S / 1S, 5R) -1- (3-chlorophenyl) ) -3-azabicyclo [3.1. Ojhexane (116 mg).

NMR (1H, DMSO): d 9.88 (bs, 1 H), 8.58 (s, 1 H), 7.43 (d, 1 H), 7.4-7.2 (m, 3H), 4.06 (dd, 1 H) , 3.75 (dd, 1 H), 3.7 (s, 3H), 3.62-3.54 (tm, 2H), 3.5- 3.3 (bm, 4H), 2.39 (s, 3H), 2.25 (m, 1 H), 2.15 (m, 2H), 1.46-1.19 (2m, 2H). MS (m / z): 431 [MHJ +. Example 22 was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AD-H, 25 x 0.46 cm, eluent C02 containing 15% (ethanol + 0.1% isopropylamine), flow rate 22 mL / min, P 188.1 atmospheres, T 36 ° C, UV detection at 220 nm, Handle 1 mL. The retention times provided were obtained using semipreparative chromatography in supercritical fluid (Berger) using Chiralpak chiral column AD-H, 25 x 0.46 cm, eluent C02 containing 15% (ethanol + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 176.4 atmospheres, T35 ° C, UV detection at 220 nm. Enantiomer 1 was recovered in 18 mg yield as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 29.6 minutes. 100% a / a purity by UV. The enantiomer 2 was recovered in 16 mg yield as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 32.0 minutes. 100% a / a purity by UV Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than the enantiomer 2.

EXAMPLE 23 Hydrochloride of (1 S.5R 1 R.5SM - (3-Fluorophenyl) -3- (3-f r4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1 , 2,4-triazol-3-antimony.} Propyl) -3-azabiciclof3.1.Olhexane K-Cl The title compound was prepared in analogy to the method described in Example 1 with yield of 150 mg as a slightly hygroscopic solid of white color from (1 R, 5S / 1S, 5R) -1- (3- fluorophenyl) -3-azabicyclo [3.1.Ojhexane (116 mg). NMR (1H, DMSO): d 10.21 (bs, 1 H), 8.58 (d, 1 H), 7.4 (m, 1 H), 7.2-7.0 (m, 3H), 4.03 (dd, 1 H), 3.75 (dd, 1 H), 3.7 (s, 3H), 3.61 (t / m, 1 H), 3.52 (m, 1 H), 3.3 (m, 2H), 3.28 (í, 2H), 2.38 (s, 3H), 2.25 (m, 1 H), 2.16 (m, 2H), 1.57-1.17 (t / m, 2H). MS (m / z): 414 [MHJ +. Example 23 was separated to produce the separated enantiomers by semipreparairic chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 2.1 cm, eluent C02 containing 7% (ethanol + 0.1% isopropylamine), flow rate 22 mL / minute, P 188.1 aminospheres, T36 ° C, UV detection at 220 nm, 1 mL handle. The retention times provided were obtained using a semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 0.46 cm, eluent C02 containing 6% (ethanol + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 186.2 atmospheres, T 35 ° C, UV detection at 220 nm. Enantiomer 1 was recovered with rediminishing 12 mg as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 24.6 minutes. Purity >; 99% a / a by UV The enantiomer 2 was recovered with 14.5 mg restores as a white solid, hydrochloride salt from the racemate (40 mg). Rí. = 26.0 minutes, purity > 99% a / a by UV Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than the enantiomer 2.

EXAMPLE 24 Hydrochloride of (1 S.5R 1 R.5S) -3- (3-f l4-methyl-5- (4-methyl-1, 3-oxazol-5-n-4H-1,2,4 -triazol-3-iptio.}. propyl) -1-f3- (methyloxy) phenan-3-azabiciclof3.1. i i-CI The title compound was prepared in analogy to the method described in Example 1 in 140 mg yield as a slightly hygroscopic white solid from (1 R, 5S / 1S, 5R) -1- (3-meloxyphenyl) - 3-azabicyclo [3.1.Ojhexane (116 mg).

NMR (H, DMSO): d 10.16 (bs, 1H), 8.58 (d, 1 H), 7.26 (dd, 1 H), 6.85 (m, 3H), 4.03 (dd, 1H), 3.77 (s, 3H) ), 3.72 (dd, 1H), 3.7 (s, 3H), 3.6-3.3 (bm, 4H), 3.28 (l / m, 2H), 2.39 (s, 3H), 2.18 (m, 3H), 1.53- 1.1 (t / m, 2H). MS (m / z): 426 [MH] +. Example 24 was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralcel OJ-H, 25 x 2.1 cm, eluent C02 containing 13% (2-propanol + 0.1% isopropylamine), flow rate 22 mL / minute, P 196 atmospheres, T36 ° C, UV detection at 220 nm. The retention times provided were obtained using semi-preparative chromatography in supercritical fluid (Berger) using a chiral column Chiralcel OJ-H, 25 x 0.46 cm, eluent C02 containing 13% (2-propanol + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 176.4 atmospheres, T 35 ° C, UV detection at 220 nm. The enantiomer 1 was recovered with yield of 13.5 mg as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 24.2 minutes. Purity > 99% a / a through UV. The enantiomer 2 was recovered in yield of 13.5 mg as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 26.8 minutes. Purity > 99% a / a through UV. Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than the enantiomer 2.

EXAMPLE 25 Hydrochloride of d S.5R1- - (4-Bromophenin-3- (3- (r4-methyl-5- (tetrahydro-2H-pyran-4-yl) -4H-1,2,4-triazole-3-intio .}. propyl) -3-azabiciclof3.1. Olhexane The title compound was prepared in analogy to the method described in Example 1 in 33 mg yield as a slightly hygroscopic white solid from (1S, 5R) -1- (4-bromophenyl) -3-azabicyclo [3.1 . Ojhexane (preparation 32, 30 mg). NMR (1H, CD3OD): d 7.54 (d, 2H), 7.28 (d, 2H), 4.08 (m, 3H), 3.8- 3.6 (m, 2H), 3.72 (s, 3H), 3.65 (m, 3H) ), 3.47 (t, 2H), 3.3 (m, 3H), 2.25 (m, 3H), 1.93 (m, 4H), 1.48-1.34 (2m, 2H). MS (m / z): 478 [MHJ +.

EXAMPLE 26 (1S.5R) -1- (4-Bromophenyl) -3-r3 - ((4-methyl-5-r4- (trifluoromethyl) phenyl-4H-1,2,4-triazol-3-yl] hydrochloride. thio) propyl1-3-azabicyclo [3.1.Olhexane The title compound was prepared in analogy to the method described in Example 1 with a yield of 36 mg as a slightly hygroscopic white solid from (1S, 5R) -1- (4-bromophenyl) -3-azabicyclo [3.1 .0] hexane (preparation 32, 30 mg). NMR (1H, CD3OD): d 7.96 (m, 4H), 7.54 (d, 2H), 7.29 (t, 2H), 4.14 (d, 1H), 3.90 (m, 1 H), 3.75 (s, 3H) , 3.66 (m, 2H), 3.50 (m, 2H), 3.43 (1, 2H), 2.30 (m, 3H), 1.50 (m, 1 H), 1.34 (i, 1 H). MS (m / z): 578 [MH] +.

EXAMPLE 27 S.5R Hydrochloride) -1- (4-Bromophenyl) -3- (3-fr4-methyl-5- (3-pyridinyl) -4H-1, 2,4-triazole-3-intio> propyl -3-azabiciclof3.1.Olhexano The compound of the tíulo was prepared in analogy to the method described in example 1 with yield of 49 mg as a slightly hygroscopic white solid from (1S, 5R) -1- (4-bromophenyl) -3-azabicyclo [3.1 . Ojhexane (preparation 32, 30 mg). NMR (1H, CD3OD): d 8.97 (m, 1 H), 8.82 (m, 1 H), 8.31 (m, 1 H), 7.75 (m, 1 H), 7.53 (d, 2H), 7.29 (t , 2H), 4.15 (d, 1 H), 3.90 (d, 1 H), 3.75 (s, 3H), 3.67 (m, 2H), 3.50 (m, 2H), 3.42 (í, 2H), 2.29 ( m, 3H), 1.51 (m, 1 H), 1.34 (t, 1 H). MS (m / z): 471 [MHJ +.

EXAMPLE 28 dS, 5R) -1- (4-Bromophenin-3- (3-r5- (3,4-difluorophenyl) -4-methyl-4H-1,2,4-triazole-3-illthio hydrochloride .}. propyl) -3-azabicyclo? 3.1.Olhexane The title compound was prepared in analogy to the method described in Example 1 in 26 mg yield as a slightly hygroscopic white solid from (1S, 5R) -1- (4-bromophenyl) -3-azabicyclo [3.1 . Ojhexane (preparation 32, 30 mg). NMR (1H, CD3OD): d 7.72 (m, 1H), 7.55 (m, 4H), 7.28 (d, 2H), 4. 13 (d, 1 H), 3.89 (d, 1 H), 3.7 (s, 3H), 3.64 (m, 2H), 3.43 (t, 2H), 3.38 (m, 2H), 2.29 (m, 3H) , 1.48 (m, 1 H), 1.34 (1, 1 H). MS (m / z): 506 [MHJ +.

EXAMPLE 29 Hydrochloride of 6-r5- (. {3-r (1S.5R / 1R, 5S) -1- (4-chlorophenyl) -3- azabicyclo3.1.Olhex-3-Ulpropil) thio) -4- methyl-4H-1, 2,4-triazol-3-p-2-methylquinoline H-CI The compound of the title was prepared in analogy to the method described in example 1 with yield of 110 mg as a slightly hygroscopic solid of white color from (1 R, 5S / 1S, 5R) -1- (4- chlorophenyl) -3-azabicyclo [3.1. Ojhexane (87 mg). NMR (1H, CD3OD): d 8.95 (d, 1H), 8.39 (d, 1H), 8.28 (t, 1H), 8.13 (d, 1 H), 7.96 (d, 1 H), 7.37 (m, 4 H), 4.17 (d, 1 H), 3.93 (d, 1 H), 3.71 (m, 2 H), 3.62 (s, 3 H) ), 3.5 (2m, 4H), 3.04 (s, 3H), 2.37 (m, 2H), 2.27 (m, 1H), 1.55 (m, 1 H), 1.31 (m, 1 H). MS (m / z): 490 [MH] +. Example 29 was separated to produce the separated enanlomers by semipreparative chromatography in supercritical fluid (Gilson) using Chiralpak chiral column AD-H, 25 x 0.46 cm, eluent C02 containing 25% (ethanol + 0.1% isopropylamine), flow rate 22 mL / minute, P 195 atmospheres, T 36 ° C, UV detection at 220 nm. The reention times provided were obtained using a semipreparative chromatography in supercritical fluid (Berger) using a chiral column Chiralpak AD-H, 25 x 0.46 cm, eluyenie C02 that contains 25% (ethylene + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 176.4 merobes, T 35 ° C, UV deletion at 220 nm. The enaniomer 1 was recovered with yield of 13.5 mg as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 24.3 minutes. Purity 87.6% a / a through UV. The enantiomer 2 was recovered in 5 mg yield as a white solid, hydrochloride salt from! racemate (40 mg). Rt. = 26. 5 minutes. Purity 100% a / a mediated UV.

Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than enaniomer 2.

EXAMPLE 30 Hydrochloride of d S.5R71R, 5S) -3- (3- { 4,4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H- 1,2,4- triazole-3-intio) propin-1- (4-r (trifluoromethinoxphenyl -3- azabiciclof3.1.OJhexano HCl The thiful compound was prepared in analogy to the method described in Example 1 with a yield of 246 mg as a slightly hygroscopic solid of white color from (1 R, 5S / 1S, 5R) -1-. { 4 - [(ialifluoromethyl) oxy] phenyl} -3-azabicyclo [3.1. Ojhexane (205 mg). NMR (1H, DMSO): d 10.33 (bs, 1 H), 8.58 (s, 1H), 7.43 (d, 2H), 7. 36 (d, 2H), 4.04 (dd, 1 H), 3.73 (dd, 1 H), 3.7 (s, 3H), 3.6-3.2 (bm, 6H), 2.39 (s, 3H), 2.2 (m, 3H), 1.61-1.16 (2t, 2H). MS (m / z): 480 [MH] +. Example 30 was separated to produce the separated enantiomers by semipreparative HPLC using a chiral column Chirapak AS-H, 25 x 2 cm, eluent A: n-hexane; B: isopropanol, isocratic gradient 15% B v / v, flow rate 7 mL / minute, UV detection at 220 nm. The retention times provided were obtained using a Chiracel OD chiral column, 25 x 0.46 cm, eluent A: n-hexane; B: sopropanol, gradient Socratic 10% B v / v, flow rate 1 mL / minute, UV detection at 220 nm. The enantiomer 1 was recovered in 15 mg yield as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 28.3 minutes. Purity > 99% a / a through UV. The enantiomer 2 was recovered in 16 mg yield as a white solid, hydrochloride salt from the racemate (40 mg). Rt. = 50.6 minutes. Purity > 99% a / a through UV. Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than the enantiomer 2.

EXAMPLE 31 Hydrochloride of (1S.5R 1R, 5S) -3- (3- (4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1,2,4-triazole-3 -intio> propyl) -1-r2-methyl-4- (trifluoromethyl) phenyl-3-azabicyclo [3.1.Ojhexane The title compound was prepared in analogy to the method described in Example 1 with yield of 46 mg as a slightly hygroscopic white solid from (1 R, 5S / 1S, 5R) -1- [2- methyl-4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexane (71.5 mg).

NMR (1H, DMSO): d 10.25 (bs, 1 H), 8.58 (s, 1 H), 7.6 (m, 3H), 3.97-3.7 (dd / m, 2H), 3.79 / 3.4 (dd / m, 2H), 3.69 (s, 3H), 3.27 (i, 2H), 2.5 (m, 2H), 2.48 (s, 3H), 2.38 (s, 3H), 2.2 (m, 1 H), 2.13 (quint. , 2H), 1.61-1.01 (2t, 2H). MS (m / z): 478 [MHJ +.

EXAMPLE 32 not used EXAMPLE 33 Hydrochloride of d S.5R / 1 R.5S) -3- (3-f r4-Methyl-5- (tetrahydro-2H-pyran-4-yl) -4H-1, 2,4-triazole-3 -intio.}. propil) -1-. { 4-r (trifluoromethyl) oxylphenyl} -3- azabicyclo [3.1.Olhexane H C? The title compound was prepared in analogy to the method described in Example 1 with yield of 72 mg as a slightly hygroscopic white solid from (1 R, 5S / 1S, 5R) -1-. { 4 - [(trifluoromethyl) oxy] phenyl} -3-azabicyclo [3.1.Ojhexane (100 mg). NMR (1H, DMSO): d 10. 45 (bs, 1H), 7.44 (d, 2H), 7.36 (d, 2H), 4.04 (bm, 1H), 3.94 (dm, 2H), 3.73 (bm, 1H ), 3.55 (s, 3H), 3.6-3.3 (bm, 6H), 3.22 (t, 2H), 3.13 (m, 1 H), 2.23 (m, 1H), 2.21 (m, 2H), 1.9-1.7 (m, 4H), 1.63-1.16 (2t, 2H). MS (m / z): 483 [MHJ +. Example 33 was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AS-H, 25 x 2.1 cm, eluent C02 containing 8% (2-propanol + 0.1% isopropylamine), speed flow rate 22 mL / minute, P 196 atmospheres, T36 ° C, UV de-activation at 220 nm. The retention rates provided were obtained using semi-preparative supercritical fluid chromatography (Berger) using Chiralpak AS-H chiral column, 25 x 0.46 cm, eluent C02 conining 8% (2-propanol + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 176.4 atmospheres, T 35 ° C, UV detection at 220 nm. The enantiomer 1 was recovered in 15 mg yield as a white solid, hydrochloride salt from the racemate (65 mg). Rí. = 23.2 minutiae Purity 100% a / a mediated UV. The enaniomer 2 was recovered with yield of 12 mg as a white solid, hydrochloride salt from the racemate (65 mg). Rt. = 24.6 minutes. 100% a / a purity by UV. Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than enanlimer 2.

EXAMPLE 34 (1R, 5S / 1S.5R) -1- (3-Bromophenin-3- (3-d4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H- hydrochloride 1, 2,4-triazol-3-intiopropyl) -3-azabiciclof3.1.Olhexano H-CI The title compound was prepared in 23 mg yield as a slightly hygroscopic white solid from (1 R, 5S / 1S, 5R) -1- (3-bromophenyl) -3-azabicyclo [3.1. Ojhexane (140 mg) in analogy to the method described in Example 1 and purifying the free base of the title compound by preparative HPLC using a X Terra MS C18 column 5 um, 100x19 mm, eluent A: H20 + 0.1% TFA; B: CH3CN + 0.1% TFA, gradient 10% (B) for 1 minute, from 10% (B) to 35% (B) in 12 minutes, flow rate 17 mL / minute, UV detection at 200-400 nm . The retention times provided were obtained using a column X Terra MS C18 5 um, 50 x 4.6 mm, eluent A: H2O + 0.1% TFA; B: CH3CN + 0.1% TFA, isocratic gradient 25% B v / v, flow rate 1 mL / minute, UV detection at 200-400 nm. Rt. = 6.26 minutes. Purity 96.4% a / a by UV. NMR (1H, DMSO): d 9.9 (bs, 1 H), 8.58 (s, 1 H), 7.57 (s, 1 H), 7.47. (m, 1 H), 7.3 (m, 2H), 4.04 (m, 1 H), 3.75 (dd, 1 H), 3.7-3.2 (m, 6H), 3.7 (s, 3H), 2.39 (s, 3H), 2.23 (m, 1 H), 2.15 (m, 2H), 1.47 (í, 1 H), 1.2 (t, 1 H). MS (m / z): 512 [MHJ +.

