The present invention relates to 2-a2a-bicyclo[3.1.0]hexane derivatives of formula (I) and their use as pharmaceuticals. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more compounds of formula (I), and especially their use as orexin receptor antagonists. Orexins (orexin A or OX-A and orexin B or OX-B) are novel neuropeptides found in 1998 by two research groups, orexin A is a 33 amino acid peptide and orexin B is a 28 amino acid peptide (Sakurai T. et al.. Cell, 1998, 92, 573-585). Orexins are produced in discrete neurons of the lateral hypothalamus and bind to G-protein-coupled receptors (0X| and 0X2 receptors). The orexin-1 receptor (OXi) is selective for OX-A, and the orexin-2 receptor (OX2) is capable to bind OX-A as well as OX-B. Orexins are found to stimulate food consumption in rats suggesting a physiological role for these peptides as mediators in the central feedback mechanism that regulates feeding behaviour (Sakurai T. et al.. Cell, 1998, 92, 573-585). On the other hand, it was also observed that orexins regulate states of sleep and wakefulness opening potentially novel therapeutic approaches to narcolepsy as well as insomnia and other sleep disorders (Chemelli R.M. et al.. Cell, 1999, 98, 437-451). Orexin receptors are found in the mammalian brain and may have numerous implications in pathologies as known from the literature. The present invention provides 2-aza-bicyclo[3.1.0]hexane derivatives, which are non-peptide antagonists of human orexin receptors. These compounds are in particular of potential use in the treatment of e.g. eating disorders, drinking disorders, sleep disorders, or cognitive dysfunctions in psychiatric and neurologic disorders. Up to now, several low molecular weight compounds are known having a potential to antagonise either specifically OXi or OX2, or both receptors at the same time. Piperidine derivatives useful as orexin receptor antagonists are disclosed in WOOI/096302. The present invention describes for the first time 2-aza-bicyclo[3.l.0]hexane derivatives as orexin receptor antagonists. i) A first aspect of the invention relates to compounds of formula (1) wherein A represents aryl or heterocyclyl, wherein the aryl or heterocyclyl is unsubstituted or independently mono- or di-substituted, wherein the substituents are independently selected from the group consisting of (Ci.4)alkyl. (CvrOcycloalkyl. (C2-6)alkinyl, (Ci.4)alkoxy, NR^R^, halogen and unsubstituted or independently mono- or di-substituted phenyl or pyridyl. wherein the substituents are independently selected from the group consisting of (Ci-4)alkyl, (Ci.4)alkoxy, trifluoromethyl. trifluoromethoxy, fluorine and chlorine: B represents an aryl- or heterocyclyl-group. wherein the aryl or heterocyclyl is unsubstituted or independently mono-, di-, or tri-substituted, wherein the substituents are independently selected from the group consisting of (C|.4)alkyl. (Ci.4)alkoxy, trifluoromethyl, -NR^R\ -NHS02-(C,.4)alkyl, -N(R^)C(0)R^ and halogen: n represents the integer 0 or 1; R' represents aryl or heterocyclyl, wherein the aryl or heterocyclyl is unsubstituted or independently mono-, di-, or tri-substituted wherein the substituents are independently selected from the group consisting of (Ci.4)alkyl, (Ci.4)alkoxy, halogen, trifluoromethyl, cyano, (Ci.4)alkyl-thio, (C2-6)alkinyl and -NR^R^; or R' represents a 2,3-dihydro-benzofuranyl-, a benzo[l,3]dioxolyl-, a 2,3-dihydro-benzo[l,4]dioxinyl-, a 4//-benzo[l,3]dioxinyl-, a 2//-chromenyl, a chromanyl-, a 2,3-dihydro-thieno[3,4-b][l,4]dioxinyl-, a 3,4-dihydro-2//-benzo[l,4]oxazinyl-. or a 4-morpholino-phenyl-group wherein said groups are unsubstituted or mono- or di-substituted wherein the substituents are independently selected from the group consisting of (C|.4)alkyl, (Ci.4)alkoxy and halogen; R^ represents hydrogen or (C].4)alkyl; and R" represents hydrogen or (C]-4)alkyl. The invention also relates to salts, especially pharmaceutically acceptable salts, of the compounds of formula (1). The compounds of formula (I) and/or (la) may contain one or more stereogenic or asymmetric centers, such as one or more asymmetric carbon atoms. Substituents at a double bond or a ring may be present in cis- (^^ Z-) or trans (= E-) form unless indicated otherwise. The compounds of formula (I) and/or (la) may thus be present as mixtures of stereoisomers or preferably as pure stereoisomers. Mixtures of stereoisomers may be separated in a manner known to a person skilled in the art. hi this patent application, an arrow shows the point of attachment of the radical drawn. For example, the radical drawn below ^^"^' "^1 ^L is the 5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl group. The term "halogen" means fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine. The term "(Ci.4)alkyr', alone or in combination, means a straight-chain or branched-chain alkyl group with 1 to 4 carbon atoms. Examples of (Ci.4)alkyl groups are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec.-butyl or tert.-butyl. Preferred are methyl and ethyl. Most preferred is methyl. The term "(C2-6)alkinyr', alone or in combination, means a straight-chain or branched-chain alkinyl group with 2 to 6 carbon atoms. Examples of (C2-6)alkinyl groups are ethinyl, 1-propinyl, 1-butinyl, 3-methyl-l-butinyl, 1-pentinyl, 3,3-dimethyl-l-butinyl, 3-methyl-l-pentinyl, 4-methyl-I-pentinyl or !-hexinyl. Preferred is ethinyl. The term "(C3.6)cycloalkyr', alone or in combination, means a cycloalkyl group with 3 to 6 carbon atoms. Examples of (C3-6)cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. Preferred is cyclopropyl. The term "(C|.4)alkoxy". alone or in combination, means a group of the formula (C|.4)alkyl-0- in which the term "(Ci-4)alkyl" has the previously given significance, such as methoxy. ethoxy. n-propoxy, isopropoxy. n-butoxy. isobutoxy. sec.-butoxy or tert.-butoxy. Preferred are methoxy and ethoxy. Most preferred is methoxy. The term "aryl", alone or in combination, means a phenyl or a naphthyl group. Preferred is a phenyl group. The aryl group may be unsubstituted or mono-, di-, or tri-substituted wherein the substituents are independently selected from the group consisting of (Ci-4)alkyl. (C3.6)cycloalkyi, (C2-6)alkinyl, (Ci.4)alkoxy, NR'R^ halogen, trifluoromethyl, -NHS02-(Ci.4)alkyl. -N(R^)C(0)R\ cyano, (Ci.4)alkyl-thio and unsubstituted or independently mono- or di-substituted phenyl or pyridyl, wherein the substituents are independently selected from the group consisting of (Ci-4)alkyl. (C|.4)alkoxy. trifluoromethyl. trifluoromethoxy. fluorine and chlorine. In case "A" represents "aryl" the term preferably means the above-mentioned group which is unsubstituted or mono- or di-substituted, wherein the substituents are independently selected from the group consisting of (Ci.4)alkyl, (C3-6)cycloalkyI, (C2.6)alkinyl, (C|.4)alkoxy, -NR^R^, halogen and unsubstituted or independently mono- or di-substituted phenyl or pyridyl, wherein the substituents are independently selected from the group consisting of (Ci.4)alkyl, (Ci.4)alkoxy, trifluoromethyl, trifluoromethoxy, fluorine and chlorine. Especially the substituents are independently selected from the group consisting of (C|.4)alkyl, (C3.6)cyc!oaIkyl, (C2.6)alkinyl, (CM)alkoxy, -NR^R\ halogen and unsubstituted or independently mono- or di-substituted phenyl or pyridyl, wherein the substituents are independently selected from the group consisting of (Ci.4)alkyl. (Ci-4)alkoxy, trifluoromethyl, trifluoromethoxy, fluorine and chlorine. A preferred example wherein "A" represents "ar\T" is unsubstituted phenyl. In another embodiment, preferred examples wherein "A" represents "aryl" are unsubstituted or mono- or di-substituted phenyl (preferred mono-substituted phenyl), wherein the substituents are independently selected from the group consisting of (Ci.4)alkyl, (C3.6)cycloalkyl, (Ci.4)alkoxy and -NR"R^. In addition to the above-mentioned substituents, the substituent "A" is also substituted by the substituent "B". wherein B is preferably attached in ortho position to the point of attachment of the carbonyl group which links A to the 2-aza-bicyclo[3.l.0]hexane moiety. In case "B" represents "aryl" the term preferably means the above-mentioned group which is unsubstituted or mono-, di-, or tri-substituted, wherein the substituents are independently selected from the group consisting of (Ci.4)alkyl, (C)-4)aIkoxy, trifluoromethyl, -NR'R , -NHS02-(Ci-4)aii t / Ws VV^ N-N /,' „ ,^ W /--N ^/ II // In another embodiment, in case n represents the integer 0. a preferred example wherein "R'" represents "heterocyclyl" is mono-, or di-substituted heterocyclyl; wherein the heterocyclyl is pyrimidyl (especially pyrimidin-2-yl); wherein the substituents are independently selected from (Ci.4)alkyl, (Ci.4)alkoxy, halogen, trifluoromethyh cyano. and -NR'R"'. Especially, said pyrimidinyl is di-substituted with (Ci.4)alkoxy. or mono-substituted with (Ci-4)alkyl. halogen or trifluoromethyl. Particular examples are 5-bromo-pyrimidin-2-yl (preferred), 4-trifluoromethyl-pyrimidin-2-yl, 4,6-dimethoxy-pyriiTiidin-2-yi, 5-ethyl-pyrimidin-2-yI, and 4-amino-5-cyano-pyrimidin-2-yl. Further groups as used for the substituent "R'" are preferably substituted as follows: 2.3-dihydro-benzofuranyl-groups (especially 2.3-dihydro-benzofiiran-4-yl or 2.3-dihydro- benzofuran-7-yl) are preferably unsubstituted, or di-substituted in position 2 with methyl; benzo[I,3]dioxolyl-groups (especially benzo[l,3]dioxol-4-yl) are preferably unsubstituted. or di-substituted in position 2 with tluoro; 4/:/-benzo[l,3]dioxinyl-groups (especially 4//-benzo[1.3]dioxin-8-yl or 4//-benzo[l,3]dioxin-5-yl) are preferably unsubstituted, or mono-substituted in position 6 with fluoro; 3,4-dihydro-27/-benzo[l,4]oxazinyl-groups (especially 3,4-dihydro-2//-benzo[l,4]oxazin-5-yl or 3,4-dihydro-2//-benzo[l,4]oxazin- 8-yl) are preferably unsubstituted, or mono-substituted on the nitrogen atom with methyl; 2,3-dihydro-benzo[l,4]dioxinyI- (especially 2,3-dihydro-benzo[l,4]dioxin-5-yl). 2//-chromenyl (especially chromen-5-yl), chromanyl- (especially chroman-5-yl or chroman-8-yl), 2,3-dihydro-thieno[3.4-b][l,4]dioxinyl- (especially 2,3-dihydro-thieno [3,4-b][l,4]dioxine-5-yl), and 4-morphoIino-phenyl-groups are preferably unsubstituted. Ihe term "NR'R " means for example NHo and N(CH3)2. The term "-NHS02-(Ci.4)aikyl" means for example -NHSO2-CH3. The term "-N(R^)C(0)R^" means for example the group -NHC(0)CH3. The term "(C,4)alkyl-thio" means a group of the formula (Ci.4)alkyl-S- in which the term "(Ci.4)alkyl" has the previously given significance. An example is methyl-thio. ii) A further embodiment of the invention relates to compounds according to embodiment i), wherein at least one, preferably all of the following characteristics are present: A represents aryl or heterocyclyl, wherein the aryl or heterocyclyl is unsubstituted or independently mono- or disubstituted, wherein the substituents are independently selected from the group consisting of (C|.4)alkyl, (C3.6)cycloalkyl, (C2-6)alkinyl, (Ci.4)alkoxy, 1? NR"R . halogen and unsubstituted or independently mono- or disubstituted phenyl or pyridyi. wherein the substituents are independently selected from the group consisting of (Cu4)alkyl, (Ci-4)alkoxy, trifluoromethyl. trifluoromethoxy, fluorine and chlorine; B represents an aryl- or heterocyclyl-group, wherein the aryl or heterocyclyl is unsubstituted or independently mono-, di-, or trisubstituted, wherein the substituents are independently selected from the group consisting of (Ci-4)alkyl (Ci.4)alkoxy. trifluoromethyl, NR'R' and halogen; R' represents aryl or heterocyclyl, wherein the aryl or heterocyclyl is unsubstituted or independently mono-, di-, or trisubstituted wherein the substituents are independently selected from the group consisting of (C|.4)ali<.yl, (Ci.4)alkoxy, halogen, trinuoromethy! and NR-R^; or R represents a 2,3-dihydro-benzofuranyl-. a benzo[1.3]dioxolyl-. a 2.3-dihydro-benzo[l,4]dioxinyl- or a 4//-benzo[1.3]dioxinyl group which groups are unsubstituted or independently mono- or disubstituted with (Ci-4)alkyl, (Ci.4)alkoxy and halogen. iii) A further embodiment of the invention relates to compounds of formula (1) according to embodiments i) or ii), which are also compounds of formula (la), wherein the stereogenic centers are in absolute (lS,3S,5S)-configuration (S) B Formula (la). iv) A further embodiment of the invention relates to compounds according to any one of embodiments i) to iii), wherein at least one. preferably all of the following characteristics are present: A represents aryl or heterocyclyl, wherein the aryl or heterocyclyl is unsubstituted or independently mono- or di-substituted, wherein the substituents are independently selected from the group consisting of (Ci.4)alkyl, (C3-6)cycloalkyl, (C].4)alkoxy and NR^R^; B represents aryl or heterocyclyl, wherein the aryl or heterocyclyl is unsubstituted or independently mono-, di- or tri-substituted, wherein the substituents are independently selected from the group consisting of (Ci-4)alkyl. (Ci-4)alkoxy. trifluoromethyl. NR'R^ and halogen: R' represents aryl or heterocyclyl. wherein the aryl or heterocyciyl is unsubstituted or independently mono-, di-, or tri-substituted wherein the substituents are independently selected from the group consisting of (Ci.4)alkyl, (Ci.4)alkoxy, trifluoromethyl and halogen; or R' represents a 2,3-dihydro-benzofuranyl-, a benzo[1.3]dioxolyl-, a 2,3-dihydro- benzo[],4]dioxinyl- or a 4//-benzo[l,3]dioxinyl-group which groups are unsubstituted or mono- or di-substituted, wherein the substituents independently selected from the group consisting of (Ci_4)alkyl, (Ci.4)alkoxy and halogen. v) A further embodiment of the invention relates to compounds according to any one of embodiments i) to iv),wherein at least one, preferably all of the following characteristics are present: A represents heterocyclyl, wherein the heterocyclyl is unsubstituted or mono-substituted. wherein the substituent is selected from the group consisting of (Ci.4)alkyl and NR'R''; B represents aryl, wherein the aryl is unsubstituted or mono-, di- or tri-substituted, wherein the substituents are independently selected from the group consisting of (Ci.4)all THF r-. Boc 2) TFAA QQ^ CH2I2, DCM g^^ ^ H 1 DIBAL . "^^y^OH THF, -78°C Boc 5 Dess-Martin Periodinane. DCM Boc NaBH(0Ac)3 goo DCM N^R' R^COOH r:j~^. ^ 1 1)HCI,dioxane ^T--, H EtOH goc TBTU 8 9 orB-A-COCI ^ 10 Scheme 1: Synthesis of compounds of formula (I) and/or (la) The preparation of the 2-aza-bicyclo[3.].0]hexane derivatives started with protection of the nitrogen atom of the known pyroglutamic acid derivative (1) with B0C2O. Reduction of the lactam with e.g. super-hydride and elimination with trifluoroacetic anhydride resulted in the formation of dihydro-pyrrole (3) which could be transferred to (4) by cyclopropanation with e.g. diethylzinc and diiodomethane. After reduction with DIBAL at low temperatures the respective alcohol (5) was oxidized to the corresponding aldehyde (6) with e.g. Dess-Martin periodinane. After reductive amination of (6) with benzylamine in the presence of a reducing agent like sodium triacetoxyborohydride the benzyl group was removed b\ hydrogenolysis to yield the primary amine (8). The acylation of (8) with a carboxylic acid R'COOH in the presence of a coupling reagent like TBTU resulted in the formation of amides (9) which after removal of the Boc-group were transferred to compounds of formula (1) and/or (la) by amide coupling (e.g. B-A-COOH, TBTU or B-A-COCl). Another approach to compounds of formula (1) and/or (la) started with the protection of amine (8) with trifluoroacetic anhydride to give amides (11) which were Boc-deprotected with an acid like HCl in a solvent like dioxane. The obtained amine (12) could be coupled with a carboxylic acid B-A-COOH in the presence of a coupling reagent like TBTU or with an acid chloride B-A-COCI to an amide (13). After deprotection with for instance K2CO3 in MeOH/water mixtures amines (14) were obtained which were coupled with a carboxylic acid R'COOH in the presence of a coupling reagent like TBTU to compounds (10) of formula (I) and/or (la). H 'N,XF3 ^':x. N BOG NH; TFAA X?" ~N 'Y TEA, DCM Boo O 11 HCI dioxan H 6 12 ,NHc H B-A-COOH _Jm^ \^N^CF3 orB-A-COCI^XQ 0 B 13 K2CO3 N H2O / MeOH . Ap, 60X ^ "14 R^COOH TBTU A-^O O B 10 Scheme 2: Alternative synthesis of compounds of formula (1) and/or (la) Compounds of formula (I) and/or (la) in which n equals 0 could be synthesized according to one of the pathways described in scheme 5. Starting from the Boc-protected compound (8) heterocyclyl-substituted compounds (15) might be obtained in a substitution reaction with for instance heterocyclyl chlorides or bromides in the presence of a base like K2CO:, and/or DIPEA at elevated temperatures. After acid catalyzed removal of the Boc-protecting group compounds (16) of formula (1) and/or (la) were obtained by amide coupling with the respective carboxylic B-A-COOH in the presence of a coupling reagent like for instance TBTU or by reaction with an acid chloride like B-A-COCl in the presence of a base like DIPEA. Alternatively compounds (14) might be transferred to compounds (16) of formula (I) and/or (la) by substitution reaction with for instance heterocyclyl chlorides or bromides in the presence of a base like K2CO3 and/or DIPEA at elevated temperatures. Boc 8 N A-^0 B ,NH, ,NH, 14 K2CO3 DIPEA xylene, A ^ V-^R- Boc 15 1)H* 2) B-A-COOH I TBTU, or * B-A-COCI R-X H NR1 A-^O B 16 K2CO3 DIPEA xylene, A 37 Scheme 3: Alternative synthesis of compounds of formula (I) and/or (la), wherein n equals 0, R' represents a heterocyclyl group and X represents chlorine or bromine Thiazole-4-carboxylic acid derivatives of formula B-A-COOH were for instance synthesised according to scheme 4. By reaction of methyl dichloroacetate (17; commercially available) with an aldehyde in the presence of a base like potassium terr.-butoxide the 3-chloro-2-oxo-propionic ester derivatives (18) were obtained which were transformed in a reaction with thioamides [R = (C|.4)alkyl or (C3.6)cycIoalkyI] to 2-alkyl- or 2-cycloalkyl-substituted thiazole derivatives (19) or in a reaction with thioureas (R = NRV)to2 -amino-substituted thiazole derivatives (19). Saponification of the ester function with an aq. solution of e.g. NaOH in a solvent like MeOH resulted in the formation of the desired carboxylic acids (20, R = (Ci.4)alkyl, (C3.6)cycloalkyl or NR^R"). 2-Bromo-thiazole derivatives (21) were for instance obtained by reaction of the respective 2-amino-thiazole derivative (19, R = NH2) with isoamylnitrite in the presence of copper(II)bromide. The ester derivatives (21) were either transferred to 2-amino-substituted thiazole derivatives (22) by reaction of (21) with amines HNR'R^ and subsequent saponification or to 2-alkoxy substituted analogues (23) by reaction with sodium alkoxide and subsequent saponification with sodium hydroxide solution. In addition compounds (25) which are unsubsituted in 2-position were synthesized by hydrogenation of (21) in the presence of palladium on charcoal and subsequent saponification of the intermediate ester (24). cu o CI 17 O" B CHO KOf-Bu THF B Cl O A, O 18 O" s R'^NH2 R- N .COOMe 19 OH" N COOH ' R-^f I [R = (Ci.4)alkyl, S-^B 20 (C3.6)cycloalkyl, NR2R3] CuBrj, MeCN isoamylnitrite (R = NH2) 1)R^R^NH 2)0H- COOH \ Pd/C, H2 \ EtOH ivj COOMe Br--NH2 T ^^-N / ' ^ VH M R R^ 53 54 55 b^S toluene Rb^S ^N ^b^S^ ^N DBu AKrs OH- AKr? EtOjC N^ . HOsC^ N^^b DMF ^s^ R" ^i R 56 57 Pathway D O ^N ^"""^CFs FsC^N POCI3 FaCx^N NaCI02 FJC^^N ^S acetone ^N J' DMF OHC N J* NaH2P04 H0.^-^N J' b 58 59 60 61 R^ = R" = H Scheme 7: Synthesis of imidazo[2,l-b]thiazole-carboxylic acid derivatives wherein R is methyl or ethyl. R^ is hydrogen or methyl, R*' is hydrogen or methyl Following pathway A iiTiidazo[2.1-b]thiazole-carboxylic acid derivatives were synthesized starting from 2-chloro-3-oxo-butyric acid methyl ester (44: commercially available) by reaction with thiourea in a solvent like EtOH at elevated temperatures. The obtained amino-thiazole (45) was converted to the imidazo[2,l-b]thiazole derivative (46) by alkylation and subsequent cyclization with bromoacetaldehyde diethyl acetal in the presence of an acid like concentrated hydrochloric acid. By saponification of (46) with for instance NaOH in solvents like THF and MeOH the desired acids (47) were obtained. Alternatively (pathway B) the imidazole derivative (48) may be transferred to the acetal (49) by alkylation with a bromoacetaldehyde dialkyl acetal derivative in the presence of a base like sodium ethoxide. Cj'clization under acidic conditions /e.g. aq. hydrochloric acid) and dehydration of the intermediate (50) with for instance phosphorus oxychloride led to ester (51) which was transformed to the desired acid (52) by saponification with for instance NaOH in solvents like THF and MeOH. In still an alternative procedure (pathway C) the respective amino-thiazole (53; commercially available) was converted to the formamidine derivative (54) by heating (53) with MA'-dimethylformamide dimethylacetale in a solvent like toluene. After alkylation with ethyl bromoacetate the respective thiazolium bromide (55) was cyclised with DBU to yield the ester (56) which was saponified to the desired acid (57) with for instance NaOH in solvents like THF and MeOH. Finally pathway D started with the alkylation of 2-amino-thiazole with 3-bromo-l.l.l-trifluoroacetone to yield the trifluoromethy!-substituted imidazo[2,l-b]thiazole derivative (59) which was formylated to the aldehyde (60) by reaction with phosphorus oxychloride in a solvent like DMF. By oxidation of aldehyde (60) with sodium chlorite the desired imidazo[2J-b]thiazole-carboxylic acid (61) was obtained. In analogy, the commercially available chlorinated aldehyde (60, being substituted with CI instead of CF3) was oxidized to the corresponding acid. Derivatives of formula R'-COOH wherein R' is benzoxazole were for instance synthesised according to the pathway shown in scheme 8. COsH CO2H ^^^OH R'C(0R)3 ^^o , II I i ' ^-R^ \^NH2 '^-^^N 62 63 Scheme 8: Synthesis of benzoxazole-carboxylic acid derivatives wherein R is methyl or ethyl and R^ is hydrogen or methyl By reaction of 3-aminosalicylic acid (62) with the respective ortho ester derivative the desired benzoxazole-7-carboxylic acid derivatives (63) could be obtained. The reaction might be catalyzed by addition of an acid like PTSA. The respective benzoxazole-4-carboxylic acid derivatives might be synthesized in analogy starting from 2-amino-3-hydroxy-benzoic acid. Derivatives of formula R'-COOH wherein R' is benzothiazole were for instance synthesised according to the pathway shown in scheme 9. COaMe \ KSCN C02Me fS ^ ^^N-^NH2 H 65 C02Me Br2 C02Me 66 H S 1 ^-;**^f^H crown ether 64 HOAc, OX CO2 reflux UAN^ H2O, MeOH 'W- N^ THF 67 68 Scheme 9: Synthesis of benzothiazole-carboxylic acid derivatives By reaction of 3-amino-benzoic acid methyl ester (64) with potassium thiocyanate the respective thiourea derivatives (65) were obtained which could be cyclised by treatment with an oxidizing reagent like bromine in an acid like acetic acid to 2-amino-benzothiazole derivatives (66). The amino group could be removed with, for instance, isoamyl nitrite to give ester derivatives (67) which were saponified to acid derivatives (68) with a base like sodium hydroxide in solvents or mixtures of solvents like water. MeOH and THF. Derivatives of formula R'-COOH wherein R' is a substituted benzofuran were for instance synthesised according to the pathway shown in scheme 10. COzEt ,Br COzH COzEt EtOH OH H^ "OH K2CO3 X acetone x 69 70 71 OH COzEt X 72 CO2H COzEt COjEt 2) MesS ^y^O X 73 H" 1)03 OH NaOH MeOH H2O X "2'-' X 74 75 Scheme 10: Synthesis of benzofuran-carboxylic acid derivatives wherein X is fluorine or bromine By acid catalyzed esteritlcation of the respective 3-hydroxy-benzoic acid derivative (69) phenols (70) were obtained which could be allylated with for instance allyl bromide in the presence of a base like K2CO3 in a solvent like acetone. The respective allylether derivatives (71) might be rearranged to compounds (72) by heating to high temperatures (e.g. 190°C) which could be cyclised to (73) by treatment with ozone and reductive work¬up with for instance dimethyl sulfide. After acid-catalyzed (e.g. PTSA) dehydration at elevated temperatures benzofuran derivatives (74) were obtained which could be saponified to acids (75) with a base like sodium hydroxide in a solvent or solvent mixture like water and MeOH. Whenever the compounds of formula (I) are obtained in the form of mixtures of cnantiomcrs. the cnantiomers can be separated using methods known to one skilled in the art: e.g. by formation and separation of diastereomeric salts or by HPLC over a chiral stationary phase such as a Regis Whelk-Ol(R.R) (10 \xm) column, a Daicel ChiralCel OD-H (5-10 \im) column, or a Daicel ChiralPak lA (10 fim) or AD-H (5 ^m) column. Typical conditions of chiral HPLC are an isocratic mixture of eluent A (EtOH, in presence or absence of an amine such as TEA, diethylamine) and eluent B (hexane), at a flow rate of 0.8 to ]50mL/min. Experimental Section Abbrevations (as used herein and in the description before): ^er/-Butoxycarbonyl Bovine serum aibumiiie Ciiinese iiamster ovary Boc BSA CHO cone. Concentrated d Day(s) DBU 1,8-Diazabicyclo[5.4.0]undec-7-ene DCM Dichloromethane DIBAL Diisobutylaluminium hydride DIPEA Diisopropylethylamine DMAP 4-Dimethy!aminopyridine DMF iV.A'-Dimethylformamide eq Equivalent(s) ES Electron spray ether Diethyl ether EtOAc Ethyl acetate EtOH ethanol PCS Foatal calf serum FLIPR Fluorescent imaging plate reader h Hour(s) HBSS Hank's balanced salt solution HEPES 4-(2-hydroxyethyl)-piperazine-l-ethanesulfonic acid HPLC High performance liquid chromatography LC Liquid chromatography M Molar(ity) MeOH Methanol min IVIinute(s) MS Mass spectroscopy prep. Preparative PTSA para-ToluenesuIfonic acid monohydrate RT Room temperature sat Saturated tR Retention time TBME tert-Buty\ methyl ether TBTU (9-Benzotriazoi-l -yl-MMA'",A' '-tetramethyluronium tetrafluoroborate TEA Triethylamine TFA Trifluoroacetic acid TFAA Trifluoroacetic anhydride THF Tetrahydrofuran I-Chemistry The following examples illustrate the preparation of pharmacologically active compounds of the invention but do not at all limit the scope thereof All temperatures are stated in °C. Compounds are characterized by: H-NMR: 300 MHz Varian Oxford or 400 MHz Bruker Avance; chemical shifts are given in ppm relative to the solvent used; multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, b = broad, coupling constants are given in Hz; LC-MS: Agilent 1100 series with DAD and MS detection (MS: Finnigan single quadrupole); columns (4.6x50 mm, 5 |j,m): Zorbax SB-AQ, Zorbax Extend CI 8 or Waters XBridgeClS; conditions (if not otherwise stated the acidic gradient is used): basic: elucnt A: MeCN. elucnt B: cone. NH3 in water (1.0 mL/L). 