Background of the invention Glucose is the major energy substrate in mammals and regulation of blood glucose levels within a narrow range seems to be of crucial importance to devoid serious physiological complications as seen in diabetes (DeFronzo, Bonadonna, & Ferrannini. 1992). Blood glu- cose homeostasis is maintained by dietary intake of carbohydrates, the uptake of glucose by peripheral tissues and the brain, and storage or release of glucose from the liver. The liver therefore seems to play a major role in the homeostatic regulation of blood glucose levels.

Gluconeogenesis and glycogenolysis are the two metabolic pathways from which glucose can be produced in the liver. These pathways are under tight hormonal control. Insulin re- sistance and insulin deficiency have a substantial impact on glucose production in the liver (Consoli. 1992; DeFronzo, Bonadonna, & Ferrannini. 1992; Clore, Stillman, Stevens, Blackard, Levy, & Richmond. 1996). Glucose-6-phosphatase (G-6-Pase) catalyses the ter- minal step in the above mentioned pathways by converting glucose-6-phosphate (G-6-P) to glucose, and is largely situated in the liver, with some expression in the kidney after pro- longed fasting. The G-6-Pase is a multicomponent system comprising of the G-6-Pase cata- lytic enzyme with its active site located at the luminal site of the endoplasmic reticulum (microsomal fraction), a specific transporter T1 which mediates entry of G-6-P into the lumi- nal compartment, and transporter T2 and T3 which mediates export to the cytosol of inor- ganic phosphate and glucose, respectively (Nordlie, Bode, & Foster. 1993; Sukalski & Nord- lie. 1989). It has been shown that the rate of hydrolysis of G-6-P and the hepatic glucose output were increased under diabetic conditions (Lyall, Grant, Scott, & Burchell. 1992; De- Fronzo, Bonadonna, & Ferrannini. 1992). The increased activity could mainly be accounted for by increased G-6-Pase catalytic enzyme protein (Argaud, Zhang, Pan, Maitra, Pilkis, &

Lange. 1996; Burchell & Cain. 1985). This makes G-6-Pase enzyme a potential target in control of excess glucose production seen in diabetes.

Bibliography Argaud, D., Zhang, Q., Pan, W., Maitra, S., Pilkis, S. J., & Lange, A. (1996). Regulation of rat liver glucose-6-phosphatase gene expression in different nutritional and hormonal states.

Diabetes, 45 : 1563-1571.

Arion, J. M., Lange, A. J., & Walls, H. E. (1980). Microsomal membrane integrity and the inter- actions of phlorizin with the glucose-6-phosphatase system. J Biol Chem, 255 : 10387-10395.

Burchell, A., & Cain, D. 1. (1985). Rat hepatic microsomal glucose-6-phosphatase protein lev- els are increased in streptozotocin-induced diabetes. Diabetologia, 28 : (852). 856 Clore, J. N., Stillman, J. S., Stevens, W., Blackard, W. G., Levy, J., & Richmond, V. A. (1996).

Chronic hyperinsulinemia supresses glucose-6-phosphatase mRNA. Diabetes, 44 (suppl 1) : 253A Consoli, A. (1992). Role of liver in pathophysiology of NIDDM. Diabetes Care, 15 : 430-441.

DeFronzo, R. A., Bonadonna, R. C., & Ferrannini, E. (1992). Pathogenesis of NIDDM : A Bal- anced overview. Diabetes Care, 15 : 318-368.

Lyall, H., Grant, A., Scott, H. M., & Burchell, A. (1992). Regulation of the hepatic microsomal glucose-6-phosphatase enzyme. Biochem Soc Trans, 20,271 S (abstract).

Nordie, R. C., Bode, A. M., & Foster, J. D. (1993). Recent advances in hepatic glucose 6- phosphatase regulation and function. Proc Soc Exp Biol Med, 203 : 274-285.

Sukalski, K. A., & Nordie, R. C. (1989). Glucose-6-phosphatase : Two concepts of membrane function relationship. In A. Meister (Ed.), Advances in Enzymology and realted areas of mo- lecular biology. (pp. 93-117). New York: John Wiley and Sons.

Description of the invention The present invention relates to compounds of the general formula) : 0 wherein A together with the double bond of formula I forms a cyclic system selected from the group consisting of benzene, thiophene, furan, pyridine, pyrimidine, pyrazine, pyridazine, pyrrole, indole, pyrazol, imidazole, oxazol, isoxazole or thiazole, R'is C, _6-alkyl, or aryl, optionally substituted with one or more substituents, R2 is C, _s alkyl, aralkyl, or COR3 optionally substituted with one or more substituents, R3 is C, 6-alkyl, aralkyl, or aryl, optionally substitued with one or more substituents, R4 and Rs independently are hydrogen, halogen, perhalomethyl, optionally substituted C, 4-alkyl, hydroxy, optionally substituted C, 4-alkoxy, nitro, cyano, amino, optionally substi- tuted mono-or di-C, 4-alkylamino, acylamino, C, 4-alkoxycarbonyl, carboxy or carbamoyl, n is 0, 1, or 2, and m is 0, 1, or 2, or a salt thereof with a pharmaceutical acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form.