EXAMPLE 35 Hydrochloride of d S.5R) -3- (1-methyl-3-n-4-methyl-5- (4-methyl-1,3-oxazol-5-in-4H-1,2,4-triazole-3- illthiopropyl) -1-r4- (trifluoromethyl) phenyl-3-azabicyclo [3.1.Olhexane A mixture of (1S, 5R) -3- (3-Cioro-1-meitylpropyl) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexane hexane (preparation 20, 105 mg), 4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -2,4-dihydro-3H-1, 2,4-triazole-3- Iona (0.43 millimoles), TEA (0.46 millimoles) and Nal (0.43 millimoles) in DMF (anhydrous, 1.6 mL) was heated at 60 ° C for 12 hours. After removal of the solvent under vacuum, the residue was dissolved in ethyl acetate and the organic layer was washed with H20 and dried over Na2SO4. This solution was concentrated under vacuum, treated with cyclohexane and filtered to yield 125 mg of the free base of the title compound. To a solution of this material in dichloromethane (0.2 mL) was added 0.34 millimoles of HCl (1 M in Et20), the solvent was evaporated under vacuum and the material thus obtained was flushed with Et20 to yield 105 mg of the title compound as a slightly hygroscopic solid of white color. MS (m / z): 478 [MH] +. Example 35 was separated to produce the separated diastereoisomers by semipreparative HPLC using a Chirapak AD chiral column, 25 x 2 cm, eluent A: n-hexane; B: ethanol + 0.1% isopropylamine, isocratic gradient 15% B v / v, flow rate 7 mL / minute, UV wavelength range 220-400 nm. The retention times provided were obtained using a chiral column Chiralpak AD-H, 25 x 0.46 cm, eluent A: n-hexane; B: ethanol + 0.1% isopropylamine, isocratic gradient 17% B v / v, flow rate 1 mL / minute, UV wavelength range 200-400 nm. The diastereoisomer 1 was recovered in 30 mg yield as a white solid, hydrochloride salt from the diastereomeric mixture (105 mg). Rt. = 17.9 minutes. Purity 99.4% a / a by UV NMR (1H, DMSO): d 10.33 (bs, 1 H), 8.58 (s, 1 H), 7.71 (d, 2H), 7.53 (d, 2H), 4.07 (dd, 1 H), 3.78 (dd, 1 H), 3.7 (s, 3H), 3.7 (m, 1 H), 3.56 (bs, 2H), 3.4 (m, 1 H), 3.18 (m, 1 H), 2.4 (s, 3H), 2.4-2.3 (m, 1H), 2.26-2.09 (m, 2H), 1.72 (m, 1 H), 1.42 (d, 3H), 1.2 (m, 1 H). MS (m / z): 478 [MHJ +. The diastereomer 2 was recovered in 46 mg yield as a white solid, hydrochloride salt from the diastereomeric mixture (105 mg). Rt = 21.2 minutes. Purity > 99% a / a through UV NMR (1H, DMSO): d 10.26 (bs, 1 H), 8.58 (s, 1 H), 7.7 (d, 2H), 7.51 (d, 2H), 4.14 (dd, 1 H), 3.8-3.6 ( m, 3H), 3.7 (s, 3H), 3.53 (bs, 1 H), 3.4 (m, 1 H), 3.18 (m, 1 H), 2.38 (s, 3H), 2.4-2.25 (m, 2H) ), 2.1 (m, 1 H), 1.69 (m, 1 H), 1.39 (d, 3H), 1.2 (m, 1 H). MS (m / z): 478 [MHJ +.

EXAMPLE 36 Hydrochloride of d R.5S / 1 S, 5R) -1-r2-Fluoro-5- (trifluoromethyl) phenin-3- (3 { R4-methyl-5- (4-methyl-1,3-oxazole-5 -in-4H-1.2.4-triazole-3-intio> propyl) -3- azabiciclof3.1.Olhexano H-Cl The compound aei IITUIO was prepared in analogy to the method Described in Example 1 with yield of 144 mg as a slightly hygroscopic white solid from 1 (1 R, 5S / 1S, 5R) - [2-fIuoro-5- (trifluoromethyl) phenylJ-3-azabicyclo [3.1 .Oxhexane (109 mg).

NMR (1H, CD3OD): d 8.41 (s, 1 H), 7.8 (m, 1 H), 7.74 (m, 1 H), 7.39 (t, 1 H), 4.13 (d, 1H), 3.95 (d, 1 H), 3.81 (s, 3H), 3.73 (bd, 1 H), 3.54 (d, 1 H), 3.48 (m, 2H) ), 3.41 (m, 2H), 2.48 (s, 3H), 2.39 (m, 1 H), 2.28 (q, 2H), 1.58 (m, 1 H), 1.35 (m, 1 H). MS (m / z): 482 [MHJ +. Example 36 was separated to produce the enantiomers separated by semipreparative CLAR using a chiral column Chirapak AS-H, 25 x 2 cm, eluent A: n-hexane; B: isopropanol + 0.1% of isopropylamine, isocratic gradient 10% B v / v, flow rate 7 mL / minute, UV detection at 220 nm. The referencing times provided were obtained using semipreparative chromatography in supercrylic fluid (Berger) using a chiral column Chiralpak AD-H, 25 x 0.46 cm, eluent C02 containing 7% (ethanol + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 176.4 atmospheres, T 35 ° C, UV detection at 220 nm. Enantiomer 1 was recovered in 48 mg yield as a white solid, hydrochloride salt from the racemate (138 mg). Rt. = 21.2 minutes. 100% a / a purity by UV The enantiomer 2 was recovered in 46 mg yield as a white solid, hydrochloride salt from the racemate (138 mg). Rt. = 22.7 minutes. Purity 99% a / a by UV Enantiomer 2 showed a fpKi (D3) > 1 log unit greater than enanlimer 1.

EXAMPLE 37 1-r4-l * Hydrochloride (1R, 5S / 1S.5R) -3- (3- (r4-Methyl-5- (4-methyl-1,3-oxazol-5-l) -4H-1.2 .4-triazole-3-intio propyl) -3-azabicyclo3.1.01hex-1-in-2- (methyloxy) phenilletanone The title compound was prepared in analogy to the method described in Example 1 with a yield of 70 mg as a slightly hygroscopic white solid from 1- [4 - [(1S, 5R / 1R, 5S) -3- azabicyclo [3.1.0] hex-1-yl] -2- (methyloxy) phenyl] ethanone (87 mg).

NMR (1 H, CDCl 3) of the corresponding free base: d 8.0 (s, 1 H), 7.7 (d, 1 H), 6.7-6.8 (m, 2 H), 3.9 (s, 3 H), 3.7 (s, 3 H) ), 3.35 (m, 4H), 3.1 (d, 1 H), 2.6 (m, 3H), 2.55 (s, 3H), 2.5 (s, 3H), 2.45 (m, 1 H), 2.0 (m, 2H), 1.75 (m, 1 H), 0.8 (m, 1 H). MS (m / z): 468 [MH] +.

EXAMPLE 38 1-F4 - Hydrochloride, (1R, 5S / 1S.5R) -3- (3- (4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H- 1.2.4-triazol-3-intio propyl-3-azabicichlor3.1.0lhex-1-in-2- (methyloxy) phenyl-1-propanone The title compound was prepared in analogy to the method described in Example 1 with a yield of 75 mg as a slightly hygroscopic white solid from 1 - [(1S, 5R 1 R, 5S) -3-azabicyclo [3.1. 0] hex-1 -yl) -2- (methyloxy) phenyl] -1-propanone (106 mg). NMR of the free base (1H, CDCl 3): d 7.9 (s, 1H), 6.65 (d, 1 H), 6.7 (m, 2H), 3.9 (s, 3H), 3.7 (s, 3H), 3.35 ( m, 3H), 3.1 (d, 1 H), 2.9 (m, 2H), 2.6 (m, 3H), 2.5 (s, 3H), 2.45 (m, 1 H), 2.0 (m, 2H), 1.8 (m, 1 H), 1.1 (m, 3H), 0.8 (m, 1 H). MS (m / z): 482 [MH] +.

EXAMPLE 39 Hydrochloride of (1 R.5S / 1 S, 5R) -3- (3 { R4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H- 1.2.4- triazol-3-intio propip-1-r2- (trifluoromethyl) phenan-3-azabiciclof3.1.Olhexane The title compound was prepared in analogy to the method described in Example 1 with a yield of 7 mg as a slightly hygroscopic solid of white color from (1 R, 5S / 1S, 5R) -1- [2- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.0] hexane (53 mg). NMR (1H, DMSO): d 10.48 (bs, 1 H), 8.55 (s, 1 H), 7.9-7.6 (m, 4H), 3.9-3.1 (bm, 8H), 3.68 (s, 3H), 2.36 (s, 3H), 2.13 (m, 2H), 1.66 (m, 1 H), 1.2 (m, 1 H), 1.1 (m, 1 H). MS (m / z): 464 [MH] +.

EXAMPLE 40 Hydrochloride of (1 S.5R1-1-l ~ 2-f luoro-4- (trifluoromethyl) phenyl1-3- (3- (r4-methyl-5- (4-methylene-1,3- oxazol-5-yl) -4H-1,2,4-triazol-3-illthio) propyl) -3- azabicyclo3.1.Olhexane The free base of the title compound was prepared in analogy to the method described in Example 1 from (1S, 5R) -1- [2-fluoro-4- (trifluoromethyl) phenylJ-3-azabicyclo [3.1. Ojhexano. A mixture of (1S, 5R) -1- [2-fluoro-4- (trifluoromethyl) phenylj-3-azabicyclo [3.1. Ojhexane (preparation 39, 727 mg, 2.97 mmol), 3 - [(3-chloropropyl) thio] -4-methyl-5- (4-meityl-1, 3-oxazol-5-yl) -4H-1, 2 , 4-triazole (preparation 14, 3.6 moles), K2CO3 (3.6 millimoles) and Nal (2.97 millimoles) in anhydrous DMF was heated at 60 ° C for 24 hours. After removal of the solvent under vacuum, the residue was dissolved in ethyl acetate and the organic layer was washed with salted aqueous NaHC 3 and dried over Na 2 SO. This solution was filtered and the filtrate was concentrated in vacuo. The unpurified product was purified by insanitary chromathography (dichloromethane to 10% MeOH in dichloromethane) to yield 940 mg of the free base of the title compound. This free base (886 mg) was converted to the hydrochloride salt (847 mg) in accordance with the method described in Example 1. The compound of the thioule was bleached as a white solid. The chiral analytical HPLC confirmed that the product is identical to the enantiomer 2 of Example 16. The NMR and MS data correspond to those reported for example 16. The absolute configuration of the title compound was confirmed using comparative VCD analysis and OR comparative analysis. the corresponding free base which is (1S, 5R) -1- [2-fluoro-4- (trifluoromethyl) phenyl] -3- (3 { [4-methyl-5- (4-meityl-1,3) -oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl] thio.] propyl) -3-azabicyclo [3.1.Ojhexane. (1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylthio .}. propyl) -1- [4- (trifluoromethyl) phenylJ-3-azabicyclo [3.1. Ojhexane (see example 14) was used as the reference. Specific optical rotation of the corresponding free base: [a] D = -42 ° (CDCI3, T = 25 ° C, c = 0.005 g / 0.8 mL).

EXAMPLES 41-52 To a solution of the respecific 3-thio-5-aryl-1, 2,4-triazole (prepared in analogy to the method described in Preparation 13, 0.131 mmol) in dry acetonitrile (2 mL) was added 2-tert-butylimino -2-diethylamino-1,3-dimethylyl-perhydro-1, 3,2-diaza-phosphorine on polystyrene (90 mg, 2.2 mmol / g) and the resulting mixture was stirred for 30 minutes at ambient temperature. (1S, 5R) -3- (3-chloropropyl) -1- [4- (trifluoromethyl) phenylJ-3-azabicyclo [3.1. Ojhexane (40 mg) and the resulting mixture was stirred at 70 ° C for three hours. After cooling, the resin was removed by filtration, washed with methanol (2 mL), and then the solvent was removed under reduced pressure. Purifications were carried out using direct mass CLAR using a Walers XTerra Prep MS C18 10 um, 30x150 mm column using the following conditions: A = H20 + 0.1% formic acid B = ACN + 0.1% formic acid Then the solvent was removed under reduced pressure to produce the respective compounds as the format salts. The residues were taken with methanol (1 mL) and loaded onto SCX SPE cartridges (1 g), washed with methanol (3 mL) and eluted with a 2M solution of ammonium in methanol (3 mL), then the solvent it was removed under reduced pressure. The residues were taken with dichloromethane (1 mL) and a solution of 1.0 M HCl in diethylether (0.131 mmol) was added, then the solvent was removed under reduced pressure to produce the compounds summarized in Table 1 as hydrochloride salts. Analytical chromatography conditions: Column: X Terra MS C18 5 mm, 50 x 4.6 mm Mobile phase: A: NH4HC03 sol. 10 mM, pH 10; B: CH3CN Gradient: 10% of (B) for 1 minute, from 10% (B) to 95% (B) in 12 minutes, 95% (B) for 3 minutes Flow rate: 1 mL / minute Length interval UV wavelength: 210-350 nm Mass range: 100-900 amu Ionization: ES + TABLE 1 EXAMPLES 53-58 To a solution of the respective 3-thio-5-aryl-1, 2,4-triazole (0.124 mmol) in dry acetoniyl (2 mL) was added 2-tert-butylimino-2-diethylamino-1,3-dimethyl- perhydro-1, 3,2-diaza-phosphorine on polystyrene (85 mg, 2.2 mmol / g) and the resulting mixture was stirred for 30 minutes at room temperature, then (1S, 5R) -3- (3-chloropropyl ) -1- [2-fluoro-4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexane (40 mg) and the resulting mixture was stirred at 50 ° C overnight. After cooling, the resin was removed by filtration, washed with meianol (2 mL) and then the solvent was removed under reduced pressure. The purifications were carried out using mass direct HPLC: Preparative chromatography conditions (preparative HPLC of 6 out of 6 compounds) Column: X Terra MS C18 5 mm, 100 x 19 mm Mobile phase: A: NH4HC03 sol. 10 mM, pH 10; B: CH3CN Gradient: 30% of (B) for 1 minute, from 30% (B) to 95% (B) in 9 minutes, 95% (B) for 3 minutes Flow rate: 17 mL / minute Length Interval UV wavelength: 210-350 nm Mass range: 100-900 amu Ionization: ES + Subsequently the solvent was removed under reduced pressure to produce compounds as free bases. The residues were taken with dichloromethane (2 mL) and a solution of 1.0 M HCl in diethylether (0.124 mmol) was added then the solvent was removed under reduced pressure to produce the product compounds summarized in Table 2 as hydrochloride salts. Analytical chromatography conditions Column: X Terra MS C18 5 mm, 50 x 4.6 mm Mobile phase: A: NH4HC03 sol. 10 mM, pH 10; B: CH3CN Gradient: 30% of (B) for 1 minute, from 30% (B) to 95% (B) in 9 minutes, 95% of (B) for 3 minutes Flow rate: 1 mL / minute Interval of UV wavelength: 210-350 nm Mass range: 100-900 amu Ionization: ES + TABLE 2 EXAMPLE 59 1- Hydrochloride. { 4-r (1R.5S / 1S, 5R) -3- (3-fr4-Methyl-5- (2-methyl-5-quinolinyl) -4H-1,2,4-triazole-3-ylthio}. -3-azabicyclo3.1.0lhex-1-illphenyl > -2- pyrrolidinone H-C! A Schlenk tube was loaded with 5- [5- (. {3 - [(1 R, 5S / 1S, 5R) -1- (4-bromophenyl) -3-azabicyclo [3.1.0] hex-3- il] propyl.} thio) -4-methyl-4H-1, 2,4-triazol-3-yl] -2-methylquinoline (cf. Example 2; 0.15 g), 2-pyrrolidinone (32 mg), tr S (di-benzylideneacetone) -dipaladium (0) (6 mg), 4,5-bis (diphenylfosphin) -9,9-dlmethylxanthene (10 mg), cesium carbonate (130 mg) and 1,4-dioxane ( 2 mL). The Schlenk tube was sealed with a Teflon thread cover and the reaction mixture was stirred at 100 ° C for 12 hours. The reaction mixture was allowed to cool to ambient temperature, dichloromethane (10 mL) was diluted, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (dichloromethane to 10% MeOH in dichloromethane) to produce 60 mg of the free base of the title compound. To a solution of this material in dichloromethane (0.4 mL) was added HCl (0.11 mL, 1 M in Et20), the solvent was evaporated in vacuo and the material so obtained was triturated with Et20 to yield 64 mg of the title compound as a solid of white color.

NMR (1 H, DMSO): d 10. 48 (bs, 1 H), 8.24 (bd, 1 H), 8.18 (d, 1 H), 7.93 (1, 1 H), 7. 81 (d, 1 H ), 7.62 (d, 2H), 7.54 (d, 1 H), 7.31 (d, 2H), 4.04 (dd, 1 H), 3.82 (i, 2H), 3.76 (dd, 1 H), 3.70 / 3.10 (bm, 8H), 3.45 (s, 3H), 2.74 (s, 3H), 2.25 (m, 2H), 2.16 (m, 1 H), 2.07 (m, 2H), 1.63 / 1.10 (t / t, 2H). MS (m / z): 539 [MH] +. EXAMPLE 60 5- (5-r (3- { DR.5S / 1S.5R) -1-r4- (1,1-Dioxido-2-isothiazolidinyl) phenin-3-azabicyclole3.1.0lhex-3-yl hydrochloride > propyl) thiol-4-methyl-4H-1,2,4-triazol-3-yl} -2-methylquinoline A Schlenk tube was loaded with 5- [5- (. {3 - [(1 R, 5S / 1S, 5R) -1- (4-bromophenyl) -3-azabicyclo [3.1.0jhex-3-il] propyl.} thio) -4-methyl-4H-1, 2,4-triazol-3-ylj-2-methylquinoline (cf. Example 2; 0.15 g), isothiazolidine 1,1-dioxide (46 mg), tr S (dibenzylidene ketone) -d -palladium (0) (6 mg), 4,5-bis (diphenylphosphino) -9,9-dimethylxanfen (10 mg), cesium carbonate (130 mg) and 1, 4-dioxane (2 mL). The Schlenk tube was sealed with a cover with iophlon thread and the reaction mixture was stirred at 100 ° C for 12 hours. The reaction mixture was allowed to cool to room temperature, diluted in dichloromethane (10 mL), filtered and concentrated in vacuo. The crude product was purified by flash chromatography (dichloromethane to 10% MeOH in dichloromethane) to yield 50 mg of the free base of the title compound. To a solution of this material in dichloromean (0.3 mL) was added HCl (0.087 mL, 1 M in El20), the solvent was evaporated in vacuo and the material thus obtained was triturated with Et20 to yield 52 mg of the title compound as a solid of white color. NMR (1H, DMSO): d 10.57 (bs, 1 H), 8.27 (bd, 1 H), 8.19 (d, 1 H), 7.94 (t, 1 H), 7.82 (d, 1 H), 7.55 ( d, 1 H), 7.32 (d, 2H), 7.18 (d, 2H), 4.03 (dd, 1 H), 3.72 (m, 3H), 3.60 / 3.20 (bm, 8H), 3.45 (s, 3H) , 2.75 (s, 3H), 2.41 (m, 2H), 2.25 (m, 2H), 2.14 (m, 1 H), 1.66 / 1.10 (t / m, 2H). MS (m / z): 575 [MH] +.

EXAMPLE 61 Hydrochloride of d R.5S / 1S.5R) -1-r3-Fluoro-4- (trifluoromethyl) phenin-5-methyl-3- (3- (r4-methyl-5- (4-methyl-1.3- oxazol-5-yl) -4H-1.2.4-triazole-3-iptio > propyl) -3-azabicyclo [3.1.Ojhexane The title compound was prepared in analogy to the method described in Example 1 with yield of 247 mg as a slightly hygroscopic white solid from (1 R, 5S / 1S, 5R) -1- [3-fIuoro-4 - (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexane (338 mg). NMR (H, CD3OD): d 8.4 (s, 1 H), 7.55 (i, 1 H), 7.37 (d, 1 H), 7.32 (d, 1 H), 4.2 (d, 1 H), 3.91 ( d, 1 H), 3.81 (s, 3H), 3.76 (d, 1 H), 3.67 (d, 1 H), 3.51 (t, 2H), 3.43 (i, 2H), 2.47 (s, 3H), 2.41 (m, 1 H), 2.31 (m, 2H), 1.61 (t, 1 H), 1.45 (t, 1 H). MS (m / z): 496 [MH] +. Example 61 was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AD-H, 25 x 2.1 cm, eluent C02 containing 12% (efanol + 0.1% isopropylamine), flow rate 22 mL / minute, P 190.1 atmospheres, T 36 ° C, UV detection at 220 nm. The retention periods provided were obilised using a semi-preparative chromalography in supercritical fluid (Berger) using a chiral column Chiralpak AD-H, 25 x 0.46 cm, eluent C02 conining 10% (ethanol + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 176.4 atmospheres, T 35 ° C, UV detection at 220 nm. The enaniomer 1 was recovered with yield of 42 mg as a white solid, hydrochloride salt from the racemate (100 mg). Rt = 27.1 minutes. Purity 100% a / a mediated UV. The enaniomer 2 was recovered with yield of 34 mg as a white solid, hydrochloride salt from the racemate (100 mg). Rt. = 31.0 minutes. Purity 100% a / a mediated UV. Enantiomer 1 showed a fpKi (D3) > 2 unit log greater than the enantiomer 2.