5% to 95% CH3CN, flow rate 4.5 mL/min; acidic: eluent A: MeCN, eluent B: TFA in water (0.4 mL/L). 5% to 95% CH3CN, flow rate 4.5 mL/min; tR is given in min; Compounds are purified by column chromatography on silica gel or by preparative HPLC using RP-C18 based columns with MeCN/water gradients and formic acid or ammonia additives. NMR measurements are done with a Bruker Avance 400 Instrument; chemical shifts are given in ppm relative to the solvent used; multiplicities: s = singlet, d = doublet, t = triplet, m = multiplet, b = broad, coupling constants are given in Hz. A. Preparation of precursors and intermediates: A.l Synthesis of thiazole-4-carbGxylic acid derivatives A.1.1 Synthesis of 3-ch[oro-2-oxo-propionic ester derivatives (general procedure) ^r^-^ Ck > /CHO B CI 0 CI o A solution of the respective aldehyde (338 mmol. 1.0 eq) and methyl dichloroacetate (338 mmol, 1.0 eq) in THF (100 mL) is added dropwise to a cold (-60°C) suspension of KOtBu (335 mmol, 1.0 eq) in THF (420 mL). After 4 h the mixture is allowed to reach RT, stirred over night and concentrated in vacuo. DCM and ice-cold water are added, the layers are separated and the aq. layer is extracted twice with DCM. The combined organic layers are washed with ice-cold water and brine, dried over MgS04 and concentrated in vacuo to give the desired 3-chloro-2-oxo-propionic ester derivative which is used without further purification. 3-Chloro-2-oxo-3-m-tolyl-propionic acid methyl ester prepared by reaction of 3-methyl-benzaldehyde with methyl dichloroacetate. 3-Chloro-2-oxo-3-p-tolyl-propionic acid methyl ester prepared by reaction of 4-methyl-benzaldehyde with methyl dichloroacetate. 3-Chloro-3-(3-methoxy-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 3-methoxy-benzaldehyde with methyl dichloro-acetate. 3-Chloro-3-(2-fluoro-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 2-fluoro-benzaldehyde with methyl dichloro-acetate. 3-Chloro-3-(3-fluoro-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 3-fluoro-benzaldehyde with methyl dichloroacetate. 3-Chloro-3-(4-fluoro-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 4-fluoro-benzaldehyde with methyl dichloroacetate. 3-Chloro-3-(3-chloro-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 3-chloro-benzaldehyde with methyl dichloro-acetate. 3-Chloro-2-oxo-3-(2-trifluoromethyl-phenyl)-propionic acid methyl ester prepared by reaction of 2-trifluoromethyl-benzaldehyde with methyl dichloro-acetate. 3-Chloro-2-oxo-3-(3-trifluoromethyl-phenyI)-propionic acid methyl ester prepared by reaction of 3-trifluoromethyl-benzaldehyde with methyl dichloro-acetate. 3-Chloro-3-(3,4-dimethyl-phenyI)-2-oxo-propionic acid methyl ester prepared by reaction of 3,4-dimethyl-benzaldehyde with methyl dichloro-acetate. 3-Chloro-3-(2,3-dimethyl-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 2,3-dimethyl-benzaldehyde with methyl dichloro-acetate. 3-Chloro-3-(2,4-dimethyl-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 2,4-dimethyl-benzaldehyde with methyl dichloro-acetate. 3-Chloro-3-(3,5-dimethyl-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 3,5-dimethyl-benzaldehyde with methyl dichloro-acetate. 3-(3-Bromo-4-fluoro-phenyl)-3-chloro-2-oxo-propionic acid methyl ester prepared by reaction of 3-bromo-4-fluoro-benzaldehyde with methyl dichloro-acetate. 3-Chloro-3-(3,4-dichloro-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 3,4-dichloro-benzaidehyde with methyl dichloro-acetate. 3-Chloro-3-(3,4-difluoro-phenyI)-2-oxo-propionic acid methyl ester prepared by reaction of 3,4-difIuoro-benzaldehyde with methyl dichloro-acetate. 3-Chloro-3-(3-fluoro-4-methyl-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction or3-nuoro-4-methy|-benzaldehyde with methyl dichloro-acetate. 3-Chloro-3-(3-fluoro-5-trifluoromethyl-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 3-fluoro-5-trifluoromethyl-benzaldehyde with methyl dichloro-acetate. 3-Chloro-3-(3-fluoro-2-methyl-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 3-fluoro-2-iTiethyl-benzaidehyde with methyl dichloro-acetate. 3-Chloro-2-oxo-3-phenyl-propionic acid methyl ester prepared by reaction of benzaldehyde with methyl dichloro-acetate. 3-(4-Bromo-phenyI)-3-chloro-2-oxo-propionic acid methyl ester prepared by reaction of 4-bromo-benzaldehyde with methyl dichloro-acetate. 3-Chloro-3-(2,3-dichIoro-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 2,3-dichloro-benzaldehyde with methyl dichloro-acetate. 3-Chloro-3-(3-nitro-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 3-nitro-benzaldehyde with methyl dichloro-acetate. 3-Chloro-3-(2-chloro-6-fluoro-phenyl)-2-oxo-propionic acid methyl ester prepared by reaction of 2-chloro-6-fluoro-benzaldehyde with methyl dichloro-acetate. A.1.2 Synthesis of thiazole-4-carboxylic acid methyl ester derivatives (general procedure) S Ct O ANH, N_/C00CH3 0 A solution of thioacetamide (132 mmol, 1.0 eq) in MeCN (250 mL) is added to a mixture of the respective 3-chloro-2-oxo-propionic ester derivative (132 mmol, 1.0 eq) and molecular sieves (4A. 12 g) in MeCN (60 mL). After stirring for 5 h the mixture is cooled in an ice-bath and the obtained precipitate is filtered off. The residue is washed with cold MeCN. dried, d issolved in MeOH (280 niL) and stirred at 50°C for 6 h. The solvents are removed in vacuo to give the desired thiazole derivatives as a white solid. 2-methyI-5-m-toIyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chIoro-2-oxo-3-m-tolyl-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.94 min; [M+Hf = 248.0. 5-(3-fluoro-phenyI)-2-methyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3-fluoro-phenyl)-2-oxo-propiGnic acid methyl ester with thioacetamide. LC-MS: tR = 0.91 min; [M+H]" = 252.1. 5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(4-fluoro-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. 'H-NMR (CDCh): 5 = 2.75 (s, 3H); 3.84 (s, 3H); 7.10 (m, 2H): 7.47 (m, 2H). 2-methyl-5-(3-trifluoromethyl-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3-trifluoromethyl-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.98 min; [M+H]"" = 302.2. 2-methyl-5-(2-trifluoromethyl-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(2-trifluoromethyl-phenyI)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.94 min; [M+H]" = 302.3. 5-(3-chloro-phenyl)-2-methyl-thiazoIe-4-carboxyIic acid methyl ester prepared by reaction of 3-chloro-3-(3-chloro-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: IR = 0.95 min; [M+H]^ = 268.0. 5-(3,4-dimethyl-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3,4-dimethyl-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.96 min; [M+H]"' = 262.3. 2-MethyI-5-phenyl-thiazole-4-carboxyIic acid methyl ester prepared by reaction of 3-chioro-2-oxo-3-phenyl-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.87 min; [M+H]" = 234.3. 5-(4-Bromo-phenyI)-2-inethyl-thiazoIe-4-carboxylic acid methyl ester prepared by reaction of 3-(4-broino-phenyl)-3-chloro-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.95 min: [M+H]"' = 312.1. 5-(2,3-Dichloro-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(2,3-dichloro-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.97 min; [M+H]"" = 302.2. 5-(2,3-Dimethyl-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(2.3-dimethyl-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.95 min; [M-t-H]^ = 262.3. 5-(3-Fluoro-2-methyl-phenyI)-2-methyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3-fluoro-2-methyl-phenyI)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.93 min; [M-t-H]"" = 266.3. 5-(3-Bromo-4-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-(3-bromo-4-fluoro-phenyl)-3-chloro-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.95 min; [M+H]"" = 330.2. 5-(3,4-Dichloro-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3.4-dichloro-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.99 min; [M+H]^ = 302.2. 5-(3,4-Difluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3,4-difluoro-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.92 min; [M+Hf = 270.3. 5-(3-FIuoro-4-methyI-phenyl)-2-inethyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3-fluoro-4-methyl-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 1.00 min; [M+H]^ = 266.0. 5-(3,5-Dimethyl-phenyl)-2-methyI-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3,5-dimethyl-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.97 min; [M+H]^ = 262.3. 5-(3-FIuoro-5-trifluoromethyl-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3-fluoro-5-trifluoromethyl-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 1.03 min; [M+Hf = 319.8. 5-(2,4-Dimethyl-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(2.4-dimethyl-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.96 min; [M+H]"" = 262.3. 5-(2-Chloro-6-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(2-chloro-6-fluoro-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.92 min; [M+Hf = 286.2. 2-Methyl-5-(3-nitro-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3-nitro-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR = 0.94 min; [M+H]" = 279.3. A.1.3 Synthesis of 2-cyclopropyI-thiazole-4-carboxylic acid methyl ester derivatives Synthesis of cyclopropanecarbothioic acid amide 2.4-Bis-(4-methoxyphenyl)-l,3-dithia-2,4-diphosphetane 2,4-disulfide (Lawesson reagent. 173 mmol) is added to a mixture of cyclopropanecarboxamide (173 mmol) and NaiCOs (173 mmol) in THF (750 mL). The reaction mixture is stirred at reflux for 3h, concentrated in vacuo and diluted with ether (500 mL) and water (500 mL). The layers are separated and the aqueous layer is extracted with ether (250 mL). The combined organic layers are washed with brine (100 mL), dried over MgS04 and concentrated in vacuo to give a crude product which is used without further purification. 'H-NMR (DMSO-d6): 5 = 0.81-0.88 (m. 2H): 0.96-1.00 (m. 2H): 2.00 (tl. .1 = 8.0 Hz. .1 =4.3 Hz. IH): 9.23 (bs. IH): 9.33 (bs. IH). Synthesis of 2-cyclopropyI-thiazole-4-carboxylic acid methyl ester derivatives (general procedure) S CI 0 'rr^ NH2 COOCH3 // I 0 ^B A solution of cyclopropanecarbothioic acid amide (33.9 mmoi, 1.0 eq) in MeCN (45 mL) is added to a mixture of the respective 3-chloro-2-oxo-propionic ester derivative (33.9 mmol. 1.0 eq) and NaHCOs (102 mmol, 3.0eq) in MeCN (45 mL). After stirring for 2d at RT the mixture is concentrated in vacuo and the residue is diluted with EtOAc (150 mL) and water (150 mL). The layers are separated and the aqueous layer is extracted with EtOAc (100 mL). The combined organic layers are washed with brine (100 mL), dried over MgS04 and concentrated in vacuo. The residue is dissolved in MeOH (70 mL) and treated with concentrated H2SO4 (0.18 mL). The mixture is stirred at 60°C for 16 h and concentrated in vacuo to give the respective crude product which is used without further purification. 2-Cyclopropyl-5-phenyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-2-oxo-3-phenyl-propionic acid methyl ester with cyclopropanecarbothioic acid amide. LC-MS: tR = 0.99 min; [M+H]' = 260.5. 2-Cyclopropyl-5-(2-fluoro-phenyI)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(2-fluoro-phenyl)-2-oxo-propionic acid methyl ester with cyclopropanecarbothioic acid amide. LC-MS: tR = 1.00 min; [M+H]"^ = 278.3. 2-Cyclopropyl-5-(3-fluoro-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chIoro-3-(3-fluoro-phenyl)-2-oxo-propionic acid methyl ester with cyclopropanecarbothioic acid amide. LC-MS: tR = 1.02 min; [M+Hf = 278.0. 2-Cyclopropyl-5-(4-fluoro-phenyl)-thiazoIe-4-carboxylic acid methyl ester prepared by reaction of 3-chIoro-3-(4-fluoro-phenyl)-2-oxo-propionic acid methyl ester with cyclopropanecarbothioic acid amide. LC-MS: IR = 1.01 min; [M+H]' = 278.3. 2-Cyclopropyl-5-(3-trifluoromethyI-phenyI)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3-trifluoroiTiethyl-phenyl)-2-oxo-propionic acid methyl ester with cyclopropanecarbothioic acid amide. LC-MS: IR = 1.07 min; [M+H]^ = 328.2. 2-CycIopropyI-5-p-tolyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-2-oxo-3-p-tolyl-propionic acid methyl ester with cyclopropanecarbothioic acid amide. LC-MS; tR = 1.04 min; [M+H]^ = 274.4. 2-Cyclopropyl-5-(3-fluoro-4-methyl-phenyI)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3-fluoro-4-iTiethyl-phenyl)-2-oxo-propionic acid methyl ester with cyclopropanecarbothioic acid amide. LC-MS: IR = 1.06 min; [M+H]^ = 292.1. A. 1.4 Synthesis of 2-amino-thiazole-4-carboxylic acid methyl ester derivatives (general procedure) S CI 9 HpN-^NH, N^°°^^3 H,N- ^ T ° 0 A .solution of the respective 3-chloro-2-oxo-propionic esler derivative (22.1 nimoL 1.0 cq) in acetone (25 mL) is added to a suspension of thiourea (22.1 mmol, 1.0 eq) in acetone (45 mL). The mixture is heated to 57°C (bath temperature), stirred for 24h and concentrated to half of the volume. The obtained suspension is filtered and the residue is washed with acetone. After drying the desired amino-thiazole derivative is obtained as a solid. 2-amino-5-m-tolyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-2-oxo-3-m-tolyl-propionic acid methyl ester with thiourea. LC-MS: tR = 0.78 min; [M+H]^ = 249.0. 2-amino-5-(3-nuoro-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3-fluoro-phenyl)-2-oxo-propionic acid methyl ester with thiourea. LC-MS: IR = 0.78 min: [M+Hf = 252.9. 2-Amino-5-(2-fluoro-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-ch!oro-3-(2-fluoro-phenyl)-2-oxo-propionic acid methyl ester with thiourea. LC-MS: h = 0.76 min; [M+Hf = 253.2. 2-Amino-5-(4-fluoro-phenyl)-thiazoIe-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(4-fluoro-phenyl)-2-oxo-propionic acid methyl ester with thiourea. LC-MS: tR = 0.75 min; [M+Hf = 253.2. 2-Amino-5-(3-methoxy-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3-methoxy-phenyl)-2-oxo-propionic acid methyl ester with thiourea. LC-MS: tR = 0.75 min; [M+Hf = 265.3. 2-Amino-5-(3-chloro-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3-chloro-phenyl)-2-oxo-propionic acid methyl ester with thiourea. LC-MS: tR = 0.82 min; [M+H]"" = 269.2. 2-Amino-5-(3-trifluoromethyl-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-3-(3-trifluoromethyl-phenyl)-2-oxo-propionic acid methyl ester with thiourea. LC-MS: tR = 0.86 min; [M+Hf = 303.3. 2-Amino-5-phenyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 3-chloro-2-oxo-3-phenyl-propionic acid methyl ester with thiourea. LC-MS: tR = 0.77 min; [M+Hf = 235.1. A. 1.5 Synthesis of 2-bromo-thiazole-4-carboxyIic acid methyl ester derivatives (general procedure) ^ „C00CH3 cuBr2 f^^^^COOCHs HjN—f 1 ► Br—<■;' ll S'^'-g isoamyl nitrite S'^'^B At 15°C under an atmosphere of nitrogen the respective 2-amino-thiazole-4-carboxylic acid methyl ester (7.10 mmol) is added portionwise to a mixture of CuBra (7.10 mmol) and isoamyl nitrite (10.6 mmol) in MeCN (30 mL). The mixture is stirred for 20 min at 15°C, for 30 min at 40°C and for 90 min at 65°C. The solvents are removed in vacuo and the crude product is either purified by flash chromatography (DCM/MeOH or EtOAc/heptane) or used without further purification. 2-Bromo-5-m-tolyI-thiazoie-4-carboxylic acid methyl ester prepared by reaction of 2-amino-5-m-toly!-thiazole-4-carboxylic acid methyl ester with CuBr2 and isoamyl nitrite. LC-MS: tR = 1.01 min; [M+Hf = 311.8. 2-Bromo-5-(2-fluoro-phenyI)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 2-amino-5-(2-fluoro-phenyl)-thiazole-4-carboxylic acid methyl ester with CuBra and isoamyl nitrite. LC-MS: tR = 0.96 min; [M+H]"" = 316.1. 2-Bromo-5-(3-fluoro-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 2-amino-5-(3-fluoro-phenyl)-thiazole-4-carboxylic acid methyl esier with CuBr2 and isoamyl nitrite. LC-MS: tK = 1.08 min; [M^H]^ = 316.0. 2-Bromo-5-(4-fluoro-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 2-amino-5-(4-fluoro-phenyl)-thiazole-4-carboxylic acid methyl ester with CuBr2 and isoamyl nitrite. LC-MS: tR = 0.97 min; [M+H]"" = 316.1. 2-Bromo-5-(3-methoxy-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 2-amino-5-(3-methoxy-phenyl)-thiazole-4-carboxylic acid methyl ester with CuBra and isoamyl nitrite. LC-MS: tR = 0.97 min; [M+Hf = 328.2. 2-Broino-5-(3-chIoro-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by reaction of 2-ainino-5-(3-chloro-phenyl)-thiazole-4-carboxylic acid methyl ester with CuBr2 and isoamyl nitrite. LC-MS; tR = 1.00 min: [M+H]"" = 332.2. 2-Broino-5-(3-trifluoromethyI-phenyl)-thiazole-4-carboxyIic acid methyl ester prepared by reaction of 2-aiTiino-5-(3-trifluoromethyl-phenyl)-thiazole-4-carboxylic acid methyl ester with CuBr2 and isoamyl nitrite. LC-MS: tR = 1.03 min; [M+H]^ = 366.2. 2-Bromo-5-phenyl-thiazole-4-carboxylic acid methyl ester prepared by reaction of 2-amino-5-phenyl-thiazole-4-carboxylic acid methyl ester with CuBr2 and isoamyl nitrite. LC-MS: tR = 1.07 min; [M+H]^ = 297.9. A.L6 Synthesis of thiazole-4-carboxyUc acid methyl ester derivatives lacking a substituent in 2-position (general procedure) ^ COOCH3 H2, Pd/C N^-C00CH3 Br-/ J^ ~ ► H-/ S" B S^ "B A solution/suspension of the respective 2-bromo-thiazole-4-carboxylic acid methyl ester (3.17 mmol) in EtOH (20 mL) is added to a suspension of Pd/C (600 mg, 10%) in EtOH (20 mL) and stirred under a hydrogen atmosphere (1 bar) for 18 h. After filtration through celite and removal of the solvents the desired product is obtained which is used without further purification. 5-m-Tolyl-thiazole-4-carboxylic acid methyl ester prepared by hydrogenation of 2-bromo-5-rn-tolyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.90 min; [M+H]^ = 233.9. 5-(2-Fluoro-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by hydrogenation of 2-bromo-5-(2-fluoro-phenyl)-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.91 min; [M+Hf = 238.0. 5-(4-FIuoro-phenyl)-thiazo!e-4-carboxylic acid methyl ester prepared by hydrogenation of 2-bromo-5-(4-fIuoro-phenyl)-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.92 min; [M+H]^ = 238.1. 5-(3-Methoxy-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by hydrogenation of 2-bromo-5-(3-methoxy-phenyl)-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.92 min; [M+H]" = 250.1. 5-(3-Chloro-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by hydrogenation of 2-bromo-5-(3-chloro-phenyl)-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.91 min; [M+Hf = 253.9. 5-(3-Trifluoromethyl-phenyl)-thiazole-4-carboxylic acid methyl ester prepared by hydrogenation of 2-bromo-5-(3-trifluoromethyl-phenyl)-thiazole-4-carbo.xyric acid methyl ester. LC-MS: tR = 0.99 min; [M+H]"" = 288.0. A. 1.7 Synthesis of 5-(3-amino-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester Iron powder (53.7 mmol) is added to a suspension of 2-methyl-5-(3-nitro-phenyl)-thiazole-4-carboxylic acid methyl ester (44.1 mmol) and ammonium chloride (221 mmol) in a mixture of EtOH (100 mL) and water (50 mL). The mixture is stirred at 80°C for 4h, iron powder (53.7 mmol) is added and heating is continued for additional 3h. After addition of a third portion of iron powder (26.8 mmol) the mixture is heated at 80°C for additional 3h. cooled to RT. diluted with DCM and filtered through Celite. The residue is washed with DCM and water and the filtrate is concentrated in vacuo. A sat. aqueous NaHCOa solution and DCM are added and the layers are separated. The organic layer is washed with water, dried over MgS04 and concentrated in vacuo to give a crude product which is used without further purification. LC-MS: tR = 0.67 min; [M+H]^ = 249.4. A.L8 Synthesis of 5-(3-methanesulfonylamino-phenyl)-2-methyI-thiazole-4-carboxylic acid methyl ester MethanesulforiyI chloride (5.27 mmol) and 4-methylmorpholine (4.86 mmol) are added successively to a solution of 5-(3-amino-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester (4.05 mmol) in DCM (50 mL). .-^fter stirring for 2h water is added, the layers are separated and the aqueous layer is extracted once with DCM. The combined organic layers are washed with citric acid (10% solution in water), dried over MgS04 and concentrated in vacuo to give a crude product which is used without further purification. LC-MS: tR = 0.84 min; [M+Hf = 327.2. A. 1.9 Synthesis of 5-(3-acetylainino-phenyl)-2-inethyl-thiazole-4-carboxylic acid methyl ester Triethylamine (14.2 mmol) and DMAP (4.05 mmol) are added successively to a solution of 5-(3-amino-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester (4.05 mmol) in acetic anhydride (25 mL). After stirring for 30 min EtOAc and water are added, the layers are separated and the aqueous layer is extracted once with EtOAc. The combined organic layers are washed with sat. aqueous NH4CI solution, sat. aqueous NaHCOa solution and water, dried over MgS04 and concentrated in vacuo to give a crude product which is diluted with ether. The obtained suspension is filtered. The residue is washed with ether and dried in vacuo to give the desired product which is used without further purification. LC-MS: tR = 0.81 min; [M+Hf = 291.3. A. 1.10 Synthesis of thiazole-4-carboxylic acid derivatives (general procedure) M /COOCH3 M ,COOH N~Y^ ^ NaOH )^-~Y R-\ i ► R—( i A solution of the respective thiazole-4-carboxylic acid ester (96.2 mmol) in a mixture of THF (150 mL) and either MeOH or isopropanol (50 mL) is treated with an aq. NaOH solution (1.0 M, 192 mL). After stirring for 3 h a white suspension is formed and the organic volatiles are removed in vacuo. The remaining mixture is diluted with water (100 mL), cooled in an ice-bath and made acidic (pH = 3-4) by addition of aq. HCI solution (1.0 M). The suspension is filtered and the residue is washed with cold water. After drying the desired acid is obtained as a white solid. 2-methyl-5-in-tolyl-fhiazoIe-4-carboxylic acid prepared by saponification of 2-methyl-5-m-tolyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.83 min; [M+H]^ = 234.0. 5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid prepared by saponification of 5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.82 min; [M+Hf = 238.1. 5-(4-fluoro-phenyI)-2-methyl-thiazole-4-carboxylic acid prepared by saponification of 5-(4-fIuoro-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. 'H-NMR (DMS0-d6): 5 = 2.67 (s, 3H); 7.27 (m, 2H); 7.53 (m, 2H); 12.89 (br.s. IH). 2-niethyl-5-(3-trifluoromethyl-phenyl)-thiazole-4-carboxylic acid prepared by saponification of 2-methyl-5-(3-trifluoromethyl-phenyl)-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.88 min; [M+H]"" = 288.0. 2-inethyl-5-(2-trifluoromethy!-phenyl)-thiazole-4-carboxylic acid prepared by saponification of 2-methyl-5-(2-trifluoromethyl-phenyl)-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.84 min; [M+H]* = 288.3. 5-(3-chloro-phenyI)-2-niethyl-thiazole-4-carboxylic acid prepared by saponification of 5-(3-chloro-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.84 min; [M+Hf = 254.0. 5-(3,4-dimethyl-phenyl)-2-methyl-thiazole-4-carboxylic acid prepared by saponification of 5-(3,4-dimethyl-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: IR = 0.86 min; [M+H]^ = 248.3. 2-amino-5-m-tolyl-thiazole-4-carboxylic acid prepared by saponification of 2-amino-5-m-tolyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.65 min; [M+Hf = 235.0. 2-aniino-5-(3-fIuoro-phenyl)-thiazoIe-4-carboxylic acid prepared by saponification of 2-amino-5-(3-fiuoro-phenyl)-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.62 min: [M+H]^ = 239.1. 