EXAMPLE 62 1-f2- (Methyl) oxy) -5- d R.5S / 1S, 5R) -3-r3 - ((4-methyl-5-r4- (trifluoromethyl) phenin-4H-1.2,4 hydrochloride -triazol-3-ylthio) propyl] -3-azabicyclo3.1.01hex-1-yl. phenyl) ethanone The title compound was prepared in analogy to the method described in Example 1 with a yield of 51 mg as a white solid (y = 60%) from 1- [5 - [(1 R, 5S / 1S, 5R ) -3-azabicyclo [3.1.0Jhex-1-yl] -2- (methyloxy) phenyl-ketanone (35 mg) and 3 - [(3-chloropropyl) lyo] -4-methyl-5- [4- (trifluoromethyl) phenyl] ] -4H-1, 2,4-triazole (60 mg, prepared in analogy to the method described in Preparation 13). NMR (1H, CDCl 3, free base): d 7.80-7.70 (m, 4H), 7.50 (s, 1H), 7.27-7.20 (m, 1 H), 6.85 (d, 1 H), 3.86 (s, 3H ), 3.62 (s, 3H), 3.40-3.24 (m, 3H), 3.15 (d, 1 H), 2.58 (s, 3H), 2.65-2.55 (m, 2H), 2.54-2.45 (m, 2H) , 2.10-1.90 (quint, 2H), 1.65-1.57 (m, 1 H), 1.35 (m, 1 H), 0.75 (m, 1 H). MS (m / z): 531 [MHJ +.

EXAMPLE 63 1-1 * 54 Hydrochloride (1 R, 5S / 1S, 5R) -3- (3- (r5- (3 .4-Difluorophenin-4-methyl-4H-1, 2,4-triazole-3-iptium propyl) -3-azabicyclo3.1.01hex-1 -ill-2- (methyloxy) fenilletanone The title compound was prepared in analogy to the method described in Example 1 in 40 mg yield as a white solid (y = 50%) from 1- [5 - [(1 R, 5S / 1S, 5R ) -3-azabicyclo [3.1.0] hex-1-ylJ-2- (methyloxy) phenyl] ethanone (35 mg) and 3 - [(3-chloropropyl) thioJ-5- (3,4-difluorophenyl) -4 -methyl-4H-1, 2,4-triazole (54 mg, prepared in analogy to the method described in Preparation 13). NMR (1H, CDCl 3, free base): d 7.56-7.19 (m, 5H), 6.84 (d, 1 H), 3.86 (s, 3H), 3.62 (s, 3H), 3.38-3.24 (m, 3H) , 3.10 (d, 1 H), 2.58 (s, 3H), 2.65-2.42 (m, 4H), 2.10-1.90 (quint, 2H), 1.65-1.57 (m, 1 H), 1.35 (m, 1 H ), 0.75 (m, 1 H). MS (m / z): 499 [MHJ +.

EXAMPLE 64 Hydrochloride of 1 -. { 2- (Methyloxy) -5-r (1 R.5S / 1S, 5R) -3- (3- (4-methyl-5- (3-pyridinin-4H-1,2,4-triazole-3-iptio} propyl) -3-azabicyclo3.1.0lhex-1-infenil > -etanone The title compound was prepared in analogy to the method described in Example 1 in 32 mg yield as a yellow solid (y = 42%) from 1- [5 - [(1R, 5S / 1S, 5R) 3-azabicyclo [3.1.0] hex-1-ylj-2- (methyloxy) phenyl-ketanone (35 mg) and 3-. { 5 - [(3-chloropropyl) thio] -4-methyl-4H-1, 2,4-triazol-3-yl} pyridine (48 mg, prepared in analogy to the method described in preparation 13). NMR (H, CDCl 3, free base): d 8.87 (s, 1 H), 8.70 (d, 1H), 8.0 (d, 1H), 7.48 (s, 1H), 7.43 (m, 1 H), 7.23 (m, 1H), 6.84 (d, 1 H), 3.86 (s, 3H), 3.62 (s, 3H), 3.40-3.25 (m, 3H), 3.10 (d, 1 H), 2.58 (s, 3H), 2.67-2.42 (m, 4H), 2.10- 1.90 (quint, 2H), 1.65-1.57 (m, 1 H), 1.35 (m, 1 H), 0.75 (m, 1 H). MS (m / z): 464 [MH] +.

EXAMPLE 65 1-r5-r Hydrochloride (1R.5S / 1S.5R) -3- (3- (r4-Methyl-5- (2-methyl-5-quinolinyl) - 4H-1.2.4-tr Azole-3-intio> propyl) -3-azabicyclo3.1.Olhex-1 -ill-2- (methyloxy) phenyl] ethanone The title compound was prepared in analogy to the method described in Example 1 in 50 mg yield as a yellow solid (y = 60%) from 1- [5 - [(1 R, 5S / 1S, 5R ) -3-azabicyclo [3.1.0] hex-1-iI] -2- (methyloxy) phenyl] ethanone (35 mg) and 5-. { 5 - [(3-Chloropropyl) -io] -4-meityl-4H-1, 2,4-triazol-3-yl} -2-Melylquinone (60 mg). NMR (1H, DMSO): d 10.38 (bs, 1H), 8.2 (m, 2H), 7.91 (t, 1H), 7.78 (d, 1 H), 7.5 (m, 3H), 7.17 (d, 1 H) ), 4.02 (d, 1 H), 3.89 (s, 3H), 3.74 (dd, 1 H), 3.6-3.2 (m, 6H), 3.45 (s, 3H), 2.72 (s, 3H), 2.5 ( s, 3H), 2.23 (quiñi, 2H), 2.11 (quiñi, 1 H), 1.57 (t, 1 H), 1.1 (í, 1 H). MS (m / z): 528 [MHJ + EXAMPLE 66 1- Hydrochloride. { 2- (Methyloxy) -5-rdR.5S / 1S.5R) -3- (3-fr4-methyl-5- (tetrahydro-2H-pyran-4-yl) -4H-1, 2,4-triazole- 3-antio) propyl) -3-azabiciclof3.1.OIhex-1-yl] phenyl} Etanone The title compound was prepared in analogy to the method described in Example 1 with a yield of 24 mg as a white solid (y = 32%) from 1- [5 - [(1 R, 5S / 1S, 5R ) -3-azabicyclo [3.1.0] hex-1-yl] -2- (methyloxy) phenyl] ethanone (35 mg) and 3 - [(3-chloropropyl) thio] -4-methyl-5- (tetrahydroxy) 2H-pyran-4-yl) -4H-1, 2,4-Iriazole (50 mg, prepared in analogy to the method described in Preparation 13). NMR (1H, CDCl 3, free base): d 7.49 (s, 1H), 7.24 (m, 1H), 6.85 (d, 1 H), 4.14-4.05 (m, 2H), 3.86 (s, 3H), 3.62 (s, 3H), 3.57-3.40 (m, 2H), 3.29-3.15 (m, 3H), 3.05 (d, 1 H), 2.82-2.95 (m, 1 H), 2.63-2.40 (m, 4H) , 2.58 (s, 3H), 2.15-1.77 (m, 6H), 1.62 (m, 1 H), 1.32 (m, 1 H), 0.70 (m, 1 H). MS (m / z): 471 [MH] +.

EXAMPLE 67 1- (2-Hydroxy-5-. {(1 R.5S / 1 S.5R) -3-r3-g4-methyl-5-r4- (trifluoromethyl) phenyl] -4H-1 hydrochloride 2,4-triazol-3-yl.} Thio) propyl-3-azabiciclof3.1.0lhex-1-yl} phenyl) ethanone The title compound was prepared in analogy to the method described in Example 1 in 35 mg yield as a white solid (y = 33%) from 1-. { 5 - [(1 R, 5S / 1S, 5R) -3-azabicyclo [3.1.0] hex-1-yl] -2-hydroxyphenyl-ketanone (43 mg) and 3 - [(3-chloropropyl) thio] -4- Melyl-5- [4- (trifluoromethyl) phenyl] -4H-1, 2,4-triazole (80 mg, prepared in analogy to the method described in Preparation 13). NMR (1H, CDCl 3, free base): d 12.2 (s, 1 H), 7.80-7.70 (m, 4H), 7.50 (s, 1 H), 7.30 (m, 1 H), 6.88 (d, 1 H) ), 3.86 (s, 3H), 3.40-3.25 (m, 3H), 3.10 (d, 1 H), 2.58 (s, 3H), 2.65-2.35 (m, 4H), 2.0 (quint, 2H), 1.58 (m, 1 H), 1.35 (m, 1H), 0.70 (m, 1 H). MS (m / z): 517 [MH] +.

EXAMPLE 68 Hydrochloride 1- (5-r (1R, 5S / 1 S.5R) -3- (3- (r5- (3,4-Difluorophenyl) -4-methyl-4H-1,2,4-triazole-3 -int¡o> propyl) -3-azabicicior3.1.01hex-1-n-2-hydroxyphenyl.} ethanone The title compound was prepared in analogy to the method described in Example 1 with yield of 27 mg as a solid white (y = 29%) from 1- { 5 - [(1 R, 5S / 1S, 5R) -3-azabicyclo [3.1.0] hex-1-yl] -2-hydroxyphenyl-ketanone (40 mg) and 3 - [(3-chloropropyl) thio] -5- (3,4-difluorophenyl) -4-methyl-4H-1, 2,4-iriazole (67 mg, prepared in analogy to the method described in Preparation 13) NMR (1H, DMSO): d 11.82 (s, 1 H), 10.26 (bs, 1 H), 7.85 (m, 1 H), 7.76 (d, 1H), 7.67 (m, 1 H ), 7.61 (m, 1 H), 7.51 (dd, 1H), 6.97 (d, 1 H), 4.02 (dd, 1H), 3.74 (dd, 1 H), 3.64 (s, 3H), 3.55 (m , 2H), 3.3 (m, 4H), 2.67 (s, 3H), 2.15 (m, 3H), 1.52 (1, 1 H), 1.13 (1, 1 H), MS (m / z): 485 [ MH] + - EXAMPLE 69 1- (2-Hydroxy-5-r (1R.5S / 1S.5R) -3- (3 { R4-methyl-5- (4-methyl-1,3-oxazol-5-yl) hydrochloride ) -4H-1,2,4-triazole-3-intio> propyl) -3-azabicyclo3.1.0lhex-1- illfeniDetanone The title compound was prepared in analogy to the method described in Example 1 in 36 mg yield as a white solid (y = 43%) from 1-. { 5 - [(1 R, 5S / 1S, 5R) -3-azabicyclo [3.1.0] hex-1-ylJ-2-hydroxyphenyl-ketanone (38 mg) and 3 - [(3-chloropropyl) thio] -4-methyl -5- (4-meityl-l, 3-oxazol-5-yl) -4H-1, 2,4-iriazole (57 mg). NMR (1H, CDCl 3, free base): d 12.2 (s, 1 H), 7.88 (s, 1 H), 7.50 (s, 1 H), 7.24 (m, 1 H), 6.58 (d, 1 H) , 3.68 (s, 3H), 3.32 (m, 3H), 3.10 (d, 1 H), 2.58-2.47 (m, 4H), 2.58 (s, 3H), 2.47 (s, 3H), 2.0 (m, 2H), 1.62 (m, 1 H), 1.35 (m, 1 H), 0.68 (m, 1 H). MS (m / z): 454 [MH] +.

EXAMPLE 70 1- Hydrochloride. { 2-hydroxy-5-f (1R.5S / 1S.5R) -3- (3-fr4-methyl-5- (2-methyl-5-quinolinyl) -4H-1,2,4-triazole-3- intio.}. propyl) -3-azabiciclof3.1.0lhex-1-pfenil} Etanone The title compound was prepared in analogy to the method described in Example 1 in 24 mg yield as a yellow solid (y = 32%) from 1-. { 5 - [(1 R, 5S / 1S, 5R) -3-azabicyclo [3.1.0] hex-1-ylJ-2-hydroxyphenyl-vinytanone (30 mg) and 5-. { 5 - [(3-chloropropyl) thio] -4-methyl-4H-1, 2,4-triazol-3-yl} -2-methylquinoline (55 mg). NMR (1H, CDCl 3) free base): d 12.1 (s, 1 H), 8.10 (dd, 2H), 7.67 (t, 1 H), 7.50 (m, 2H), 7.23 (m, 2H), 6.85 ( d, 1H), 3.45-3.23 (m, 3H), 3.40 (s, 3H), 3.08 (d, 1 H), 2.67 (s, 3H), 2.65-2.41 (m, 4H), 2.55 (s, 3H) ), 2.02 (m, 2H), 1.58 (m, 1 H), 1.32 (m, 1 H), 0.64 (m, 1 H). MS (m / z): 514 [MHJ +.

EXAMPLE 71 1-r5-f Hydrochloride (1 R.5S / 1 S.5R) -3- (3- (r4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H -1,2,4-triazole-3-intio> propyl) -3-azabicyclo3.1.0lhex-1-n-2- (methyloxy) phenyl-1-propanone The compound of the extract was prepared in analogy to the method described in Example 1 with yield of 51 mg as a white solid (y = 47%) from 1- [5 - [(1R, 5S) -3-azabicyclo [3.1.0] hex-1-yl] -2- (methyloxy) phenyl-1-propanone (52 mg, prepared in analogy to the method described in preparations 43-45) and 3 - [(3-chloropropyl) thio] -4-meityl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazole (69 mg). NMR (1H, DMSO): d 10.24 (bs, 1 H), 8.52 (m, 1 H), 7.42 (d, 1 H), 7.40 (dd, 1 H), 7.08 (d, 1 H), 3.93 ( dd, 1 H), 3.81 (s, 3H), 3.67 (dd, 1 H), 3.64 (s, 3H), 3.48 (m, 2H), 3.28 (m, 2H), 3.22 (t, 2H), 2.86 (q, 2H), 2.33 (s, 3H), 2.1 (m, 2H), 2.03 (m, 1 H), 1.48 (t, 1 H), 1.0 (t, 1 H), 1.04 (t, 3H) . MS (m / z): 482 [MH] +. The compound of the title was separated to produce the separated enantiomers by HPLC was my-preparative using a Chi-chiral chiral column AS-H 5 m, 250 x 21 mm, eluent A: n-hexane; B: ethylene + 0.1% isopropylamine, isocratic gradient 40% B, flow rate 7 mL / minute, UV detection at 200-400 nm. The retention times provided were obtained using an analytical HPLC using a chiralpak AS-H 5n chiral column. m, 250 x 4.6 mm, eluent A: n-hexane; B: ethanol + 0.1% isopropylamine, isocratic gradient 40% B, flow rate 0.8 mL / minute, UV deficit at 200-400 nm. The enaniomer 1 was recovered with yield of 10 mg as a white solid (y = 30%) from the racemate (66 mg). Rt. = 17.2 minutes. The enantiomer 2 was recovered in 10 mg yield as a white solid (y = 30%) from the racemate (66 mg). Rt. = 19.1 minutes. Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than the enantiomer 2.

EXAMPLE 72 2-Methyl-5-rdR.5S / 1S, 5R) -3- (3 { R4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1.2 hydrochloride .4-triazole-3-iptio.}. Propyl) -3-azab? Cyclor3.1.OIhex-l-ill-1, 3-benzothiazole - [(1 R, 5S) -3-Azabicyclo [3.1.0] hex-1-yl] -2-methyl-1,3-benzothiazole dihydrochloride was prepared from 2-methyl-1, 3- benzoyiazol-5-amine in analogy to the method described in the preparations 15, 16 and 17. From this material the compound of the title was obtained as a yellow solid following the method described by examples 14 and 15. NMR (1H , DMSO): d 10.54 (bs, 1 H), 8.58 (m, 1 H), 8.0 (d, 1 H), 7.9 (d, 1 H), 7.34 (dd, 1 H), 4.0 (dd, 1 H), 3.75 (dd, 1 H), 3.70 (s, 3H), 3.65 (m, 1 H), 3.57 (m, 1 H), 3.35 (m, 2H), 3.30 (t, 2H), 2.8 ( s, 3H), 2.39 (s, 3H), 2.27 (m, 1 H), 2.19 (m, 2H), 1.7 (í, 1 H), 1.19 (í, 1 H). MS (m / z): 467 [MH] +. The thioule compound was separated to produce the separated enaniomers by semipreparative HPLC using a chiralpak AS-H 5 m chiral column, 250 x 21 mm, eluent A: n-hexane; B: ethanol +0.1% isopropylamine, 13% B socractic gradient, flow rate 7 mL / minute, UV detection at 200-400 nm. The retention times provided were obtained using an analytical HPLC using a chiralpak AS-H 5 um chiral column, 250 x 4.6 mm, eluyenfe A: n-hexane; B: ethanol + 0.1% isopropylamine, isocratic gradient 13% B, flow rate 1 mL / minute, UV detection at 200-400 nm. Enantiomer 1 was recovered in 17 mg yield as a white solid (y = 62%) from the racemate (55 mg). Rt. = 17.1 minutes. The enantiomer 2 was recovered in 18 mg yield as a white solid (y = 65%) from the racemate (55 mg). Rt. = 19.3 minutes. Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than the enantiomer 2.EXAMPLE 73 2-Methyl-6-l * d R, 5S / 1S.5R) -3- (3-. {14-Methyl-5- (4-methyl-1,3-oxazole-5-in-4H-hydrochloride -1.2.4-triazole-3-antiopropyl) -3-azabicyclo3.1.0lhex-1-in-1,3-benzothiazole 6 - [(1 R, 5S / 1S, 5R) -3-Azabicyclo [3.1.0] hex-1-yl] -2-methyl-1,3-benzothiazole was prepared from 2-methyl-1, 3 -benzoliazole-6-amine in analogy to the method described in preparations 15, 16 and 5. From this material the title compound was obtained as a yellow solid following the method described by examples 14 and 15. NMR ( 1H, CD3OD): d 8.39 (s, 1 H), 7.98 (d, 1 H), 7.89 (d, 1 H), 7.5 (dd, 1 H), 4.19 (d, 1 H), 3.92 (d, 1 H), 3.8 (s, 3H), 3.72 (d, 2H), 3.52 (t, 2H), 3.42 (t, 2H), 2.85 (s, 3H), 2.47 (s, 3H), 2.31 (m, 3H), 1.54 (t, 1 H), 1.41 (t, 1 H). MS (m / z): 467 [MHJ +.

EXAMPLE 74 1-Methyl-5-rd R, 5S / 1S, 5R) -3- (3-tt4-methyl-5- (4-methyl-1,3-oxazol-5-yl) - 4H-1.2.4 hydrochloride -triazol-3-intio.}. propyl) -3-azabicyclo3.1.0lhex-1-in-1H-indazole - [(1 R.5S / 1 S, 5R) -3-Azabicyclo [3.1.0] hex-1-yl-1-methyl-1 H-indazole was prepared from 1-methyl-1 H-indazole -5-amine in analogy to the method described in Preparations 15, 16 and 5. From this material the title compound was bleached as a yellow solid following the method described by Examples 14 and 15. NMR (1H, DMSO): d 10.4 (bs, 1 H), 8.58 (m, 1 H), 8.01 (s, 1 H), 7.70 (d, 1 H), 7.63 (d, 1 H), 7.39 (dd, 1 H) ), 4.05 (m, 1 H), 4.04 (s, 3H), 3.75 (d, 1H), 3.70 (s, 3H), 3.59 (m, 2H), 3.39 (t, 2H), 3.26 (t, 2H) ), 2.39 (s, 3H), 2.18 (m, 3H), 1.61 (t, 1 H), 1.14 (t, 1H). MS (m / z): 450 [MHJ +. The compound of the title was separated to produce the separated enantiomers by semi-preparative SFC (Gilson) using a chiralpak AS-H chiral column, 250 x 21 mm, modifier: ethanol + 0.1% isopropylamine 12%, flow rate 22 mL / minute, P 196 atmospheres, T 36 ° C, UV detection at 220 nm. The retention times provided were obtained using an analytical SFC (Berger) using a chiralpak chiralpak column AS-H 5 um, 250 x 46 mm, modifier: ethanoH- 0.1% isopropylamine 12%, flow rate 2.5 mL / minute, P 176.4 atmospheres, T 35 ° C, UV detection at 220 nm. Enantiomer 1 was recovered in 25 mg yield as a white solid (y = 62%) from the racemate (80 mg). Rt. = 19.5 minutes. The enantiomer 2 was recovered in 28 mg yield as a white solid (y = 70%) from the racemate (80 mg). Rt. = 22.8 minutes. Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than the enantiomer 2.

EXAMPLE 75 Hydrochloride of d R.5S / 1 S, 5R) -3- (3- (r4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1,2,4-triazole -3-illthio.) Propyl) -1-r6- (trifluoromethyl) -3-pyridinium-3-azabicyclo [3.1.O-hexane (1 R.5S / 1 S, 5R) -1 - [6- (Trifluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1. Ojhexane was prepared from 6- (trifluoromethyl) -3-pyridinamine in analogy to the method described in Preparations 37 and 5. From this material the title compound was obtained as a yellow solid following the method described for examples 14 and 15.

NMR (1H, DMSO): d 10. 46 (bs, 1 H), 8.73 (bs, 1 H), 8.58 (m, 1 H), 8. 0 (dd, 1 H), 7.90 (d, 1 H), 4.12 (m, 1 H), 3.78 (d, 1 H), 3.70 (s, 3H), 3.7 (m, 1 H), 3. 54 (m, 1H), 3.39 (t, 2H), 3.29 (s, 2H), 2.39 (m, 3H), 2.47 (m, 1 H), 2.18 (m, 2H) r 1.71 (m, 1H), 1.33 (m, 1H). NMR (19 F, DMSO): d -66.2 (s). MS (m / z): 465 [MH] +.

EXAMPLES 76-94 To a solution of the respective 3-thio-5-aryl-1, 2,4-triazole (prepared in analogy to the method described in Preparation 13, 0.063 mmol) in dry acetonitrile (2 mL) was added 2-tert-butylimino-2. dimethylamino-1, 3-dimethyl-perhydro-1, 3,2-diaza-phosphorine on polystyrene (43 mg, 2.2 mmol / g) and the resulting mixture was stirred for 1 hour at room temperature, then added (1 R). , 5S / 1S, 5R) -1- (4-bromophenyl) -3- (3-chloropropyl) -3-azabicyclo- [3.1.0] hexane (20 mg) was added and the resulting mixture was stirred at 70 °. C for 3.5 hours. After cooling, the resin was removed by filtration, washed with dichloromethane (2 mL) and methanol (2 mL) and the collected liquid phase was evaporated under reduced pressure. Two isomers were formed by S- and N-alkylation, the major isomer being the desired S-alkylated. Two isomers were separated using direct mass CLAR using a Waters column XTerra Prep MS C18 10 um, 30x150 mm using the following conditions: A = H20 + 0.1% formic acid B = acetonitrile + 0.1% formic acid Then the solvent was removed under reduced pressure to produce the title compounds as format salts. In the case of examples 93 and 94, the isomers were separated by insanitary chromatography on silica gel. The S-alkylated isomers were dissolved in dry diethyl ether and cooled to 0 ° C. Slowly 1.2 equivalents of HCl were added (as a 1.0 M solution in diethyl ether). The resulting precipitate was decanted, washed with pentane and filtered, yielding the products as the hydrochloride salts. Analytical conditions: EXAMPLES 76-90: EXAMPLE 91 EXAMPLE 93 EXAMPLE 94 EXAMPLE 96 3- (3. {R4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazole-3-intiopropyl) -dR hydrochloride. 5R / 1S, 5S) -1-r5- (trifluoromethyl-2-pyridinin-3-azabicyclo [3.1.Olhexane The compound of the title was prepared in analogy to the method described in Example 1 as a slightly hygroscopic white solid (70 mg, 45%), from 1- [5- (trifluoromethyl) -2-pyridinyl-3-azabicyclo [3.1.Ojhexano. NMR (corresponding free base, 1H, CD3OD): d 8.71 (s, 1 H), 7.93 (s, 1 H), 7.78 (dd, 1H), 7.15 (d, 1 H), 3.72 (s, 3H), 3.41 (d, 1 H), 3.36 (t, 2H), 3.13 (d, 1 H), 2.8 (d, 1 H), 2.68 (m, 2H), 2.54 (s, 3H), 2.48 (dd, 1 H), 2.04 (m, 3H), 1.6 (m, 1 H), 1.26 (dd, 1 H). MS (m / z): 465 [MHJ +. Example 96 was separated to produce the separated enaniomers by semipreparative HPLC using a chiral column Chirapak AD-H 5um, 250 x 4.6 mm, eluent A: n-hexane; B: ethanol + 0.1% isopropylamine, isocratic gradient 30% B v / v, flow rate 6 mL / minute, UV detection at 270 nm. The retention times provided were obtained using a chiral column Chirapak AD-H 5 um, 250 x 4.6 mm, elute A: n-hexane; B: aeolol, isocratic gradient 30% B v / v, flow rate 0.8 mL / min, UV detection at 200-400 nm.

The enantiomer 1 was recovered in 18 mg yield as a white solid, hydrochloride salt from the racemate (70 mg). Rt. = 19.09 minutes. 100% a / a purity by UV The enantiomer 2 was recovered in 18 mg yield as a white solid, hydrochloride salt from the racemate (70 mg). Rt. = 21.6 minutes. Purity 99% a / a by UV. The enantiomer 2 showed an fpKi (D3) > 1 log unit greater than enantiomer 1.

EXAMPLE 97 3- (3-4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1,2,4-triazole-3-ptio) propyl H 1 R, 5 R / 1 S, 5 S dihydrochloride ) -1-r6- (trifluoromethyl) -2-pyridinyl-3-azabicyclo [3.1.Ojhexane] 3- (Phenylimethyl) -1- [5- (trifluoromethyl) -2-pyridinyl] -3-azabicyclo [3.1. Ojhexane (0.19 millimoles) was dissolved in 1,2-dichloroethane (1 mL) and 1-chloroethylchloridocarbonate (0.21 mmol) was added. After two microwave cycles (5 minutes at 120 ° C and 10 minutes at 140 ° C) the solvent was removed under reduced pressure. Methanol (2 mL) was added and the solution was subjected to an additional microwave cycle (10 minutes, 120 ° C). The solvent was removed under reduced pressure to yield 47 mg of the intermediate which was used without further purification and treated analogously to the method described in Example 1 to produce the title compound (5 mg, 5%) as a slightly hygroscopic solid. White color . NMR (1H, CD3OD): d 8.38 (s, 1 H), 7.99 (dd, 1 H), 7.67 (dd, 1 H), 7.48 (dd, 1 H), 4.18 (d, 1H), 4.06 (d , 1 H), 3.88 (d, 1 H), 3.79 (s, 3H), 3.63 (dd, 1 H), 3.50 (m, 2H), 3.41 (t, 2H), 2.49 (m, 1 H), 2.44 (s, 3H), 2.31 (m, 2H), 1.69 (m, 1H), 1.65 (dd, 1 H). MS (m / z): 465 [MHJ +.

EXAMPLE 98 Hydrochloride of d R.5S / 1S.5R) -1-r3-Fluoro-4- (1H-pyrrol-1-ylmethyl) phenin-3- (3-f4-methyl-5- (4-methyl-1.3 -oxazole-5-n-4H-1,2,4-triazole-3-intio> propyl) -3-azabicyclo [3.1.O-hexane The title compound was prepared in analogy to the method described in Example 1 as a slightly hygroscopic white solid (5.4 mg, yield = 19%), from 1- [3-fluoro-4- (1 H-pyrrole -1-ylmethyl) phenyl] -3-azabicyclo [3.1. Ojhexano (preparation 57). NMR (as a format salt) (1H, CDCl 3): d 7.9 (s, 1 H), 6.8 (m, 4H), 6.65 (s, 2H), 6.15 (s, 2H), 5.05 (s, 2H), 3.66 (s, 3H), 3.4 (d, 1 H), 3.25 (t, 2H), 3.2 (d, 1H), 2.75 (t, 2H), 2.6 (d, 1 H), 2.55 (m, 1H), 2.5 (s, 3H), 2.0 (m, 2H), 1.7 (m, 1 H) ), 1.45 (t, 1 H), 0.8 (m, 1 H); acid proton not observed. MS (hydrochloride salt) (m / z): 475 [MH] +.

EXAMPLES 99-104 Examples 99-104 were prepared as slightly hygroscopic white solids from (1 R, 5S / 1S, 5R) -3- (3-chloropropyl) -1- [6- (trifluoromethyl) -3-pyridinylJ-3 -azabiciclo [3.1. Ojhexane (40 mg) in analogy to the method described for examples 53-58.

EXAMPLES 105-109 Examples 105-109 were prepared as slightly hygroscopic white solids from 5 - [(1 R, 5S / 1S, 5R) -3- (3-chloropropyl) -3-azabicyclo [3.1.0jhex-1-il ] -2-methyl-1,3-benzo-thiazole (40 mg) in analogy to the methods described in Examples 53-58.

EXAMPLE 110 Hydrochloride of d R.5S / 1S, 5R) -1-r3-Fluoro-5- (trifluoromethyl) phenyl-3- (3- (4-methyl-5- (4-methyl-1,3-oxazole-5- il) -4H-1.2.4-triazole-3-intio propyl) - azabicyclo [3.1.Olhexane The title compound was prepared in analogy to the method described in Example 1 with a yield of 383 mg as a slightly hygroscopic white solid (y = 46%) from (1 R, 5S / 1 S, 5R) -1 - [3-Fluoro-5- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.Ojhexane (400 mg). NMR (H, CD3OD): d 8.46 (s, 1 H), 7.54 (bs, 1 H), 7.47 (bd, 1 H), 7.41 (bd, 1 H), 4.19 (d, 1 H), 3.09 ( d, 1 H), 3.87 (s, 3H), 3.71 (m, 2H), 3.51 (t, 2H), 3.46 (t, 2H), 2.49 (s, 3H), 2.33 (m, 3H), 1.67 ( m, 1 H), 1.39 (m, 1 H). MS (m / z): 482 [MH] +.

Chlorhydrate (1 R, 5S / 1S, 5R) -1- [3-Fluoro-5- (trifluoromethyl) pheny] -3- (3- {[4-mephyl-5- (4-methyl- 1 l3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] -ioio}. Propyl) -azabicyclo [3.1. Ojhexane was separated to produce the separated enantiomers by means of semipreparaive chroma- tography in supercritical fluid (Gilson) using a chiral column Chiralcel AD-H, 25 x 2.1 cm, eluent 0O2 that contains 9% (ethylene + 0.1% isopropylamine), flow rate 22 mL / minute, P 188.1 atmospheres, T 36 ° C, UV detection at 220 nm, Handle 2 mL. The retention times provided were obtained using semi-preparative chromatography in supercrylic fluid (Gilson) using a chiral column Chiralpak AD-H, 25 x 0.46 cm, eluyenie C02 conining 10% (ethylene + 0.1% isopropylamine), flow rate 2.5 mL / minute, P 176.4 atmospheres, T35 ° C, UV detection at 220 nm. Enantiomer 1 was recovered in 19.4 mg yield as a white solid, hydrochloride salt from the racemate (100 mg). Rt. = 12.6 minutes. Purity > 99% a / a by UV The enantiomer 2 was recovered in 18.3 mg yield as a white solid, hydrochloride salt from the racemate (100 mg). Rt. = 14.7 minutiae. Purity > 99% a / a UV media The enaniomer 1 showed a fpKi (D3) > 1 log unit greater than enanfimer 2.

EXAMPLE 110 Hydrochloride of d R, 5S / 1S.5R) -1-r3-fluoro-5- (trifluoromethyl) phenan-3- (3- { R4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1,2,4-triazole-3-intio.} Propyl) -azabicyclo [3.1.Ohexan The title compound was prepared in analogy to the method described in Example 1 in 383 mg yield as a slightly hygroscopic white solid (y = 46%) from (1 R, 5S / 1 S, 5R) -1 - [3-Fluoro-5- (trifluoromethyl) phenylJ-3-azabicyclo [3.1.Ojhexane (400 mg). NMR (1H, CD3OD): d 8.46 (s, 1 H), 7.54 (bs, 1 H), 7.47 (bd, 1 H), 7.41 (bd, 1 H), 4.19 (d, 1H), 3.09 (d , 1H), 3.87 (s, 3H), 3.71 (m, 2H), 3.51 (t, 2H), 3.46 (m, 2H), 2.49 (s, 3H), 2.33 (m, 3H), 1.67 (m, 1 H), 1.39 (m, 1 H). MS (m / z): 481 [MHJ +.

Hydrochloride of (1 R, 5S / 1 S, 5R) -1 - [3-Fluoro-5- (trifluoromethyl) phenyl] -3- (3 { [4-methyl-5- (4-methyl) -1, 3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl-jiio}. Propyl) -azabicyclo [3.1. Ojhexane was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralcel AD-H, 25 x 2.1 cm, eluent C02 containing 9% (ethanol + 0.1% isopropylamine), flow rate 22 mL / minute, P 188.1 atmospheres, T 36 ° C, UV detection at 220 nm, Handle 2 mL.

The retention times provided were obtained using semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AD-H, 25 x 0.46 cm, eluent C02 containing 10% (ethanol + 0.1% of sopropylamine), flow rate 2.5 mL / minute, P 176.4 atmospheres, T35 ° C, UV detection at 220 nm. The enaniomer 1 was recovered in 19.4 mg yield as a white solid, hydrochloride salt from the racemate (100 mg). Rt. = 12.6 minutes. Purity > 99% a / a UV action The enantiomer 2 was recovered in 18.3 mg yield as a white solid, hydrochloride salt from the racemate (100 mg). Rt. = 14.7 minutes. Purity > 99% a / a by UV Enantiomer 1 showed a fpKi (D3) > 1 log unit greater than the enantiomer 2.

EXAMPLE 111 Hydrochloride of d R.5S / 1S.5R) -1-r2-Fluoro-3- (trifluoromethylphenin-3- (3- (4-methyl-5- (4-methyl-1,3-oxazole- 5-yl) -4H-1.2.4-triazole-3-antium> propyl) -azabicyclo 3.1.Olhexane The title compound was prepared in analogy to the method described in Example 1 with a yield of 349 mg as a slightly hygroscopic white solid (y = 45%) from (1R, 5S / 1S, 5R) -1 - [ 2-fluoro-3- (trifluoromethyl) phenyl-3-azabicyclo [3.1.Ojhexane (400 mg). NMR (H, CD3OD): d 8.46 (s, 1 H), 7.75-7.65 (m, 2H), 7.38 (t, 1 H), 4.1 (d, 1 H), 3.93 (d, 1 H), 3.78 (s, 3H), 3.71 (d, 1 H), 3.54 (d, 1 H), 3.48 (t, 2H), 3.38 (t, 2H), 2.45 (s, 3H), 2.36 (m, 1 H) , 2.25 (m, 2H), 1.54 (m, 1H), 1.34 (m, 1 H). MS (m / z): 481 [MHJ +.

Hydrochloride of (I R.dS / IS.dRH - ^ - fluoro-S-trifluoromethyl) phenyl J-S- (3- {[4-methyl-5- (4-meityl-1, 3-oxazol-5-yl ) -4H-1, 2,4-Iriazol-3-yl] thio} propyl) -azabicyclo [3.1] Ojhexane was separated to produce the separated enantiomers by semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AD-H, 250 x 4.6 mm, eluent n-hexane / ethanol 88/12 (isocratic), flow rate 1 mL / minute, P 196-392 atmospheres, T 36 ° C, UV deletion at 200-400 nm, Handle 2 mL The retention times provided were obtained using a semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AD-H, 250 x 4.6 mm, eluent n-hexane / ethanol 88/12 (isocratic), flow 1 mL / minute, P 196-392 atmopheres, T 36 ° C, UV detection at 200-400 nm Enantiomer 1 was recovered in 37 mg yield as a white solid, hydrochloride salt from the racemate ( 98 mg). Rt. = 20.4 m inute Purity 98.5% a / a by UV The enantiomer 2 was recovered with yield of 35 mg as a white solid, hydrochloride salt from the racemate (98 mg). Rt. = 23.0 minutes. Purity 99.5% a / a by UV Enantiomer 2 showed a fpKi (D3) > 1 log unit greater than enantiomer 1.

EXAMPLE 112 Hydrochloride of d R.5S / 1S.5R) -1-r4- (methyloxy) -5- (trifluoromethyl) phenyl-3- (3- { R4-methyl-5- (4-methyl- 1,3-oxazol-5-yl) -4H-1,2,4-triazol-3-inpropyl) - azabicyclo [3.1.Olhexane H-C! The title compound was prepared in analogy to the method described in Example 1 with a yield of 658 mg as a slightly hygroscopic white solid (y = 76%) from (1 R, 5 S / 1 S, 5 R) -1 - [4- (Methyloxy) -5- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.0] hexane (430 mg).

NMR (1H, CD3OD): d 8.37 (s, 1 H), 7.57 (m, 2H), 7.17 (d, 1 H) 3.9 (m, 4H), 3.77 (s, 3H), 3.74 (m, 1 H), 3.65-3.30 (m, 6H), 2.44 (s, 3H), 2.21 (m, 2H), 2.13 (m, 1 H) ), 1.43 (t, 1 H), 1.24 (m, 1 H). MS (m / z): 494 [MHJ +.