2-Bromo-5-ni-tolyl-thiazole-4-carboxylic acid prepared by saponification of 2-Broino-5-ni-tolyl-tliiazole-4-carboxylic acid methyl ester. LC-MS (basic): tR = 0.57 min: [M+Hf = 297.8. 2-Methyl-5-phenyl-thiazoIe-4-carboxyIic acid prepared by saponification of 2-methyi-5-phenyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.77 min; [M+Hf = 220.3. 5-(4-Bromo-phenyl)-2-methyl-thiazole-4-carboxylic acid prepared by saponification of 5-(4-bromo-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.85 min; [M+Hf = 298.2. 5-(2,3-Dichloro-phenyl)-2-methyl-thiazole-4-carboxylic acid prepared by saponification of 5-(2,3-dichloro-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.86 min; [M+H]^ = 288.2. 5-(2,3-Diinethyl-phenyl)-2-methyl-thiazole-4-carboxylic acid prepared by saponification of 5-(2,3-dimethyl-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.84 min; [M+H]^ = 248.3. 5-(3-Fluoro-2-inethyl-phenyl)-2-methyI-thiazo!e-4-carboxylic acid prepared by saponification of 5-(3-fluoro-2-methyI-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: IR = 0.83 min: [M+H]^ = 252.2, 5-(3-Bromo-4-fluoro-phenyI)-2-methyI-thiazoie-4-carboxylic acid prepared by saponification of 5-(3-bromo-4-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.86 min: [M+H]^ = 316.2. 5-(3,4-DichIoro-phenyl)-2-methyl-thiazole-4-carboxYlic acid prepared by saponification of 5-(3.4-diciiioro-piienyn-2-methyl-thiazole-4-carboxyIic acid methyl ester. LC-MS: tR = 0.88 min; [M+H]"" = 288.2. 5-(3,4-DifIuoro-phenyl)-2-methyI-thiazole-4-carboxylic acid prepared by saponification of 5-(3.4-difluoro-phenyl)-2-methy]-thiazole-4-carboxylic acid methyl ester. LC-MS: tp = 0.82 min: [M+Hf = 256.3. 5-(3-FIuoro-4-methyl-phenyl)-2-methyl-thiazole-4-carboxyIic acid prepared by saponification of 5-(3-fluoro-4-methyl-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.89 min; [M+H]"" = 252.0. 5-(3,5-DiniethyI-phenyl)-2-methyI-thiazole-4-carboxylic acid prepared by saponification of 5-(3.5-dimethyl-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.86 min; [M+H]" = 248.3. 5-(3-Fluoro-5-trifluoromethyl-phenyl)-2-inethyl-thiazole-4-carboxylic acid prepared by saponification of 5-(3-fluoro-5-trifluoroiTiethyl-phenyl)-2-inethyi-thiazoie-4-carboxylic acid methyl ester. LC-MS: tR = 0.94 min; [M+H]^ = 306.0. 5-(2,4-Dimethyl-phenyl)-2-methyI-thiazole-4-carboxylic acid prepared by saponification of 5-(2,4-dimethyl-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.85 min; [M+H]^ = 248.3. 5-(2-Chloro-6-fluoro-phenyl)-2-methyl-thiazoIe-4-carboxylic acid prepared by saponification of 5-(2-chloro-6-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.82 min: [M+Hf = 272.2. 5-(2-Fluoro-phenyi)-thiazoIe-4-carboxylic acid prepared by saponification of 5-(2-fluoro-phenyl)-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.80 min; [M+H]" = 224.1. 5-(3-Methoxy-phenyI)-thiazoIe-4-carboxylic acid prepared b\ saponification of 5-(3-methoxy-phenyD-tliiazole-4-carboxylic acid metliyl ester. LC-MS: tR = 0.81 min; [M+H]" = 236.1. 5-(3-Chloro-phenyl)-thiazole-4-carboxylic acid prepared by saponification of 5-(3-chloro-piienyl)-tiiiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.85 min; [M+H]^ = 240.0. 5-(3-Trifluoroniethyl-phenyl)-thiazoIe-4-carboxyIic acid prepared by saponification of 5-(3-trifluoromethyl-phenyl)-thiazoie-4-carboxylic acid methyl ester. LC-MS: tR = 0.89 min; [M+H]^ = 274.0. 5-(4-Fluoro-phenyl)-thiazole-4-carboxylic acid prepared by saponification of 5-{4-fluoro-phenyl)-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.80 min; [M+Hf = 224.1. 5-(3-Methanesulfonylamino-phenyl)-2-methyl-tliiazole-4-carboxylic acid prepared by saponification of 5-(3-methanesulfonylamino-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.77 min; [M+H]"" = 313.2. 5-(3-AcetyIainino-phenyl)-2-inethyl-thiazole-4-carboxylic acid prepared by saponification of 5-(3-acetylamino-phenyl)-2-methyl-thiazole-4-carboxylic acid methyl ester. LC-MS: IR = 0.74 min; [M+H]" = 277.2. 2-CycIopropyl-5-phenyl-thiazole-4-carboxylic acid prepared by saponification of 2-cyclopropyl-5-phenyI-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.91 min; [M+H]^ = 246.4. 2-Cyclopropyl-5-(2-fluoro-phenyl)-thiazole-4-carboxylic acid prepared by saponification of 2-cyclopropyl-5-(2-fluoro-phenyI)-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.91 min; [M+Hf = 264.3. 2-Cyclopropyl-5-(3-fluoro-phenyl)-thiazoIe-4-carboxylicacid prepared by saponification of 2-cyclopropyl-5-(3-f1uoro-phenyl)-thiazole-4-carboxylic acid methyl ester. LC-MS: IR = 0.92 min; [M+H]" = 264.0. 2-Cyclopropyl-5-(4-fluoro-phenyl)-thiazole-4-carboxylic acid prepared by saponification of 2-cyclopropyl-5-(4-nuoro-phenyl)-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0,88 min; [M+H]^ = 264.0. 2-Cyclopropyl-5-(3-trifluoromethyl-phenyl)-thiazole-4-carboxylicacid prepared by saponification of 2-cyclopropyi-5-(3-trilluoromethyl-phenyi)-thiazole-4-carboxyiic acid methyl ester. LC-MS: tR = 1.00 min; [M+H]"" = 314.3. 2-Cyclopropyl-5-p-tolyl-thiazole-4-carboxylic acid prepared by saponification of 2-cyclopropyl-5-p-tolyl-thiazole-4-carboxylic acid methyl ester. LC-MS: tR = 0.91 min; [M+H]'' = 260.0. 2-Cyclopropyl-5-(3-fluoro-4-methyl-phenyI)-tliiazole-4-carboxyIic acid prepared by saponification of 2-cyclopropyl-5-(3-tluoro-4-rnethyl-phenyl)-thiazole-4-carboxylic acid methyl ester. LC-MS: h = 0.97 min; [M+H]"" = 278.1. A.l.Tl Syntliesis of 2-diniethvlainino-tliiazole-4-carboxvlic acid derivatives (general procedure) COOCH3 M ,COOH Br-/ T ^ \-// B An aqueous solution of dimethylamine (40%, 13 mL) is added to a solution of the respective 2-bromo-thiazole-4-carboxylic acid methyl ester derivative (6.71 mmol) in acetonitrile (38 mL). After 2h an additional portion of an aqueous dimethylamine solution (40%. 13 mL) is added. After stirring at RT for 2d THF (13.6 mL), MeOH (6.8 mL) and aqueous NaOH solution (1.0 M, 13.4 mL) are added successively and the mixture is stirred for 16h. The solvents are removed in vacuo and the residue is diluted with water (30 mL). lilt suspension is inaue aciuic ^ph JJ oy auuuion OT aqueous cicric acia ^iU7o; anu extracted three times with EtOAc. The combined organic layers are washed twice vvith brine, dried over iVlgS04 and concentrated in vacuo to give the desired acid which is used without further purification. 2-Dimethylamino-5-(3-fluoro-phenyl)-thiazole-4-carboxylic acid prepared by reaction of 2-bromo-5-(3-fluoro-phenyl)-thiazole-4-carbo.\ylic acid methyl ester with dimethylamine. LC-MS: tR = 0.87 mini [M+Hf = 267.0. 2-Dimethylainino-5-phenyl-thiazole-4-carboxylic acid prepared by reaction of 2-bromo-5-phenyi-thiazolc-T-carboxyiic acid mcthvl esicr vvith dimethylamine. LC-MS: tR = 0.81 min: [M+H]" = 249.1. A.1.12 Synthesis of 2-alkoxv-thiazole-4-carboxvlic acid derivatives (general procedure) ^ ,C00CH3 p, ^ ,,COOH Br-^ 1 ^ 0-/ 1 R = (C|.4)alkyi At 0°C under an atmosphere of nitrogen the respective alcohol (0.96 mmol) is added to a suspension of sodium hydride (0.96 mmol) in THF (2.0 mL). After 5 min a solution of the respective 2-bromo-thiazole-4-carboxylic acid methyl ester (0.48 mmol) in DMF (0.2 mL) and THF (1.0 mL) is added dropwise. The mixture is stirred for 16 h at RT, cooled to 0°C and treated with water (0.5 mL) and aq. NaOH solution (1.0 M, 0.5 mL). After 2 h the solvents are removed in vacuo and the residue is dissolved in warm water (1.0 mL). Ether is added, the layers are separated and the aq. layer is concentrated partially in vacuo to remove traces of ether. The mixture is cooled to 0°C and made acidic (pH 4) by addition of hydrochloric acid (2.0 M). The precipitate is filtered off, washed with water and dried in vacuo to give the desired product. 2-Methoxy-5-m-toIyI-thiazoIe-4-carboxyIic acid prepared by reaction of 2-bromo-5-m-tolyl-thiazole-4-carboxylic acid methyl ester with MeOH. LC-MS: tR = 0.88 min; [M+Hf = 250.3. 5-(3-ChIoro-phenyl)-2-ethoxy-thiazole-4-carboxyIic acid prepared by reaction of 2-bromo-5-(3-chloro-phenyl)-thiazole-4-carboxylic acid methyl ester with EtOH. LC-MS: tR = 0.98 min; [M+H]^ = 284.0. A.2 Synthesis of imidazo[2,l-b]thiazole derivatives A.2.1 Synthesis of 2-amino-4-methyl-thiazole-5-carboxylic acid methyl ester A mixture of thiourea (59.8 mmol) and 2-chloro-3-oxo-butyric acid methyl ester (59.8 mmol) in EtOH (140 mL) is heated at reflux for ]4h and concentrated in vacuo. Water and aq. NaHCOa are added and the mixture is extracted several times with EtOAc. The combined organic layers are dried and concentrated in vacuo to give the desired amino-thiazole derivative. LC-MS: tR = 0.51 min: [M+H]''= 173.0. A.2.2 Synthesis of 3-methyl-imidazo[2,l-b]thiazole-2-carboxylic acid methyl ester A mixture of bromoacetaldehyde diethyl acetal (29.3 mmol, 1.26eq) in water (200 mL) is treated dropwise with cone, hydrochloric acid (3.0 mL), stirred for 14h at RT and heated for additional 30 min at 80°C. After cooling to RT NaHCOa (37.9 mmol) is added carefully and the mixture is stirred for 2h and treated with 2-Amino-4-methyl-thiazole-5-carboxylic acid methyl ester (23.2 mmol, l.OOeq). After Ih dioxane (130 mL) is added and the mixture is stirred at RT for 30 min and at 100°C for 48h. The organic solvents are removed in vacuo and the mixture is extracted several times with DCM and chloroform. The combined organic layers are dried over Na2S04 and concentrated in vacuo to give the desired ester which is used without further purification. LC-MS: tR = 0.55 min; [M+H]^ = 197.0. A.2.3 Synthesis of 5-methyl-2-thioxo-2,3-dihydro-IH-imidazoIe-4-carboxylic acid ethyl ester Pd/C (10%. 1.00 g) is added to a solution of 2-hydroxyimino-3-oxo-butyric acid ethyl ester (62.8 mmol) in hydrochloric acid (1.25 M in EtOH, 75 mL) and the mixture is stirred at RT under a hydrogen atmosphere (4 bar) for 48 h. After filtration through celite and removal of the solvents crude 2-amino-3-oxo-butyric acid ethyl ester hydrochloride is obtained which is dissolved in a mixture of water (220 mL), EtOH (30 mL) and cone hydrochloric acid (37%. 2.5 mL). A solution of potassium thiocyanate (49.9 mmol) in water (25 mL) is added and the mixture is stirred for 2h at reflux. By cooling in an ice bath the desired product precipitates and is collected by filtration. LC-MS: IR = 0.59 min; [M+H]"" = 187.2.... A.2.4 Synthesis of 2-(2,2-dialkoxy-ethylsulfanyl)-5-methyl-lH-imidazole-4-carboxylic acid ethyl ester derivatives (general procedure) A solution of sodium ethoxide (5.37 mmol) in EtOH (3.3 mL) is added to a solution of 5-methyl-2-thioxo-2.3-dihydro-1H-imidazole-4-carboxylic acid ethyl ester (5.37 mmol) in EtOH (7.0 mL). The respective alky! bromide (5.37 mmmol) is added and the mixture is stirred at reflux for 12h. After cooling to RT the mixture is filtered and concentrated in vacuo to give the desired product which is used without further purification. 2-(2,2-diethoxy-ethylsulfanyl)-5-methyl-lH-iniidazole-4-carboxylic acid ethyl ester prepared by reaction of 5-methyl-2-thioxo-2,3-dihydro-lH-imidazole-4-carboxylic acid ethyl ester with bromoacetaldehyde diethyl acetal. LC-MS: tR = 0.70 min: [M+H]"" = 303.4. A.2.5 Synthesis of 3-hydroxy-2,3-dihydro-imidazo[2,l-b]thiazole-6-carboxylic acid ethyl ester derivatives (general procedure) A mixture of the respective 2-(2.2-dialkoxy-ethylsulfanyl)-5-methyl-lH-imidazoIe-4-carboxylic acid ethyl ester derivative (10.0 mmol) in hydrochloric acid (15%, 8,0 mL) is stirred for Ih at RT and neutralized by addition of aq. Na2C03 solution. The obtained precipitate is filtered off to give the desired product which is used without further purification. 3-hydroxy-5-methyl-2,3-dihydro-imidazo[2,l-b]thiazole-6-carboxylic acid ethyl ester prepared by cyclization of 2-(2,2-diethoxy-ethylsulfanyl)-5-methyl-lH-imidazole-4-carboxylic acid ethyl ester. LC-MS: tR = 0.55 min; [M+H]^ = 229.3. A.2.6 Synthesis of imidazo[2,l-b]thiazole-6-carboxylic acid ethyl ester derivatives (general procedure) The respective 3-hydroxy-2,3-dihydro-imidazo[2.]-b]thiazole-6-carboxylic acid ethyl ester derivative (4.00 mmoi) is added to POCI3 (9.3 mL), stirred at reflux for 3h (respectively I6h) and concentrated in vacuo. Chloroform and ice-water are added successively and the mixture is neutralized by addition of Na2C03. The layers are separated and the aq. layer is extracted with chloroform. The combined organic layers are dried over Na2S04 and concentrated in vacuo to give the desired product which is purified by CC (heptane/EtOAc 1/1 toEtOAc). 5-methyl-imidazo[2,l-b]thiazole-6-carboxylic acid ethyl ester prepared by dehydration of 3-hydroxy-5-methyl-2,3-dihydro-imidazo[2J-b]thiazole-6-carboxylic acid ethyl ester. LC-MS: tR = 0.66 min: [M+H]"" = 211.0. A.2.7 Synthesis of N,N-dimethyI-N'-thiazol-2-yl-forniamidine derivatives (general procedure) N.N-Dlmethylformamide dimethyl acetale (89.9 mmol, 2.0eq) is added dropwise to a solution of the respective 2-aminothiazole (44.9 mmol, l.Oeq) in toluene (30 mL). The mixture is heated at reflux for 22h, cooled to RT and concentrated in vacuo. A small amount of hexane is added and the obtained precipitate is filtered off to give the respective formamidine derivative. N,N-diniethyl-N'-thiazol-2-yl-formaniidine prepared by reaction of 2-aminothiazole with N,N-dimethylformamide dimethyl acetale. LC-MS: tR = 0.40 min; [M+Hf = 156.0. N,N-dimethyi-N'-(5-methyl-thiazol-2-yl)-fornianiidine prepared by reaction of 5-methyl-thiazol-2-ylamine with N,N-dimethylformamide dimethyl acetale. LC-MS: tR = 0.52 min; [M+Hf = 170.2. N,N-diniethyl-N'-(4-methyl-thiazol-2-yl)-forniamidine prepared by reaction of 4-methyl-thiazol-2-ylamine with N,N-dimethylformamide dimethyl acetale. LC-MS: tR = 0.51 min; [M+H]^ = 170.1. A.2.8 Synthesis of 3-ethoxycarbonylmethyl-thiazol-3-iuin bromide derivatives (general procedure) The respective N.N-dimethyl-N'-thiazol-2-Yl-fonTiamidine derivative (45.1 mmol. I .OOeq) is added portionwise to vigorously stirred ethyl bromoacetate (225 mmol. 5.0eq). After 2h toluene (12 mL) is added and the mixture is stirred for 24h. The obtained precipitate is filtered off and the residue is recrystallized from MeCN to give the respective thiazolium bromide. 2-(diniethylamino-methyleneamino)-3-ethoxycarbonylmethyl-thiazol-3-iuni bromide prepared by reaction of ethyl bromoacetate with N.N-dimethyl-N'-thiazol-2-yl-formamidine. LC-MS: tR = 0.58 min; [M+H]^ = 242.1. 2-(dimethylaniino-methyleneamino)-3-ethoxycarbonylmethyl-5-methyl-thiazol-3-ium bromide prepared by reaction of ethyl bromoacetate with N.N-dimethyl-N'-(5-methyl-thiazol-2-yl)-formamidine. LC-MS: tR = 0.63 min; [M+H]^ = 256.2. 2-(dimethyIamino-methyleneamino)-3-ethoxycarbonylmetliyl-4-methyl-thiazol-3-ium bromide prepared by reaction of ethyl bromoacetate with N,N-dimethyl-N'-(4-methyl-thiazol-2-yl)-formamidine. LC-MS: tR = 0.61 min: [M+H]^ = 256.0. A.2.9 Synthesis of imidazo[2,l-b]thiazoie-5-carboxyIic acid ethyl ester derivatives (general procedure) DBU (68.9 mmol. 1.58eq) is added to a suspension of the respective thiazolium bromide derivative (43.6 mmol, 1 .OOeq) in DMF (50 mL). The solution is stirred for 24h and diluted with ice-cold water. The obtained precipitate is filtered off to give the respective imidazo-thiazole derivative. imidazo[2,l-b]thiazoIe-5-carboxylic acid ethyl ester prepared by cyclisation of 2-(dimethylamino-methyleneamino)-3-ethoxycarbonyl-methyl-thiazol-3-ium bromide. LC-MS: tR = 0.76 min: [M+H]^ = 197.0. 2-methyi-iinidazo[2,l-b]thiazole-5-carboxylic acid ethyl ester prepared by cyclisation of 2-(dimethyIamino-methyleneamino)-3-ethoxycarbonyl-methyl-5-methyl-thiazol-3-ium bromide. LC-MS: IR = 0.83 min; [M+H]"" = 211.0. 3-methyl-iiTiidazo[2,l-b]thiazole-5-carboxyIic acid ethyl ester prepared by cyclisation of 2-(diiTiethylamino-methyleneamino)-3-ethoxycarbonyl-methyl-4-methyl-thiazol-3-ium bromide. LC-MS: tR = 0.83 min; [M+H]"" = 211.0. A.2.10 Synthesis of imidazo[2,l-blthiazole-carboxylic acid derivatives (general procedure) An aq. NaOH solution (l.OM, 23 mL) is added to a solution of the respective carboxylic ester derivative (11.3 mmol) in THF (12 mL) and MeOH (4.0 inL). The mixture is stirred for 16h, the organic volatiles are removed in vacuo and water (10 mL) is added. The mixture is cooled to 0°C and made acidic (pH = 3-4) by addition of hydrochloric acid (1.0 M). The obtained precipitate is filtered off, washed with cold water and dried in vacuo to give the desired acid which is used without further purification. 3-methyl-imidazo[2,l-blthiazole-2-carboxylic acid prepared by saponification of 3-methyl-imidazo[2,l-b]thiazole-2-carboxy!ic acid methyl ester. LC-MS: tR = 0.24 min; [M+Hf = 183.0. 5-methyl-imidazo[2,l-b]thiazole-6-carboxylic acid prepared by saponification of 5-methyl-imidazo[2.1-b]thiazole-6-carboxylic acid ethyl ester. LC-MS: tR = 0.39 min; [M+H]^ = 183.0. iniidazo|2,l-b]thiazole-5-carboxylic acid prepared by saponification of imidazo[2,l-b]thiazole-5-carboxylic acid ethyl ester. LC-MS: tR = 0.39 min; [M+H]^ = 169.0. 2-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid prepared by saponification of 2-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid ethyl ester. LC-MS: tR = 0.51 min; [M+H]^ = 183.0. 3-methyl-imidazo[2,l-b]thiazole-5-carboxylicacid prepared by saponification of 3-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid ethyl ester. LC-MS: tR = 0.53 min; [M+Hf = 183.0. A.2.11 Synthesis of 6-trifluoromethyl-imidazo[2,l-b]thiazole 3-Bromo-l.],l-trifluoroacetone (11.0 mmol) is added to a solution of 2-aminothiazole (10.0 mmol) in acetone (20 mL) and the mixture is stirred at reflux for 20h. The obtained precipitate is filtered off, treated with hydrobromic acid (2.0 M, 40 mL), stirred at reflux for Ih and cooled to RT. The mixture is made basic by addition of ammonium hydroxide solution (15%) and the resulting free base is crystallized from EtOH to give the desired product. LC-MS; tR = 0.78 min; [M+H]^ = 192.95. A.2.12 Synthesis of 6-trif!uoromethyl-imidazo[2,l-b]thiazole-5-carboxyIic acid At 0°C POCI3 (17.1 mmol) is added dropwise to a solution of DMF (20.6 mmol) in chloroform (5.0 mL). A solution of 6-trifluoromethyl-imidazo[2,l-b]thiazole (3.17 mmol) in chloroform (15 mL) is added dropwise at 0°C and the mixture is stirred for 3h at RT. After heating for 2.5d to reflux the mixture is poured into ice, extracted three times with DCM, dried over MgS04 and concentrated under reduced pressure. DCM is added, the obtained precipitate is filtered off and the filtrate is concentrated in vacuo to give a crude product which is dissolved in tert.-butanol (19.5 mL). A solution of sodium chlorite (23.0 mmol) and NaH2P04(17.6 mmol) in water (19.5 mL) is added dropwise and the mixture is stirred for 90 min at RT. The solvents are partially removed in vacuo and the obtained precipitate is filtered off to give the desired product as a white solid. LC-MS: tR = 0.73 min: [M+H]* = 237.2. A.2.13 Synthesis of 6-chloro-imidazo[2,l-b]thiazoie-5-carboxylic acid A solution of NaOCI (230 mmol) and NaH2P04 (176 mmol) in water (195 mL) is added dropwise to a solution of 6-chloro-imidazo[2,l-b]thiazole-5-carbaldehyde (26.8 mmol) in tert.-butanol (195 mL) and the mixture is stirred for 8h at RT. The solvents are partially removed in vacuo and the obtained precipitate is filtered off. The filtrate is made acidic and the obtained precipitate is filtered off to give the desired product as a white solid. LC-MS; tR = 0.67 min; [M+Hf = 202.9. A.3 Synthesis of benzo[l,4]oxazine-carboxyIic acid derivatives A.3.1 Synthesis of 3-aniino-2-hydroxy-benzoic acid methyl ester A solution of methyl 3-nitrosalicylate (26.6 mmol) in MeOH (50 mL) is treated with Pd/C (10%, 500 mg) and stirred at RT under a hydrogen atmosphere (I bar) for 16 h. After filtration through celite and removal of the solvents the desired product is obtained which is used without further purification. LC-MS: tR = 0.5) min; [M+H]" = 168.0. A.3.2 Synthesis of 3-oxo-3,4-dihydro-2H-benzo[l,4]oxazine-8-carboxylic acid methyl ester At RT chloro-acetyl chloride (29.0 mmol) is added dropwise to a solution of 3-amino-2-hydroxy-benzoic acid methyl ester (26.4 mmol) in DMF (100 mL). After 20 min K2CO3 (126 mmol) is added portionwise, the mixture is stirred for 16h at RT and the solvents are removed in vacuo. Water and DCM are added, the layers are separated and the organic layer is washed with brine and dried over Na2S04. The solvents are removed in vacuo to give a crude product which is used without further purification. LC-MS; tR = 0.68 min; [M+H]^ = 208.0. A.3.3 Synthesis of 3,4-dihydro-2H-benzo(l,4]oxazine-8-carboxylic acid methyl ester Boron trifluoride diethyl etherate (10.1 mmol) is added dropwise to a mixture of 3-oxo-3,4-dihydro-2H-benzo[L4]oxazine-8-carboxylic acid methyl ester (4.83 mmol) in THF (12 mL) to keep the temperature below 5°C. After 20 min NaBH4 (10.1 mmol) is added and the mixture is stirred at 5°C for 60 min. EtOAc (6.0 mL) and hydrochloric acid (1.0 M, 6.0 mL) are added dropwise. The mixture is made basic by addition of sat. aq. NaHCOa solution, the layers are separated and the aq. layer is extracted with EtOAc. The combined organic layers are dried over MgS04 and concentrated in vacuo to give a crude product which is purified by CC (heptane to heptane/EtOAc 3/7). LC-MS: tR = 0.69 min; [M+H]"" = 194.0. A.3.4 Synthesis of 4-methyl-3,4-dihydro-2H-benzo[l,4]oxazine-8-carboxylic acid methyl ester K2CO3 (4.76 mmol) is added to a solution of 3,4-dihydro-2H-benzo[l,4]oxazine-8-carboxylic acid methyl ester (2.07 mmol) in DMF (3.0 mL). After 30 min methyl iodide (4.14 mmol) is added and the mixture is stirred for 2h at 75°C. Cold water and EtOAc are added, the layers are separated and the aq. layer is extracted with EtOAc. The combined organic layers are washed with water and brine, dried over MgS04 and concentrated in vacuo to give a crude product which is used without further purification. LC-MS: tR = 0.83 min; [M+Hf = 208.1. A.3.5 Synthesis of 2-amino-3-hydroxy-benzoic acid methyl ester A solution of (trimethylsilyl)diazomethane in hexane (2.0 M, 10.9 mmol) is added dropwise (10 min) to a mixture of 3-hydroxyanthranilic acid (9.93 mmol) in MeOH (10.5 mL) and toluene (42 mL). The mixture is stirred for 16h, concentrated in vacuo, diluted with ether and EtOAc and washed several times with water. The organic layer is dried over MgS04 and concentrated under reduced pressure. The residue is purified by CC (heptane to heptane/EtOAc 7/3) to give the desired ester as a brown solid. LC-MS: tR = 0.70 min: [M+Hr= 168.0. A.3.6 Synthesis of 3-oxo-3,4-dihydro-2H-benzo[l,4]oxazine-5-carboxyIic acid methyl ester At RT chloro-acetyl chloride (8.06 mmol) is added dropwise to a solution of 2-amino-3-hydroxy-benzoic acid methyl ester (7.33 mmol) in DMF (50 mL). After 20 min K2CO3 (34.9 mmol) is added portionwise, the mixture is stirred for 16h at RT and the solvents are removed in vacuo. Water and DCM are added, the layers are separated and the organic layer is washed with brine and dried over Na2S04. The solvents are removed in vacuo to give a crude product which is purified by CC (heptane to heptane/EtOAc 6/4). LC-MS: IR = 0.82 min; [M+CHsCN+H]^ = 249.0. A.3.7 Synthesis of 3,4-dihydro-2H-benzo[l,41oxazine-5-carboxylic acid methyl ester Boron trifluoride diethyl etherate (7.10 mmol) is added dropwise to a mixture of 3-oxo-3.4-dihydro-2H-benzofl.4]oxazine-5-carboxylic acid methyl ester (3.38 mmol) in THF (10 mL) to keep the temperature below 5°C. After 20 min NaBH4 (7.10 mmol) is added and the mixture is stirred at 5°C for 90 min. EtOAc (6.0 mL) and hydrochloric acid (1.0 M. 6.0 mL) are added dropwise. The mixture is made basic by addition of aq. NaaCOa solution, the layers are separated and the aq. layer is extracted with EtOAc. The combined organic layers are dried over MgS04 and concentrated in vacuo to give a crude product which is purified by CC (heptane to heptane/EtOAc 3/7). LC-MS: tR = 0.90 min; [M+CHaCN+H]^ = 235.3. A.3.8 Synthesis of benzo[l,4]oxazine-carboxylic acid derivatives by ester hydrolysis (general procedure) A soiution of NaOH (4.00 mmol) in a mixture of MeOH (3.0 mL) and water (6.8 ml) is added to the respective ester derivative (2.00 mmol). The mixture is stirred at 55°C for 16h. partially concentrated in vacuo to remove MeOH and made acidic by addition of hydrochloric acid (l.OM). The respective carboxylic acid precipitates and is collected by filtration. 3,4-dihydro-2H-benzo[l,4]oxazine-8-carboxylic acid prepared by saponification of 3,4-dihydro-2H-benzo[l,4]oxazine-8-carboxylic acid methyl ester. LC-MS: tR = 0.55 min; [M+Hf = 180.0. 4-methyl-3,4-dihydro-2H-benzo(l,4]oxazine-8-carboxylic acid prepared by saponification of 4-methyl-3,4-dihydro-2H-benzo[L4]oxazine-8-carboxylic acid methyl ester. LC-MS: tR = 0.72 min; [M+H]* = 194.1. 3,4-dihydro-2H-benzo[l,4]oxazine-5-carboxylic acid prepared by saponification of 3,4-dihydro-2H-benzo[L4]oxazine-5-carboxylic acid methyl ester. LC-MS: tR = 0.76 min; [M+H]" = 180.2. A.4 Synthesis of chroman-carboxylic acid derivatives A.4.1 Synthesis of 3-prop-2-ynyIoxy-benzoic acid methyl ester A solution of propargyl bromide in toluene (80%, 68.7 mmol, 7.40 mL) is added to a solution of 3-hydroxy-benzoic acid methyl ester (48.6 mmol) in DMF (45 mL). K2CO3 is added and the mixture is stirred at RT for 4h. Water and ether are added, the layers are separated and the organic layer is washed with aq. NaOH solution (5%) and brine. The solvents are removed in vacuo to give the desired ester as a pale yellow solid. H-NMR (CDCI3): 5 = 2.56 (s, IH); 3.94 (s, 3H); 4.76 (s, 2H); 7.20 (d, J = 8.04 Hz, IH); 7.39 (t, J = 8.16 Hz. IH); 7.66 (bs, IH); 7.71 (d, J = 7.78 Hz, IH). A.4.2 Synthesis of 2H-chromene-5-carboxylic acid methyl ester A solution of 3-prop-2-ynyloxy-benzoic acid methyl ester (10.5 mmol) in N,N-diethylaniline (20 mL) is heated to reflux for 15h. The mixture is cooled to RT. diluted with ether and washed with hydrochloric acid (5%) and brine. The solvents are removed in vacuo and the residue is purified by chromatography (silica, heptane to heptane/EtOAc 95/5) to give the desired chromene derivative. 'H-NMR (CDCI3): 5 = 3.91 (s, 3H); 4.80 (bs, 2H); 5.93-5.98 (m, IH); 6.99 (d, J = 8.03 Hz, IH); 7.16 (t, J = 7.66 Hz, IH); 7.34 (d, J = 10.3 Hz. IH); 7.50 (d, J = 7.28 Hz, IH). .4.4.3 Synthesis of 2H-chromene-5-earboxylic acid A solution of NaOH (7.26 mmol) in a mixture of MeOH (5.4 mL) and water (12.1 mL) is added to 2H-chromene-5-carboxylic acid methyl ester (4.84 mmol). The mixture is stirred at 55°C for 3h, partially concentrated in vacuo to remove MeOH and made acidic by addition of hydrochloric acid (l.OM). The desired carboxylic acid precipitates and is collected by filtration. 'H-NMR (DMSO-de): 5 = 4.75 (bs, 2H); 5.99-6.05 (m. IH): 6.98 (d. J = 7.78 Hz, IH); 7.19 (t, J = 7.78 Hz. IH); 7.25 (d. J = 10.3 Hz, IH); 7.40 (d, J = 7.78 Hz. IH); 13.0 (bs, IH). A.4.4 Synthesis of chroman-5-carboxylic acid A solution of 2H-chromene-5-carboxylic acid (1.42 mmol) in MeOH (5.0 mL) is treated with Pd/C (10%. 50 mg) and stirred at RT under a hydrogen atmosphere (1 bar) for 16 h. After filtration through celite and removal of the solvents the desired product is obtained which is used without further purification. 'H-NMR (DMSO-de): 5 = 1.90 (m, 2H); 2.98 (m. 2H); 4.13 (m,2H); 6.89-6.94 (m, IH); 7.11-7.17 (m, IH); 7.31-7.36 (m, IH); 12.8 (bs, IH). A.4.5 Synthesis of chroman A solution of 4-chromanone (19.6 mmol) in HOAc (30 mL) is added to a suspension of zinc powder (445 mmol) in HOAc (60 mL). The mixture is stirred at 100°C for 4h, cooled to RT, filtered through celite and concentrated in vacuo. EtOAc and aq. NaOH solution (1.0 M) are added, the layers are separated and the aq. layer is extracted twice with EtOAc. The combined organic layers are dried over MgS04 and concentrated in vacuo to give the desired product which is used without further purification. 'H-NMR (CDCI3): 5 = 2.04 (m, 2H): 2.82 (m, 2H); 4.21 (m, 2H); 6.80-6.89 (m. 2H); 7.04-7.14 (m. 2H). A.4.6 Synthesis of chroman-8-carboxylic acid At RT a solution of chroman (17.7 mmol) in ether (15 mL) is added over 10 min to a solution of n-BuLi (19.5 mmol) in a mixture of hexane (12.2 mL) and ether (15 mL). The mixture is stirred at reflux for 150 min. allowed to reach RT and poured into a mixture of dry ice and ether. Ice water is added and the layers are separated. The aq. layer is made acidic and extracted with a mixture of ether and EtOAc. The combined organic layers are washed with water, dried over Na2S04 and concentrated in vacuo to give a crude product which is purified by CC (heptane/EtOAc 9/1 to EtOAc). LC-MS: tR = 0.76 min; [M+CHaCN+Hf = 220.1. A.5 Synthesis of 2,3-dihydro-benzofuran-4-carboxylic acid Benzofuran-4-carboxylic acid (30.8 mmol, M.A. Eissenstat et al. J. Med. Chein. 1995, 38. 3094-3105) is added to a suspension of Pd/C (10%, 2.00 g) in EtOH (25 mL). Additional EtOH (75 mL) is added and the mixture is stirred at RT under a hydrogen atmosphere (4 bar) for 16 h. After filtration through celite and removal of the solvents the desired product is obtained which is used without further purification. 'H-NMR (DMS0-d6): 5 = 3.45 (t, J = 8.79 Hz, 2H); 4.55 (t. J = 8.79 Hz, 2H); 6.99 (d, J = 7.78 Hz, 1H); 7.21 (t, J = 7.91 Hz, 1H); 7.39 (d, J = 7.78 Hz, IH); 12.9 (bs, IH). A.6 Synthesis of benzooxazole-4-carboxylic acid A solution of 2-amino-3-hydroxy-benzoic acid (13.1 mmol) in trimethyl orthoformate (20.0 mL) is refluxed for 4h, cooled to RT and concentrated in vacuo to give a crude product which is used without further purification. LC-MS: tR = 0.66 min; [M+H] = 164.1. A.7 Synthesis of benzo[d]isothiazole-3-carboxylic acid A.7.1 Synthesis of benzo[b]thiophene-2,3-dione A solution of oxalyl chloride (73.1 mmol) in ether (14 mL) is added to a solution of thiophenol (45.4 mmol) in ether (20 mL). The mixture is heated to reflux for 90 min, cooled to RT and concentrated in vacuo. The residue is dissolved in DCM (85 mL), cooled to 0°C and treated portionwise with aluminum chloride (54.5 mmol). The mixture is heated to reflux for 30 min. cooled to RT and poured with stirring into ice-water. The layers are separated and the organic layer is washed with aqueous NaHCOa solution, water and brine. After drying over MgS04 the solvents are removed in vacuo and the residue is purified by flash chromatography (gradient: EtOAc/heptane 1/9 to 1/1) to give the desired product. 'H-NMR (CDCI3): 5 = 7.37 (t, J = 7.62 Hz, IH); 7.42 (d. J = 7.62 Hz, IH); 7.68 (t, J = 7.62 Hz, IH); 7.82 (d, J = 7.62 Hz, !H). A.7.2 Synthesis of benzofdlisothiazoIe-3-carboxylic acid amide An aqueous solution of hydrogen peroxide (35%. 3.9 mL) is added to a mixture of benzo[bJthiophene-2,3-dione (8.53 mmol) in an aqueous solution of ammonium hydroxide (30%. 47 mL). After stirring for I6h the precipitate is filtered off washed with water and dried in vacuo to give the desired product which is used without further purification. LC-MS: tR = 0.74 min; [M+CHsCN+Hf = 220.1. A.7,3 Synthesis of benzo[d]isothiazoIe-3-carboxylic acid A solution of benzo[d]isothiazole-3-carboxylic acid amide (5.05 mmol) in MeOH (100 mL) is treated with an aqueous NaOH solution (10 M, 10.0 mL) and heated to reflux for I6h. The mixture is cooled to RT, concentrated in vacuo, made acidic by addition of hydrochloric acid (pH < 2) and kept for 2h at 0°C. The obtained precipitate is filtered off and dried in vacuo to give the desired product which is used without further purification. LC-MS: tR = 0.73 min: [M+H]^ = 180.0. A.8 Synthesis of benzooxazole-7-carboxyIic acid A solution of 3-amino-2-hydroxy-benzoic acid (12.5 mmol) in trimethyl orthoformate (19.2 mL) is heated to reflux for 20h and concentrated in vacuo. The residue is washed three times with hot MeOH, the filtrates are combined and the solvent is removed in vacuo to give the desired product which is used without further purification. H-NMR (DMSO-d6): 5 = 13.4 (bs, IH); 8.87 (s. IH) ; 8.08 (d. J = 8.0 Hz. IH); 7.96 (d, .1 = 7.5 Hz, IH); 7.52 (t, J = 7.9 Hz, IH). A.9 Synthesis of 2-niethyl-benzooxazole-7-carboxylic acid A solution of 3-amino-2-hydroxy-benzoic acid (9.40 mmol) and PTSA(0.34 mmol) in triethyl orthoacetate (5.77 mL) is heated to reflux for 5h and concentrated in vacuo. The residue is washed with ether and dried in vacuo to give the desired product which is used without further purification. LC-MS: IR = 0.67 min: [M+Hf = 178.0. A. 10 Synthesis of benzothiazole-7-carboxylic acid A. 10.1 Synthesis of 3-thioureido-benzoic acid methyl ester At -10°C sulfuric acid (0.46 mL) is added dropwise to a solution of methyl 3-aminobenzoate (17.2 mmol) in chlorobenzene (19 mL). After 15 min potassium thiocyanate (18.2 mmol) is added portionwise over 30 min. The mixture is treated with 18-crown-6. heated to 100°C for 16h and allowed to cool to RT. After 4h the obtained precipitate is filtered off and washed successively with chlorobenzene (33 mL) and hexane (three times 130 mL). The residue is diluted with water (390 mL) and the suspension is stirred for 30 min. After filtration the residue is washed twice with water (130 mL each), concentrated in vacuo and dried additionally by azeotropic removal of water with toluene. The obtained product is used without further purification. LC-MS: IR = 0.66 min; [M+H]^ = 211.0. A. 10.2 Synthesis of 2-aniino-benzothiazole-7-carboxylic acid methyl ester At 0°C a solution of bromine (13.4 mmol) in acetic acid (9.4 mL) is added dropwise to a vigorously stirred solution of 3-thioureido-benzoic acid methyl ester (12.5 ml) in acetic acid (37 mL). The mixture is allowed to reach RT, stirred at 70°C for 4h and cooled to RT. Ether is added and the precipitate is filtered off The residue is stirred vigorously in a sat aqueous NaHCOa solution, filtered off and washed with water. The obtained solid is dried in vacuo to give the desired product which is used without further purification. LC-MS: tR = 0.62 min; [M+Hf = 209.0. A.10.3 Synthesis of benzothiazole-7-carboxylic acid methyl ester Isoamyl nitrite (22.0 mmol) is added to a solution of 2-aiTiino-benzothiazole-7-carboxylic acid methyl ester (10.1 mmol) in THF (29 mL). The mixture is heated to reflux for 4h, the solvents are removed in vacuo and the residue is purified by flash chromatography (gradient: heptane to EtO.Ac/heptane 4/6) to give the desired product. LC-MS: tR = 0.85 min;[M+Hf = 194.0. A.10.4 Synthesis of benzothiazole-7-carboxylic acid At 0°C an aqueous NaOH solution (50%. 6.0 mL) is added to a solution of benzothiazole-7-carboxylic acid methyl ester in a mixture of MeOH (39 mL). THF (11.7 mL) and water (3.0 mL). The mixture is stirred for 4h and concentrated in vacuo. At 0"C water (60 mL) is added and the mixture is made acidic (pH 5) by addition of cone, hydrochloric acid. After 30 min the precipitate is filtered off, washed with water and dried in vacuo to give the desired product. LC-MS: tR = 0.77 min: [M+CH3CN+H]"' = 221.1. A. 11 Synthesis of 7-fIuoro-benzofuran-4-carboxylic acid A. 11.1 Synthesis of 4-fluoro-3-hydroxy-benzoic acid ethyl ester A solution of 4-fluoro-3-hydroxy-benzoic acid (32.0 mmol) in EtOH (120 mL) is treated with cone, sulfuric acid (25.7 mL) and heated to reflux for 16h. Water (600 mL), NaHCOa (100 g) and ether (300 mL) are added successively, the layers are separated and the aqueous layer is extracted twice with ether. The combined organic layers are washed twice with brine, dried over MgS04 and concentrated in vacuo to give the desired product which is used without further purification. 'H-NMR (DMSO-dfe): 8 = 7.75 (d. J = 8.5 Hz, IH); 7.58-7.63 (m, 1H); 7.12 (t, J = 9.3 Hz. 1H); 6.21 (bs. 1H): 4.39 (q, J = 7.0 Hz, 2H): 1.40 (t. J = 7.0 Hz, 3H). A. 11.2 Synthesis of 3-allyloxy-4-fluoro-benzoic acid ethyl ester K2CO3 (96.9 mmol) and 3-bromo-l-propen (64.6 mmol) are added to a solution of 4-fluoro-3-hydroxy-benzoic acid ethyl ester (32.3 mmol) in acetone (50 mL). The mixture is heated to reflux for 16h. filtered and cooled to RT. The solvents are removed in vacuo to give the desired product which is used without further purification. LC-MS: tR = 1.01 min; [M+CHaCN+H]^ = 266.0. A. 11.3 Synthesis of 2-allyl-4-fluoro-3-hydroxy-benzoic acid ethyl ester 3-Aliyloxy-4-tluoro-benzoic acid ethyl ester (30.4 mmol) is heated to 190°C for 19h, cooled to RT and purified by flash chromatography (gradient: heptane to heptane/EtOAc 9/1) to give the desired product as an orange oil. LC-MS: tR = 0.93 min; [M+H]^ = 225.0. A.11.4 Synthesis of 7-fluoro-2-hydroxy-2,3-dihydro-benzofuran-4-carboxylic acid ethyl ester At -78°C ozone is passed through a solution of 2-allyl-4-fluoro-3-hydroxy-benzoic acid ethyl ester (9.68 mmol) in a mixture of DCM (37 mL) and MeOH (4 mL) for 40 min. After further 20 min nitrogen gas is passed through the mixture. Dimethyl sulfide (25.7 mmol) is added and the mixture is allowed to reach RT during 3h. DCM and water are added, the layers are separated and the aqueous layer is extracted twice with DCM. The combined organic layers are washed with brine, dried over Na2S04 and concentrated in vacuo to give a mixture of 7-fluoro-2-hydroxy-2,3-dihydro-benzofuran-4-carboxylic acid ethyl ester and 7-fluoro-2-methoxy-2,3-dihydro-benzofuran-4-carboxylic acid ethyl ester which is used without purification in the next step. LC-MS: tR = 0.85 min; [M+H]"^ = 227.0. A.11.5 Synthesis of 7-fluoro-benzofuran-4-carboxylic acid ethyl ester A mixture of 7-fluoro-2-hydroxy-2,3-dihydro-benzofuran-4-carboxylic acid ethyl ester and 7-f]uoro-2-methoxy-2,3-dihydro-benzofuran-4-carboxylic acid ethyl ester (1.15 g, see above) in toluene (6.0 mL) is added dropwise to a solution of PTSA(0.25 mmol) in toluene (5.0 mL) which is heated to reflux. Heating is continued for 5h. an additional portion of PTSA(0.25 mmol) is added and the mixture is again heated to reflux for 7h. The solvents are removed in vacuo and the residue is purified by flash chromatography (gradient: heptane to heptane/EtOAc 95/5) to give the desired product. 'H-NMR (CDCI3): 5 = 7.99 (dd, .f = 8.3 Hz, J = 4.3 Hz, IH); 7.78 (s, 1H): 7.44 (bs, IH); 7.10 (t, J = 9.3 Hz, 1H); 4.46 (q, J = 7.0 Hz, 2H); 1.47 (t, J = 7.0 Hz, 3H). A.n.6 Synthesis of 7-fluoro-benzofuran-4-carboxylic acid A mixture of 7-fluoro-benzofuran-4-carboxylic acid ethyl ester (1.54 mmol) and sodium hydroxide (2.31 mmol) in MeOH (1.7 mL) and water (1.7 mL) is heated to 55°C for 90 min. The mixture is concentrated in vacuo and made acidic by addition of hydrochloric acid (1.0 M). The obtained precipitate is filtered off and dried in vacuo to give the desired product. 'H-NMR (DMS0-d6):§= 13.19 (bs. ]H);8.25(s. IH); 7.89-7.94 (m. IH); 7.41 (s, lH);7.36(t. J = 9.5 Hz, IH). A.12 Synthesis of 7-chloro-benzofuran-4-carboxylic acid A.12.1 Synthesis of 4-chloro-3-hydroxy-benzoic acid ethyl ester A solution of 4-chloro-3-hydroxy-benzoic acid (29.3 mmoi) in EtOH (110 mL) is treated with cone, sulfuric acid (23.6 mL) and heated to reflux for 16h. Water (600 mL), NaHCOs (100 g) and ether (300 mL) are added successively, the layers are separated and the aqueous layer is extracted twice with ether. The combined organic layers are washed twice with brine, dried over MgS04 and concentrated in vacuo to give the desired product which is used without further purification. 'H-NMR (CDC13): 5 = 7.73 (s, IH): 7.58 (d, J = 8.3 Hz, IH); 7.40 (d, J = 8.3 Hz, lH);5.87(s, IH): 4.39 (q, J = 7.0 Hz. 2H); 1.41 (t, J = 7.0 Hz. 3H). A. 12.2 Synthesis of 3-allyIoxy-4-chIoro-benzoic acid ethyl ester K2CO3 (78.5 mmol) and 3-bromo-l-propen (52.3 mmol) are added to a solution of 4-chloro-3-hydroxy-benzoic acid ethyl ester (26.2 mmol) in acetone (50 mL). The mixture is heated to reflux for 16h and cooled to RT. The solvents are removed in vacuo to give the desired product which is used without further purification. LC-MS: tR = 1.05 min; [M+H]"^ = 240.9. A.12.3 Synthesis of 2-allyl-4-chloro-3-hydroxy-benzoic acid ethyl ester 3-Allyloxy-4-chloro-benzoic acid ethyl ester (26.2 mmol) is heated to 190°C for 19h, cooled to RT and purified by flash chromatography (gradient: heptane to heptane/EtOAc 9/1) to give the desired product as a white solid. LC-MS; tR = 0.98 min; [M+H]"" = 241.0. A.12.4 Synthesis of a mixture of 7-chloro-2-hydroxy-2,3-dihydro-benzofuran-4- carboxylic acid ethyl ester and 7-chloro-2-methoxy-2,3-dihydro-benzofuran-4-carboxylic acid ethyl ester At -78°C ozone is passed through a solution of 2-allyl-4-chloro-3-hydroxy-benzoic acid ethyl ester (13.6 mmol) in a mixture of DCM (52 mL) and MeOH (5.5 mL) for 40 min. After further 20 min nitrogen gas is passed through the mixture. Dimethyl sulfide (36.1 mmol) is added and the mixture is allowed to reach RT during 3h. DCM and water are added, the layers are separated and the aqueous layer is extracted twice with DCM. The combined organic layers are washed with brine, dried over Na2S04 and concentrated in vacuo to give a mixture of 7-chloro-2-hvdroxv-2.3-dihvdro-benzofuran-4-carboxylic acid ethyl ester and 7-chloro-2-methoxy-2.3-dihydro-benzofuran-4-carboxylic acid ethyl ester which is used without purification in the next step. LC-MS: IR = 0.89 min; [M+H]" = 243.0 (hydroxy) and tR = 0.95 min: [M+H]^ = 257.0 (methoxy). A.12.5 Synthesis of 7-chloro-benzofuran-4-carboxyIic acid ethyl ester A mixture of 7-chloro-2-hydroxy-2,3-dihydro-benzofuran-4-carboxylic acid ethyl ester and 7-chloro-2-methoxy-2,3-dihydro-benzofuran-4-carboxylic acid ethyl ester (3.36 g, see above) in toluene (20 mL) is added dropwise to a solution of PTSA(0.69 mmol) in toluene (14 niL) which is heated to reflux. Heating is continued for 5h. an additional portion of PTSA(0.69 mmol) is added and the mixture is again heated to reflux for 150 min. The solvents are removed in vacuo and the residue is purified by flash chromatography (gradient: heptane to heptane/EtOAc 95/5) to give the desired product. 'H-NMR (CDCb): 5 = 7,95 (d. J = 8.3 Hz, IH); 7.81 (s, IH); 7.45 (s, IH); 7.38 (d, J = 8.0 Hz. IH); 4.47 (q, J = 7.0 Hz. 2H): 1.48 (t. J = 7.0 Hz. 3H). 7-chloro-2-methoxy-2,3-dihydro-benzofuran-4-carboxylic acid ethyl ester is isolated as pure by-product after flash chromatography. 'H-NMR (CDCb): 8 = 7.54 (d, J = 8.5 Hz, IH); 7.25 (d, J = 8.5 Hz, IH); 5.79 (d, J = 5.5 Hz, IH); 4.37 (q, J = 7.0 Hz, 2H); 3.67 (dd, J = 18.3 Hz, J = 6.5 Hz, IH); 3.60 (s, 3H); 3.53 (d, J = 18.1 Hz, IH); 1.4] (t, J = 7.0 Hz, 3H). A.12.6 Synthesis of 7-chloro-benzofuran-4-carboxy[ic acid A mixture of 7-chloro-benzofuran-4-carboxylic acid ethyl ester (3.90 mmol) and sodium hydroxide (5.85 mmol) in MeOH (4.4 mL) and water (4.4 mL) is heated to 55°C for 90 min. The mixture is concentrated in vacuo and made acidic by addition of hydrochloric acid (1.0 M). The obtained precipitate is filtered off and dried in vacuo to give the desired product 'H-NMR (DMSO-dg): 5 = 13.3 (bs. IH); 8.27 (s, IH); 7.89 (d, J = 8.3 Hz, IH); 7.56 (d, J = 8.3 Hz. IH); 7.42 (s, IH). A. 13 Synthesis of 7-chloro-2-methoxy-2,3-dihydro-benzofuran-4-carboxylic acid A mixture of 7-chloro-2-methoxy-2,3-dihydro-benzofuran-4-carboxylic acid ethyl ester (1.17 mmol) and sodium hydroxide (1.75 mmol) in MeOH (1.3 mL) and water (1.3 mL) is heated to 55°C for 90 min. The mixture is concentrated in vacuo and made acidic by addition of hydrochloric acid (1.0 M). The obtained precipitate is filtered off and dried in vacuo to give the desired product. 'H-NMR (DMSO-de): 5 = 13.1 (bs. IH); 7.45 (d. J = 8.3 Hz, !H): 7.38 (d, J = 8.5 Hz. IH); 5.87 (d, J = 6.3 Hz. IH); 3.67 (dd, J = 18.1 Hz. J = 6.0 Hz. IH): 3.47 (S.3H); 3.30 (d. IH). A.14 Synthesis of pyrrolo[2,l-b]thiazole-7-carboxylic acid A.14.1 Synthesis of pyrrolo[2,l-b|thiazole-7-carboxyIic acid ethyl ester Under nitrogen atmosphere (trimethylsilyl)methyl trifluoromethanesulfonate (16.3 mmol) is added dropwise to a mixture of 2-methylthio-1.3-thiazole (15.5 mmol) in acetonitrile (75 mL). The mixture is treated with propynoic acid ethyl ester (23.2 mmol), kept with occasional shaking for 30 min at RT and added dropwise to a vigorously stirred solution of CsF (21.7 mmol) and propynoic acid ethyl ester (23.2 mmol) in acetonitrile (75 mL). After stirring for Ih the mixture is concentrated in vacuo, diluted with DCM (100 mL), washed twice with water and twice with brine and dried over Na2S04. The solvents are removed in vacuo and the residue is purified by flash chromatography (gradient: heptane to heptane/EtOAc 8/2) to give the desired product. LC-MS: tg = 0.87 min; [M+H]^ = 196.0. A.14.2 Synthesis of pyrrolo[2,l-b]thiazole-7-carboxylic acid A mixture of pyrrolo[2,l-b]thiazole-7-carboxylic acid ethyl ester (5.12 mmol) and sodium hydroxide (7.68 mmol) in MeOH (5.8 mL) and water (5.8 mL) is heated to 55°C for 23h. The mixture is concentrated in vacuo and made acidic by addition of hydrochloric acid (1.0 M). The obtained precipitate is filtered off and dried in vacuo to give the desired product. LC-MS: tR = 0.87 min; [M+Hf = 168.0. A.15 Synthesis of 6-methyI-pyrrolo[2,l-b]thiazole-7-carboxylic acid A.15.1 Synthesis of 6-bromo-pyrrolo[2,l-b]thiazoIe-7-carboxylic acid ethyl ester N-Bromosuccinimide (0.56 mmol) is added to a solution of pyrrolo[2.1-b]thiazole-7-carboxylic acid ethyl ester (0.56 mmol) in DCM (6.0 mL). After 30 min water (5.0 mL) is added, the layers are separated and the aqueous layer is extracted with DCM (5.0 mL). The combined organic layers are dried over Na SO and the solvents are removed in vacuo to give the desired product which is used without further purification. LC-MS: tR = 1.02 min; [M+Hr = 273.9. A.15.2 Synthesis of 6-methyl-pyrrolo[2,l-b]thiazole-7-carboxync acid ethyl ester Under nitrogen atmosphere a solution of dimethylzinc in toluene (1.2 M. 19.1 mL) is added to a mixture of 6-bromo-pyrrolo[2,l-b]thiazole-7-carboxylic acid ethyl ester (11.4 mmol) and [l,r-Bis(diphenylphosphino)ferrocene]dichloropa'!adium(Il) (0.23 mmol, complex with CH2CI2) in dioxane (35 mL). The mixture is heated to reflux for 2h, stirred at RT for 12h and diluted by addition of MeOH (2.3 mL) and TBME. The mixture Is washed with hydrochloric acid (1.0 M) and water, dried over MgS04, concentrated in vacuo and purified by flash chromatography (gradient: heptane to heptane/EtOAc 8/2) to give the desired product. IC-MS: tR = 0.91 min: [M+H]"" = 210.0. A.15.3 Synthesis of 6-niethyl-pyrroIo[2,l-b]thiazole-7-carboxylic acid A mixture of 6-methyl-pyrrolo[2,l-b]thiazole-7-carboxylic acid ethyl ester (7.29 mmol) and sodium hydroxide (10.9 mmol) in EtOH (11.8 mL) and water (11.8 mL) is heated to 75°C for 3d. The mixture is concentrated in vacuo and made acidic by addition of hydrochloric acid (1.0 M). The obtained precipitate is filtered off and dried in vacuo to give the desired product. LC-MS: tR = 0.73 min; [M+H]"" = 182.0. A.16 Synthesis of (lS,3S,5S)-3-aminoniethyI-2-aza-bicyclo[3.1.0]hexane-2- carboxylic acid tert-butyl ester A.16.1 Synthesis of (S)-5-oxo-pyrrolidine-l,2-dicarboxylic acid 1-tert-butyI ester 2- ethyl ester A solution of di-ers are separated and the aqueous layer is extracted with EtOAc (3x70 mL). The combined organic layers are washed with aqueous NaOH solution (1.0 M) and brine, dried over Na2S04 and concentrated in vacuo to give the desired alcohol as a colourless oil. LC-MS (acidic): IR = 0.79 min; [M+H]" = 214.3. A.16.5 Synthesis of (lS,3S,5S)-3-formyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyi ester Dess-Martin periodinane (39.4 mmoK 2.1eq) is added to a solution of (lS.3S,5S)-3-hydroxymethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester (18.8 mmol, 1 .Oeq) in DCM (300 mL). After 2 h sat. NaHC03 solution and aqueous Na2S203 solution are added, the layers are separated and the aqueous layer is extracted twice with DCM. The combined organic layers are washed twice with NaOH solution (1.0 M), water and brine, dried over ]Ma2S04 and concentrated in vacuo to give the desired product as an orange oil which is used without further purification. A.16.6 Synthesis of (lS,3S,5S)-3-(benzyiamino-methyl)-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester Benzylamine (17.5 mmol, l.Oeq) is added to a solution of (lS,3S,5S)-3-fo^Tlyl-2-aza-bicyclo[3.1.0]hexane-2-ca^boxylic acid tert-butyl ester (17.5 mmol, l.Oeq) in DCM (100 mL). The mixture is treated with sodium triacetoxyborohydride (24.5 mmol, 1.4eq), stirred for additional 14 h, poured into water (200 mL) and stirred vigorously for 10 min. The layers are separated and the aqueous layer is extracted twice with DCM (2x100 mL). The combined organic layers are washed with sat. NaHC03 solution (100 mL) and water (100 mL). dried over Na2S04 and concentrated in vacuo to give the desired benzylamine as a brownish oil which is used without further purification. LC-MS (basic): tR = 0.96 min; [M+Hf = 303.3. A.16.7 Synthesis of (lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hexane-2- carboxylic acid tert-butyl ester A solution of (lS.3S,5S)-3-(benzylamino-methyl)-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester (16.7 mmol) in EtOH (100 mL) is treated with Pd/C (2.0 g, 50% H2O) and stirred under a hydrogen atmosphere (1 bar) for Id. An additional amount of Pd/C (2.0 g) is added and the mixture is stirred "-- ''■■■-'-- ''■^ ^^■- f-^*"-^'^'- f\..r.,.r.h ^^lit^ and removal of the solvents the desired amine is obtained which is used without further purification. LC-MS (acidic): tR = 0.64 min; [M+H]*- 213.3. A.17 Synthesis of acylated (lS,3S,5S)-3-(aniino-methyl)-2-aza-bicyclo[3,1.0]hexane derivatives A.17.1 Synthesis of acylated (lS,3S,5S)-3-(amino-methyl)-2-aza-bicyclo(3.1.0]hexane- 2-carboxylic acid tert-butyl ester derivatives (general procedure) u yO-^O ^0^0 O TBTU (1.24 mmol. i.05eq) is added to a solution of the respective carboxylic acid (1.18 mmol. l.Oeq). (lS.3S.5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester (1.18 mmol. l.Oeq) and DIPEA (1.77 mmol. 1.5eq) in DCM. DMF or acetonitrile (10 mL). After 2h the mixture is washed with water, hydrochloric acid (0.5 M) and water. The organic layer is dried over Na2S04, the solvents are removed in vacuo and the residue is purified by prep. HPLC or by flash chromatography (EtOAc/heptane). (lS,3S,5S)-3-{[(benzofuran-4-carbonyl)-amino]-methyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester prepared by reaction of (lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1,0]hexane-2-carboxylic acid tert-butyl ester with benzofuran-4-carboxylic acid (M.A. Eissenstat et al../. Med. Chem. 1995, 28, 3094-3105). LC-MS (acidic): IR = 1.00 min; [M+Hf = 357.1. 