Hydrochloride of (1 R, 5S / 1S, 5R) -1- [4- (methyloxy) -5- (trifluoromethyl) pheny] -3- (3 { [4-methyl-5- (4- methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylthio} propyl) -azabicyclo [3.1. Ojhexane was separated to produce the separated enantiomers by semipreparative chromatography in supercritical fluid (Gílson) using a chiral column Chiralpak AD-H, 250 x 4.6 mm, eluent n-hexane / eilanol + 0.1% isopropylamine 70/30 (isocráic), flow 6 mL / minute, UV detection at 270 nm, Handle 2 mL. The reference periods provided were obtained using a semi-preparative chromatography in supercritical fluid (Gilson) using a chiral column Chiralpak AD-H, 250 x 4.6 mm, eluent n-hexane / eianol 70/30 (isocracyc), flow rate 0.8 mL / minute, UV detection at 200-400 nm. The enantiomer 1 was recovered in 18.3 mg yield as a white solid, hydrochloride salt from the racemate (100 mg). Rt. = 15.5 minutes. Purity >; 99% a / a by UV The enanlimer 2 was recovered in 22.2 mg yield as a white solid, hydrochloride salt from the racemate (100 mg). Rt. = 17.5 minutes. Purity > 99% a / a by UV Enantiomer 2 showed a fpKi (D3) > 2 log units greater than the enantiomer 1.

EXAMPLE 113 d, R, 5S / 1S, 5R) -1-r4- (4-chloro-2-fluorophenin-3- (3-p4-methyl-5- (4-methyl-1,3-oxazole-5) hydrochloride -yl) -4H-1, 2,4-triazol-3-iptio) propyl) -azabicyclo [3.1.Olhexane The title compound was prepared in analogy to the method described in Example 1 with a yield of 112 mg as a slightly hygroscopic white solid from (1 R, 5S / 1S, 5R) -1- [4-chloro-2 -fluorophenyl] -3-azabicyclo [3.1. Ojhexane (130 mg). NMR (1H, CD3OD): d 8.27 (s, 1 H), 7.3 (t, 1 H), 7.1 (m, 2H), 3.95 (d, 1H), 3.8 (d, 1 H), 3.67 (s, 3H), 3.56 (dd, 1H), 3.4-3.2 (m, 5H), 2.34 (s, 3H), 2.15 (m, 3H), 1.4 (t, 1 H), 1.18 (t, 1 H). MS (m / z): 448 [MHJ +.

EXAMPLE 114 Hydrochloride of d R.5S / 1S.5RM -r3- (2- { R4-Methyl-5- (4-methyl-1,3-oxazol-5-n-4H-1.2.4-triazole-3 -intium &propylene) -1- (3-r (trifluoromethyl) oxylphenyl > -3-azabicyclo [3.1.O-hexane H-CÍ The thioule compound was prepared in analogy to the method described in Example 1 with yield of 160 mg as a slightly hygroscopic solid of white from 1 -. { 3 - [(ialifluoromethyl) oxy] phenyl} -3-azabicyclo [3.1. Ojhexane (150 mg). NMR (1H, CD3OD): d 8.41 (s, 1 H), 7.49 (l, 1 H), 7.3 (s, 1 H), 7.37 (d, 1 H), 7.24 (m, 1 H), 4.17 ( d, 1 H), 3.9 (d, 1 H), 3.8 (s, 3H), 3.69 (d, 2H), 3.51 (t, 2H), 3.42 (t, 2H), 2.47 (s, 3H), 2.3 (m, 3H), 1.57 (dd, 1 H), 1.36 (t, 1 H). MS (m / z): 480 [MHJ +.

EXAMPLE 115 Hydrochloride of d R.5S / 1S.5R) -1 - (2-fluoro-4-methylphenyl) -3- (3- (4-methyl-5- (4-methyl-1,3-oxazole-5 -yl) -4H-1, 2,4-triazol-3-iptio) propyl) -3-azabicyclo [3.1.Ojhexane H-C! The title compound was prepared in analogy to the method described in Example 1 in 60 mg yield as a slightly hygroscopic white solid from 1- (2-fluoro-4-methylphenyl) -3-azabicyclo [3.1. Ojhexane (148 mg). NMR (1H, CD3OD): d 8.39 (s, 1 H), 7.26 (t, 1 H), 7.01 (m, 2H), 3.93 (m, 1 H), 3.77 (m, 4H), 3.61 (m, 1 H), 3.41-3.38 (m, 5H), 2.47 (s, 3H), 2.36 (s, 3H), 2.23 (m, 2H), 2.19 (m, 1 H), 1.45 (t, 1 H), 1.21 (t, 1 H). MS (m / z): 428 [MH] +.

EXAMPLE 116 Hydrochloride of (1 R.5S / 1 S, 5R) -1-r3-chloro-4- (methyloxy) phenyl * | -3- (2- (r4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1.2.4-triazole-3-antimony> propyl) -3-azabicyclo3.1.Olhexane - CI The title compound was prepared in analogy to the method described in Example 1 with 56 mg yield as a slightly hygroscopic white solid from 1- [3-chloro-4- (methyloxy) phenyl] -3- azabicyclo [3.1. Ojhexane (60 mg). NMR (1H, CD3OD): d 8.4 (s, 1 H), 7.35 (m, 1 H), 7.1 (m, 2H), 4.01 (m, 1 H), 3.89 (m, 4H), 3.8 (s, 3H), 3.6-3.3 (m, 6H), 2.47 (s, 3H), 2.23 (m, 2H), 2.19 (m, 1 H), 1.4 (m, 1 H), 1.2 (m, 1 H). MS (m / z): 460 [MH] +.

EXAMPLE 117 Hydrochloride of d R.5S / 1S.5R) -1-γ4- (2,4-Dimethyl-1,3-thiazol-5-yl) phenin-3- (3-f-4-methyl-5- (4-methyl- 1,3-oxazol-5-yl) -4H-1,2,4-triazole-3-intiopropyl) -3-azabicyclo [3.1.Olhexane A mixture of (1 R, 5S / 1S, 5R) -1- [4- (2, 4-dimethyl-1,3-thiazol-5-yl) phenyl] -3-aza-bicyclo [3.1. Ojhexane (70 mg), 3 - [(3-chloropropyl) thioJ-4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazole (85 mg ), potassium carbonate (43 mg), Na 2 CO 3 and sodium iodide (45 mg) in anhydrous DMF (0.6 mL) was heated at 60 ° C for 24 hours. After removal of the solvent in vacuo the residue was dissolved in ethyl acetate and the organic phase was washed with aqueous saturated sodium bicarbonate, dried over sodium sulfate and concentrated in vacuo. The unpurified product was purified by means of insanatose chromathography (dichloromean at 10% MeOH in dichloromean) to yield 65 mg of the free base of the thixture compound. To a solution of this material in dichloromethane (1 mL) was added HCl (1M in Et20, 0.13 mL), the solvent was evaporated under vacuum and the material thus obtained was triiodinated with E20 to yield 69 mg of the compound of the product as a solid of white color (50% yield). NMR (1H, DMSO): d 10.39 (bs, 1H), 8.56 (s, 1 H), 7.39 (d, 2H), 7.35 (d, 2H), 4.02 (m, 1 H), 3.72 (m, 1 H), 3.68 (s, 3H), 3.60 (t, 1 H), 3.51 (bm, 1 H), 3.27 (m, 4H), 2.60 (s, 3H), 2.37 (s, 3H), 2.35 (s, 3H), 2.19 (m, 1 H), 2.16 (m, 2H), 1.62 (m, 1 H), 1.15 (m, 1 H); MS (m / z): 507.2 [MH].

EXAMPLE 118 Hydrochloride of (1 R.5S / 1 S, 5R) -3- (3-fl * 4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H- 1.2.4- triazole-3-intiopropyl) -1-4-r6- (trifluoromethyl-2-pyridin-phenyl) -3- azabicyclo [3.1.Olhexane The title compound was prepared in analogy to the method described in example 117 (using (1 R, 5S / 1S, 5R) -1-. {4- [6- (trifluoromethyl) -2-pyridinyl} phenyl}. -3-azabicyclo [3.1 Ojhexane) with 55% yield as a white solid. NMR (1H, CDCl 3): d 10.44 (bs, 1H), 8. 56 (s, 1 H), 8.29 (d, 1 H), 8. 17 (t, 1 H), 8.09 (d, 2H), 7.84 (d, 1 H), 7.43 (d, 2H), 4. 08 (m, 1 H), 3.75 (m, 1H), 3.68 (s) , 3H), 3.64 (t, 1 H), 3.53 (bm, 1 H), 3.28 (m, 4H), 2.37 (s, 3H), 2.27 (m, 1 H), 2.17 (m, 2H), 1.68 (m, 1 H), 1.17 (m, 1 H); MS (m / z): 541.2 [MHJ +.

EXAMPLE 119 Hydrochloride of d R.5S / 1 S, 5R) -1 -r3- (2,4-Dimethyl-1,3-thiazol-5-yl) phen.p-3- (3 ~ p * 4-methyl) -5- (4-Methyl-1,3-oxazol-5-yl) -4H-1,2,4-triazol-3-ylthiopropyl) -3-azabicyclo [3.1.Olhexane] The title compound was prepared in analogy to the method described in example 117 (using (1 R, 5S / 1S, 5R) -1- [3- (2,4-dimethyl-1,3-thiazol-5-yl) phenyl] -3-azabicyclo [3.1.0J-hexane) with yield of 53% as a white solid. NMR (1H, CDCl 3): d 10.53 (b, 1 H), 8.58 (s, 1 H), 7.43 (d, 1 H), 7.28-7.38 (m, 3H), 4.07 (dd, 1 H), 3.73 (dd, 1 H), 3.70 (s, 3H), 3.61 (1, 1 H), 3.53 (m, 1 H), 3.34 (m, 2H), 3.29 (t, 2H), 2.64 (s, 3H) , 2.39 (s, 3H), 2.73 (s, 3H), 2.23 (m, 1 H), 2.20 (m, 2H), 1.68 (t, 1 H), 1.16 (t, 1 H); MS (m / z): 507.1 [MH] +.

EXAMPLE 120 Hydrochloride of (1 R.5S / 1 S, 5R) -3- (3 { R4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4- triazole-3-intio propyl) -1-r3- (5-methyl-2-thienyl) phenin-3-azabicyclo3.1.Olhexane The title compound was prepared in analogy to the method described in Example 117 (using (1R, 5S / 1S, 5R) -1- [3- (5-methyl-2-thienyl) phenyl] -3-azabicyclo [3.1. Ojhexano) with 51% yield as a white solid. NMR (1H, CDCl 3): d 10.44 (b, 1H), 8.58 (s, 1H), 7.49 (d, 1H), 7.45 (dt, 1H), 7.37 (t, 2H), 7.18 (dt, 1H), 6.84 (t, 1H), 4.08 (dd, 1H), 3.76 (dd, 1H), 3.70 (s, 3H), 3.62 (t, 1H), 3.54 (tm, 1H), 3.28 (t, 4H), 2.48 (s, 3H), 2.39 (s, 3H), 2.24 (m, 1H), 2.19 (t, 2H), 1.65 (t, 1H), 1.16 (t, 1H); MS (m / z): 472.0 [MHJ +.

EXAMPLE 121 (1 R.5S / 1 S.5R) -1-f4- (3, 5-Dimethyl-4-isoxazolyl) phenan-3- (3- (4-methyl-5- (4-methyl- 1,3-oxazol-5-yl) -4H-1,2,4-triazol-3-intiopropyl) -3-azabiciclof3.1.Olhexane The title compound was prepared in analogy to the method described in Example 117 (using (1 R, 5S / 1S, 5R) -1- [4- (3,5-dimethyI-4-isoxazolyl) phenyl] -3-azabicyclo [3.1.Ojhexano), with 55% yield as a white solid. MS (m / z): 491.2 [MHJ +. EXAMPLE 122 Hydrochloride of d S.5R) -3- (3- (f5- (2,4-Dimethyl-1,3-oxazol-5-yl) -4-methyl-4H-1,2,4-triazol-3-ylthio> propyl ) -1-r2-fluoro-4- (trifluoromethyphenin-3-azabicyclo [3.1.01-hexane] A mixture of (1S, 5R) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexane (preparation 18, 60 mg), 3 - [(3-chloropropyl) thio] -5- (2,4-dimethyl-1,3-oxazol-5-yl) -4-meityl-4H-1, 2, 4-triazole (preparation 78, 78 mg), 2-ér-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1, 3,2-diaza-phosphorine on polystyrene (2.2 mmol / g, 140 mg) and a catalytic amount of Nal in dry acetonitrile (3 ml) was heated at 70 ° C for 4 hours, and then overnight at 55 ° C. The resin was removed by filtration and washed with acetonitrile (2 x 3 ml). The solvent was removed under vacuum, the remaining solid was dissolved in dry DMF (0.5 ml), 3 - [(3-chloropropyl) lioJ-5- (2,4-dimethyl-1,3-oxazole-5) was added. -yl) -4-methyl-4H-1, 2,4-triazole (preparation 78, 60 mg) followed by potassium carbonate (118 mg). The resulting suspension was heated to 60 ° C overnight. At room temperature a saturated solution of sodium bicarbonate (4 ml) was added and the suspension was extracted with DCM (2 x 6 ml). The resulting solution was loaded onto an SCX column and eluted with MeOH followed by MeOH / 0.25M NH3. The resulting material was purified by preparative HPLC and then converted to the hydrochloride salt following the method described by Example 15 to produce the compound of the title as a slightly hygroscopic white solid (37 mg, yield of 27%). NMR (1H, DMSO): d 10.38 (b, 1 H), 7.71 (d, 1 H), 7.64 (t, 1H), 7.59 (d, 1 H), 3.98 (bd, 1 H), 3.76 (bd) , 1 H), 3.65 (s, 3H), 3.54 (b, 1 H), 3.44 (bt, 1 H), 3.31 (b, 2H), 3.24 (t, 2H), 2.47 (s, 3H), 2.35 (m, 1 H), 2.29 (s, 3H), 2.11 (m, 2H), 1.63 (t, 1 H), 1.13 (1, 1 H). MS (m / z): 496 [MH] +. All publications, including but not limited to patents and patent applications, cited in this specification are incorporated herein by reference as if each individual publication was specifically and individually indicated to be incorporated by reference in the present invention as shown. which was completely established.

It should be understood that the present invention encompasses all combinations of particular groups described above in the present invention. The application of this description and claims form a part and can be used as a basis for priority with respect to any subsequent request. The claims of said subsequent application can be directed to any characteristic or combination of features described in the present invention. These may take the form of a product, composition, process, or use of the claims and may include, by way of example and without limitation, the following claims:

Claims (27)

NOVELTY OF THE INVENTION CLAIMS

1. - A compound of formula (I) or a pharmaceutically acceptable salt thereof,

1. wherein • G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; p is an integer having a range of 0 to 5; Ri is independently selected from the group consisting of: halogen, hydroxy, cyano, C? - alkyl, C1-4 haloalkyl, C1- alkoxy, C? - haloalkoxy, C? -4 alkanoyl; or corresponds to a group R5; R2 is hydrogen or C? - alkyl; R3 is C? - alkyl; R is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or an 8- or 11-membered bicyclic group, any of said groups being optionally substituted by 1, 2, 3 or 4 selected substituents starting from the group consisting of: halogen, cyano, C? -4 alquiloalkyl, haloalkyl of C -? --4, C? - alkoxy, C alca? alkanoyl; R5 is a portion selected from the group consisting of: isoxazolyl, -CH2-N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2-pyrrolidinonyl, and said group is optionally substituted by one or two substituents selected from: halogen, cyano, C, alkyl, C1-haloalkyl, C4-alkoxy, Ct-4 alkanoyl; and when Ri is chloro and p is 1, said R-i is not present in the ortho position with respect to the binding link to the rest of the molecule; and when Ri corresponds to R5, p is 1.

2. A compound of formula (I) ', according to claim 1, or a pharmaceutically acceptable salt thereof, wherein G, p, Ri, R2, R3, R4, and R5 were defined as in claim 1.

3. The compound according to claim 1, further characterized in that Ri is bromo, fluoro, trifluoromethoxy, cyano, hydroxy , chloro, methoxy, tert-butyl, trifluoromethyl; and R 5 is isoxazolyl, 2-pyrrolidinonyl, -CH 2 -N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, 2-thienyl, 2-pyridyl, 2-thiazolyl.

4. The compound according to any of claims 1-3, further characterized in that p is 1 or 2.

5. The compound according to any of claims 1-4, further characterized in that R2 is hydrogen.

6. The compound according to any of claims 1-4, further characterized in that R4 is an optionally substituted phenyl, an optionally substituted quinolinyl, an optionally substituted pyranyl, an optionally substituted pyridinyl, an optionally substituted pyrazolyl, an optionally substituted pyrimidyl , an optionally substituted pyridazinyl, an optionally substituted pyrazinyl, an optionally substituted furanyl, an optionally substituted thienyl, an optionally substituted oxazolyl, an optionally substituted isoxazolyl, an optionally substituted thiazolyl, an optionally substituted triazolyl.

7. A compound of formula (IB) or a pharmaceutically acceptable salt thereof in which Ri, p, R3 and R4 are as defined in any of claims 1-6.

8. A compound of formula (IC) or a pharmaceutically acceptable salt thereof, wherein R-i, p, R3 and R4 are as defined in any of claims 1-6.

9. A compound of formula (ID) or a pharmaceutically acceptable salt thereof, wherein R-i, p, R3 and R4 are as defined in any of claims 1-6.

10. A compound of formula (IE) or a pharmaceutically acceptable salt thereof, wherein G is 2-pyridyl or 3-pyridyl and Ri, p, R3 and R4 are as defined in any of claims 1-6.

11. - A compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R-i, p, R3 and R4 are as defined in any of claims 1-6.

12. - A stereochemically isomer enriched in the configuration (1S.5R) of formula (IA) or a pharmaceutically acceptable salt thereof G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; p is an integer having a range of 0 to 5; Ri is independently selected from the group consisting of: halogen, hydroxy, cyano, C 1 - alkyl, C 1 - haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, C 1-4 alkanoyl; or corresponds to a group R5; R 2 is hydrogen or C 1-4 alkyl; R3 is C1- alkyl; R4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or an 8- or 11-membered bicyclic group, any of said groups being optionally substituted by 1, 2, 3 or 4 substituents selected from starting from the group consisting of: halogen, cyano, C? - alkyl, C | -4 haloalkyl, C | - alkoxy, C? -4 alkanoyl; R5 is a portion selected from the group consisting of: isoxazolyl, -CH2-N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2-pyrrolidinonyl, and said group is optionally substituted by one or two substituents selected from: halogen, cyano, C -? - 4 alkyl, C? -4 haloalkyl, C 1-4 alkoxy, C? - alkanoyl; and when R1 is chloro and p is 1, said R1 is not present in the ortho position with respect to the binding link to the rest of the molecule; and when Ri, corresponds to Rs, P is 1.

13.- A stereochemical isomer enriched in the (1S, 5R) configuration of formula (IB) 'or a pharmaceutically acceptable salt thereof, wherein Ri, p, R3 and R4 they are as defined in any of claims 1-6.