'H-NMR(CDCl3):6 = 0.58(bs, IH); 0.80-0.86 (m. IH); 1.52 (s, 911); 1.52-1.59 (m. Ill); 1.79 (bd. .1 = 13.3 Hz. IH); 2.51-2.60 (m. IH); 3.24-3.30 (m, IH); 3.60-3.64 (m, 2H); 4.45-4.52 (m. IH): 7.32 (t, J = 7.9 Hz, IH); 7.47 (bs, IH); 7.61 (d, J = 8.2 Hz. IH); 7.65 (d, J = 7.5 Hz, IH); 7.70 (bs, IH); 8.43 (bs, IH). (lS,3S,5S)-3-{[(6-methyl-iniidazo[2,l-b]thiazole-5-carbonyl)-amino]-niethyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester prepared by reaction of (lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester with 6-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid. LC-MS (acidic): tR = 0.84 min; [M+H]* = 377.1. 'H-NMR (CDCb): 5 = 0.54 (bs, IH); 0.80-0.86 (m. IH); 1.50 (s. 9H); 1.51-1.58 (m, IH); 1.77 (bd, J = 1 1.8 Hz, IH); 2.53-2.61 (m, IH); 2.68 (s. 3H); 3.17-3.24 (m. IH); 3.59-3.69 (m. 2H); 4.39-4.45 (m, IH); 6.84 (d, J = 4.3 Hz. 1H); 7.79 (bs, 1H); 8.27 (d, J = 4.4, i H). (lS,3S,5S)-3-{[(2,3-dihydro-benzo[l,41dioxine-5-carbonyI)-amino]-methyl}-2-aza-bicyclof3.I.0]hexane-2-carboxyIic acid tert-but>'l ester prepared by reaction of (lS.3S,5S)-3-aminomethyl-2-aza-bicyclo[3.].0]hexane-2-carboxylic acid tert-butyl ester with 2,3-dihydro-benzo[l,4]dioxine-5-carboxyIic acid. LC-MS (acidic): tR = 0.97 min; [M+Hf = 375.1. 'H-NMR (CDCb): 5 = 0.61 (bs, IH); 0.76-0.82 (m, IH); 1.47-1.52 (m, IH); 1.51 (s, 9H); 1.89 (bd. J = 13.2 Hz, IH); 2.42-2.47 (m, IH): 3.34-3.74 (m. 3H): 4.30-4.35 (m. IH): 4.32 (bs. 2H); 4.44 (bs. 2H); 6.91-7.05 (m, 2H): 7.67-7.73 (m. IH): 8.43 (bs.NH). (lS,3S,5S)-3-{[(3,5-diniethyl-isoxazole-4-carbonyl)-ainino]-inethyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester prepared by reaction of (lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester with 3,5-dimethyl-isoxazole-4-carboxylic acid. LC-MS (acidic): tR = 0.93 min; [M+H]^ = 336,2. 'H-NMR (CDCI3): 5 = 0.51 (bs, IH); 0.81-0.87 (m, IH); 1.49 (s, 9H); 1.50-1.56 (m. IH); 1.74 (bd, J = 13.5 Hz, IH); 2.47 (s, 3H); 2.52-2.62 (m. IH); 2.64 (s, 3H); 3.05-3.11 (m, IH); 3.57-3.65 (m, 2H); 4.32-4.40 (m, IH); 7.95 (bs, IH). (lS,3S,5S)-3-{f(Imidazo[l,2-a]pyridine-3-carbonyl)-amino]-methyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester prepared by reaction of (lS.3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester with imidazo[l,2-a]pyridine-3-carboxylic acid. LC-MS (acidic): tR = 0.74 min; [M+Hf = 357.1. (lS,3S,5S)-3-{((IsoquinoIine-l-carbonyl)-amino]-methyI}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester prepared by reaction of (lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester with isoquinoline-1-carboxylic acid. LC-MS (acidic): IR = 1.04 min; [M+Hf = 368.1. (lS,3S,5S)-3-{((2,3-Dihydro-benzofuran-4-carbonyl)-aminol-inethyl}-2-aza-bicyclo[3.1,0]hexane-2-carboxyiic acid tert-butyl ester prepared by reaction of (lS,3S.5S)-3-aminomethyl-2-aza-bicycto[3.1.0]hexane-2-carboxylic acid tert-butyl ester with 2,3-dihydro-benzofuran-4-carboxylic acid. LC-MS (acidic): tR= 1.01 min: [M+Hf = 359.1, (lS,3S,5S)-3-((3-Bromo-benzoyIamino)-inethyl]-2-aza-bicycIof3.1.0jhexane-2-carboxylic acid tert-butyl ester prepared by reaction of (lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester with 3-bromo-benzoic acid. LC-MS (acidic): tR = 1.08 min; [M+H]^ = 394.9. (lS,3S,5S)-3-{[(Quinoline-8-carbonyl)-ainino|-methyl}-2-aza-bicyclof3.1.0]hexane-2-carboxylic acid tert-butyl ester prepared by reaction of (]S.3S,5S)-3-aminomethyl-2-aza-bicyclo[3.L0]hexane-2-carboxyiic acid tert-butyl ester with quinoline-8-carboxylic acid. LC-MS (acidic): tR = 0.95 min; [M+Hr = 368.1. (lS,3S,5S)-3-{[(Benzo|d]isoxazole-3-carbonyl)-ainino]-methyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester prepared by reaction of (]S,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester with benzo[d]isoxazole-3-carboxylic acid. LC-MS (acidic): tR = 0.92 min; [M+Hf = 358.2. (lS,3S,5S)-3-{((2,3-Dihydro-thieno[3,4-b][l,4Idioxine-5-carbonyl)-amino]-methyl}-2-aza-bicyclo[3.L0]hexane-2-carboxylic acid tert-butyl ester prepared by reaction of (lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester with 2,3-dihydro-thieno[3,4-b][l,4]dioxine-5-carboxylic acid. LC-MS (acidic): tR = 0.98 min; [M+H]"" = 381.1. A.17.2 Synthesis of acylated (lS,3S,5S)-3-(ainino-methyl)-2-aza-bicyclof3.1.0]hexane derivatives (general procedure) ^0^0 O H O A solution of HCl in dioxane (4.0 M. 2.0 mL) is added to a solution of the respective Boc-protected 2-aza-bicyclo[3.1.0]hexane derivative (0.47 mmol) in dioxane (2.0 inL). After LC-MS indicated complete reaction (2-3h) the mixture is concentrated in vacuo to give the respective deprotected product which is used without further purification. benzofuran-4-carboxylic acid [(lS,3S,5S)-2-aza-bicycio{3.1.0jhex-3-yimethyl]-amide prepared by deprotection of (lS,3S.5S)-3-{[(benzofuran-4-carbonyl)-amino]-methyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester. LC-MS (acidic): tR = 0.59 min; [M+Hr = 257.1. 6-methyl-imidazo[2,l-bJthiazoIe-5-carboxyHc acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-ainide prepared by deprotection of (lS,3S,5S)-3-{[(6-methyl-imidazo[2,l-b]thiazole-5-carbonyl)-amino]-lnethyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester. LC-MS (acidic): tR = 0.51 min; [M+Hf = 277.0. 2,3-dihydro-benzo[ 1,4]dioxine-5-carboxylic acid [(1 S,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmetljyI]-aniide prepared by deprotection of (lS,3S,5S)-3-{[(2,3-dihydro-benzo[l,4]dioxine-5-carbonyl)-amino]-methyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester. LC-MS (acidic): tR = 0.63 min: [M+Hf = 275.1. 3,5-diniethyl-isoxazoIe-4-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyi]-amide prepared by deprotection of (lS.3S,5S)-3-{[(3,5-dimethyl-isoxazole-4-carbonyl)-amino]-methyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester. LC-MS (acidic): tR = 0.51 min; [M+Hf = 236.1. Imidazo[l,2-a|pyridine-3-carboxylic acid [(lS,3S,5S)-l-(2-aza-bicyc!o[3.1.0]hex-3-yl)methyl]-aniide prepared by deprotection of (]S.3S.5S)-3-{[(imidazo[l,2-a]pyridine-3-carbonyl)-amino]-iTiethyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester. LC-MS (acidic): IR = 0.47 min;[M+Hf = 257.1. Isoquinoline-1-carboxylic acid [(lS,3S,5S)-l-(2-aza-bicyclo[3.1.0]hex-3-yllmetliyll-amide prepared by deprotection of (lS,3S,5S)-3-{[(isoquinoline-l-carbonyI)-amino]-methyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester. LC-MS (acidic): IR = 0.67 min; [M+Hr = 268.1. 2,3-Dihydro-benzofuran-4-carboxylic acid f(lS,3S,5S)-l-(2-aza-bicyclo|3.1.0]hex-3-yl)methyl]-amide prepared by deprotection of (lS.3S,5S)-3-{[(2.3-dihydro-benzofuran-4-carbonyl)-amino]-lTlethyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester. LC-MS (acidic): IR = 0.65 min; [M+Hf = 259.1. N-[(lS,3S,5S)-l-(2-Aza-bicyclo[3.1.0]hex-3-yl)inethyl]-3-bromo-benzamide prepared by deprotection of (lS.3S,5S)-3-[(3-bromo-benzoylamino)-methyl]-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester. LC-MS (acidic): IR = 0.70 min; [M+Hf = 295.0. Quinoline-8-carboxylic acid [(lS,3S,5S)-l-(2-aza-bicyclo[3.1.0]hex-3-yl)inethyl]-amide prepared by deprotection of (lSJS,5S)-3-{[(quinoline-8-carbonyl)-amino]-methy!}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester. LC-MS (acidic): IR = 0.63 min; [M+Hr = 268.1. Benzotd]isoxazole-3-carboxylic acid [(lS,3S,5S)-l-(2-aza-bicyclo[3.1.0]liex-3- yl)methyl]-amide prepared by deprotection of (lS,3S,5S)-3-{[(benzo[d]isoxazole-3-carbonyl)-amino]-methyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester. LC-MS (basic): tR = 0.69min;[M+Hf = 258.1. 2,3-Dihydro-tbienof3,4-b][l,4]dioxine-5-carboxylJc acid [(lS,3S,5S)-l-(2-aza- bicyclo[3.1.0]hex-3-yl)methyl]-ainide prepared by deprotection of (lS.3S.5S)-3-{[(2,3-dihydro-thieno[3,4-b][1.4]dioxine-5-carbonyl)-amino]-methyl}-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester. LC-MS (acidic): tR = 0.63 min; [M+Hf = 281.1. A,18 Synthesis of 2-substituted (lS,3S,5S)-3-aminomethyl-2-aza- bicyclo[3.1.0]hexane derivatives A.18.1 Synthesis of (lS,3S,5S)-3-[(2,2,2-trifluoro-acetylamino)-methyl]-2-aza- bicyclo[3,1.0]hexane-2-carboxylic acid tert-butyl ester At 0°C trifluoroacetic anhydride (13.5 mmol, 1.20eq) is added dropwise to a solution of (]S,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester (11.2 mmol, l.OOeq) and TEA (16.8 mmol, 1.50eq) in DCM (25 mL). After 30 min the mixture is diluted with DCM and washed with water (2x50 mL), sat aqueous NaHCOa solution (50 mL) and water (3x50 mL). The organic layer is dried over Na2S04 and concentrated in vacuo to give a crude oil which is purified by flash chromatography (DCM). LC-MS (acidic): tR = 0.96 min; [M+H]^ = 309.1. A.18.2 Synthesis of N-[(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-2,2,2-trinuoro-acetamide A solution of HCl in dioxane (4 M. 25 mL) is added to a solution of (lS,3S,5S)-3-[(2,2,2-trifluoro-acetylamino)-methyl]-2-aza-bicyclo[3.1 .0]hexane-2-carboxylic acid tert-butyl ester (5.74 mmol) in dioxane (25 mL). After 2h the solvents are removed in vacuo to give the desired product as a white solid which is used without further purification in the next step. LC-MS (acidic): tR = 0.30 min: [M+Hf = 209.0. A.18.3 Synthesis of 2,2,2-trifluoro-N-{(lS,3S,5S)-2-[5-(3-fluoro-phenyI)-2-methyi-thiazoie-4-carbonyl] -2-aza-bicyclo[3.1.0] hex-3-ylmethyI}-acetamide TBTU (3.22 mmol, 1.05eq) is added to a solution of 5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid (3.07 mmol, l.Oeq), N-[(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-yImethyl]-2,2,2-trifluoro-acetamide (3.07 mmol. l.Oeq) and DIPEA (9.20 mmol, 3.0eq) in DCM (15 mL). After 2h the mixture is washed twice with water, once with sat. aqueous NaHCOs solution, once with hydrochloric acid (0.2 M) and three times with water. The organic layer is dried over Na2S04. the solvents are removed in vacuo and the residue is purified by flash chromatography (gradient: DCM to DCM/MeOH 19/1) and preparative TLC (DCM/MeOH 19/1) to give the desired product as an orange foam. LC-MS (acidic): tR = 0.97 min;[M+Hf = 428.1. A.18.4 Synthesis of N-{(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4- carbonyl]-2-aza-bicydo[3.1,0jhex-3-ylmethyl}-2,2,2-trifluoro-acetaniide TBTU (3.22 mmol. 1.05eq) is added to a solution of 2-amino-5-(3-fluoro-phenyl)-thiazole-4-carboxylic acid (3.07 mmol. l.Oeq). N-[(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-2,2,2-trifluoro-acetamide (3.07 mmol, l.Oeq) and DIPEA (9.20 mmol, 3.0eq) in DCM (15 mL) and DMF (3.0 mL). After 2h the mixture is washed twice with water, once with sat. aqueous NaHCOa solution, once with hydrochloric acid (0.2 M) and three times with water. The organic layer is dried over Na2S04, the solvents are removed in vacuo and the residue is purified by preparative TLC (DCM/MeOH 9/1) to give the desired product as an orange foam. LC-MS (acidic): tR = 0.87 min: [M+Hf = 429.1. A.18.5 Synthesis of 2,2,2-trifluoro-N-[(lS,3S,5S)-2-(5-phenyl-thiazoIe-4-carbonyl)-2-aza-bicycIo[3.1.0]hex-3-yImethyIJ-acetamide derivatives (general procedure) TBTU (7.19 mmol, Lleq) is added to a solution of the respective 5-phenyl-thiazole-4-carboxylic acid derivative (7.19 mmol, 1.1 eq) and DIPEA (9.81 mmol. 1.5 eq) in DMF (10 mL). The mixture is stirred for 10 min and treated with a solution of N-[(]S,3S,5S)-2-aza-bicyclof3.1.0]hex-3-ylmethyl]-2,2.2-trifluoro-acetamide (6.54 mmol. l.Oeq) and DIPEA (9.81 mmol, 1.5eq) in DMF (10 mL). After 16h the mixture is diluted with TBME (100 mL) and washed twice with water (50 mL each), twice with hydrochloric acid (0.5 M. 50 mL each) and twice with water (50 mL each). The organic layer is dried over Na2S04 and concentrated in vacuo to give a crude product which is used without further purification. 2,2,2-Trifluoro-N-[(lS,3S,5S)-2-(2-methyI-5-m-tolyI-thiazole-4-carbonyl)-2-aza-bicyclo(3.1.0]hex-3-yIniethyI]-acetaniide prepared by reaction of N-[(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-2,2,2-trif^uoro-acetamide with 2-methyl-5-m-tolyl-thiazole-4-carboxylic acid. LC-MS (acidic): tR = 0.99 min; [M+H]^ = 424.1. N-{(lS,3S,5S)-2-[5-(3-Chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclof3.1.0] hex-3-ylmethyI}-2.2,2-trifluoro-acetamide prepared by reaction of N-[(lS.3S.5S)-2-aza-bicyclo[3.1.0]hex-3-yllnethyl]-2.2.2-trit^uol•o-acetamide with 5-(3-chloro-phenyl)-2-methyl-thiazole-4-carboxylic acid. LC-MS (acidic): tR = 0.99min; [M+H]" - 444.1. N-[(lS,3S,5S)-2-(2-Amino-5-in-tolyl-thiazole-4-carbonyI)-2-aza-bicyclo[3.1.0]hex-3-yImethyI]-2,,2,2-trifluoro-acetamide prepared by reaction of N-[(l S.3S.5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-2,2,2-trifluoro-acetamide with 2-amino-5-iTi-tolyl-thiazole-4-carboxylic acid. LC-MS (acidic): tR = 0.87 min;[M+Hf = 425.1. A.18.6 Synthesis of [(lS,3S,5S)-(3-aminomethyl-2-aza-bicyclo[3.1.01hex-2-yl)l-(5-phenyl-thiazol-4-yl)-methanone derivatives (general procedure) A solution of the respective 2.2,2-trifluoro-N-[(lS,3S,5S)-2-(5-phenyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-acetamide derivative (1.58 mmol) in MeOH (7 mL) is treated with a sat. aqueous K2CO3 solution (7 mL) and stirred at 60°C for 30 min. The mixture is partiaiiy concentrated in vacuo to remove MeOH and extracted four times with DCM. The combined organic layers are dried overNaaSOA and concentrated in vacuo to give the desired product which is used without further purification. |(lS,3S,5S)-3-Aminomethyl-2-aza-bicyc)o[3.1.0]hex-2-yl]-|5-(3-fluoro-phenyI)-2-methyi-tliiazoi-4-yl|-methanone prepared by deprotection of 2,2,2-trifluoro-N-{(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2- methyl-thiazole-4-carbonyl]-2-aza-bicycIo[3.1.0]hex-3-ylmethyl}-acetamide. LC-MS (acidic): tR = 0.71 min; [M+Hf = 332.0. [2-Amino-5-(3-fluoro-phenyI)-thiazoI-4-yIl-((lS,3S,5S)-3-aniinoniethyl-2-aza-bicyclo[3.L0]hex-2-yl)-methanone prepared by deprotection of N-{(lS.3S,5S)-2-[2-aniino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-2,2,2-trifluoro-acetamide. LC-MS (acidic): tR = 0.66 min; [M+H]^ = 333.0. ((1 S,3S;5S)-3-Aminomethyl-2-aza-bicycIo[3.1.0] hex-2-yI)-(2-methyl-5-ni-tolyl-thiazol-4-yl)-methanone prepared by deprotection of 2,2.2-trifluoro-^I-[(lS.3S.5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-acetamide. LC-MS (acidic): tR = 0.72 min;[M+Hf = 328.1. ((lS,3S,5S)-3-Aminoinethyl-2-aza-bicycIo[3.1.0]hex-2-yl)-[5-(3-chloro-phenyl)-2-inethyl-thiazoi-4-yI]-methanone prepared by deprotection of N-{(lS,3S,5S)-2-[5-(3-Chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1 .0]hex-3-ylmethyl}-2,2,2-trifluoro-acetamide. LC-MS (acidic): tR = 0.72 min;[M+Hf = 348.1. A. 18.7 Synthesis of ((1 S,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-(2-ainino-5-in-tolyl-thiazol-4-yl)-methanone A solution of N-[(lS.3S,5S)-2-(2-amino-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-2.2.2-trifluoro-acetamide (2.33 mmol) in MeOH (7.7 mL) is treated with a sat. aqueous K2CO3 solution (0.62 mL) and stirred at 60°C for 5h. After stirring for additional 16h at RT the mixture is made basic by slow addition of aqueous NaOH solution (32%). Equal volumes of TBME and EtOAc are added and the mixture is stirred vigorously for Ih. The layers are separated, the aqueous layer is extracted with a mixture of TBME and EtOAc and the combined organic layers are dried over Na2S04. The solvents are removed in vacuo to give the desired product which is used without further purification. LC-MS (basic): tR = 0.67 min; [M+H]^ = 329.0. A.19 Synthesis of [(lS,3S,5S)-l-(2-aza-bicyclo[3.L0]hex-3-yl)methyl]-(5-bromo- pyrimidin-2-yl)-amine A.19.1 Synthesis of (lS,3S,5S)-3-|(5-bromo-pyrimidin-2-ylamino)-methyi]-2-aza- bicyclo(3.L0]hexane-2-carboxylic acid tert-butyl ester 5-Bromo-2-chloro-pyrimidine (18.4 mmol) is added to a solution of (]S,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester (14.1 mmol) in o-xylene (28 mL). K2CO3 (42.4 mmol) and DIPEA (42.4 mmol) are added and the mixture is heated to 138°C for 16h. The mixture is cooled to RT and filtered. The residue is washed with DCM and the combined filtrates are concentrated in vacuo to give a crude product which is purified by flash chromatography (gradient: heptane/EtOAc 90/10 to 85/15). LC-MS: tR = 1.05 min; [M+Hf = 369.0. A.19.2 Synthesis of [(lS,3S,5S)-l-(2-aza-bicycIo|3.1.0]hex-3-yl)methyll-(5-broino-pyrimidin-2-yl)-ainine A solution of HCI in dioxane (4.0 M. 30 mL) is added to a solution of (lS,3S,5S)-3-[(5-bromo-pyrimidin-2-yIamino)-methyl]-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester (5.40 mmol) in dioxane (30 mL). After 2h the solvents are removed in vacuo to give a crude product which is used without further purification. LC-MS: tR = 0.63 min; [M+Hf = 269.0. B. Preparation of compounds of formula (I): B.l Synthesis of carboxylic amide derivatives (general procedure) Yk—y^i " B To a solution of the respective carboxylic acid (0.033 mmol. 1.2eq) in DMF (0.25 mL) is added successively a solution of DIPEA (0.054 mmol, 2.0eq) in DMF (0.15 mL) and a solution of TBTU (0.033 mmol, 1.2eq) in DMF (0.15 niL). The obtained mixture is treated with a solution of the respective 2-aza-bicyclo[3.1.0]hexane derivative (0.027 mmol. I .Oeq, hydrochloride salt) and DIPEA (0.068 mmol. 2.5eq) in DMF (0.15 mL). The mixture is shaken over night and purified by prep. HPLC to give the respective amide derivative. Example 1 benzofuran-4-carboxylic acid {(lS,3S,5S)-2-[2-methyl-5-(2-trifluoromethyl-phenyl)- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of benzofuran-4-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 2-methyl-5-(2-trifluoromethyl-phenyl)-thiazole-4-carboxylic acid. LC-MS (basic): tR = 1.43 min; [M+Hf = 526.1. Example 2 benzofuran-4-carboxylic acid [(lS,3S,5S)-2-(2-methyl-5-m-tolyl-thiazoIe-4-carbonyl)- 2-aza-bicyclof3.1.01hex-3-yImethyIl-amide prepared by reaction of benzofuran-4-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 2-methyl-5-m-tolyl-thiazole-4-carboxylic acid. LC-MS (basic): tR = 1.42 min; [M+Hf = 472.1. Example 3 benzofuran-4-carboxylic acid {(lS,3S,5S)-2-(5-(3-fluoro-phenyl)-2-methyl-thiazole-4- carbonyl]-2-aza-bicyclo[3.1.0] hex-3-ylmethyl}-amide prepared by reaction of ben2ofuran-4-carboxylic acid [(]S,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid. LC-MS (basic): tR = 1.38 min; [M+H]^ = 476.1. Example 4 benzofuran-4-carboxylJc acid [(lS,3S,5S)-2-(2-amino-5-m-folyl-thiazole-4-carbonyI)- 2-aza-bicyclof 3. LO] hex-3-ylmethyl]-amide prepared by reaction of benzofuran-4-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 2-amino-5-m-tolyl-thiazoie-4-carboxylic acid. LC-MS (basic): tR = 1.33 min;[M+H]* = 473.L Example 5 benzofuran-4-carboxylic acid {(1 S,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4- carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amJde prepared by reaction of benzofuran-4-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-aiTiide with 2-amino-5-(3-fluoro-phenyl)-thiazole-4-carboxylic acid. LC-MS (basic): tR = 1.31 min: [M+H]^ = 477.1. Example 6 benzofuran-4-carboxylic acid {(1 S,3S,5S)-2-[5-(4-fluoro-phenyl)-2-methyl-thiazole-4- carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of benzofuran-4-carboxyiic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-yliTiethyl]-amide with 5-(4-fluoro-pheny))-2-methyl-thiazole-4-carboxylic acid. LC-MS (basic): tR = 1.38 min; [M+H]^ = 476.1. Example 7 benzofuran-4-carboxylic acid [(lS,3S,5S)-2-(2'-fluoro-biphenyl-2-carbonyl)-2-aza- bicyclo[3.1.0]hex-3-yImethyIJ-amide prepared by reaction of benzofuran-4-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 2'-fluoro-biphenyl-2-carboxylic acid. LC-MS (basic): tR = 1.43 min; [M+Hr = 455.1. Example 8 benzofuran-4-carboxylic acid [(lS,3S,5S)-2-(3'-chloro-biphenyl-2-carbonyl)-2-aza- bicyclo[3.1.0]hex-3-ylniethyI]-amide prepared by reaction of benzofuran-4-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 3'-chloro-biphenyl-2-carboxylic acid. LC-MS (basic): ta = 1.46 min;[M-fH]^ = 47Li. Example 9 benzofuran-4-carboxylic acid [(lS,3S,5S)-2-(2-methyl-4-phenyl-pyrimidine-5- carbonyl)-2-aza-bicycIo[3.1.0] hex-3-ylmethyl]-amide prepared by reaction of benzofuran-4-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 2-iTiethyi-4-phenyl-pyrimidine-5-carboxylic acid. LC-MS (basic): tR= L31 min;[M+Hr = 453.2. Example 10 benzofuran-4-carboxylic acid {(1 S,3S,5S)-2-[2-(2-amino-thiazol-4-yl)-benzoyIl-2-aza- bicyclo[3.1.0]hex-3-ylmethyI}-amide prepared by reaction of benzofuran-4-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.L0]hex-3-yhTiethyl]-amide with 2-(2-amino-thiazol-4-yl)-benzoic acid. LC-MS (basic): IR = L28 min;[M+Hf = 458.9. Example 11 6-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid [(lS,3S,5S)-2-(2-methyl-5-m-tolyl- thiazole-4-carbonyl)-2-aza-bicyclof3.1.0]hex-3-ylmethyI]-amide prepared by reaction of 6-methyl-imidazo[2,l-b]thiazole-5-carboxyhc acid [(lS,3S,5S)-2-aza-bicyclo[3.L0]hex-3-ylmethyl]-amide with 2-methyl-5-m-tolyl-thiazole-4-carboxylic acid. LC-MS (basic): tR = 1.33 min; [M+H]" = 492.1. Example 12 6-methyl-imidazo[2,l-b]thiazole-5-carboxy!ic acid [(lS,3S,5S)-2-[5-(3-fluoro-phenyl)- 2-inethyI-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylinethyl}-aniide prepared by reaction of 6-iTiethyl-iiTiidazo[2,l-b]thiazole-5-carboxylic acid [(lS.3S,5S)-2-aza-bicyclo[3.1.0]hex-3-yhTiethyl]-amide with 5-(3,-fluoro-phenyl)-2-methyl-thiazole-4-carboxyiic acid. LC-MS (basic): IR = 1.30 min; [M+Hf = 496.1. Example 13 6-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid [(lS,3S,5S)-2-(2-amino-5-m-tolyl- thiazole-4-carbonyI)-2-aza-bicyclo[3.1.01hex-3-ylmethyIl-amide prepared by reaction of 6-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 2-amino-5-iTi-tolyl-thiazole-4-carboxylic acid. LC-MS (basic): IR = 1.24 min: [M+H]^ = 493.1. Example 14 6-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of 6-methyI-imidazo[2,l-b]thiazoie-5-carboxylic acid [(iS,3S.5S)-2-aza-bicyclo[3.] .0]hex-3-ylmethyl]-amide with 2-amino-5-(3-fIuoro-phenyl)-thiazole-4-carboxylic acid. LC-MS (basic): tR = 1.21 min: [M+Hf = 497.1. Example 15 6-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid {(lS,3S,5S)-2-[5-(4-fluoro-phenyl)- 2-methyl-thiazole-4-carbonyl]-2-aza-bicycIo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of 6-methy!-imidazo[2,l-b]thiazole-5-carboxylic acid [(]S,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid. LC-MS (basic): tR = 1.29 min; [M+Hf = 496.1. Example 16 6-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid [(lS,3S,5S)-2-(2'-fluoro-biphenyl-2- carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylinethyll-amide prepared by reaction of 6-methyl-iiTiidazo[2.l-b]thiazoie-5-carboxyiic acid [(lS,3S,5S)-2-aza-bicyclo[3.].0]hex-3-ylmethyl]-amide with 2'-fluoro-biphenyl-2-carboxylic acid. LC-MS (basic): ta = 1.34 min; [M+H]^ = 475.2. Example 17 6-methyl-imidazo[2,l-blthiazole-5-carboxylic acid f(lS,3S,5S)-2-(3'-chloro-biphenyl- 2-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide prepared by reaction of 6-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid [(lS,3S,5S)-2-aza-bicycio[3.1.0]hex-3-yhTiethyl]-amide with 3'-chloro-biphenyl-2-carboxylic acid. LC-MS (basic): tR = 1.38 min; [M+Hf = 490.9. Example 18 6-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid [(lS,3S,5S)-2-(2-methyl-4-phenyl- pyrimidine-5-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-y!methyI]-amide prepared by reaction of 6-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 2-methyI-4-phenyl-pyrimidine-5-carboxylic acid. LC-MS (basic): tR = 1.19 min: [M+Hf = 473.2. Example 19 6-methyl-imidazo|2,l-b]thiazole-5-carboxylic acid {(lS,3S,5S)-2-l2-(2-amino-thiazol- 4-yl)-benzoyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of 6-methyl-imidazo[2,l-b]thia2ole-5-carboxyiic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 2-(2-amino-thiazol-4-yl)-benzoic acid. LC-MS (basic): tR = 1.16 min; [M+H]^ = 479.1. Example 20 6-mefhyl-imidazof2,l-b]thiazoIe-5-carboxylic acid [(lS,3S,5S)-2-(2-pyrazoH-yI- benzoyI)-2-aza-bicydo[3.1.0]hex-3-ylmethyl]-amide prepared by reaction of 6-methyl-iinidazo[2J-b]thiazoie-5-carboxylic acid [{lS3S,5S)-2-aza-bicyclo[3.].0]hex-3-yliTiethyl]-amide with 2-pyra2ol-l-yl-benzoic acid. LC-MS (basic): IR = ]. 