14. - A skeletal isomer enriched in the configuration (1S.5R) of formula (IC) 'or a pharmaceutically acceptable salt thereof, wherein R-i, p, R3 and R4 are as defined in any of claims 1-6.

15. A stereospecific isomer enriched in the configuration (1S.5R) of formula (ID) 'or a pharmaceutically acceptable salt thereof, wherein R-i, p, R3 and R4 are as defined in any of claims 1-6. [ÍDV

16. - A stereochemical isomer enriched in the configuration (1S.5R) or in the configuration (1R, 5R) of formula (IE) 'or a pharmaceutically acceptable salt thereof, wherein G is 2-pyridyl or 3-pyridyl and Ri. P, R3 and R4 are as defined in any of claims 1-6.

17. - A stereochemical isomer enriched in the (1S, 5R) configuration of formula (IF) 'or a pharmaceuically acceptable salt thereof, wherein R-i, p, R3 and R4 are as defined in any of claims 1-6.

18. - A stereospecific isomer enriched in the configuration (1 R, 5S) selected from the group consisting of: 5- [5- (. {3 - [(1 R, 5S) -1 - (4-Methoxyphenyl) - 3-azabicyclo [3.1.0] hex-3-yl] propyl.} Lyo) -4-meityl-4H-1, 2,4-triazol-3-yl] -2-meitylquinoline, enantiomer 2; 5- [5- ( { 3 - [(1 R, 5S) -1 - (4-Bromophenyl) -3-azabicyclo [3.1.0Jhex-3-ylpropyl.] Thio) -4-methyl-4H- 1, 2,4-triazol-3-yl-2-methylquinoline, enantiomer 1; 5- [5- ( { 3 - [(1 R, 5S) -1- (4-tert-butylphenyl) -3-azabicicio [3.1.0] hex-3-yl-propyl.} T, o) - 4-meiiii-4H-1, 2,4-triazol-3-yl] -2-methylenequinoline, enaniomer 1; (1 R, 5S) -3- (3- { [4-Mephyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazole-3- il.]. propyl) -1- [3- (n-fluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexane, enanimer 2; (1 R, 5S) -1- (3-chlorophenyl) -5-meityl-3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) ) -4H-1, 2,4-Iriazol-3-ylchthio.] Propyl) -3-azabicyclo [3.1. Ojhexane, enaniomer 2: 1- [5 - [(1 R, 5S) -3- (3 { [4-Meityl-5- (4-meityl-1,3-oxazol-5-yl) -4H -1, 2,4-triazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1.0] hex-1 -yl] -2- (methyloxy) phenyl-1-propanone, enantiomer 2; 2-Methyl-5 - [(1 R, 5S) -3- (3 { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2 , 4-Iriazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.0] hex-1-ylj-1,3-benzothiazole, enantiomer 2; or a pharmaceutically acceptable salt thereof.

19. The compound or a pharmaceutically acceptable salt thereof according to any of claims 1-17, further characterized in that it is selected from a group consisting of: 5- [5- (. {3 - [( 1 R, 5S / 1S, 5R) -1- (4-Methoxyphenyl) -3-azabicyclo [3.1.OJhex-3-yl-propii.]. -io) -4-mephyl-4H-1, 2,4-triazole- 3-ylj-2-methylquinoline; 5- [5- ( { 3 - [(1S, 5R) -1 - (4-Methoxyphenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl.] Thio) -4- methyl-4H-1, 2,4-triazol-3-yl] -2-methylquinoline, enaniomer 1; 5- [5- ( { 3 [(1 R.5S / 1 S, 5R) -1 - (4-Bromophenyl) -3-azabicyclo [3.1.0Jhex-3-yl] propyl.] Thio) - 4-meityl-4H-1, 2,4-iazol-3-yl] -2-methylquinoline; 5- [5- (. {3 - [(1S, 5R) -1- (4-Bromophenyl) -3 -azabicyclo [3.1.0] hex-3-yl] propyl] thio) -4-methyl-4H-1, 2,4-friazol-3-yl] -2-methylenequinoline, enantiomer 2; 2-Methyl-5- [4-methyl-5- (. {3 - [(1 R, 5S / 1S, 5R) -1-phenyl-3-azabicyclo [3.1.0Jhex-3-ylpropyl.] thio) -4H-1, 2,4-Iriazol-3-yl] quinoline; 2-Meityl-5- [4-methyl-5- (. {3 - [(1S, 5R) -1-phenyl-3-azabicyclo [3.1.0] hex-3-yl] propyl.} Lio) -4H-1, 2,4-Iriazol-3-yl] quinoline, enantiomer 2; 5- [5- ( { 3 - [(1 R, 5S / 1S, 5R) -1- (3,4-Dichlorophenyl) -3-azabicyclo [3.1.0] hex-3-ylpropyl. ) -4-Methyl-4H-1, 2,4-Iriazol-3-yl] -2-methylquinolinei 5- [5- (. {3 - [(1S, 5R) -1- (3,4-D) Chlorophenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl.] Thio) -4-methyl-4H-1, 2,4-triazol-3-yl] -2-methylquinoline, enantiomer 1; 5- [5- ( {3 - [(1 R.5S / 1 S, 5R) -1 - (4-tert-butylphenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl} thio) -4-methyl-4H-1, 2,4-triazol-3-yl] -2-methylenequinoline; 5- [5- ( { 3 - [(1 s, 5R) -1 - (4-tert-butylphenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl. thio) -4-methyl-4H-1, 2,4-triazol-3-yl] -2-methylquinoline, enaniomer 2; .4-i (1 R, 5S / 1 S, 5R) -3- (3- { [4-Methyl-5- (2-methylquinolin-5-yl) -4H-1, 2,4-triazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1.OJhex-1 - il] benzonitrile; .4 - [(1 R.5S / 1 S, 5R) -3- (3 { [4-Methyl-5- (2-methylquinolin-5-ii) -4H-1, 2,4-Iriazol-3-yl] io.}. PropiI) -3-azabicyclo [3.1.Ojhex-1-yl] phenol; 5- [5- ( { 3 - [(1 R, 5S) -1- (4-Methoxyphenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl} thio) - 4-methyl-4H-1, 2,4-Iriazol-3-yl] -2- meylylquinoline, enaniomer 2; 5- [5- ( { 3 - [(1R, 5S) -1- (4-Bromophenyl) -3- azabicyclo [3.1.0] hex-3-yl] propyl.} Thio) -4-methyl -4H-1, 2,4-Iriazol-3-yl-2-yl-quinoline, enaniomer 1: 5- [5- (. {3 - [(1 R, 5S) -1- (4-yer-buil-phenyl)) -3-azabicyclo [3.1.0Jhex-3-ii-propyl.} -io) -4-methyl-4H-1, 2,4-lyrol-3-yl-2-yl-quinoline, enantiomer 1: (1 R, 5S) - 3- (3- { [4-Methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.} Propyl ) -1- [3- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.Oxhexane, enantiomer 2: (1 R, 5S) -1- (3-chlorophenyl) -5-methyl-3- (3-. { . [4-meylyl-5- (4-mephile-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1 .Oxhexane, enanfomer 2: 1- [5 - [(1 R, 5S) -3- (3 { [4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) - 4H-1, 2,4-triazol-3-yl] thio.]. Propyl) -3-azabicyclo [3.1.0] hex-1-yl-2- (methyloxy) phenyl-1-propanone, enaniomer 2; 2-Meityl-5 - [(1 R, 5S) -3- (3 { [4-meityl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2 , 4-triazol-3-ylchthio}. Propyl) -3-azabicyclo [3.1.0] hex-1-yl] -1,3-benzoyiazole, enaniomer 2; or a pharmaceutically acceptable salt thereof.