19 min; [M+H]^ = 447.1. Example 21 2,3-dihydro-benzofl,4]dioxine-5-carboxylic acid {{lS,3S,5S)-2-(2-methyl-5-(2- triflluoromefhyJ-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo|3.1.0]hex-3-ylmethyl}- amide prepared by reaction of 2,3-dihydro-benzo[l,4]dioxine-5-carboxyiic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-arnide with 2-melhyl-5-(2-trifluoromethyl-phenyl)-thiazole-4-carboxylic acid. LC-MS (basic): IR = L40 min; [M+H]"" = 544. L Example 22 2,3-dihydro-benzo[l,4]dioxine-5-carboxylic acid [(lS,3S,5S)-2-(2-methyl-5-m-tolyl- thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide prepared by reaction of 2,3-dihydro-benzo[l,4]dioxine-5-carboxyiic acid [(lS.3S,5S)-2-aza-bicyclo[3.LO]hex-3-yhnethyl]-amide with 2-methyl-5-m-tolyl-thiazole-4-carboxylic acid. LC-MS (basic): tR = 1.38 min: [M+Hf = 489.8. Example 23 2,3-dihydro-benzo[l,4]dioxine-5-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2- methyl-thiazoIe-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-yImethyl}-amide prepared by reaction of 2,3-dihydro-benzo[L4]dioxine-5-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.LO]hex-3-ylmethyl]-amide with 5-(3-fluoro-phenyl)-2-methyi-thiazole-4-carboxylic acid. LC-MS (basic): tR = L35 min; [M+Hf = 494.L Example 24 2,3-dihydro-benzo[l,4]dioxine-5-carboxylic acid [(lS,3S,5S)-2-(2-amino-5-m-tolyl- thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]liex-3-ylmethyl]-amide prepared by reaction of 2.3-dihydro-benzo[],4]dioxine-5-carboxylic acid [(]S.3S,5S)-2-aza-bicycio[3.1.0]hex-3-yimethyl]-amide with 2-aiTiino-5-m-toiyl-thiazole-4-carboxyiic acid. LC-MS (basic): U. = 1.30 min: [M+Hf = 491.0. Example 25 2,3-dihydro-benzo[l,4]dioxine-5-carboxyIic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.01hex-3-yimethyl}-amide prepared by reaction of 2,3-dihydro-benzo[L4]dioxine-5-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-yliTiethyl]-amide with 2-amino-5-(3-fIuoro-phenyl)-thiazole-4-carboxylic acid. LC-MS (basic): IR = 1.28 min: [M+H]" = 495.1. Example 26 2,3-dihydro-benzo[l,4]dioxine-5-carboxylic acid {(lS,3S,5S)-2-[5-(4-fluoro-phenyl)-2- methyI-thiazoIe-4-carbonyI]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of 2,3-dihydro-benzo[l,4]dioxine-5-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid. LC-MS (basic): tR = 1.35 min; [M+Hf = 494.1. Example 27 2,3-dihydro-benzo[l,4]dioxine-5-carboxylic acid [(lS,3S,5S)-2-(2'-fluoro-biphenyl-2- carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyll-amide prepared by reaction of 2,3-dihydro-benzo[l,4]dioxine-5-carboxylic acid [(]S.3S,5S)-2-aza-bicycIo[3.1.0]hex-3-ylmethyl]-amide with 2'-fIuoro-biphenyl-2-carboxylic acid. LC-MS (basic): tR - 1.39 min; [M+H]" = 473.1. Example 28 2,3-dihydro-benzo[l,4]dioxine-5-carboxyIic acid ((lS,3S,5S)-2-(3'-chloro-biphenyl-2- carbonyI)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide prepared by reaction of 2.3-dihydro-benzo[l,4]dioxine-5-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-yImethyl]-ainide with 3'-chloro-biphenyl-2-carboxylic acid. LC-MS (basic); XR = 1.43 min; [M+H]^ = 489.0. Example 29 2,3-dihydro-benzo[l,4]dioxine-5-carboxyIic acid [(lS,3S,5S)-2-(2-methyl-4-phenyl- pyrimidine-5-carbonyl)-2-aza-bicycIof3.1.01hex-3-yImethyll-amide prepared by reaction of 2.3-dihydro-benzo[l,4]dioxine-5-carboxylic acid [(lS.3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-aiTiide with 2-methyl-4-phenyl-pyrimidine-5-carboxylic acid. LC-MS (basic); IR = 1.27 min; [M+H]^ = 471.2. Example 30 2,3-dihydro-benzo[l,4]dioxine-5-carboxync acid {(lS,3S,5S)-2-[2-(2-amino-thiazol-4- yl)-benzoyl]-2-aza-bicyclo[3.1.0]hex-3-yimethyl}-amide prepared by reaction of 2,3-dihydro-benzo[l,4]dioxine-5-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyi]-amide with 2-(2-amino-thiazoi-4-yi)-benzoic acid. LC-MS (basic); IR = 1.24 min: [M+H]^ = 477.1. Example 31 2,3-dihydro-benzo[l,4]dioxine-5-carboxylic acid {(lS,3S,5S)-2-[5-(4-methoxy-phenyl)- oxazoIe-4-carbonyl]-2-aza-bicyclo{3.1.0]hex-3-ylmethyI}-amide prepared by reaction of 2,3-dihydro-benzo[1.4]dioxine-5-carboxyIic acid [(lS.3S.5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 5-(4-methoxy-phenyl)-oxazole-4-carboxylic acid. LC-MS (basic); ta = L31 min; [M+H]^ = 476.1. Example 32 3,5-diniethyl-isoxazoIe-4-carboxyUc acid [(1 S,3S,5S)-2-(2-methyl-5-ni-tolyl-thiazole-4- carbonyl)-2-aza-bicyclo[3.1.01hex-3-ylmethyI]-ainide prepared by reaction of 3,5-dimethyl-isoxazole-4-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 2-methyl-5-m-tolyi-thiazole-4-carboxylic acid. LC-MS (basic): tR = 1.35 min; [M+Hf - 451.1. Example 33 3,5-dimethyl-isoxazoIe-4-carboxylic acid [(1 S,3S,5S)-2-(2-amino-5-m-toIyI-tliiazole-4- carbonyl)-2-a2a-bicyclof3.1.0]hex-3-ylmethyl]-amide prepared by reaction of 3,5-diiTiethyi-isoxazole-4-carboxylic acid [(]S,3S.5S)-2-aza-bicyclo[3.].0]hex-3-ylmethyl]-amide with 2-amino-5-m-tolyl-thiazoIe-4-carboxylic acid. LC-MS (basic): ta = 1.26 min; [M+Hf = 452.2. Example 34 3,5-dimethyl-isoxazoIe-4-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyI}-amide prepared by reaction of 3,5-dimethyl-isoxazole-4-carboxylic acid [(lS,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 2-amino-5-(3-fluoro-phenyr)-thiazole-4-carboxylic acid. LC-MS (basic): tR = 1.23 min; [M-^Hf = 456.1. B.2 Synthesis of carboxylic amide derivatives (general procedure II) u A^O A-^O ° B B To a solution of the respective carboxylic acid (0.029 mmoi, I.3eq) in DMF (0.20 mL) is added successively a solution of DIPEA (0.08 mmol, 3.5eq) in DMF (0.15 mL) and a solution of TBTU (0.024 mmol, 1.05eq) in DMF (0.15 mL). The obtained mixture is treated with a solution of the respective 2-aza-bicyclo[3.1.0]hexane derivative (0.023 mmol, 1 .Oeq) in DMF (0.40 mL). The mixture is shaken over night and purified by prep. HPLC to give the respective amide derivatives. Example 35 imidazo[2,l-bJthiazole-5-carboxylic acid {(lS,3S,5S)-2-[5-(3-iluoro-phenyl)-2-metliyl- thiazole-4-carbonyll-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [(lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yi]-[5-(3-fluoro-phenyi)-2-l■n'='thyl-thiazol-4-yl]-lTlethanone with iiTiidazo[2, i-b]thiazoie-5-carboxyiic acid. LC-MS (basic): IR = 0.80 min; [M+H]^ = 482.1. Example 36 l-methyl-lH-indole-3-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl- thiazole-4-carbonyll-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [(lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl]-[5-(3-t1uoro-phenyl)-2-iTiethyl-thiazol-4-yl]-iTiethanone with 1-methyl-l H-indole-3-carboxylic acid. LC-MS (basic): tR = 0.88 min; [M+H]^ = 489.1. Example 37 l-ethyl-3-methyI-lH-pyrazoIe-4-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2- methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-yImethyl}-amide prepared by reaction of [(lS,3S,5S)-3-aminomethyi-2-aza-bicyclo[3.1.0]hex-2-yl]-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone with l-ethyl-3-methyl-lH-pyrazole-4-carboxylic acid. LC-MS (basic): tR = 0.79 min; [M+H]"" = 468.2. Example 38 isoquinoline-1-carboxylic acid {(lS,3S,5S)-2-|5-(3-fluoro-phenyl)-2-methyI-thiazole-4- carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [(lS.3S.5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl]-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone with isoquinoIine-1-carboxylic acid. LC-MS (basic): tR = 0.92 min: [M+H]" = 487.1. Example 39 lH-indazole-3-carboxylic acid {(lS,3S,5S)-2-|5-(3-fluoro-phenyl)-2-methyl-thiazole-4- carbonyl|-2-aza-bicyclo[3.1.0Jhex-3-ylmethyl}-amide prepared by reaction of [(1 S,3S,5S)-3-aminomethyl-2-aza-bicycio[3.i .0]hex-2-yi]-[5-(3-fluoro-phenyl)-2-methyl-thiazoi-4-yl]-methanone with lH-indazole-3-carboxyiic acid. LC-MS (basic): tR = 0.85 min; [M+H]^ = 476.1. Example 40 4-methoxy-quinoIine-2-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl- thiazole-4-carbonyl]-2-aza-bicycIo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [(lS,3S,5S)-3-al■ninomethyl-2-aza-bicyclo[3.1.0]hex-2-yl]-[5-(3-f^lloro-phenyi)-2-l•nethyl-thiazol-4-yl]-methanone with 4-rnethoxy-quinoline-2-carboxyiic acid. LC-MS (basic): tR = 0.96 min; [M+H]* = 517.2. Example 41 quinoline-2-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyI-thiazole-4- carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [(lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl]-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone with quinoline-2-carboxylic acid. LC-MS (basic): IR = 0.93 min; [M+H]* = 487.2. Example 42 6-fluoro-4H-benzo[l,3]dioxine-8-carboxylic acid {(lS,3S,5S)-2-|5-(3-fluoro-phenyl)-2- methyl-thiazole-4-carbonyI]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [(lS,3S.5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl]-[5-(3-fluoro-phenyl)-2-methyI-thiazol-4-yl]-methanone with 6-fluoro-4H-benzo[].3]dioxine-8-carbo.xylic acid. LC-MS (basic): tR = 0.89 min; [M+H]^ = 512.1. Example 43 benzo[l,2,3]thiadiazole-5-carboxync acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyP|-amide prepared by reaction of [(lS.3S.5S)-3-aminoniethyi-2-aza-bicyclo[3.1.0]he\-2-yi]-[5-{3-f^uo^o-phenyl)-2-methyl-thiazol-4-yl]-methanone with benzo[l,2,3]thiadiazole-5-carboxylic acid. LC-MS (basic): tR = 0.88 min; [M+H]^ = 494.1. Example 44 benzofd]isoxazole-3-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [(lS,3S,5S)-3-aminolTlethyl-2-aza-bicyclo[3.1.0]hex-2-yi]-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yi]-methanone with benzo[d]isoxazole-3-carboxylic acid. LC-MS (basic): tR = 0.90 min; [M+H]^ = 477.1. Example 45 2,2-dimethyl-2,3-d>hydro-benzofuran-7-carboxylic acid {(lS,3S,5S)-2-|5-(3-fluoro- phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [(lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl]-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone with 2,2-dimethyl-2,3-dihydro-benzofuran-7-carboxylic acid. LC-MS (basic): IR = 0.96 min; [M+H] = 506.2. Example 46 2,2-difluoro-benzo[l,3]dioxole-4-carboxyIic acid {(lS,3S,5S)-2-|5-(3-fluoro-phenyl)-2- methyl-thiazole-4-carbonyI]-2-aza-bicyclo(3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [(lS,3S,5S)-3-aminomethyi-2-aza-bicyclo[3.L0]hex-2-yl]-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yi]-methanone with 2,2-difluoro-benzo[L3]dioxoIe-4-carboxylic acid. LC-MS (basic): tR = 0.94 min; [M+H]"" = 516.L Example 47 benzo[l,3]dioxoIe-4-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyI)-2-metiiyI- thiazole-4-carbonyI]-2-aza-bicycIof3.1.0]hex-3-ylmethyl}-ainide prepared by reaction of [(lS.3S,5S)-3-aminoinethyl-2-aza-bicyclo[3.1.0]hex-2-yl]-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yl]-iTiethanone with benzo[l ,3]dioxole-4-carboxylic acid. LC-MS (basic): h = 0.87 min; [M+Hf = 480.1. Example 48 2-ethyl-5-methyl-2H-pyrazole-3-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2- methyl-thiazole-4-carbonyll-2-aza-bicycIo[3.1.01hex-3-ylmethyI}-amide prepared by reaction of [(lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl]-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone with 2-ethyl-5-methyl-2H-pyrazole-3-carboxylic acid. LC-MS (basic): IR = 0.85 min; [M+H]"" - 468.2. Example 49 l-methyl-5-trifluoromethyl-lH-pyrazole-4-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro- phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [(lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl]-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone with l-methyl-5-trifluoromethyl-lH-pyrazoie-4-carboxylic acid. LC-MS (basic): tR = 0.85 min; [M+H]"" = 508. L Example 50 2,5-dimethyl-2H-pyrazole-3-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2- methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [(lS,3S,5S)-3-aminomethyi-2-aza-bicyclo[3.L0]hex-2-yl]-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone with 2,5-dimethyl-2H-pyrazole-3-carboxylic acid. LC-MS (basic): tR = 0.82 min; [M+H]^ = 454.2. Example 51 2,3-dihydro-benzofuran-4-carboxylic acid {(lS,3S,5S)-2-[5-(3-fIuoro-phenyl)-2- methyl-thiazole-4-carbonyl)-2-aza-bicyclo|3.1.01hex-3-ylmethyi}-amide prepared by reaction of [(]S,3S,5S)-3-aminolTlethyl-2-aza-bicyclo[3.1.0]hex-2-yl]-[5-(3-f^lloro-phenyl)-2-methyl-thiazoi-4-yl]-n1etha^one with 2,3-dihydro-benzofuran-4-carboxylic acid (WO99/33460). LC-MS (basic): tR = 0.88 min; [M+Hf = 478.1. Example 52 5-fluoro-lH-indole-2-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl- thiazole-4-carbonyl]-2-aza-bicyclof3.1.01hex-3-ylmethyl}-amide prepared by reaction of [(lS.3S,5S)-3-aminolTlethyl-2-aza-bicyclo[3.1.0]hex-2-yl]-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yi]-methanone with 5-fluoro-lH-indole-2-carboxyiic acid. LC-MS (basic): tR = 0.91 min; [M+H]^ = 493.1. Example 53 7-fluoro-lH-indole-2-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyI)-2-methyl- thiazole-4-carbonyl]-2-aza-bicyclof3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [(1 S3S.5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl]-[5-(3-fluoro-phenyl)-2-methyi-thiazol-4-yl]-methanone with 7-fluoro-l H-indole-2-carboxylic acid. LC-MS (basic): tR = 0.92 min; [M+H]^ = 493.1. Example 54 l,2-dimethyl-lH-indole-3-carboxyIicacid {(lS,3S,5S)-2-I5-(3-fluoro-phenyl)-2-methyl- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyI}-amide prepared by reaction of [(]S,3S,5S)-3-aminomethyl-2-aza-bicycIo[3.1.0]hex-2-yl]-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone with 1,2-dimethyl-l H-indole-3-carboxylic acid. LC-MS (basic): tR = 0.90 min; [M+H]* = 503.2. Example 55 3-methyI-imidazo[2,l-b]thiazole-5-carboxylic acid {(lS,3S,5S)-2-[2-aiTiino-5-(3-fluoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicyclof3.1.0]hex-3-ylmethyl}-ainide prepared by reaction of f2-amino-5-(3-fluoro-phenyl)-thiazoI-4-yl]-((lS.3S.5S)-3-am!nomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-metlianone with 3-metiiyi-imidazo[2,l-b]thiazole-5-carboxy)ic acid. LC-MS (basic): IR = 0.76 min; [M+H]" = 497.1. Example 56 2-methyl-imidazof2,l-blthiazole-5-carboxyIic acid {(lS,3S,5S)-2-f2-amino-5-(3-fluoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.01hex-3-ylmethyI}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyi)-thiazoI-4-yl]-((lS,3S,5S)-3-aminoiTiethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with 2-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid. LC-MS (basic): tR = 0.78 min: [M+H]' = 497.1. Example 57 imidazo[2,l-b]thiazole-5-carboxylic acid {(lS,3S,5S)-2-|2-amino-5-(3-fluoro-phenyl)- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fiuoro-phenyl)-thiazol-4-yl]-((lS.3S.5S)-3-aminornethyi-2-aza-bicycio[3,I.0]hex-2-yl)-methanone with imidazo[2.1-b]thiazoIe-5-carboxylic acid. LC-MS (basic): tR = 0.74 min; [M+H]"" = 483.0. Example 58 l-methyl-lH-indole-3-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0jhex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS,3S.5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with 1-methyl-1 H-indo!e-3-carboxylic acid. LC-MS (basic): tR = 0.81 min; [M+H]"" = 489.9. Example 59 3-methyI-imidazo[2,l-bjthiazole-2-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-ainide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-tiiiazol-4-yl]-{(lS.3S.5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with 3-iTiethyl-imidazo[2,l-b]thiazole-2-carboxylic acid. LC-MS (basic): tR - 0.74 min: [M+H]* = 497.2. Example 60 l-ethyl-3-methyl-lH-pyrazole-4-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro- phenyI)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0|liex-3-yImethyI}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yiJ-((IS,3S.5S)-3-aminoiTiethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with 1 -ethyl-3-methyi-l H-pyrazoie-4-carboxy!ic acid. LC-MS (basic): IR = 0.73 min; [M+H]" = 469.2. Example 61 5-/eA-/-butyl-2-methyI-2H-pyrazole-3-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3- fluoro-phenyI)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-ainino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS,3S,5S)-3-aminomethyi-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with 5-/e/-f-butyl-2-methyi-2H-pyrazole-3-carboxylic acid. LC-MS (basic): tR = 0.85 min; [M+H]^ = 497.2. Example 62 quinoline-4-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4- carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-pheny!)-thiazol-4-yl]-((lS.3S.5S)-3-aminomethyl-2-aza-bicycIo[3.1.0]hex-2-yl)-methanone with quinoline-4-carboxylic acid. LC-MS (basic): tR = 0.77 min; [M+Hf = 488.1. Example 63 isoquinoiine-1-carboxyIic acid {(lS,3S,5S)-2-[2-aniino-5-(3-fluoro-phenyl)-thiazole-4- carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yi]-((lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-inethanone with isoquinoline-1-carboxylic acid. LC-MS (basic): IR = 0.84 min; [M+Hf = 488.1. Example 64 quinoline-5-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4- carbonyll-2-aza-bicyclo[3.1.01hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS,3S,5S)-3-aminomethyi-2-aza-bicyclo[3.1.0]hex-2-yl)-iTiethanone with quinoline-5-carboxylic acid. LC-MS (basic): tR = 0.75 min; [M+Hf = 488.2. Example 65 lH-indazole-3-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4- carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS,3S.5S)-3-aminornethyl-2-aza-bicyclo[3.1.0]hex-2-yi)-iTiethanone with 1 H-indazole-3-carboxylic acid. LC-MS (basic): tR = 0.79 min; [M+H]" = 477.1. Example 66 4-methoxy-quinoline-2-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazoi-4-yi]-((lS.3S,5S)-3-aminomethyl-2-aza-bicycio[3.1.0]hex-2-yl)-methanone with 4-methoxy-quinoline-2-carboxylic acid. LC-MS (basic): tR = 0.88 min; [M+Hf = 518.1. Example 67 lH-indole-3-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4- carbonyl]-2-aza-bicycIo[3.1.0]hex-3-ylmethyl}-ainide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazoi-4-yi]-((IS,3S.5S)-3-aminoniethyl-2-aza-bicycIo[3.1.0]hex-2-yl)-methanone with lH-indole-3-carboxylic acid. LC-MS (basic): tR = 0.78 min; [M+Hf = 476.3. Example 68 6-fluoro-4H-benzo[l,3]dioxine-8-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro- phenylHliiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS,3S,5S)-3- aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with 6-fluoro-4H- benzo[K3]dioxine-8-carboxylic acid. LC-MS (basic): tR = 0.82 min; [M+H]^ = 513.2. Example 69 isoquinoline-5-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4- carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS,3S,5S)-3-aminometliyl-2-aza-bicyclo[3.1.0]hex-2-yl)-iTiethanone with isoquinoline-5-carboxyiic acid. LC-MS (basic): tR = 0.74 min; [M+Hf = 488.1. Example 70 3-methyl-5-trifluoromethyl-isoxazole-4-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3- fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyI}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS.3S,5S)-3-aminomethyl-2-aza-bicycio[3.1.0]hex-2-yl)-methanone with 3-methyl-5-trifluoromethyl-isoxazole-4-carboxyiic acid. LC-MS (basic): tR = 0.85 min; [M+H]^ = 510.2. Example 71 benzo[l,2,3Jthiadiazole-5-carboxj'Jic acid {(lS.3S;5S)-2-f2-amino-5-(3-fluoro-phenyl)- thiazole-4-carbonyl]-2-aza-bicycIo[3.1.01hex-3-ylmethyI}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((]S.3S,5S)-3-aiTiinomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with benzo[l,2,3]thiadiazole-5-carboxyiic acid. LC-MS (basic): tR = 0.81 min; [M+Hf = 495.0. Example 72 benzo[d]isoxazole-3-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)- thiazoIe-4-carbonyll-2-aza-bicyclo[3.1.01hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-{(lS,3S,5S)-3-aiTiinomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with benzo[d]isoxazole-3-carboxylic acid. LC-MS (basic): tR = 0.83 min; [M+H]"" = 478.2. Example 73 2,2-dimethyl-2,3-dihydro-benzofuran-7-carboxyIic acid {(lS,3S,5S)-2-[2-amino-5-(3- fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1,0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyi)-thiazol-4-yl]-((lS,3S,5S)-3-aminomethyi-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with 2,2-diniethyl-2,3-dihydro-benzofuran-7-carboxyIic acid. LC-MS (basic): tR ~ 0.87 min; [M+H]^ = 507.2. Example 74 2,2-difluoro-benzo[l,3]dioxole-4-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS,3S,5S)-3- aminomethyl-2-aza-bicyclo[3.L0]hex-2-yl)-methanone with 2,2-difluoro- benzo[ 1,3]dioxole-4-carboxylic acid. LC-MS (basic): tR = 0.86 min; [M+H]"" = 517. L Example 75 benzol l,3]dioxole-4-carboxyiic acid {(lS,3S,5S)-2-[2-ainino-5-(3-fluoro-phenyI)- thiazole-4-carbonyl]-2-aza-bicycIo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fliioro-phenyl)-thiazol-4-yl]-((lS,3S,5S)-3-aminomethy!-2-aza-bicyclo[3.1.0]hex-2-yl)-metlianone with benzo[l,3]dioxoIe-4-carboxylic acid. LC-MS (basic): IR = 0.80 min; [M+Hf = 48] .1. Example 76 2-ethyl-5-methyl-2H-pyrazole-3-carboxylic acid {(lS,3S,5S)-2-|2-amino-5-(3-fluoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicycio[3.1.01hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with 2-ethyl-5-methyl-2H-pyrazoie-3-carboxyiic acid. LC-MS (basic): IR = 0.78 min; [M+H]"" = 469.2. Example 77 2-methyl-2H-indazole-3-carboxylic acid {{lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with 2-methyl-2H-indazoie-3-carboxylic acid. LC-MS (basic): tR = 0.80 min; [M+H]^ = 491.0. Example 78 l-methyl-5-trifluoromethyi-lH-pyrazole-4-carboxylic acid {(lS,3S,5S)-2-[2-amino-5- (3-fluoro-phenyI)-thiazoIe-4-carbonyI]-2-aza-bicyclo[3.1.0]hex-3-yImethyI}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS,3S.5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-y])-methanone with 1 -methyl-5-trifluoromethyl-lH-pyrazole-4-carboxylic acid. LC-MS (basic): tR = 0.79 min; [M+H]^ = 509.2. Example 79 l,3.5-trimethyl-lH-pyrazole-4-carboxyIic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro- phenyl)-thiazole-4-carbonyll-2-aza-bicyclof3.1.0]hex-3-ylniethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-ptienyI)-thiazol-4-yl]-((lS.3S.5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]'nex-2-yl)-iTiethanone with 1,3,5-trimethyl-lH-pyrazole-4-carboxyiic acid. LC-MS (basic): IR = 0.71 min; [M+H]^ = 469.2. Example 80 2,5-dimethyl-2H-pyrazole-3-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo(3.1.0]hex-3-yImethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazoi-4-yl]-((lS,3S,5S)-3-aminoiTiethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-metlianone with 2,5-diinethyl-2H-pyrazole-3-carboxylic acid. LC-MS (basic): tR = 0.75 min; [M+H]"" = 455.2. Example 81 2,5-dimethyl-oxazole-4-carboxync acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0] hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]liex-2-yl)-methanone with 2,5-dimethyl-oxazole-4-carboxyh'c acid. LC-MS (basic): IR = 0.78 min; [M+H]^ = 456.1. Example 82 4-methyl-thiazole-5-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)- thiazole-4-carbonyl]-2-aza-bicyclo(3.1.0] hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS,3S,5S)-3-aminomethyI-2-aza-bicycio[3.1.0]hex-2-yl)-methanone with 4-methyl-thiazoie-5-carboxyjic acid. LC-MS (basic): tR = 0.73 min; [M+H]"" = 457.8. Example 83 2,3-dihydro-benzofuraii-4-carboxylic acid {(lS,3S,5S)-2-[2-aniino-5-(3-fluoro-phenyl)- thiazole-4-carbonyI]-2-aza-bicyclo[3.1.0]hex-3-ylmethyi}-amide prepared by reaction of [2-amino-5-{3-f!iioro-plienyl)-thiazoi-4-y]]-((lS.3S.5S)-3-aminomethyl-2-aza-bicycio[3.1.0]hex-2-yl)-methanone witli 2,3-dihydro-benzofuran-4-carboxylic acid. LC-MS (basic): tR = 0.81 min; [M+H]"" = 479.2. Example 84 l,3-dimethyl-lH-pyrazole-4-carboxylic acid {(lS.3S,5S)-2-[2-amino-5-(3-fluoro- phenyI)-thiazole-4-carbonyI]-2-aza-bieyclof3.1.0|hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-plienyr)-thiazoi-4-yl]-((lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]liex-2-yl)-metlianone with ],3-dimethyl-lH-pyrazoie-4-carboxylic acid. LC-MS (basic): tR = 0.71 min; [M+H]"" = 455.2. Example 85 5-ethyl-3-methyl-isoxazole-4-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro- phenyl)-thiazole-4-carbonyll-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS,3S,5S)-3-aminomethyl-2-aza-bicycIo[3.1.0]hex-2-yl)-methanone with 5-ethyl-3-iTiethyi-isoxazole-4-carboxylic acid. LC-MS (basic): tR = 0.80 min; [M+H]^ = 470.1. Example 86 l,2-dimethyl-lH-indole-3-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)- thiazole-4-carbonyl|-2-aza-bicycIo(3.1.01hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazoI-4-yl]-((lS.3S.5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with 1,2-dimethyl-1 H-indole-3-carboxylic acid. LC-MS (basic): tR = 0.83 min; [M+H]"" = 504.2. Example 87 N-{(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazoIe-4-carbonyll-2-aza- bicyclof3.1.0)hex-3-yImethyl}-2,3-dimethyl-benzamide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazoi-4-yl]-((lS.3S.5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with 2.3-dimethyl-benzoic acid. LC-MS (basic): IR = 0.83 min; [M+H]^ = 465.2. Example 88 quinoline-8-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4- carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-tluoro-phenyl)-thiazol-4-yl]-((lS.3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yi)-methanone with quinoiine-8-carboxylic acid. LC-MS (basic): tR = 0.82 min; [M+Hf = 488.2. Example 89 5-fluoro-l-methyl-lH-indole-2-carboxylic acid {(lS,3S,SS)-2-[2-amino-5-(3-fluoro- phenyl)-thiazoIe-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((lS.3S.5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with 5-fIuoro-l-methyl-lH-indoie-2-carboxylic acid. LC-MS (basic): tR = 0.88 min: [M-HH]^ = 508.L Examples 90-176: The following examples are prepared in analogy by coupling of the respective 2-aza-bicyclo[3.1 .OJhexane derivative with the respective carboxylic acid derivative. Starting from ((lS.3S.5S)-3-aminomethyi-2-aza-bicyclo[3.1.0]hex-2-yi)-(2-methyl-5-m-tolyl-thiazol-4-yl)-methanone: mixture is stirred for 30 min and purified by prep. HPLC to give the desored product. LC-.MS (acidic): tR = 1.06 min; [M+H]"" = 523.0. B.5 Synthesis of benzothiazole-4-carboxylic acid [(lS,3S,5S)-2-(2-inethyl-5-in-tolyi-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0)hex-3-ylmethyl]-amide (Example 248) 2-Chloro-benzothiazole-4-carboxylic acid [{] S.3S.5S)-2-(2-meti^yl-5-m-toly)-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]l^ex-3-ylmethyl]-amide (4.2 mg) is added to a suspension of Pd/C (10%. 10.0 mg) in MeOH (1.0 mL). The mixture is stirred at RT under a hydrogen atmosphere (1 bar) for 3h. After filtration through celite and washing with MeOH the solvents are removed in vacuo to give the desired product. LC-MS (acidic): tR = 1.01 min; [M+Hf = 489.1. B.6 Synthesis of carboxylic amide derivatives (general procedure IV) To a solution of the respective carboxylic acid (0.41 mmol. l.leq) in DMF (1.0 mL) is added successively TBTU (0.44 mmol, 1.2eq) and, after 45 min. DIPEA (1.48 mmol. 4.0eq). After 30 min the obtained mixture is treated with a solution of [(lS,3S,5S)-l-(2-aza-bicyclo[3.1.0]hex-3-yI)methyl]-(5-bromo-pyrimidin-2-yl)-amine (0.37 mmol. l.Oeq, hydrochloride salt) in DMF (1.0 mL). The mixture is stirred over night and purified by prep. HPLC to give the respective amide derivative. \ \ LC-MS I Example I Name —; 1—}—. ; i... . ,,-:^! ! ^ , eluent IIR [mm] [M+H] ; i .J . \ i j \ 249 i{(lS,3S,5S)-3-[(5-Bromo-pyrimidin-2- 'acidic \ 1.08 ' 503.8 I i : ; i i I lylamino)-methyl]-2-aza-bicycio[3.1.0]hex-2- i i yl}-[5-(3-chloro-phenyl)-2-methyl-thiazol-4-yl]- i i methanone \ ^ i I I 250 {(1 S.3S.5S)-3-[(5-Bromo-pyrimidin-2- :ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2- |yl}-[5-(3-fluoro-phenyl)-2-methyl-thiazol-4-yl]- methanone 251 {{lS.3S.5S)-3-[(5-Bromo-pyrimidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2-yl}-f5-(4-fluoro-phenyl)-2-iTiethyl-thiazol-4-yl]-methanone acidic 1 1.05 | 487.9 j 487.9 1.05 acidic 252 i{(lS.3S,5S)-3-[(5-Bromo-pyrimidin-2- iylamino)-i'nethyl]-2-aza-bicyclo[3.1.01hex-2- yl}-(2-methyl-5-m-tolyl-thiazol-4-yl)- methanone i acidic .08 483.9 I 253 {(lS,3S,5S)-3-[(5-Bromo-pyrimidin-2- ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2- yl}-[2-methyl-5-(3-trifIuoromethyl-phenyi)- thiazol-4-yl]-methanone 254 [5-(4-Bromo-phenyl)-2-methyl-thiazoI-4-yl]-{(]S,3S,5S)-3-[(5-bromo-pyrii'nidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2-yI} -methanone acidic acidic .09 1.09 537.8 547.7 255 j{(lS,3S,5S)-3-[(5-Bromo-pyrimidin-2- Vlamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2- yl}-[5-(3,5-dimethyl-phenyl)-2-methyl-thiazol- 4-yl]-methanone acidic i 1.12 497.9 256 {(1 S,3S,5S)-3-[(5-Bromo-pyrimidin-2-i !yiamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2- |yl} -[5-(2,3-dimethyl-phenyl)-2-methy 1-thiazol- i |4-yl]-methanone acidic .09 497.9 257 {{lSJS,5S)-3-[(5-Bromo-pyrimidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2-yl}-[5-(2,3-dichloro-pheny!)-2-methyl-thiazol-4-yl]-methanone acidic 1.10 537.7 258 [5-(3-BroiTio-4-fIuoro-phenyl)-2-met!iyl-thiazol-j acidic 4-yl]-{(!S.3S.5S)-3-[(5-bromo-pyrimidin-2- ^ |ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2- j yi}-methanone 1.09 565.7 259 {(lS,3S,5S)-3-[(5-Bromo-pyriiTiidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2-yl}-[5-(3,4-difluoro-phenyl)-2-methyl-thiazol-4-lylj-methanone acidic 1.06 505.9 260 (1 S.3S,5S)-3-[(5-BroiTio-pyriiTiidin-2-iylamino)-methyil-2-aza-bicycIo[3.1 .G]hex-2-yl}-[5-(3,4-dichloro-phenyi)-2-methyl-thiazol-4-yl]-methanone acidic ' 1.11 537.7 261 acidic 1.11 497.9 {(lS,3S,5S)-3-[(5-Bromo-pyrimidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2-yr}-[5-(3,4-dimethyl-phenyl)-2-methyl-thiazol 4-yl]-methanone acidic 0.94 526.8 262 N-[3-(4-{(lS,3S,5S)-3-[(5-BroiTio-pyrimidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hexane-2-carbonyl}-2-methyl-thiazol-5-yl)-phenyl]-acetamide 1 263 {(1 S,3S,5S)-3-[(5-Bromo-pyrimidin-2- yIamino)-methyl]-2-aza-bicyclof3.1.0]hex-2- yl}-[5-(2-chloro-6-fluoro-phenyl)-2-methyl- thiazol-4-yl]-methanone acidic 1.06 521.8 264 {(lS,3S,5S)-3-[(5-Bromo-pyrimidin-2-ylamino)-rnethyl]-2-aza-bicyc]o[3.1.0]hex-2- acidic 1.04 469.9 yl}-(2-methyl-5-phenyl-thiazol-4-yl)-methanone! 265 {(1 S,3S,5S)-3-[(5-Bromo-pyrimidin-2- acidic 1.09 495.9 ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2- j yl}-(2-cyclopropyl-5-phenyl-thiazol-4-yl)-methanone 266 {(lS.3S.5S)-3-[(5-Bromo-pyrimidin-2- > laiTiino)-methyi]-2-aza-bicycio[3.1.0]hex-2- 'Yi)-[5-(3-chloro-phenyl)-thiazol-4-yl]- {(lS,3S.5S)-3 [(5-Bromo-pyrimidin-2-yIamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2-yI}-[5-(3-trifluoromethyl-phenyl)-thiazol-4-yl]-methanone methanone {(1 S,3S.5S)-3-[(5-BroiTio-pyrimidin-2-y!amino)-methyll-2-aza-bicyclof3.1,0]he>i-2-yl}-[5-(3-methoxy-phenyl)-thiazol-4-yI]-methanone 269 {(lS,3S,5S)-3-[(5-Bromo-pyrimidin-2-yIamino)-methyl]-2-aza-bicycIo[3.1.0]hex-2- acidic .02 473.9 1 yl}-[5-(4-fluoro-phenyl)-thiazol-4-yl]- methanone i [ 270 {(lS,3S,5S)-3-[(5-Bromo-pyrimidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2-yl}-[5-(3-fluoro-4-methyl-phenyl)-2-methyl-th i azoI-4-y 1] -methanone acidic 1.09 501.9 271 {(I S,3S,5S)-3-[(5-Bromo-pyrimidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2- acidic l.IO i I 555.8 yl}-[5-(3-fluoro-5-trifluoromethyl-phenyl)-2-methyl-thiazol-4-yl]-methanone 272 {(lS,3S,5S)-3-[(5-Bromo-pyrimidin-2- ylamino)-methyI]-2-aza-bicyclo[3.1.0]hex-2- yl}-[2-cyclopropyl-5-(3-fluoro-4-methyl- acidic 1.14 527.8 1 phenyl)-thiazoi-4-yl]-methanone | I 273 {(lSJS,5S)-3-[(5-Bromo-pyrimidin-2- j acidic ylaiTiino)-methyl]-2-aza-bicyc!o[3.1.0]hex-2- j 1.10 513.8 yl}-[2-cyclopropyl-5-(3-fiuoro-phenyl)-thiazol-4-yl]-methanone B.7 Synthesis of 2-amino-pyrimidine derivatives (general procedure V) H ^^NH2 .^^t^^ A-^O A-^O B B A solution of ((lS,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-(2-methyl-5-m-tolyl-thiazol-4-yl)-methanone (0.34 mmol) in a mixture of o-xylene (1.0 mL) and DCM (0.4 mL) is added to the respective pyrimidine derivative (0.44 mmol). The mixture is heated in an open vial to 67°C to remove DCM. cooled to 30°C and treated successively with K:CO-, {L02 mmol) and DIPEA 1.02 mmol). The mixture is stirred at HOT for 16h. filtered and purified by prep. HPLC to give the respective product. Example Name LC-MS eluent tR[min] [M+Hf 274 (2-Methyl-5-m-tolyl-thiazol-4-yl)-{( 1 S,3S,5S)-3-[(4-trifluoromethyl-pyrimidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2-yl}-methanone acidic 1.10 474.0 275 4-Amino-2-{[(]S,3S,5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethy!]-amino}-pyrimidine-5-carbonitrile acidic 0.87 446.0 276 {(lS.3S.5S)-3-[(4.6-Dimethoxy-pyrimidin-2- acidic 1.00 466.0 ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2- yl}-(2-methyl-5-m-tolyl-thiazol-4-yl)- methanone 277 {(lS.3S,5S)-3-[(5-Ethyl-pyrimidin-2-ylamino)-methy l]-2-aza-bicyclo[3.1.0]hex-2-y 1} -(2-methyl-5-m-tolyl-thia2ol-4-yl)-methanone acidic 0.91 434.0 B.8 Synthesis of carboxylic amide derivatives (general procedure II) B A-^O O B The following examples are synthesised according to general procedure II starting from ((]S,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.].0]hex-2-yl)-(2-amino-5-m-tolyI-thiazol-4-yl)-methanone and the respective carboxylic acid. 1+ 1 Example! Name LC-MS eluent itR [min] [M+H] 0.85 278 Benzo[d]isothiazole-3-carboxylic acid [(1 S,3S,5S)-2-(2-amino-5-m-tolyl-thiazole-4- carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]- amide 279 Benzooxazole-4-carboxylic acid [(1 S,3S,5S)-2-!(2-amino-5-m-tolyl-thiazole-4-carbonyl)-2-aza-jbicyclo[3.1.0]hex-3-ylmethyl]-amide acidic i 0.92 acidic 490.1 i 474.1 II-Biological assays In vitro assay The orexin receptor antagonistic activity of the compounds of formula (I) is determined in accordance with the following experimental method. Experimental method: Intracellular calcium measurements: Chinese hamster ovary (CHO) cells expressing the human orexin-1 receptor and the human orexin-2 receptor, respectively, are grown in culture medium (Ham F-12 with L-Glutamine) containing 300 \iglxn\ G418, 100 U/ml penicillin, 100 (.tg/ml streptomycin and 10 % inactivated fetal calf serum (FCS). The cells are seeded at SO'OOO cells / well into 96-well black clear bottom sterile plates (Costar) which have been precoated with 1% gelatine in Hanks" Balanced Salt Solution (BBSS). All reagents are from Gibco BRL. The seeded plates are incubated overnight at 37°C in 5% CO2. Human orexin-A as an agonist is prepared as I mM stock solution in MeOH: water (1:1). diluted in HBSS containing 0.1 % bovine serum albumin (BSA) and 2 mM HEPES for use in the assay at a final concentration of 10 nM. Antagonists are prepared as 10 mM stock solution in DMSO. then diluted in 96-well plates, first in DMSO, then in HBSS containing 0.1 % bovine serum albumin (BSA) and 2 mM HEPES. On the day of the assay, 100 |j.l of loading medium (HBSS containing 1% PCS. 2 mM HEPES, 5 mM probenecid (Sigma) and 3 |j.M of the fluorescent calcium indicator fluo-3 AM (I mM stock solution in DMSO with 10% pluronic acid) (Molecular Probes) is added to each well. The 96-well plates are incubated for 60 min at 37° C in 5% COi. The loading solution is then aspirated and cells are washed 3 times with 200 |j.l HBSS containing 2.5 mM probenecid, 0.1% BSA, 2 mM HEPES. 100 |al of that same buffer is left in each well. Within the Fluorescent Imaging Plate Reader (FLIPR, Molecular Devices), antagonists are added to the plate in a volume of 50 |^l, incubated for 20 min and finally 100 \x\ of agonist is added. Fluorescence is measured for each well at 1 second intervals, and the height of each fluorescence peak is compared to the height of the fluorescence peak induced by 10 nM orexin-A with buffer in place of antagonist. For each antagonist, IC50 value (the concentration of compound needed to inhibit 50 % of the agonistic response) is determined. Antagonistic activities (IC50 values) of all exemplified compounds are below 1000 nM with respect to the OXi and/or the OX2 receptor. Antagonistic activities (1C50 values) of 269 exemplified compounds are in the range of 4-8665 nM with an average of 450 nM with respect to the OXl receptor. IC50 values of 277 exemplified compounds are in the range of 6-7630 nM with an average of 397 nM with respect to the 0X2 receptor. Antagonistic acfivities of selected compounds are displayed in Table 1. Compound of Example OX, ICso (nM) 0X2IC50 (nM) 8 45 78 11 7 24 17 15 60 25 80 14 33 129 94 38 104 358 57 12 11 93 14 40 99 42 15 101 42 57 123 1980 74 130 76 129 147 51 74 163 62 57 176 45 57 192 no 35 199 139 41 208 58 34 212 109 102 230 13 100 235 88 452 246 20 44 255 37 291 259 62 145 265 131 68 274 110 98 277 42 154 .— ,— — Table 1 WE CLAIM: 1. A compound of formula (1) wherein A represents aryl or heterocyclyl, wherein the aryl or heterocyclyl is unsubstituted or independently mono- or di-substituted, wherein the substituents are independently selected from the group consisting of (C1-4)alkyl. (C3.6)cycioa!kyl, (C2-6)alkinyl. (C1-4)alkoxy. NR~R3. halogen and unsubstituted or independently mono- or di-substituted phenyl or pyridyl, wherein the substituents are independently selected from the group consisting of (Ci-4)alkyl, {C1-4)alkoxy, trifluoromethyl, trifluoromethoxy, fluorine and chlorine; B represents an aryl- or heterocyclyl-group, wherein the aryl or heterocyclyl is unsubstituted or independently mono-, di-, or tri-substituted, wherein the substituents are independently selected from the group consisting of (C1-4)alkyK (C1-4)alkoxy, trifluoromethyl, -NR-R^ -NHS02-(C,.4)alkyl. -N(R')C(0)R^ and halogen: n represents the integer 0 or 1; R' represents aryl or heterocyclyl, wherein the aryl or heterocyclyl is unsubstituted or independently mono-, di-. or tri-substituted wherein the substituents are independently selected from the group consisting of (CM)alkyl. (C|.4)alkoxy, halogen, trifluoromethyl, (C,4)alkyl-thio, (C2^)alkinyl and -NR2R3; or R1 represents a 2,3-dihydrCo-benzofuranyl-, a benzo[l,3]dioxolyl-, a 2,3-dihydro-benzo[l,4]dioxinyl-, a 4H-benzo[l,3]dioxinyl-, a 2H-chromenyl. a chromanyl-, a 2,3-dihydro-thieno[3.4-b][l,4]dioxinyl-, a 3,4-dihydro-2H-benzo[1.4]oxazinyl-, or a 4-morpholino-phenyl-group wherein said groups are unsubstituted or mono- or di-substituted wherein the substituents are independently selected from the group consisting of (CM)alkyl. (C1-4)alkoxy and halogen; R" represents hydrogen or (C1-4)alkyl; and R3 represents hydrogen or (1-4)alkyl; or a pharmaceulically acceptable salt of such a compound. 2. A compound of formula (1) according to claim 1. which is also a compound of formula (la), wherein the stereogenic centers are in absolute (lS.3S,5S)-configuration or a pharmaceutically acceptable salt of such a compound. 3. A compound according to any one of claims 1 to 2, wherein n represents the integer 1; or a pharmaceutically acceptable salt of such a compound. 4. A compound according to any one of claims 1 to 3, wherein A represents 5- to 6-membered monocyclic heterocyclyl. wherein the heterocyclyl is unsubstituted or mono- or di-substituted wherein the substituents are independently selected from the group consisting of (Ci-4)alkyl, (C3.6)cycloalkyl, (Ci.4)alkoxy and NR'R^ or a pharmaceutically acceptable salt of such a compound. 5. A compound according to any one of claims 1 to 4. wherein B represents aryl. wherein the aryl is unsubstituted or mono-, di-. or tri-substituted, wherein the substituents are independently selected from the group consisting of (Ci4)alkyl. (Ci.4)alkoxy. trifluoromethyl, -NHS02-(Ci.4)alkyl, -N(R-)C(0)r and halogen: or a pharmaceutically acceptable salt of such a compound. 6. A compound according to any one of claims 1 to 5. wherein R1 represents aryl or heterocyclyl, wherein the aryl or heterocyclyl is unsubstituted or independently mono-, di-, or tri-substituted, wherein the substituents are independently selected from the group consisting of {C1-4)alkyl, (Ci.4)alkoxy, halogen and trifluoromethyl; or R' represents a 2,3-dihydro-benzofuranyl-, a benzo[l,3]dioxolyl-, a 2,3-dihydro-benzo[l,4]dioxinyl-, a 4//-benzo[l,3]dioxinyl-, a 2//-chromenyl, a chromanyl-, a 2.3-dihydro-thieno[3,4-b][l,4]dioxinyl-. or a 3.4-dihydro-2//-benzo[l,4]oxazinyl-group wherein said groups are unsubstituted or mono- or di-substituted, wherein the substituents are independently selected from the group consisting of (C|.4)alkyl, (Ci_>)alkoxy and halogen; or a pharmaceutically acceptable salt of such a compound. 7. A compound according to any one of claims 1 to 6, wherein R' represents heterocyclyl, wherein the heterocyclyl is unsubstituted or mono-, di-, or tri- substituted. wherein the substituents are independently selected from the group consisting of (Ci.4)alkyi, (C|.4)alkoxy, halogen and trifluoromethyl; or R represents a 2,3-dihydro-benzofurany!-, a 2.3-dihydro-benzo[].4]dioxinyl-, a 2//-chromenyl. a chromanyl-. a 2,3-dihydro-thieno[3,4-b][1.4]dioxinyl-, or a 3.4-dihydro- 2//-benzo[!,4]oxazinyl-group, wherein said groups are unsubstituted or mono- or di- substituted wherein the substituents are independently selected from the group consisting of (Ci-4)alkyl, (Ci.4)alkoxy and halogen; or a pharmaceutically acceptable salt of such a compound. 8. A compound according to any one of claims I to 7, wherein, in case R' represents heterocyclyl, said heterocyclyl is selected from oxazolyl, isoxazolyl. thiazolyl. pyrazolyl, indolyl, benzofuranyl, benzothiophenyl, indazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzoisothiazolyl, benzothiadiazolyl, quinolinyl, isoquinolinyl, pyrrolo[2,]-b]thiazoly!, imidazo[l,2-a]pyridyl and imidazo[2,l-b]thiazolyl, wherein said heterocyclyl is unsubstituted or mono-, di-, or tri-substituted, wherein the substituents are independently selected from the group consisting of (C|.4)alkyi. (C|_t)alkoxy. halogen and trifluoromethyl; or a pharmaceutically acceptable salt of such a compound. 9. A compound according to any one of claims 1 to 8 selected from the group consisting of: benzofuran-4-carboxylic acid {(] S,3S,5S)-2-[2-methyl-5-(2-trifluoromethyl-phenyl)- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; benzofuran-4-carboxylic acid [(1 S,3S,5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbonyl)-2- aza-bicyclo[3.].0]hex-3-ylmethyl]-amide; benzofuran-4-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl-thiazole-4- carbonyl]-2-aza-bicyclo[3.].0]hex-3-ylmethyl}-amide; benzofuran-4-carboxylic acid [(1 S,3S,5S)-2-(2-amino-5-m-tolyl-thiazole-4-carbonyl)-2- aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; benzofuran-4-carboxylic acid {(1 S.3S.5S)-2-[2-amino-5-{3-fluoro-phenyl)-thiazole-4-cal•bon>l]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide: benzofuran-4-carboxylic acid {(lS,3S.5S)-2-[5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carbonyi]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; benzofurar)-4-carboxylic acid [(lS,3S,5S)-2-(2'-fluoro-biphenyl-2-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-y)iTiethyl]-amide; benzofuran-4-carboxylic acid [(1 S.3S,5S)-2-(3'-chloro-biphenyl-2-carbonyl)-2-aza-bicyclo[3.1 .0]hex-3-ylmethyl]-amide; benzofuran-4-carboxylic acid [(1 S,3S,5S)-2-(2-methyl-4-phenyl-pyrilnidine-5-carbonyl)-2-aza-bicyclo[3.1 .0]hex-3-yimethyI]-amide; benzofuran-4-carboxylic acid {(1 S,3S,5S)-2-[2-(2-amino-thiazol-4-yi)-benzoyi]-2-aza-bicyclo[3.1.0]hex-3-ylmethyi}-amide; 6-methyl-imidazo[2,I-b]tiiiazole-5-carboxyIic acid [(IS,3S,5S)-2-(2-metiiyl-5-m-toiyl-thiazole-4-carbonyl)-2-aza-bicycio[3.1.0]iT[ex-3-ylmethyi]-amide; 6-methyl-imidazo[2, l-b]thiazole-5-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2-iTiethyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 6-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid [(lS,3S,5S)-2-(2-amino-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 6-methyl-imidazo[2,]-b]thiazole-5-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 6-methyl-imidazo[2,1 -b]thiazole-5-carboxylic acid {(1 S,3S.5S)-2-[5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicycIo[3.1.0]hex-3-ylmethyl}-amide; 6-methyi-imidazo[2.1 -b]thiazole-5-carboxylic acid [(1 S.3S.5S)-2-(2'-tluoro-bipheny 1-2-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 6-methyi-imidazo[2.1-b]thiazole-5-carboxylic acid [(lS,3S.5S)-2-{3'-chloro-biphenyl-2-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 6-methyl-imidazo[2,l-b]thiazole-5-carboxylicacid [(]S,3S,5S)-2-(2-methyl-4-phenyl-pyrimidine-5-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 6-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid {(lS,3S.5S)-2-[2-(2-amino-thiazol-4-yl)-benzoyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 6-methyl-imidazo[2,]-b]thiazole-5-carboxylic acid [(lS,3S,5S)-2-(2-pyrazol-l-yi-benzoyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 2.3-dih\dro-benzo[ 1.4]dioxine-5-carboxyiic acid {{1 S.3S.5S)-2-[2-inethyi-5-(2-trifluoromethyl-phenyi)-tliiazole-4-carbonyt]-2-aza-bicyclo[3.1.0]hex-3-yliTiethyl}-amide: 2.3-dihydro-benzo[1.4]dioxine-5-carboxy!ic acid [(IS.3S.5S)-2-(2-metliyl-5-m-tolyl-thiazole-4-carbonyi)-2-aza-bicyclo[3.1.0]liex-3-ylmethyl]-amide; 2,3-dihydro-benzo[l,4]dioxine-5-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2,3-dihydro-benzo[l ,4]dioxine-5-carboxylic acid [(1 S,3S,5S)-2-(2-amino-5-m-tolyl-ti^iazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 2,3-diliydro-benzo[l,4]dioxine-5-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2.3-dihydro-benzo[l,4]dioxine-5-carboxylic acid {(lS,3S.5S)-2-[5-(4-fluoro-phenyl)-2-methyi-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2,3-dihydro-benzo[l,4]dioxine-5-carboxylic acid [(1 S,3S,5S)-2-(2'-fluoro-biphenyl-2-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 2,3-dihydro-benzo[1.4]dioxine-5-carboxylic acid [(lS,3S,5S)-2-(3'-chloro-biphenyl-2-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 2,3-dihydro-benzo[l,4]dioxine-5-carboxylic acid [(1 S,3S,5S)-2-(2-methyl-4-phenyl-pyrimidine-5-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 2,3-dihydro-benzo[l,4]dioxine-5-carboxylic acid {(lS,3S,5S)-2-[2-(2-amino-thiazol-4-yl)-benzoyl]-2-aza-bicyclo[3.1.0]hex-3-yImethyi}-amide; 2,3-dihydro-benzo[l ,4]dioxine-5-carboxylic acid {(1 S.3S,5S)-2-[5-(4-methoxy-phenyl)-oxazole-4-carbony i]-2-aza-bicyclo[3.1.0]hex-3-y Imethyl}-am ide: 3.5-dimethyl-isoxazole-4-carboxylic acid [(1 S,3S.5S)-2-(2-methyl-5-m-tolyl-tiiiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 3,5-dimethyl-isoxazole-4-carboxylic acid [(lS,3S,5S)-2-(2-amino-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 3,5-dimethyl-isoxazole-4-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-y!methyl}-amide; imidazo[2,l-b]thiazole-5-carboxylic acid {(lS,3S,5S)-2-[5-(3-fluoro-phenyI)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyi}-amide: 1-methyl-1 H-indoie-3-carboxylic acid {(lS,3S,5S)-2-[5-(3-fIuoro-phenyi)-2-methyl-tiiiazoie-4-carbonyi]-2-aza-bicycIo[3.1.0]hex-3-yimethyi}-amide: 1 -eth)i-3-meth\I-1 H-pyrazole-4-carboxyIic acid {(1 S.3S.5S)-2-[5-{3-fluoro-phenyi)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide: isoquinoline-1-carboxyiic acid {(lS,3S,5S)-2-[5-(3-fIuoro-phenyl)-2-iTietliyl-thiazoie-4-carbonyl]-2-aza-bicyclo[3.I.0]hex-3-ylmethyl}-amide: 1 H-indazole-3-carboxylic acid {(1 S.3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-yimethyl}-amide; 4-methoxy-quinoIine-2-carboxylic acid {(] S,3S,5S)-2-[5-(3-fluoro-phenyi)-2-metl^yl-thiazoie-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-yIITlethyl}-amide; quinoIine-2-carboxylic acid ((IS.3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide: 6-tluoro-4H-benzo[1.3]dioxine-8-carboxylic acid {(IS,3S.5S)-2-[5-{3-fluoro-phenyl)-2-iTiethyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-aiTiide; benzo[l,2,3]thiadiazole-5-carboxylic acid {(lS,3S,5S)-2-[5-(3-f!uoro-phenyl)-2-methyI-thiazole-4-carbonyl]-2-aza-bicyclo[3.].0]hex-3-ylmethyl}-amide; benzo[d]isoxazole-3-carboxylic acid {(1 S,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl)-amide: 2.2-dimethyl-2.3-dihydro-benzofuran-7-carboxylic acid {(lS.3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicycIo[3.1.0]hex-3-ylmethyl }-amide; 2,2-difIuoro-benzo[l,3]dioxole-4-carboxylic acid {(lS.3S,5S)-2-[5-(3-fIuoro-phenyi)-2-methyi-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyi}-amide; benzo[l,3]dioxole-4-carboxylicacid {(lS,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl-thiazoie-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-yImethyI}-amide: 2-ethy)-5-methyl-2H-pyrazole-3-carboxylic acid {(1 S,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; i-methyl-5-trifluoromethyl-lH-pyrazole-4-carboxylic acid {(lS,3S.5S)-2-[5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-yimethyl }-amide; 2,5-dimethyl-2H-pyrazole-3-carboxy!ic acid {(1 S,3S,5S)-2-[5-(3-fIuoro-phenyi)-2-methyi-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2.3-dihydro-benzofuran-4-carboxylic acid {(1 S,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyc!o[3.1.0]hex-3-ylmethyl}-amide; 5-fluoro-lH-indole-2-carboxylicacid {(1S,3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyi-thiazole-4-carbonyl]-2-aza-bicyclo[3.].0]hex-3-ylmethyl}-amide: 7-fluoro-lH-indole-2-carboxylicacid {(lS.3S,5S)-2-[5-(3-fluoro-phenyl)-2-methyl- thiazole-4-carbon\ l]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; l,2-diiTiethyl-]H-indole-3-carboxylicacid {(lS.3S,5S)-2-[5-(3-fluoro-pheny!)-2-methyl- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]iiex-3-ylmethyl}-amide; 3-methyl-imidazo[2,l-b]thiazole-5-carboxylic acid {(lS.3S,5S)-2-[2-amino-5-(3-fluoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2-methyl-iiTiidazo[2,l-b]thiazole-5-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; imidazo[2,1 -b]tliiazoIe-5-carboxylic acid {(1 S,3S.5S)-2-[2-amino-5-(3-fluoro-phenyl)- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyI}-amide; 1-methyl-1 H-indoie-3-carboxyiic acid {(lS,3S.5S)-2-[2-amino-5-(3-fluoro-phenyl)- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 3-methyl-imidazo[2,l-b]thiazole-2-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; l-ethyl-3-methyl-lH-pyrazole-4-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide: 5-/erf-butyl-2-methyl-2H-pyrazole-3-carboxylic acid {(lS.3S,5S)-2-[2-amino-5-(3-fIuoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide: quinoline-4-carboxylic acid {(1 S,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4- carbonyl]-2-aza-bicyclo[3.1.0]hex-3-yimethyl}-amide; isoquinoline-1-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-{3-fluoro-phenyl)-tliiazole-4- carbony|]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; quinoiine-5-carboxyIic acid {(lS,3S,5S)-2-[2-amino-5-(3-tluoro-phenyi)-lhiazole-4- carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; !H-indazole-3-carboxylicacid {()S,3S,5S)-2-[2-amino-5-(3-fluoro-pheny))-thiazole-4- carbonyi]-2-aza-bicycIo[3.1.0]hex-3-yImethyi}-amide; 4-methoxy-quinoline-2-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)- thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmetiiyl}-amide: lH-indoie-3-carboxylicacid {(lS,3S,5S)-2-[2-amino-5-(3-fIuoro-phenyl)-thiazole-4- carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 6-fluoro-4H-benzo[1.3]dioxine-8-carboxylic acid {(lS.3S.5S)-2-[2-amino-5-{3-fluoro- phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; isoquinoline-5-carboxylic acid {(1 S,3S.5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4-carbon\!]