20. The compound or a pharmaceutically acceptable salt thereof according to any of claims 1-17, further characterized in that it is selected from a group consisting of: 5- [5- (. {3 - [( 1 R, 5S / 1S, 5R) -1- (4-Methoxyphenyl) -3-azabicyclo [3.1.0Jhex-3-yl] propyl.]. -io) -4-meityl-4H-1, 2,4- Iriazol-3-IJ-2-meitylquinoline; 5- [5- ( { 3 - [(1 S, 5R) -1 - (4-Methoxyphenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl] thio) - 4-meityl-4H-1, 2,4-triazol-3-yl] -2-mepholinquinoline, enaniomer 1; 5- [5- ( {3 - [(1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3-azabicyclo [3.1.0jhex-3-yl] propyl. ) - 4-methyl-4H-1, 2,4-triazol-3-yl-2-methylquinoline; 5- [5- ( { 3 - [(1S, 5R) -1- (4-Bromophenyl) -3-azabicyclo [3.1.0] hex-3-yl-propyl] -thio) -4-methyl-4H -1, 2,4-triazol-3-yl-2-methylquinoline, enantiomer 2; 2-Meityl-5- [4-methyl-5- (. {3 - [(1 R, 5S / 1S, 5R) -1-phenyl-3-azabicyclo [3.1.0] hex-3-yl-propyl.} fio) -4H-1, 2,4-Iriazol-3-ylquinoline; 2-Mephyl-5- [4-methyl-5- (. {3 - [(1S, 5R) -1-phenyl-3-azabicyclo [3.1.0Jhex-3-ylpropyl]. 4H-1, 2,4-Iriazol-3-ylquinoline, enaniomer 2; 5- [5- ( { 3 - [(1 R, 5S / 1S, 5R) -1- (3,4-Dichlorophenyl) -3-azabicyclo [3.1.0Jhex-3-yl] propyl. ) -4-meiyl-4H-1, 2,4-Iriazol-3-ylj-2-methylquinoline; 5- [5- ( { 3 - [(1 S, 5R) -1 - (3,4-Dichlorophenyl) -3-azabicyclo [3.1.OJhex-3-yl] propyl]. 4-meityl-4H-1, 2,4-triazol-3-yl] -2-methyl-quinoline, enaniomer 1: 5- [5- (. {3 - [(1 R, 5S / 1S, 5R) -1- (4-Ier-buylphenyl) -3-azabicyclo [3.1.0Jhex-3-ylpropyl.] Thio) -4-meityl-4H-1, 2,4-triazol-3-yl] -2-methylenequinoline; 5- [5- ( { 3 - [(1S, 5R) -1 - (4-tert-butylphenyl) -3-azabicyclo [3.1.0Jhex-3-yl] propyl.] Thio) -4- methyl-4H-1, 2,4-triazol-3-yl-2-methylquinoline, enantiomer 2: 4 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-Methyl- 5- (2-methylquinolin-5-yl) -4H-1, 2,4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.0Jhex-1-yljbenzonitrile; 4 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-Methyl-5- (2-methylquinolin-5-yl) -4H-1, 2,4-triazole-3 -yl] thio.} propyl) -3-azabicyclo [3.1.0] hex-1-yl] phenol; (1 R, 5S / 1S, 5R) -3- (3 { [4-methyl-5- (4-methyl-3,3-oxazol-5-yl) -4H-1, 2,4- triazol-3-yl] thio.} propyl) -1-phenyl-3-azabicicio [3.1.Ojhexane; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { (4-methyl-5- (4-methyl-1,3-oxazol-5-yl) - 4H-1, 2,4-triazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.O-hexane; (1S, 5R) -1- (4-Bromophenyl) -3- (3- { [4-methyl-5- (4-methyl-1,3-oxazoI-5-yl) -4H-1, 2,4-yriazol-3-yl] -ioio}. Propyl) -3-azabic Chloro [3.1.0] hexane, enaniomer 1; (1 R.5S / 1 S, 5R) -1 - (4-yer-butylphenyl) -3- (3 { [4-methyl-5- ( 4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl] -ioio} propyl) -3-azabicyclo [3.1 .Ojhexane; (1 R, 5S / 1S, 5R) -1- (3,4-Dichlorophenyl) -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-L-azozol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1: Ojhexane; (1S, 5R) -1- (3,4-dichlorophenyl) -3- (3- { [ 4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio}. Propyl) -3-azabicyclo [3.1.Ojhexane , enantiomer 2; (1 R, 5S / 1S, 5R) -1- (4-methoxyphenyl) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazole-5 -yl) -4H-1, 2,4-triazoi-3-yl] thio.} propyl) -3-azabicyclo [3.1.O-hexane; (1S, 5R) -1- (4-methoxyphenyl) -3- (3- { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl ) -4H-1, 2,4-triazol-3-yl] thio} propyl) -3-azabicyclo [3.1. Ojhexane, enantiomer 2: (1 R, 5S / 1S, 5R) -1- [4- (5-meityl-3-isoxazolyl) phenylJ-3- (3 { [4-methyl-5- (4- mephyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.} propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3- { [4-Meily-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazole-3- IJtio.) Propyl) -1- [4- (trifluoromethyl) phenylJ-3-azabicyclo [3.1.Ojhexane; _ (1S, 5R) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1,2,4-triazole-3- Fig. 1) .propyl) -1- [4- (trifluoromethyl) phenylJ-3-azabicyclo [3.1. Ojhexano; (1 R, 5S / 1S, 5R) -1 - [2-Fluoro-4- (trifluoromethyl) phenyl] -3- (3 { [4-methyl-5- (4-methyl-1 , 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl-jiio}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1 R, 5S / 1S, 5R) -3- (3 { [4-Meiiii-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2.4 -yriazole-3-ylthi) propyl) -1- [3- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1 R, 5S / 1S, 5R) -1- [4-Fluoro-3- (trifluoromethyl) phenylJ-3- (3 { [4-methyl-5- (4-methyl-1, 3- oxazol-5-yl) -4H-1 ^^ - triazol-S-yl-Jioio-propyl -S-azabiciclofS.I.Ojhexane; 1 - [5 - [(1S, 5R / 1R, 5S) -3- (3- {. [4-Meityl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] -io}. Propyl) -3 -azab-cyclo [3.1.0] hex-1-yl] -2- (methyloxy) phenyl] eyenone; 1- [5 - [(1S, 5R) -3- (3 { [4-Meityl- 5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yljfio.}. Propyl) -3-azabicyclo [3.1.OJhex-1-yl] - 2- (meilyloxy) phenyl-ketanone, enaniomer 1; (1S, 5R / 1R, 5S) -1- (4-chlorophenyl) -3- (3 { [4-meityl-5- (4-methyl-1 , 3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-ylthio} propyl) -3-azabicyclo [3.1.Ohexane; (1S, 5R) -1- (4-chlorophenyl) -3- (3- { [4-metii-5- (4-meyyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylthio}. Propyl) -3-azabicyclo [3.1.Ojhexane, enantiomer 1; (1 S.5R / 1 R, 5S) -1 - (4-chlorophenyl) -3- (3 { [4-methyl-5- (4- methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylthio}. propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1 - (4-chlorophenyl) -3- (3- { [4-Methyl-5- (4-meiyl-1,3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl] -io} propyl) -3-azabicyclo [3.1. Ojhexane, enantiomer 1; (1S, 5R / 1R, 5S) -1- (3-chlorophenyl) -5-methyl-3- (3 { [4-meityl-5- (4-methyl-1,3-oxazole-5 -yl) -4H-1, 2,4-triazol-3-yl] -ioio}. propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (3-chlorophenyl) -5-methyl-3- (3 { [4-meityl-5- (4-methyl-1,3-oxazol-5-yl) -4H -1, 2,4-Iriazol-3-yl-yl.}. Propyl) -3-azabicyclo [3.1. Ojhexane, enaniomer 1; (1S, 5R / 1R, 5S) -1- (3-Fluorophenyl) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazole-5-yl) -4H-1, 2,4-Iriazol-3-yl-yl.}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (3-Fluorophenyl) -3- (3 { [4-meiiii-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2 , 4-triazol-3-yl-jiio}. Propyl) -3-azabicyclo [3.1. Ojhexane, enaniomer 1; (1S, 5R / 1R, 5S) -3- (3 { [4-meityl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1,2,4 -triazol-3-ylthio}. propyl) -1- [3- (methyloxy) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazole-3- il] thio.] propyl) -1- [3- (methyloxy) phenyl] -3-azabicyclo [3.1. Ojhexane, enantiomer 1; (1S, 5R) -1- (4-Bromofenll) -3- (3 { [4-methyl-5- (1-hydra-2H-pyran-4-yl) -4H-1, 2.4 - triazole-3-ylthio}. propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- [4- (trifluoromethyl) phenylJ-4H-1, 2,4-Iriazol-3-yl .} io) propiIJ-3- azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (3-pyridinyl) -4H-1, 2,4-triazol-3-yl] io.]. - propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [5- (3,4-difluorophenyl) -4-methyl-4H-1, 2,4-lriazol-3-yl ] lio.] propyl) -3-azabicyclo [3.1. Ojhexano; 5- [5- ( { 3 - [(1S, 5R / 1R, 5S) -1- (4-chlorophenyl) -3-azabicyclo [3.1.0] hex-3-yl] propyl. ) - 4-methyl-4H-1, 2,4-triazol-3-iiJ-2-methylquinoline; 5- [5- ( { 3 - [(1S, 5R / 1 R, 5S) -1- (4-chlorophenyl) -3-azabicyclo [3.1.0Jhex-3-yl] propyl.] Iio) - 4-meityl-4H-1, 2,4-yriazol-3-yl] -2-methylquinoline, enaniomer 1: (1S, 5R / 1R, 5S) -3- (3- { [4- Melyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-ylthio} propyl) -1-. { 4 - [(ialifluoromethyl) oxy] phenyl} -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3- { [4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl ] uncle.}. -propyl) -1-. { 4- [(trifluoromethyl) oxy] phenyl} -3-azabicyclo [3.1.Ojhexane, enantiomer 1 (1S.5R / 1R, 5S) -3- (3 { [4-Meily-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4- Iriazol-3-yl-yl.}. propyl) -1- [2-meityl-4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S.5R / 1R, 5S) -3- (3- { [4-Methyl-5- (1-hydra-2H-pyran-4-yl) -4H-1, 2,4-triazole-3 -il] íio.}. propil) -1-. { 4 - [(ialifluoromethyl) oxy] phenyl} -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -3- (3 { [4-Methyl-5- (1-tetrahydro-2H-pyran-4-yl) -4H-1, 2,4-yriazol-3-yl] -io. propil) -1-. { 4- [(ialifluoromethyl) oxy] phenyl} -3-azabicyclo [3.1.Ojhexane, enaniomer 2; (1 R, 5S / 1S, 5R) -1- (3-Bromophenyl) -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) - 4H-1, 2,4-triazol-3-yl] io]. Propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (1-Methyl-3 { [4-meityl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-iriazole -3-yljiio.). Propyl) -1 - [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (1-Methyl-3 { [4-meityl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-iriazole -3-yl] thio.} Propyl) -1 - [4- (ír-trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexane, diastereoisomer 1; (1S, 5R) -3- (1-Meilyl-3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-triazole -3-yl] thio.) Propyl) -1 - [4- (trifluoromethyl) phenylJ-3-azabicyclo [3.1.Oxhexane, diastereomer 2; (1 R, 5S / 1 S, 5R) -1 - [2-Fluoro-5- (irifluoromethyl) phenyl] -3- (3 { [4-methyl-5- (4-methyl-1, 3 -oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] thio.} propyl) -3-azabicyclo [3.1.Ohexane; (1S, 5R) -1- [2-Fluoro-5- (trifluoromethyl) phenylJ-3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl ) -4H-1, 2,4-triazol-3-yl] io.}. Propyl) -3-azabicyclo [3.1.Oxhexane, enantiomer 2: 1- [4 - [(1 R.5S / 1S, 5R) -3- (3- { [4-Methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl ] thio.) propyl) -3-azabicyclo [3.1.0] hex-1 -yl] -2- (methyloxy) phenylyenanone; 1 - [4- [(1 R, 5S / 1S, 5R) -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H- 1, 2,4-triazol-3-ylJiio}. Propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2- (methyloxy) phenyl-1-propanone; (1 R.5S / 1 S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2.4 -triazol-3-yl] t, o.}. propyl) -1- [2- (trifluoromethyl) phenylJ-3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- [2-Fluoro-4- (trifluoromethyl) phenylJ-3- (3 { [4-meityl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-Methyl-5- (2-meityl-3-pyridinyl) -4H-1, 2,4-triazol-3-ylthio} propi. ) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-Methyl-5- (4-pyridazinyl) -4H-1, 2,4-yol-3-yl-jiio.} Propyl ) -1- [4- (ialifluoromethyl) phenylJ-3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3- { [5- (1, 5-Dimethyl-1 H -pyrazol-4-yl) -4-mephyl-4H-1, 2,4-triazole-3 - propylene) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-Metll-5- (5-pyridin-II) -4H-1, 2,4-friazol-3-yl-yl.} Propyl) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -3- (3 { [4-Methyl-5- (3-meityl-2-furanyl) -4H-1, 2,4-triazol-3-yl]. Propyl) -1- [4- (O-fluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-Methyl-5- (6-methyl-3-pyridinyl) -4H-1, 2,4-iazol-3-ylthio}. Propyl) -1- [4- (trifluoromethyl) phenylj-3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3- { [5- (2,4-Dimethyl-1,3-thiazol-5-yl) -4-methyl-4H-1, 2,4-triazole-3 -iljfio.}. piOpil) -1- [4- (l-trifluoromethyl) phenyl J-3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-Methyl-5- (5-methyl-2-pyridinyl) -4H-1, 2,4-triazole-3-ylthio} propyl. ) -1- [4- (ialifluoromethyl) phenylj-3-azabicyclo [3.1. Ojhexano; (1 S, 5 R) -3- (3 { [4-Methyl-5- (terahydro-2 H -pyran-4-yl) -4 H-1, 2,4-yriazol-3-yl] iio. propyl) -1- [4- (trifluoromethyl) phenyl J-3-azabicyclo [3.1. Ojhexano; 2-Methyl-6-. { 4-methyl-5 - [(3- {(1S, 5R) -1 - [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.OJhex-3-yl}. Propyl) t O] -4H-1, 2,4-Iriazol-3-yl} quinoline; 8-Fluoro-2-methyl-5-. { 4-meityl-5 - [(3- {(1S, 5R) -1- [4- (uro-fluoromethyl) phenyl] -3-azabicyclo [3.1.0] hex-3-yl} propyl) tl or] -4H-1, 2,4-Iriazol-3-yl} quinoline; 2-Meyil-5-. { 4-meityl-5 - [(3- {(1S, 5R) -1- [4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.0Jhex-3-yl}. Propyl) thioj- 4H-1, 2,4-triazole-3-ylquinoline; (1S, 5R) -1- [2-Fluoro-4- (trifluoromethyl) phenylJ-3- (3 { [4-methyl-5- (2-methyl-3-pyridyl)) -4H-1, 2,4-Iriazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- [2-Fluoro-4- (trifluoromethyl) phenyl] -3- (3 { [4-methyl-5- (4-pyridazinyl) -4H-1, 2.4- Iriazol-3-yl] io.}. propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1- [2-Fluoro-4- (trifluoromethyl) phenylJ-3- (3 { [4-methyl-5- (5-pyrimidinyl) -4H-1, 2,4-iriazole -3-yl] uncle.}. Propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -3- (3 { [5- (2,4-Dimethyl-1,3-thiazol-5-yl) -4-methyl-4H-1, 2,4-triazole- 3-yl] t, o.}. Propyl) -1- [2-fluoro-4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- [2-Fluoro-4- (trifluoromethyl) phenyl] -3- (3 { [4-methyl-5- (5-methy1-2-pyrazinyl) -4H- 1, 2,4-triazol-3-ylthio.}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) r1- [2-Fluoro-4- (trifluoromethyl) phenylj-3- [3- (. {4-methyl-5- [4- (trifluoro-methyl) phenylJ-4H-1, 2,4-triazol-3-yl.} Thio) propyI-3-azabicyclo [3.1. Ojhexano; 1-. { 4 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-Methyl-5- (2-methyl-5-quinolinyl) -4H-1, 2,4-triazole-3 -yl] io.}. propyl) -3-azabicyclo [3.1.0] hex-1-yl] phenyl} -2-pyrrolidinone; 5-. { 5 - [(3-. {(1 R, 5S / 1S, 5R) -1- [4- (1, 1-Dioxido-2-isoyiazolidinyl) phenyl] -3-azabicyclo- [3.1.0] hex- 3-yl.} Propyl) io] -4-meityl-4H-1, 2,4-iazol-3-yl} -2-methylquinoline; (1 R.5S / 1 S, 5R) -1 - [3-Fluoro-4- (l-trifluoromethyl) phenyl-5-methyl-3- (3 { [4-meityl-5- ( 4-Melyl-1, 3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.Ojhexane; 1- (2- (Meilyloxy) -5-. {(1 R, 5S / 1S, 5R) -3- [3- (. {4-methyl-5- [4- (trifluoromethyl) phenyl] -4H -1, 2,4-Iriazol-3-yl.} .io) propyl] -3-azabicyclo [3.1.0] hex-1-yl] phenyl) ethanone; 1- [5 - [(1 R, 5S / 1S, 5R) -3- (3 { [5- (3,4-Difluorophenyl) -4-methyl-4H-1, 2,4-triazole- 3-yl] io.}. Propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2- (methyloxy) phenyl] ethanone; 1-. { 2- (Meilyloxy) -5 - [(1 R, 5S / 1 S, 5R) -3- (3 { [4-meityl-5- (3-pyridinyl) -4H-1, 2,4- iriazol-3-yl-phenyl] -propyl) -3-azabicyclo [3.1.0] hex-1-yl-phenyl} ethanone; 1- [5 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-MeyI-5- (2-meityl-5-quinolinyl) -4H-1, 2, 4-Iriazol-3-ylthio}. Propyl) -3-azabicyclo [3.1.0] hex-1-yl-2- (methyloxy) phenyl-ketanone; 1-. { 2- (Methyloxy) -5- [(1 R.5S / 1 S, 5R) -3- (3 { [4-methyl-5- (tetrahydro-2H-pyran-4-yl) -4H- 1, 2,4-triazol-3-yl-jiio}. Propyl) -3-azabicyclo [3.1.0Jhex-1-yl] pheniI} ethanone; 1- (2-hydroxy-5-. {(1 R, 5S / 1 S, 5R) -3- [3- (. {4-methyl-5- [4- (ír-trifluoromethyl) phenyl] -4H -1, 2,4-triazol-3-yl.} Thio) propyl] -3-azabicyclo [3.1.0] hex-1-yl] phenyl) ethanone; 1 -. { 5 - [(1 R.5S / 1S, 5R) -3- (3- { [5- (3,4-Difluorophenyl) -4-methyl-4H-1, 2,4-iriazole- 3-yl] thio.] Propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2-hydroxyphenyl} ethanone; 1-. { 2-Hydroxy-5 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-meityl-5- (4-meityl-1,3-oxazol-5-yl) -4H -1, 2,4-Iriazol-3-yl] t, o.}. Propyl) -3-azabicyclo [3.1.0] hex-1-yl] phenyl} ethanone; 1-. { 2-hydroxy-5 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-methyl-5- (2-methyl-5-quinolinyl) -4H-1, 2 , 4-Iriazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.0] hex-1-ylphenyl} ethanone; 1- [5 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H- 1, 2,4-triazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1.OJhex-1-ylJ-2- (meliloxy) phenyl] -1-propanone; 1- [5 - [(1S, 5R) -3- (3 { [4-Methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2.4 -triazol-3-ylthio.}. -propyl) -3-azabicyclo [3.1.0Jhex-1-ylj-2- (methyloxy) phenyl] -1-propanone enantiomer 1: 2-Methyl-5 - [(1 R , 5S / 1S, 5R) -3- (3 { [4-meityl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-yriazol-3 - propylene) -3-azabicyclo [3.1.0Jhex-1 -ilj-1, 3-benzoyiazole; 2-Meityl-5 - [(1S, 5R) -3- (3 { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2, 4-Iriazol-3-ylthio}. Propyl) -3-azabicyclo [3.1.0] hex-1-yl-1,3-benzoyiazole, enaniomer 1; 2-Meyyl-6 - [(1 R.5S / 1 S, 5R) -3- (3 { [4-Methyl-5- (4-meityl-1,3-oxazole-5-yl) - 4H-1, 2,4-yl-azole-3-yl], propyl) -3-azabicyclo [3.1.0Jhex-1-yl] -1,3-benzothiazole; 1 -Methyl-5 - [(1 R, 5S / 1S, 5R) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) - 4H-1, 2,4-triazol-3-ylthio., Propyl) -3-azabicyclo [3.1.0Jhex-1-ylJ-1 H-indazole; 1-Methyl-5 - [(1S, 5R) -3- (3 { [4-meylyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2 , 4-Iriazol-3-ylchthio}. Propyl) -3-azabicyclo [3.1.0] hex-1-ylj-1 H-indazole, enanfimer 1; (1 R, 5S / 1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2, 4-triazol-3-yl] thio.} Propyl) -1- [6- (trifluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1. Ojhexano; (1 R.5S / 1 S, 5R) -1 - (4-Bromophenyl) -3- (3 { [4-methyl-5- (2-meityl-3-pyridyl) -4H -1, 2,4-Iriazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1 R, 5S / 1S, 5R) -1- (4-bromophenyl) -3- (3 { [4-methyl-5- (4-pyridazinyl) -4H-1, 2,4-iriazole- 3-ylthio.) Propyl) -3-azabicyclo [3.1. Ojhexano; (1R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [5- (5-chloro-1-methyl-1 H -pyrazol-4-yl) -4- methyl-4H-1, 2,4-triazol-3-ylthio}. propyl) -3-azabicyclo [3.1. Ojhexano; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (1-methyl-1 H-1, 2,3-Iriazole- 4-yl) -4H-1, 2,4-triazol-3-yljlio.} Propyl) -3-azabicyclo [3.1. Ojhexano; (1R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [5- (1, 5-dimethyl-1 H -pyrazol-4-yl) -4-methyl- 4H-1, 2,4-triazol-3-ylchthio}. Propyl) -3-azabicyclo [3.1.Ohexane; (1 R.5S / 1 S, 5R) -1 - (4-Bromophenyl) -3- (3 { [4-methyl-5- (5-pyrimidinyl) -4H-1, 2,4-triazole -3-yljthio.) Propyl) -3-azabicyclo [3.1.Ojhexane; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- [3- (. {4-methyl-5- [1-methyl-3- (trifluoromethyl) -1 H-pyrazole- 4-yl] -4H-1, 2,4-triazol-3-yl.}. Fio) propyl-3-azabicyclo [3.1.Ohexane; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (3-meylyl-2-furanl) -4H-1, 2,4-IriazoI-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1.Ojhexane; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (3-methyl-5-issoxazolyl) -4H-1, 2,4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1. Ojhexano; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (6-methyl-3-pyridinyl) -4H-1, 2, 4- triazol-3-yl] io.}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (1-meityl-1 H -pyrazol-5-yl) -4H -1, 2,4-triazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.Ojhexane; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (5-meityl-3-pyridinyl) -4H-1, 2,4-triazol-3-yl-jiio}. Propyl) -3-azabicyclo [3.1.Ojhexane; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- [3- (. {4-methyl-5- [2-methyl-5- (trifluoromethyl) -1,3-oxazole -4-ylj-4H-1, 2,4-triazol-3-yl.}. Mess) propyl] -3-azabicyclo [3.1.Ohexane; (1 R, 5S / 1S, 5R) -1- (4-bromophenyl) -3- (3 { [4-methyl-5- (3-melyl-2-pyridin) - 4H-1, 2,4-Iriazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1. Ojhexano; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [5- (2,4-dimethyl-1,3-thiazol-5-yl) -4- meilyl-4H-1, 2,4-lriazole-3-yl], propyl) -3-azabicyclo [3.1.Ohexane; (1 R, 5S / 1 S, 5R) -1 - (4-Bromophenyl) -3- (3 { [5- (2,5-dimethyl-3-furanyl) -4-meityl-4H-1 , 2,4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1. Ojhexano; (1R, 5S / 1S, 5R) -1- (4-bromophenyl) -3- (3. {- [5- (5-chloro-2-thienyl) -4-methyl-4H-1, 2, 4-triazol-3-ylthio.}. Propyl) -3-azabicyclo [3.1.Ojhexane; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (3-pyridinyl) -4H-1, 2,4-iriazole- 3-ylJiio.}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- [2-methyl-6- (trifluoromethyl) -3-pyridinyl] - 4H-1, 2,4-triazol-3-yl.}. Iio) propyl] -3-azabicyclo [3.1.Ojhexane; 5- [5- ( { 3- [(1 R, 5S / 1S, 5R) -1- (4-Bromophenyl) -3-azabicyclo [3.1.0] hex-3-ylpropyl.}. 4-meityl-4H-1, 2,4-friazol-3-yl] -1-methyl-3- (trifluoromethyl) -1 H -thieno [2,3-c] pyrazole; 3- (3- { [4-Melyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl] thio.} Propyl ) - (1R, 5R / 1S, 5S) -1- [5- (trifluoromethyl) -2-pyridinyl] -3-azabicyclo [3.1. Ojhexano; 3- (3- { [4-Methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl]. Propyl) - (1 R, 5R) -1- [5- (N-trifluoromethyl) -2-pyridinyl] -3-azabicyclo [3.1.Ojhexane. enaniomer 2; 3- (3- { [4-Meityl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] -iio.} Propyl ) - (1 R, 5R / 1S, 5S) -1- [6- (trifluoromethyl) -2-pyridinyl] -3-azabicyclo [3.1. Ojhexano; (1 R, 5S / 1S, 5R) -1- [3-Fluoro-4- (1 H -pyrrol-1-ylmethyl) phenyl] -3- (3 { [4-methyl-5- (4 -methyl-1,3-oxazol-5-yl) -4H-1, 2,4-iriazol-3-ylphido}. propyl) -3-azabicyclo [3.1.Ohexane; (1S.5R / 1R, 5S) -3- (3- { [4-Methyl-5- (5-methyl-2-p -razinyl) -4H-1, 2,4-Iriazole -3-yl] thio.) Propyl) -1- [6- (n-fluoromethyl] -3-pyridinyl] -3-azabicyclo [3.1.0] hexane; (1S, 5R / 1R, 5S) -3- (3 { [4-Methyl-5- (6-methyl-3-pyridinyl) -4H-1, 2,4-iriazole-3- 1-propyl) -1- [6- (trifluoromethyl) -3-pyridyl] -3-azabicyclo [3.1.Ohexane; (1S.5R / 1 R, 5S) -3- (3 { [4-Methyl-5- (2-meityl-3-pyridinyl) -4H-1, 2,4-triazole-3- The propyl) -1- [6- (trifluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R / 1R, 5S) -3- (3 { [4-Methyl-5-phenyl-4H-1, 2,4-triazol-3-yl] lio.] Propyl) -1 - [6- (Fluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R / 1R, 5S) -3- (3- {[[5- (2,4-dimethyl-1,3-thiazol-5-yl) -4-methyl-4H-1, 2, 4-triazol-3-yl] -ioio} propyl) -1- [6- (f-rifluoromethyl) -3-pyridinyl-3-azabicyclo [3.1.O-hexane; (1S.5R / 1R, 5S) -3- [3- ( {4-Mejyl-5- [4- (trifluoromethyl) phenyl] -4H-1, 2,4-Iriazole-3 - il.} thio) propyl] -1- [6- (trifluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1. Ojhexano; (1S.5R / 1R, 5S) -2-Melyl-5- [3- (3 { [4-meityl-5- (5-methyl-2-pyrazinyl) -4H-1, 2, 4-Iriazol-3-yl] thio.] Propyl) -3-azabicyclo [3.1.0] hex-1-yl-1,3-benzothiazole; (1S, 5R / 1R, 5S) -2- Meilyl-5- [3- (3 { [4-methyl-5- (6-methyl-3-pyrazinyl) -4H-1, 2.4 -triazol-3-yl] io.}. propyl) -3-azabicyclo [3.1.0] hex-1-yl] -1,3-benzothiazole; (1S.5R / 1 R, 5S) -2-Methyl-5- (3- (3 - [(4-methyl-5-phenyl-4H-1, 2,4-triazol-3-yl]]. propyl) -3-azabicyclo [3.1.0] hex-1-yl] -1,3-benzoiazole; (1 S.5R / 1 R, 5S) -5- [3- (3 { [5 - (2,4-dimethyI-1,3-thiazyl-5-yl) -4-meityl-4H-1, 2,4-triazol-3-yl] thio}. Propyl) -3-azabicyclo [3.1 .0] hex-1-yl] -2-methyl-1,3-benzoiazole; (1S, 5R / 1R, 5S) -2-Melyl-5- { 3- [3- (. { 4-methyl-5- [4- (trifluoromethyl) phenyl] -4H-1, 2,4-triazol-3-yl.} Lio) propyl] -3-azabicyclo [3.1.0] hex-1 -yl.} -1, 3-benzothiazole; (1 R, 5S / 1S, 5R) -1- [3-Fluoro-5- (trifluoromethyl) pheny] -3- { [4-methyl- 5- (4-meityl-1,3-azole-5-yl) -4H-1, 2,4-triazol-3-yl] fio.} Propyl) -3-azabicyclo [3.1 .Ojhexane; 1S, 5R) -1- [3-Fluoro-5- (trifluoromethyl) (phenyl) -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-Iriazol-3-ylthio} propyl) -azabicyclo [3.1.Ohexane, enaniomer 1; (1 R, 5S / 1S, 5R) -1- [2-Fluoro-3 - (Fluoromethyl) phenyl] -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4- triazole-3-alkyl] propyl) -azabicyclo [3.1 .Ojhexane; 1S, 5R) -1- [2-Fluoro-3- (trifluoromethyl) phenyl-3- (3-. { [4-meityl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl-yl} propyl) -azab-cyclo [3.1.Ojhexane, enantiomer 2; (1 R, 5S / 1S, 5R) -1 - [4- (Methyloxy) -5- (trifluoromethyl) phenylJ-3- (3 { [4-methyl-5- (4-methyl) 1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] fio.] Propyl) -azabicyclo [3.1.Ohexane; (1 R.5S / 1 S, 5R) -1 - [4- (4-chloro-2-fluorophenyl] -3- (3 { [4-methyl-5- (4-methyl-1,3) oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl] thio.] propyl) -azabicyclo [3.1 Ojhexane; (1 R, 5S / 1S, 5R) -1 - [3- (2- { [4-Meityl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl] -io]. propyl) -1- { 3- [(trifluoromethyl) oxy] phenyl] -3-azabicyclo [3.1. Ojhexane; (1 R, 5S / 1S, 5R) -1- (2-Chloro- 4-methylphenyl) -3- (2 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazole-3-ylthio .}. propyl) -3-azabicyclo [3.1 Ojhexane; (1 R, 5S / 1S, 5R) -1- [3-chloro-4- (methoxy) phenyl] -3- (2- { [4-Methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-lr-azo-3-yl], propyl) -3-azabicyclo [3.1 Ojhexane; (1 R, 5S / 1S, 5R) -1- [4- (2,4-Dimethyl-1, 3-thiazol-5-yl) pheny] -3- (3- { [ 4-meityl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1.0 ] hexane: (1 R, 5S / 1 S, 5R) -3- (3 { [4-meityl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylthio.} Propyl) -1 -. {4- [6- (trifluoromethyl) -2-pyridinyl] phenyl}. -3-azabicyclo [3.1 .Ojhexane; (1 R, 5S / 1S, 5R) -1- [3- (2,4-dimethyl-1,3-thiazol-5-yl) phenyl] -3- (3- { [4-methyl-5 - (4-mephyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylthio} propyl) -3-azabicyclo [3.1.O-hexane; (1 R, 5S / 1S, 5R) -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2.4 -triazol-3-yl] io.}. propyl) -1 - [3- (5-meiyl-2-tienii) phenyl] -3-azabicyclo [3.1.Ohexane; (1 R, 5S / 1S, 5R) -1- [4- (3,5-dimethyl-4-isoxazoliI) phenyl] -3- (3- { [4-methyl-5- (4-methyl) l-1,3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl] -ioio}. propyl) -3-azabicyclo [3.1.Ohexane; (1S, 5R) -3- (3 { [5- (2,4-Dimethyl-1, 3-oxazol-5-yl) -4-meityl-4H-1, 2,4-triazole-3 -ylJtio.}. propyl) -1- [2-fluoro-4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.Ojhexane.