-2-aza-bicyclo[3.1.0]hex-3-ylmethyI}-alTlide: 3-methyt-5-trifluorometliyl-isoxazole-4-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-a2a-bicyclo[3.).0]hex-3-yliTiethyI}-amide; ben7o[ 1,2,3]thiadiazoie-5-carboxyiic acid {(1 S.3S.5S)-2-[2-amino-5-(3-fiuoro-piienyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]iiex-3-yliTiethyi}-amide; beiizo[d]isoxazole-3-carboxylic acid {(1 S,3S,5S)-2-[2-amino-5-(3-f^uoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.!.0]l^ex-3-ylmethyI}-al■nide; 2.2-dimetliyi-2,3-dihydro-benzofuran-7-carboxylic acid {(lS,3S.5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2.2-difluoro-benzo[1.3]dioxole-4-carboxy!ic acid {(lS,3S.5S)-2-[2-amino-5-(3-fluoro-phenyi)-tiiiazoie-4-carbonyl]-2-aza-bicycio[3.1.0]liex-3-yimetliyl}-amide; benzo[l,3]dioxole-4-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-yImethyl}-amide; 2-ethyl-5-methyl-2H-pyrazole-3-carboxylic acid {(1 S,3S.5S)-2-[2-amino-5-(3-fIuoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2-methyl-2H-indazole-3-carboxylic acid {(1 S,3S.5S)-2-[2-amino-5-(3-fluoro-plienyi)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; l-methyi-5-trifiuorometiiyl-lH-pyrazole-4-carboxyiic acid {(lS,3S.5S)-2-[2-amino-5-(3-fluoro-piienyl)-tliiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; l,3<5-trimethyl-lH-pyrazole-4-carboxyiic acid {(lS,3S,5S)-2-[2-amino-5-(3-tluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2.5-dimethyl-2H-pyrazoie-3-carboxyiic acid {(lS.3S,5S)-2-[2-amino-5-(3-fiuoro-phenyi)-thiazoIe-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2.5-dimethyl-oxazoie-4-carboxylicacid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 4-methyl-thiazole-5-carboxylicacid {(lS,3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2,3-dihydro-benzofuran-4-carboxylicacid {(lS.3S,5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.l.0]hex-3-ylmethyl}-amide; 1.3-dimetliyl-lH-pyrazole-4-carboxylic acid {(lS,3S,5S)-2-[2-amino-5-(3-tluoro-phenyl)-thiazoie-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 5-eth\l-3-methyl-iso\azoIe-4-carboxylic acid {(lS,3S.5S)-2-[2-amino-5-(3-fluoro-phenyl)-th iazole-4-carbon\ l]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; !,2-dimethyl-lH-indole-3-carboxylic acid {(lS.3S,5S)-2-[2-aiTiino-5-(3-fluoro-phenyl)-thiazole-4-carbonyi]-2-aza-bicyclo[3.1.0]iiex-3-yimethyl}-amide; N-{(lS,3S.5S)-2-[2-amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-yliTiethyl}-2.3-dimethyl-benzamide: quinoiine-8-carboxylic acid {(lS,3S,5S)-2-[2-ainino-5-(3-fluoro-phenyl)-thiazoIe-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 5-fiuoro-1-methyl-lH-indoie-2-carboxylic acid {(lS,3S.5S)-2-[2-amino-5-(3-fIuoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.I.0]hex-3-ylmethyl}-amide; 6-fluoro-4H-benzo[l,3]dioxine-8-carboxyIic acid [(lS,3S.5S)-2-(2-methyl-5-m-tolyi-thiazoie-4-carbonyi)-2-aza-bicycIof3.1.0]hex-3-yimetiiyl]-amide; 2.2-dimethyl-2.3-dihydro-benzofuran-7-carboxylic acid [(] S,3S,5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide: quinoline-8-carboxylic acid [(1 S,3S,5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3 . 1.0]hex-3-ylmetiiyl]-amide; quinoiine-2-carboxylic acid [(1 S,3S,5S)-2-(2-methyl-5-m-toiyl-tlliazole-4-carbonyl)-2-aza-bicyclo[3. 1.0]hex-3-y!methyl]-amide; imidazo[2,1 -b]thiazole-5-carboxylic acid [(1 S.3S.5S)-2-(2-methyl-5-m-toiyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 3-methyl-imidazo[2,l-b]thiazole-2-carboxylic acid [(lS,3S,5S)-2-(2-methyl-5-m-tolyl-tiiiazoIe-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-y!methyl]-amide; 1 H-indoIe-3-carboxylic acid [(] S,3S,5S)-2-(2-meti^yl-5-m-to)yl-thiazoie-4-ca^bony^)-2-aza-bicyclo[3 . 1.0]hex-3-ylmethyl]-amide; 1 H-indazole-3-carboxylic acid [(lS,3S,5S)-2-(2-methyl-5-m-toIyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 2-ethyl-5-metiiyl-2H-pyrazole-3-carboxylic acid [(IS,3S,5S)-2-(2-methyl-5-m-toiyi-thiazole-4-carbony))-2-aza-bicycIo[3.1.0]hex-3-ylmethyl]-amide; l-ethyl-3-methyl-lH-pyrazole-4-carboxylic acid [(lS,3S,5S)-2-(2-methyl-5-m-tolyl-thiazoie-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 3-bromo-N-[(lS,3S,5S)-2-(2-metiiyl-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyi]-benzamide; N-[( 1 S.3S.5S)-2-(2-methyi-5-m-tolyl-tiiiazo!e-4-carbonyl)-2-aza-bicyclo[3. i .0]hex-3- ylmetli)l]-3-trifluoromethyl-benzaiTiide; 3-methoxy-N-[(IS.3S,5S)-2-(2-inethyi-5-m-toIyl-thiazole-4-carbonyl)-2-aza- bicycio[3.1.0]hex-3-ylmetliyl]-benzaiTiide; 4-cliloro-2-methoxy-N-[(lS,3S,5S)-2-(2-metliyi-5-m-tolyl-thiazole-4-carbonyi)-2-aza- bicyclo[3.!.0]hex-3-yImethyl]-benzaiTiide; 3-cliloro-2-methyl-N-[(lS,3S,5S)-2-(2-methyl-5-m-tolyi-tiiiazole-4-carbonyl)-2-aza- bicycio[3.1.0]lnex-3-yliTiethyl]-benzamide; 3-iodo-N-[(I S,3S,5S)-2-(2-methyl-5-m-to!yl-tiiiazo!e-4-carbonyl)-2-aza-bicycio[3.1.0]hex- 3-ylmethyl]-benzamide; 4-methoxy-N-[(IS.3S,5S)-2-(2-methyl-5-iTi-tolyl-thiazole-4-carbonyl)-2-aza- bicyclo[3.1.0]hex-3-yImetiiy[]-3-trifluoroniethyl-benzaiTiide: 2-chloro-N-[(lS.3S,5S)-2-(2-metliyl-5-m-tolyl-thiazole-4-carbonyl)-2-aza- bicyclo[3.1.0]hex-3-yliTiethyl]-benzamide; 3,4-dimetlioxy-N-[(lS,3S,5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbonyl)-2-aza- bicyclo[3.1.0]hex-3-ylmethyl]-benzamide; 6-trifIuoromethyl-imidazo[2,l-b]thiazole-5-carboxylicacid [(lS,3S,5S)-2-(2-iTiethyI-5-m- tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]iiex-3-ylmethyl]-amide; 6-chloro-imidazo[2,l-b]thiazole-5-carboxylicacid [(lS,3S.5S)-2-(2-methyl-5-m-tolyl- tliiazole-4-carbonyi)-2-aza-bicycio[3.1.0]hex-3-ylmetiiyl]-amide: 2H-chromene-5-carboxylic acid [(lS,3S,5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbonyl)-2- aza-bicyclo[3.) .0]liex-3-ylmethyl]-amide; 4-methyl-3,4-dihydro-2H-benzo[l,4]oxazine-8-carboxylic acid [{lS.3S.5S)-2-(2-methyi-5- m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; chroman-8-carboxylic acid [(1 S,3S,5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbony!)-2-aza- bicyclo[3.1.0]hex-3-ylmethyl]-amide; chroman-5-carboxyiic acid [(lS,3S,5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbonyl)-2-aza- bicyclo[3.1.0]hex-3-ylmethyl]-amide; 3,4-dihydro-2H-benzo[l,4]oxazine-5-carboxylic acid [(lS.3S,5S)-2-(2-metliyl-5-m-tolyl- tliiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; i,2-dimethyi-IH-indoie-3-carboxylicacid[(lS3S.5S)-2-(2-metliyI-5-m-tolyl-thiazoie-4- carbonyi)-2-aza-bicyclo[3.1.0]hex-3-yliTiethyl]-amide; 5-fluoro-l-meih>l-lH-indole-2-carboxylic acid [(lS.3S,5S)-2-(2-methyl-5-m-tolyl-lhiazole-4-carbony)-2-aza-bicyclo[3.1.0]liex-3-ylmetliyl]-aiTiide: 2.3-diliydro-thieno[3.4-b][1.4]dioxine-5-carboxylic acid [(lS.3S,5S)-2-(2-methyl-5-iTi-tolyl-thiazole-4-carbonyl)-2-aza-bicycio[3.1.0]hex-3-yliTiethyl]-amide; 2,5-diinethyl-2H-pyrazole-3-carboxyiic acid [(lS,3S,5S)-2-(2-methyI-5-m-tolyl-thiazole-4-carbony])-2-aza-bicyc]o[3.1.0]hex-3-ylmethyl]-aiT)ide: benzooxazole-7-carboxylic acid [(lS,3S,5S)-2-(2-methyI-5-m-tolyl-thiazoIe-4-carbonyl)-2-aza-bicycio[3.1.0]hex-3-yimethyi]-amide; 2-methyl-benzooxazoie-7-carboxylic acid [(1 S,3S.5S)-2-{2-metl^yI-5-m-tolyl-thiazole-4-carbonyi)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide: benzothiazoie-7-carboxyiic acid [(lS,3S,5S)-2-(2-niethyl-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]!iex-3-ylmetliyl]-amide; 7-chloro-benzofuran-4-carboxyiic acid [(1 S.3S,5S)-2-(2-methyl-5-iTi-tolyl-thiazoie-4-carbonyl)-2-aza-bicyclo[3,1.0]hex-3-ylmetliyl]-amide; 7-fluoro-benzofuran-4-carboxylic acid [(]S,3S,5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbonyi)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-aiTiide; Pyrrolo[2,I-b]tfiiazole-7-carboxylicacid[(lS,3S,5S)-2-(2-methyi-5-m-toiyi-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-aiTiide; 6-iTiethyl-pyrrolo[2,l-b]thiazoie-7-carboxylic acid [(lS.3S,5S)-2-(2-metiiyl-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 7-chloro-2-methoxy-2,3-dihydro-benzofuran-4-carboxylic acid [(1 S.3S,5S)-2-(2-lTlethyl-5-m-tolyl-tlliazole-4-carbonyl)-2-aza-bicycio[3.1.0]llex-3-ylmethy!]-amide: benzo[d]isoxazole-3-carboxylicacid {(lS,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2,3-diiiydro-benzo[1.4]dioxine-5-carboxyiic acid {(lS,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyl-tiiiazole-4-carbonyl]-2-aza-bicycIo[3.1.0]hex-3-ylmethyl}-amide: 6-fIuoro-4H-benzo[l,3]dioxine-8-carboxylic acid {(lS,3S,5S)-2-[5-(3-chloro-phenyi)-2-methyl-tiiiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]liex-3-ylmethyl}-amide: isoquinoline-1-carboxylicacid {(lS,3S,5S)-2-[5-(3-chIoro-phenyl)-2-methyl-thiazole-4-carbonyi]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; quinoline-2-carboxylic acid {(1 S,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 3-meth>i-iinidazo[2. i-b]thiazole-2-carboxylic acid {(lS.3S.5S)-2-[5-(3-chioro-phenyr)-2-meiii\ i-thiazole-4-carbony)]-2-aza-bicyclo[3. ] .OJliexo-ylmethyl}-amide; l,2-diiTiethyl-lH-indole-3-carboxylic acid {(lS,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyi-thiazoie-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-yimethyl}-amide; lH-indole-3-carboxy!icacid {(lS,3S,5S)-2-[5-(3-cliloro-phenyl)-2-iTiethyl-thiazole-4-carbonyi]-2-aza-bicycio[3.1.0]hex-3-yliTietiiyl}-amide; !H-indazole-3-carboxylic acid {(]S,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyl-thiazoie-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-aiTiide; 5-fluoro-l-methyl-lH-indole-2-carboxylicacid {(lS,3S.5S)-2-[5-(3-chloro-phenyl)-2-methyl-tliiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2,5-dimethyl-2H-pyrazole-3-carboxyiic acid {(lS,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyi-thiazoie-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyI}-amide; 2-ethyl-5-methyl-2H-pyrazoie-3-carboxylic acid {(1 S.3S,5S)-2-[5-(3-chIoro-pheny^)-2-metilyl-thiazoie-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide: l-ethyi-3-methyl-lH-pyrazole-4-carboxylicacid {(lS,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; N-{(lS,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicycIo[3.I.0]hex-3-yImethyi}-3-trifIuoromethyi-benzamide; N-{(lS,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-y!methyi}-3-methoxy-benzamide; N-[(lS,3S.5S)-2-(2-amino-5-m-toiyi-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-3-bromo-benzamide; 2,3-dihydro-benzofuran-4-carboxylic acid [(lS,3S,5S)-2-(2-amino-5-m-tolyl-thiazole-4-carbonyI)-2-aza-bicycio[3.1.0]hex-3-yimethyl]-amide; benzo[d]isoxazole-3-carboxylicacid [(lS,3S,5S)-2-(2-amino-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]liex-3-ylmethyl]-amide; 2.3-dihydro-benzofuran-7-carboxylic acid [(lS,3S,5S)-2-(2-amino-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; benzo[b]tliiophene-7-carboxylic acid [(1 S,3S,5S)-2-(2-amino-5-m-toIyI-thiazoie-4-carbonyl)-2-aza-bicyclo[3.1 .0]hex-3-ylmethyl]-aniide; N-[(] S,3S,5S)-2-(2-amino-5-m-tolyl-thiazole-4-carbonyi)-2-aza-bicyclo[3.1.0]hex-3-yimethyl]-3-metliylsulfanyl-benzamide; 2.3-dihydro-thieno[3.4-b][1.4]dioxine-5-carboxylic acid [(lS.3S.5S)-2-(2-aiTiino-5-m-toK l-thiazoie-4-carbon> l)-2-aza-bicyclo[3.1.0]hex-3-yliTiethyl]-amide: l-metliyi-lH-indazole-3-carboxylic acid [(lS.3S.5S)-2-(2-amino-5-m-tolyl-thiazoie-4-carbonyl)-2-aza-bicyclo[3.i.0]hex-3-ylmethyl]-amide; 3,4-dihydro-2H-benzo[l,4]oxazine-5-carboxylic acid [(lS,3S,5S)-2-(2-amino-5-m-tolyl-thiazole-4-carbonyi)-2-aza-bicyclo[3.].0]hex-3-ylmethyI]-amide; N-[(lS.3S,5S)-2-(2-amino-5-m-tolyl-tliiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-YiiTietiiyI]-3-ethynyl-benzamide: quinoiine-8-carboxylic acid [(]S,3S.5S)-2-(2-amino-5-iTi-tolyl-thiazole-4-carbonyr)-2-aza-bicycio[3.1.01hex-3-yliTiethyi]-amide; imidazo[l,2-a]pyridine-3-carboxylic acid [(lS,3S,5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbonyi)-2-aza-bicyclo[3.1.0]hex-3-yimethyl]-amide; iinidazo[l,2-a]pyridine-3-carboxylic acid {(lS,3S.5S)-2-[5-(3-bromo-4-fluoro-phenyl)-2-methyl-thiazo]e-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-yliT)ethyl}-amide; imidazo[l,2-a]pyridine-3-carboxylic acid {{lS,3S,5S)-2-[5-(3,4-dichloro-phenyl)-2-metiiyl-tiiiazole-4-carbonyl]-2-aza-bicycio[3.1.0]hex-3-ylmethyl}-amide: imidazo[l,2-a]pyridine-3-carboxylic acid {(lS,3S,5S)-2-[5-(3-chloro-phenyl)-2-ethoxy-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; imidazo[l,2-a]pyridine-3-carboxylic acid {(lS,3S.5S)-2-[5-(3-chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide: imidazo[1.2-a]pyridine-3-carboxylic acid {(lS,3S.5S)-2-[5-(3,4-dimethyi-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.] .0]hex-3-yImethyl}-amide; isoquinoline-1 -carboxylic acid [(1 S,3S,5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 2,3-dihydro-benzofuran-4-carboxyiic acid [(1 S,3S,5S)-2-(2-methyI-5-m-tolyl-thiazole-4-carbonyi)-2-aza-bicyclo[3.1.0]hex-3-ylmetiiyi]-amide; 2,3-dihydro-benzofuran-4-carboxylicacid {(lS,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmetiiyl}-amide; 2,3-dihydro-benzofuran-4-carboxylic acid {(1 S,3S,5S)-2-[5-(4-bromo-pheny!)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2,3-dihydro-benzofuran-4-carboxylic acid {(] S,3S,5S)-2-[5-(3.5-dimethyl-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.].0]hex-3-ylmethyl}-amide 2.3-dih\dro-benzofuran-4-carboxylic acid {(1 S.3S.5S)-2-[5-(2.3-dichloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-yllTlethyl)-alTlide: 2,3-diiiydro-benzofuran-4-carboxyiic acid {(lS,3S,5S)-2-[5-(3-bromo-4-fluoro-phenyl)-2-melhyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2,3-dihydro-benzofuran-4-carboxylic acid {(1 S,3S,5S)-2-[5-(3,4-difIuoro-phenyi)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2,3-dihydro-benzofuran-4-carboxylic acid {(1 S,3S,5S)-2-[5-(3-f^uoro-2-methyl-phenyl)-2-methyl-thiazoIe-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmetilyl}-amide; 2,3-dihydro-benzofuran-4-carboxylic acid {(lS,3S.5S)-2-[5-(3.4-dimethyl-piienyr)-2-methyI-thiazoie-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethy!}-amide; 2.3-diiiydro-benzofuran-4-carboxyiic acid [(1 S.3S,5S)-2-(2-methyl-5-phenyl-thiazoie-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 2,3-dihydro-benzofuran-4-carboxylic acid [(1 S,3S,5S)-2-(2-cyclopropyl-5-phenyl-thiazole-4-carbonyi)-2-aza-bicycIo[3.1.0]hex-3-yImethyI]-amide; 2,3-dihydro-benzofuran-4-carboxylic acid {(1 S,3S,5S)-2-[5-(4-fluoro-phenyl)-2-methyI-thiazole-4-carbonyl]-2-aza-bicycIo[3. ] .0]hex-3-ylmethyl}-aiTiide; 2,3-dihydro-benzofuran-4-carboxylic acid {(1 S,3S,5S)-2-[2-methyi-5-(3-trifluoro-methyi-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2,3-dihydro-benzofuran-4-carboxylic acid {(1 S,3S,5S)-2-[2-cyclopropyl-5-(3-trif!uoromethyl-piienyi)-thiazoie-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyi}-amide; 2J-dihydro-benzofuran-4-carboxylic acid {(lS,3S,5S)-2-[2-cyclopropyl-5-(4-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2.3-dihydro-benzofuran-4-carboxylic acid {(i S,3S,5Sj-2-[2-cyclopropyl-5-(2-tluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 2,3-dihydro-benzofuran-4-carboxylic acid [(lS,3S,5S)-2-(2-cyclopropyl-5-p-tolyl-thiazole-4-carbonyI)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 2,3-dihydro-benzofuran-4-carboxylicacid {(lS,3S,5S)-2-[5-(3-methoxy-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; 3-bromo-N-{(lS,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-benzamide; quinoline-8-carboxylic acid {(lS,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyc Io[3. ]. 0]hex-3-ylmethyl} -am Ida; quinolirie-8-carboxylic acid [(iS,3S,5S)-2-(2-methyi-5-phenyl-thiazoie-4-carbonyl)-2-aza-bicycio[3.1.0]hex-3-ylmethyl]-amide: quinoline-8-carboxylic acid {(lS,3S,5S)-2-[5-( carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl} quinoline-8-carboxylic acid {(lS,3S,5S)-2-[2-methyl-5-(3-trifluoromethyl-phenyl)- tiiiazo]e-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; quinoline-8-carboxylic acid [(lS,3S,5S)-2-(5-methyl-2-phenyl-furan-3-carbonyl)-2-aza- bicyclo[3.1.0]hex-3-ylmetliyl]-amide; quino!ine-8-carboxyIic acid {(1 S,3S,5S)-2-[5-(3-chioro-piienyi)-thiazole-4-carbonyl]-2- aza-bicyclo[3.1.0]hex-3-ylmethyl}-amide; quinoIine-8-carbox\!ic acid f(!S.3S.5S)-2-[5-carbon>i]-2-aza-bicycio[3.1.0]hex-3-ylmethyl quinoline-8-carboxylic acid {(lS.3S,5S)-2-[5-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl quinoline-8-carboxylic acid {(lS,3S,5S)-2-[5-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl quinoline-8-carboxylic acid {(]S,3S,5S)-2-[5-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl quinoline-8-carboxylic acid {(lS.3S.5S)-2-[5-i thiazole-4-carbonyl]-2-aza-bicyclo[3.1.0]hex-quinoline-8-carboxyiic acid {(lS,3S,5S)-2-[5-carbonyl]-2-aza-bicyclo[3.1.0]liex-3-ylmethyl quino!ine-8-carboxylic acid {(lS,3S,5S)-2-[5-tiiiazoie-4-carbonyl]-2-aza-bicycio[3.1.0]hex-quinoline-8-carboxylic acid {(]S,3S.5S)-2-[5-carbonyl]-2-aza-bicyclo[3. ] .0]hex-3-ylmethy) quinoline-8-carboxyiic acid {(lS,3S,5S)-2-[5-carbonyl]-2-aza-bicyclo[3.1.0]hex-3-ylmethyl quinoline-8-carboxyIic acid {(lS,3S,5S)-2-[5-carbonyl]-2-aza-bicyc!o[3.1.0]hex-3-ylmetliy! quinoline-8-carboxylic acid {(lS,3S,5S)-2-[5-thiazoie-4-carbonyl]-2-aza-bicyclo[3.l.0]iiex- 4-bromo-plienyl)-2-methyi-thiazoie-4- -amide: 3,5-dimethyi-phenyi)-2-methyi-thiazoie-4- -amide; 2.3-dimetliyl-piienyi)-2-methy[-thiazoie-4- amide; 2,3-dichloro-phenyl)-2-methy!-thiazoIe-4- amide; 3-bromo-4-fluoro-phenyl)-2-metliyl--ylmethyi}-amide; 3,4-ditluoro-phenyl)-2-methyl-thiazole-4- amide; 3-fluoro-2-methyl-pheny])-2-methyl-i-ylmethyl}-aiTiide: 3,4-dichloro-plienyl)-2-methyl-thiazole-4- amide; 3,4-dimetiiyI-piienyl)-2-methyi-thiazole-4--amide; 3-acetyiamino-phenyl)-2-metiiyl-thiazole-4--amide; 2-chloro-6-fluoro-plienyl)-2-metliYl- 4-fluoro-phenyl)-2-methyl-thiazole-4-amide; ylmethyl}-amide; quinoline-8-carbo.\\Iic acid {(lS,3S,5S)-2-[5-(3-methoxy-phenyl)-thiazole-4-carbony]]-2-aza-bic\clo[3.] .0]hex-3->'liTiethyl}-ainide; quinoline-8-carboxylic acid {(]S.3S.5S)-2-[5-(3-fluoro-4-methyl-phenyl)-2-methyl-tiTiazole-4-carbonyl]-2-aza-bicycio[3.1.0]iiex-3-ylinethyl}-amide: benzo[d]isoxazoie-3-carboxyIic acid [(lS,3S,5S)-2-(2-methyi-5-m-toiyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; 2,3-dihydro-thieno[3,4-b][l,4]dioxine-5-carboxylicacid {(lS,3S,5S)-2-[5-(3-chloro-phenyl)-2-methyl-thiazole-4-carbonyl]-2-aza-bicyclo[3.].0]hex-3-ylmethyl}-amide; 6-iTiethyi-imidazo[2.1-b]thiazole-5-carboxylic acid [(lS,3S,5S)-2-(2-dimethylamino-5-phenyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmetiiyi]-ainide 2-ciiloro-benzothiazole-4-carboxyIic acid [(1 S,3S,5S)-2-(2-inethyl-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; benzothiazoie-4-carboxylic acid [(1 S,3S,5S)-2-(2-methyl-5-m-tolyl-thiazole-4-carbonyl)-2-aza-bicyclo[3. 1.0]hex-3-ylmethyl]-amide; {(lS,3S,5S)-3-[(5-bromo-pyriiTiidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2-y!}-[5-(3-chloro-phenyI)-2-methyI-thiazol-4-yl]-methanone; {(IS,3S,5S)-3-[(5-bromo-pyriinidin-2-ylamino)-inethyl]-2-aza-bicyclo[3.1.0]hex-2-yl}-(2-methyi-5-m-toiyl-tiiiazoi-4-yI)-methanone; {(lS,3S,5S)-3-[(5-bromo-pyrimidin-2-ylamino)-methyl]-2-aza-bicycIo[3.1.0]hex-2-yl}-[2-methyl-5-(3-trifluoromethyl-phenyl)-thiazol-4-yl]-methanone; {(lS,3S,5S)-3-[(5-bromo-pyrimidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]iiex-2-yl}-[5-(3,5-dimethyl-phenyl)-2-methyl-thiazol-4-yl]-metlianone: {(iS,3S.5S)-3-[(5-bromo-pyrimidin-2-ylaiTiino)-methyrj-2-aza-bicyclo[3.l.0]hex-2-yl|-[5-(3,4-ditluoro-phenyl)-2-methyl-thiazoi-4-yl]-metlianone; ((lS.3S,5S)-3-[(5-bromo-pyrimidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2-yl}-[5-(3,4-dichloro-phenyl)-2-methyl-thiazol-4-yl]-methanone; {(lS,3S,5S)-3-[(5-bromo-pyrimidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2-yl}-[5-(3,4-dimethyl-phenyl)-2-methyl-thiazol-4-yl]-methanone; {(lS.3S,5S)-3-[(5-bromo-pyrimidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2-y!}-(2-methyl-5-phenyI-thiazol-4-yI)-methanone; {(lS,3S,5S)-3-[(5-bromo-pyriiTiidin-2-ylamino)-methyl]-2-aza-bicycio[3.1.0]hex-2-yi)-(2-cyclopropyi-5-phenyI-thiazoI-4-yI)-metiianone; {(I S.3S.5S)-3-[(5-bromo-pyrimidin-2-ylamino)-inethyl]-2-aza-bicycIo[3.1.0]hex-2-yl}-[5- (3-chloro-phen\'n-lhiazol-4-yl]-methanone: |(lS.3S,5S)-3-[(5-bromo-pyrimidin-2-ylaiTiino)-iTiethyl]-2-aza-bicyclo[3.I.O]hex-2-yi}-[5- (3-methoxy-phenyl)-thiazol-4-yl]-niethanone; {(lS.3S.5S)-3-[(5-bromo-pyrimidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2-yl}-[5- (3-tluoro-4-methyl-phenyl)-2-iTiethyl-thiazol-4-yl]-methanone; (2-methyl-5-m-tolyl-thiazol-4-yl)-{(lS,3S,5S)-3-[(4-trifluoromethyl-pyrimidin-2- ylaiTiino)-iTiethyI]-2-aza-bicyclo[3.1.0]hex-2-yl}-methanone; 4-aiTiino-2-{[(IS,3S,5S)-2-(2-methyl-5-iTi-tolyl-thiazoIe-4-carbonyl)-2-aza- bicycio[3.1.0]hex-3-ylmethyl]-amino}-pyrimidine-5-carbonitrile: {(lS,3S,5S)-3-[(4.6-dimethoxy-pyriiTiidin-2-ylamino)-methyl]-2-aza-bicyclo[3.1.0]hex-2- yl}-(2-methyl-5-m-tolyl-thiazol-4-y|)-iTiethanone; {(]S,3S,5S)-3-[{5-ethyl-pyrimidin-2-ylamino)-methyl]-2-aza-bicyclo[3.l.0]hex-2-yl}-(2- methyl-5-m-tolyl-thiazol-4-yl)-methanone; and benzooxazole-4-carboxylic acid [(IS,3S,5S)-2-(2-amino-5-m-tolyl-thiazole-4-carbonyl)-2- aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide; or a pharmaceutically acceptable salt of such a compound. 10. Compounds of any one of claims 1 to 9 for use as medicaments. 11. Use of a compound according to any of claims I to 9 for the preparation of a medicament for the prevention or treatment of diseases selected from the group consisting of dysthymic disorders including major depression and cyclothymia, affective neurosis, all types of manic depressive disorders, delirium, psychotic disorders, schizophrenia, catatonic schizophrenia, delusional paranoia, adjustment disorders and all clusters of personality disorders; schizoaffective disorders: anxiety disorders including generalized anxiety, obsessive compulsive disorder, posttraumatic stress disorder, panic attacks, all types of phobic anxiety and avoidance; separation anxiety; all psychoactive substance use, abuse, seeking and reinstatement; all types of psychological or physical addictions, dissociative disorders including multiple personality syndromes and psychogenic amnesias; sexual and reproductive dysfunction; psychosexual dysfunction and addiction: tolerance to narcotics or withdrawal from narcotics; increased anaesthetic risk, anaesthetic responsiveness: hypothalamic-adrenal dysfunctions; disturbed biological and circadian rhythms; sleep disturbances associated with diseases such as neurological disorders including neuropathic pain and restless leg s\ndrome; sleep apnea; narcolepsy: chronic fatigue syndrome; insomnias related to psychiatric disorders; all types of idiopathic insomnias and parasomnias: sleep-wake schedule disorders including jet-lag; all dementias and cognitive dysfunctions in the healthy population and in psychiatric and neurological disorders; mental dysfunctions of aging; all types of amnesia; severe mental retardation; dyskinesias and muscular diseases; muscle spasticity, tremors, movement disorders; spontaneous and medication-induced dyskinesias; neurodegenerative disorders including Huntington's, Creutzfeld-Jacob's, Alzheimer's diseases and Tourette syndrome; Amyotrophic lateral sclerosis; Parkinson's disease; Cushing's syndrome; traumatic lesions; spinal cord trauma; head trauma; perinatal hypoxia; hearing loss; tinnitus; demyelinating diseases; spinal and cranial nerve diseases; ocular damage; retinopathy; epilepsy; seizure disorders; absence seizures, complex partial and generalized seizures; Lennox-Gastaut syndrome: migraine and headache; pain disorders; anaesthesia and analgesia; enhanced or exaggerated sensitivity to pain such as hyperalgesia, causalgia, and allodynia; acute pain; burn pain; atypical facial pain; neuropathic pain; back pain; complex regional pain syndrome I and II; arthritic pain; sports injury pain; dental pain; pain related to infection e.g. by HIV; post-chemotherapy pain; post-stroke pain; post-operative pain; neuralgia; osteoarthritis; conditions associated with visceral pain such as irritable bowel syndrome; eating disorders; diabetes; toxic and dysmetabolic disorders including cerebral anoxia, diabetic neuropathies and alcoholism; appetite, taste, eating, or drinking disorders; somatoform disorders including hypochondriasis; vomiting/nausea; emesis; gastric dyskinesia: gastric ulcers; Kallman's syndrome (anosmia); impaired glucose tolerance; intestinal motility dyskinesias; hypothalamic diseases; hypophysis diseases; hyperthermia syndromes, pyrexia, febrile seizures, idiopathic growth deficiency; dwarfism; gigantism; acromegaly; basophil adenoma; prolactinoma; hyperprolactinemia; brain tumors, adenomas; benign prostatic hypertrophy, prostate cancer; endometrial, breast, colon cancer; all types of testicular dysfunctions, fertility control; reproductive hormone abnormalities; hot flashes; hypothalamic hypogonadism, functional or psychogenic amenorrhea; urinary bladder incontinence; asthma; allergies; all types of dermatitis, acne and cysts, sebaceous gland dysfunctions; cardiovascular disorders; heart and lung diseases, acute and congestive heart failure; hypotension; hypertension; dyslipidemias, hyperlipidemias. insulin resistance; urinary retention; osteoporosis; angina pectoris; myocardial infarction; arrhythmias, coronary diseases, left ventricular hypertrophy; ischemic or haemorrhagic stroke; all types of cerebro\ascular disorders including subarachnoid haemorrhage, ischemic and hemorrhagic stroke and vascular dementia: chronic renal failure and other renal diseases: gout; kidney cancer; urinary incontinence; and other diseases related to general orexin system dysfunctions. 12. Use of a compound according to any of claims 1 to 9 for the preparation of a medicament for the prevention or treatment of diseases selected from the group consisting of all types of sleep disorders, of stress-related syndromes, of psychoactive substance use and abuse, of cognitive dysfunctions in the healthy population and in psychiatric and neurologic disorders, of eating or drinking disorders.