21. The compound or a pharmaceutically acceptable salt thereof according to any of claims 1-17, further characterized in that it is selected from a group consisting of: 4 - [(1S, 5R) -3- ( 3- { [4-Meityl-5- (2-meitylquinolin-5-yl) -4H-1, 2,4-triazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1 .0] hex-1-yl] benzoniiryl; 4 - [(1S, 5R) -3- (3 { [4-Methyl-5- (2-methylquinolyl-5-yl) -4H -1, 2,4-Iriazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.0] hex-1-ylphenol; (1S, 5R) -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-yriazole-3 il] thio.] propyl) -1-phenyl-3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (4-tert-Butylphenyl) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1 , 2,4-triazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- [4- (5-methyl-3-isoxazolyl) phenylj-3- (3 { [4-methyl-5- (4-mephyl-1,3-oxazole-5- il) -4H-1, 2,4-Iriazol-3-ylthio.}. propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-iriazole-3-one! I), propyl) -1- [3- (trifluoromethyl) phenylJ-3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1 - [4-Fluoro-3- (trifluoromethyl) phenyl] -3- (3 { [4-meityl-5- (4-mephyl-1, 3-oxazole-5- il) -4H-1, 2,4-Iriazol-3-ylthio}. propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3- { [4-Meyyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl ] -io.} propyl) -1- [2-meityl-4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (3-Bromophenyl) -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] lio.] Propyl) -3-azabicyclo [3.1.Ojhexane; 1- [4 - [(1S, 5R) -3- (3 { [4-Meityl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2.4 -Iriazole-3-IJthio.) propyl) -3-azabicyclo [3.1.0] hex-1-ylJ-2 (methyloxy) phenyl] ethanone: 1- [4 - [(1S, 5R) -3- ( 3- { [4-meityl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-yol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.0] hex-1-yl] -2- (methyloxy) phenyl-1-propanonal; (1S, 5R) -3- (3 { [4-Methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-triazole-3- Figure imgb0004), propyl) -1- [2- (trifluoromethyl] phenyl] -3-azabicyclo [3.1.0] hexanoll-. { 4 - [(1S, 5R) -3- (3 { [4-Met.l-5- (2-methyl-5-quinolinyl) -4H-1, 2,4-triazol-3-ylthio} propyl) -3-azabicyclo [3.1.0] hex-1-yl] phenyl} -2-pyrrolidinone; { 5 - [(3-. {(1S, 5R) -1- [4- (1, 1-Dioxido-2-isothiazolidinyl) phenyl] -3-azabicyclo [3.1.0Jhex-3-yl} propyl) thio] -4-methylene-4H-1, 2,4-triazol-3-yl} -2-methylquinoline; 1- (2- (Methyloxy) -5-. {(1S, 5R) -3- (3 { [4-methyl-5- [4- (trifluoromethyl) phenyl] -4H-1, 2I4-triazol-3-yl.} Thio) propylj-3-azabicyclo [3.1.0Jhex-1-yl.] Phenyl) einone; 1- [5 - [(1S, 5R) -3- (3 { [5- (3,4-Difluorophenyl) -4-methyl-4H-1, 2,4-triazol-3-yl] thio .}. propyl) -3-azabicyclo [3.1.0Jhex-1-ylj-2- (methyloxy) phenylJetanonal 1-. { 2- (Methyloxy) -5 - [(1S, 5R) -3- (3 { [4-meityl-5- (3-pyridinyl) -4H-1, 2,4-iriazole-3- Fig. 1) .propyl) -3-azabicyclo [3.1.0] hex-1-ylphenyl} ethanone; 1- [5 - [(1S, 5R) -3- (3 { [4-Metyl-5- (2-methyl-5-quinolinyl) -4H-1, 2,4-triazole-3 -yl] lyo.} propyl) -3-azabicyclo [3.1.OJhex-1 -yl] -2- (methyloxy) phenyl-ketanone; 1-. { 2- (Melyloxy) -5 - [(1S, 5R) -3- (3 { [4-meityl-5- (tetrahydro-2H-pyran-4-yl) -4H-1, 2,4 - iriazol-3-yl] t, o.] propyl) -3-azabicyclo [3.1.0] hex-1-yl] phenyl} ethanone; 1- (2-Hydroxy-5-. {(1S, 5R) -3- (3 { [4-methyl-5- [4- (trifluoromethyl) phenyl-4H-1 , 2,4-triazol-3-yl.}., Iio) propyl] -3-azabicyclo [3.1.0] hex-1-yl.} Phenyl) ethanone; { 5 - [(IS, 5R) -3- (3- { [5- (3,4-Difluorophenol) -4-methyl-4H-1, 2,4-iriazol-3-yl] -io} propyl) -3-azabicyclo [3.1.0jhex-1-1] -2-hydroxyphenol} Etanone, # 1-. { 2-hydroxy-5 - [(1S, 5R) -3- (3 { [4-methyl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2, 4-Iriazol-3-ylthio.] Propyl) -3-azabicyclo [3.1.0Jhex-1-yl] phenyl} ethanone; 1-. { 2-Hydroxy-5 - [(1S, 5R) -3- (3 { [4-Methyl-5- (4-methyl-5-quinolinyl) -4H-1, 2,4-Iriazole- 3-yl] fio.}. Propyl) -3-azabicyclo [3.1.0] hex-1-ylphenyl} ethanone; 2-Methyl-6 - [(1S, 5R) -3- (3 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4 H -l ^^ - Iriazole-S-1-Jleyopropyl-S-azabicyclofS.I.Ojhex-1-yl-I-S-benzothiazole; (1S, 5R) -3- (3 { [4-Melyl-5- (4-methyl) -1,3-oxazol-5-yl) -4H-1, 2,4-lriazol-3-yl] thio.} Propyl) -1- [6- (trifluoromethyl) -3-pyridinyl-3-azabicyclo [ 3.1.Ojhexane; (1S, 5R) -1 - (4-Bromophenyl) -3- (3 { [4-methyl-5- (2-meityl-3-pyridinyl) -4H- 1, 2,4-triazol-3-ylthio.} Propyl) -3-azabicyclo [3.1.O-hexane; (1S, 5R) -1- (4-bromophenyl) -3- (3- { [4- methyl-5- (4-pyridazinyl) -4H-1, 2,4-triazol-3-ylthio}. propii) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1 - (4-Bromophenyl) ) -3- (3- { [5- (5-chloro-1-methyl-1 H -pyrazol-4-yl) -4-methyl-4H-1, 2,4-iriazole-3-ylthio .}. propyl) -1-azabicyclo [3.1.Ojhexane; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4- meityl-5- (1-methyl-1H -1, 2,3-Iriazol-4-yl) -4H-1, 2,4-triazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1 .Ojhexane; (1S, 5R) -1 - (4-Bromophenyl) -3- (3 { [5- (1, 5-dimethyl-1 H -pyrazol-4-yl) -4-methyl-4H-1, 2,4-triazole-3 -il] t¡o.} pr op.l) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1 - (4-Bromophenyl) -3- (3 { [4-methyl-5- (5-pyrimidinyl) -4H-1, 2,4-triazole-3- il] thio.] propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- [1-methyl-3- (trifluoromethyl) -1 H -pyrazol-4-yl-4H -1, 2,4-Iriazol-3-yl.} Thio) propyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (3-meityl-2-furanyl) -4H-1, 2,4-iriazole-3 -yl] thio.} propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-meityl-5- (3-methyl-5-isoxazolyl) -4H-1, 2,4-triazole -3-yl] io.}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (6-methyl-3-pyridinyl) -4H-1, 2,4-iriazole-3 -yl] io.}. propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (1-methyl-1 H -pyrazol-5-yl) -4H-1, 2, 4-triazole-3-amino-3-propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (5-meityl-3-pyridinyl) -4H-1, 2,4-iriazole -3-yl] thio.) Propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-meylyl-5- [2-meityl-5- (trifluoromethyl) -1,3-oxazole-4- il] -4H-1, 2,4-Iriazol-3-yl.} thio) propyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [4-methyl-5- (3-meityl-2-pyridinyl) -4H-1, 2,4-triazole-3 -IJíio.}. Propil) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [5- (2,4-dimethyI-1,3-yiazol-5-yl) -4-methyl-4H -1, 2,4-Iriazol-3-yl] thio.} Propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { [5- (2,5-dimethyl-3-furanyl) -4-meityl-4H-1, 2.4 -riazole-3-ylchthio}. propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (4-Bromophenyl) -3- (3 { - [5- (5-chloro-2-thienyl) -4-meityl-4H-1, 2,4-iriazole- 3-yl] io.}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (4-bromophenol) -3- (3 { [4-eyl-5- (3-pyridinyl) -4H-1, 2,4-Iriazol-3-yljthio .}. propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (4-Bromophenyl) -3- (3- (. {4-methyl-5- [2-methyl-6- (trifluoromethyl) -3-pyridinyl-4H-1, 2,4-Iriazol-3-yl.} Thio) propyl-3-azabicyclo [3.1.O-hexane; 5- [5- (. {3 - [((1S, 5R) -1 - (4-Bromophenyl) ) -3-azabicyclo [3.1.0] hex-3-yl-propyl.} Thio) -4-meityl-4H-1, 2,4-yriazol-3-yl] -1-meityl-3- (trifluoromethyl) - l H-Iiene [2,3-c] pyrazole; 3- (3- { [4-meityl-5- (4-methyl-1, 3-oxazol-5-yl) -4H-1, 2,4-yriazol-3-yl] thio.} Propyl ) - (1 R, 5R) -1 - [6- (trifluoromethyl) -2-pyridinyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- [3-Fluoro-4- (1 H -pyrrol-1-ylmeryl) phenyl] -3- (3 { [4-methyl-5- (4-methyl-1 , 3-oxazol-5-yl) -4H-1, 2,4-iazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-Meityl-5- (5-meityl-2-pyrazinyl) -4H-1, 2,4-yl-azole-3-yl] .}. propyl) -1- [6- (ír-fluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [4-Meyyl-5- (6-methyl-3-pyridinyl) -4H-1, 2,4-iazol-3-yl]. Propyl) - 1- [6- (trifluoromeii) -3-pyridinyl] -3-azabicyclo [3.1.Ohexane; (1S, 5R) -3- (3 { [4-Methyl-5- (2-methyl-3-pyridinyl) -4H-1, 2,4-triazol-3-yl] io.) propyl) -1- [6- (n-fluoromethyl) -3-pyridinyl-3-azabicyclo [3.1.0] hexane; (1S, 5R) -3- (3 { [4-Meityl-5-phenyl-4H-1, 2,4-triazol-3-yl) -io] propyl} -1- [6- (l-trifluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3 { [5- (2,4-Dimethy-1,3-liazol-5-yl) -4-meityl-4H-1, 2,4-triazole- 3-yl] io.}. Propyl) -1 - [6- (urea) -3-pyridinyl] -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- [3- ( { 4-Methyl-5- [4- (trifluoromethyl) phenyl] -4H-1, 2,4-triazol-3-yl} io) propyl] -1- [6- (U-fluoromethyl) -3-pyridinyl] -3-azabicyclo [3.1.0] hexane; (1S, 5R) -2-Methyl-5- [3- (3 { [4-methyl-5- (5-methyl-2-pyrazinyl) -4H-1, 2,4-triazole-3- Ill., propyl) -3-azabicyclo [3.1.0Jhex-1-yl-1, 3-benzothiazole; (1S, 5R) -2-MeyI-5- [3- (3 { [4-methyl-5- (6-meylyl-3-pyridinyl) -4H-1, 2,4-iriazole -3-yljthio.) Propyl) -3-azabicyclo [3.1.0Jhex-1-ylj-1, 3-benzoyiazole; (1S, 5R) -2- Methyl-5- (3. {3 - [(4-methyl-5-phenyl-4H-1, 2,4-triazol-3-yl) thio] propyl}. -3-azabicyclo [3.1.0] hex-1-yl) -1, 3-benzothiazole; (1S, 5R) -5- [3- (3. {[[5- (2,4-Dimethyl-1, 3-thiazol-5-yl) -4-meityl-4H-1, 2,4- Iriazol-3-IJiio.} propyl) -3-azabicyclo [3.1.0Jhex-1-ylj-2-methyl-1,3-benzothiazole; (1 S.5R / 1 R, 5S) -2-Meilyl-5. { 3- [3- ( { 4-meityl-5- [4- (trifluoromethyl) phenylj-4H-1, 2,4-triazol-3-yl.} Thio) propyl-3-azabicyclo [3.1.OJhex] -1-il} -1, 3-benzothiazoi; (1S, 5R) -1 - [4- (4-chloro-2-fluorophenyl] -3- (3 { [4-methyl-5- (4-methyl-1,3-oxazole) 5-yl) -4H-1, 2,4-triazol-3-ylthio}. Propyl) -azabicyclo [3.1.Ojhexane; (1S, 5R) -1 - [3- (2- { [4-Methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-triazole -3-ilJtio.}. Propil) -1-. { 3 - [(trifluoromethyl) oxy-phenyl} -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- (2-Chloro-4-methylphenyl) -3- (2 { [4-methyl-5- (4-meityl-1,3-oxazol-5-yl) -4H -1, 2,4-triazoI-3-yljio.}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -1- [3-chloro-4- (methyloxy) phenylJ-3- (2 { [4-meityl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-Iriazol-3-ylthio}. Propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1- [4- (2,4-Dimethy1,3-thiazol-5-yl) phenylJ-3- (3 { [4-methyl-5- (4-methyl- 1,3-oxazol-5-yl) -4H-1, 2,4-triazol-3-ylthio}. Propyl) -3-azabicyclo [3.1. Ojhexano; (1S, 5R) -3- (3- { [4-methyl-5- (4-meiyl-1,3-oxazol-5-yl) -4H-1, 2,4-triazole-3-yl! l] fio.}. propil) -1-. { 4- [6- (trifluoromethyl) -2-pyridinyl] phenyl} -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -1- [3- (2,4-dimethyl-1,3-yiazol-5-yl) phenyl] -3- (3 { [4-methyl-5- (4-methyl) -1, 3-oxazol-5-yl) -4H-1, 2,4-lriazol-3-yl] -ioio}. Propyl) -3-azabicyclo [3.1.Ojhexane; (1S, 5R) -3- (3 { [4-meityl-5- (4-meityl-1,3-oxazol-5-yl) -4H-1, 2,4-yriazole-3- Fig. 1.] propyl) -1- [3- (5-methyl-2-ynyl) phenyl] -3-azabicyclo [3.1.Ohexane; (1S, 5R) -1 - [4- (3,5-dimethyl-4-isoxazolyl) phenyl] -3- (3- {[4-meityl-5- (4-meityl-3, 3- oxazol-5-yl) -4H-1, 2,4-triazol-3-yl] -ioio}. propyl) -3-azabicyclo [3.1.Ohexane; (1S, 5R) -3- (3- { [5- (2,4-DimetiM, 3-oxazol-5-yl) -4-methyl-4H-1, 2,4-triazol-3-yl ] il] thio.] propyl) -1 - [2-fluoro-4- (trifluoromethyl) phenyl] -3-azabicyclo [3.1.0j.

22. A process for the preparation of a compound according to claim 1, the method comprising the steps of reacting a compound of formula (XIV): where R1; R2, G and p are as defined in claim 1 and X is a residual group, with a compound of formula (V): wherein R3 and R are as defined in claim 1.

23. The use of a compound as claimed in any of claims 1-21 in the manufacture of a medicament for the treatment of a condition in a mammal. for which modulation of dopamine D3 receptors is beneficial.

24.- The use as claimed in claim 23, where the condition is psychosis or a psychotic condition, or is substance abuse.

25. The use as claimed in claim 24, wherein the condition is substance abuse.

26. - The use as claimed in claim 24, wherein the psychotic condition is schizophrenia.

27. A pharmaceutical composition comprising a compound according to any of claims 1-21 and a pharmaceutically acceptable carrier. SUMMARY OF THE INVENTION The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; p is an integer that has a range of 0 to 5; R-i is independently selected from the group consisting of: halogen, hydroxy, cyano, C? - alkyl, C? -4 haloalkyl, O? -4 alkoxy, C? -4 haloalkoxy, C1- alkanoyl; or corresponds to a group R5; R2 is hydrogen or C? - alkyl; R3 is C? -4 alkyl; R 4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or a bicyclic group of 8 to 11 members, any of said groups being optionally substituted by 1, 2, 3 or 4 substituents selected from starting from the group consisting of: halogen, cyano, C 1-4 alkyl, haloalkyl of C? -, alkoxy of C? -, alkanoyl of C 1-4; R5 is a portion selected from the group consisting of: isoxazolyl, -CH2-N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2-pyrrolidinonyl, and said group is optionally substituted by one or two substitutes selected from: halogen, cyano, C1- alkyl, haloalkyl of C -4, alkoxy of C1.4, alkanoyl of C? -4; and when Ri is chlorine and p is 1, said Ri is not present in the ortho position with respect to the binding link to the molecule residue; and when R-i corresponds to R5, p is 1; Procedures for its preparation, medicinal products used in these procedures, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D3 receptors, for example to eradicate drug dependence or as antipsychotic agents. 12B P06 / 1326F