Within its scope the invention includes all isomers of compounds of formula 1, some of which are optically active, and also their mixtures including racemic mixture thereof.

The scope of the invention also includes all tautomeric forms of the compounds of formula 1.

The compounds according to the invention may optionally exist as pharmaceutically acceptable salts including pharmaceutically acceptable acid addition salts, such as hydrochloric, hydrobromic, hydroiodic, phosphoric, sulfuric, acetic, trifluoroacetic, trichloroacetic, oxalic, maleic, pyruvic, malonic, succinic, citric, tartaric, fumaric, mandelic, benzoic, cinnamic, methanesulfonic, ethanesulfonic, picric and the like, and include the pharmaceutical ac-

ceptable salts listed in Journal of Pharmaceutical Science, 66, 2 (1977) and incorporated herein by reference; pharmaceutically acceptable metal salts, such as lithium, sodium, po- tassium, or magnesium salts and the like ; or-optionally alkylated-ammonium salts ; or amine salts of the compounds of this invention, such as the sodium, potassium, Cl-6- alkylamine, di (C, $-alkyl) amine, tri (C, 4-alkyl) amine and the four (4) corresponding omega- hydroxy analogues (e. g. methylamine, ethylamine, propylamine, dimethylamine, diethylamine, dipropylamine, trimethylamine, triethylamine, tripropylamine, di (hydroxyethyl) amine, and the like ; Also intended as pharmaceutical acceptable acid addition salts are the hydrates which the present compounds are able to form. The acid addition salts may be obtained as the di- rect products of compound synthesis. In the alternative, the free base may be dissolved in a suitable solvent containing the appropriate acid, and the salt isolated by evaporating the sol- vent or otherwise separating the salt and solvent. The compounds of this invention may form solvates with standard low molecular weight solvents using methods known to the skilled artisan.

The term"C, 4-alkyl"as used herein, alone or in combination, refers to a straight or branched, saturated or unsaturated hydrocarbon chain. The C14-alkyl residues include ali- phatic hydrocarbon residues, unsaturated aliphatic hydrocarbon residues, alicyclic hydrocar- bon residues. Examples of the aliphatic hydrocarbon residues include saturated aliphatic hy- drocarbon residues having 1 to 6 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, sec. butyl, tert. butyl, n-pentyl, isopentyl, neopentyl, tert. pentyl, n-hexyl, iso- hexyl. Example of the unsaturated aliphatic hydrocarbon residues includ those having 2 to 6 carbon atoms such as ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2- methyl-1-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 3-methyl-2-butenyl, 1- hexenyl, 3-hexenyl, 2,4-hexadienyl, 5-hexenyl, ethynyl, 1-propionyl, 2-propionyl, 1-butynyl, 2- butynyl, 3-butynyl, 1-pentynyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexynyl, 3-hexynyl, 2,4- hexadiynyl, 5-hexynyl. Examples of the alicyclic hydrocarbon residue include saturated ali- cyclic hydrocarbon residues having 3 to 6 carbon atoms such as cyclopropyl, cyclobutyl, cy- clopentyl, cyclohexyl ; and C54 unsaturated alicyclic hydrocarbon residues having 5 to 6 car- bon atoms such as 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, 1-cyclohexenyl, 2- cyclohexenyl, 3-cyclohexenyl.

The terms"lower aikyl"and"lower alkoxy"mean C, 4-alkyl and C, 4-alkoxy. respectively.

The term"aryl"as used herein refers to an aryl which can be optionally substituted or a het- eroaryl which can be optionally substituted and includes phenyl, biphenyl, indene, fluoren, naphthyl (1-naphthyl, 2-naphthyl), anthracene (1-anthracenyl, 2-anthracenyl, 3-anthracenyl), pyrrolyl (2-pyrrolyl), pyrazolyl (e. g. 3-pyrazolyl, 4-pyrazolyl and 5-pyrazolyl), imidazolyl (1- imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl), triazolyl (1,2,3-triazol-1-yl, 1,2,3-triazol-2- yl 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl), oxazolyl (2-oxazolyl, 4-oxazolyl, 5-oxazolyl), thiazolyl (2-thiazolyl, 4-thiazolyl, 5-thiazolyl), pyridyl (2-pyridyl, 3-pyridyl, 4-pyridyl), pyrimidinyl (2- pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl), pyrazinyl, pyridazinyl (3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl), quinolyl (2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl), isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6- isoquinolyl, 7-isoquinolyl, 8-isoquinolyl), benzo [b] furanyl (2-benzo [b] furanyl, 3- benzo [b] furanyl, 4-benzo [b] furanyl, 5-benzo [b] furanyl, 6-benzo [b] furanyl, 7-benzo [b] furanyl), 2,3-dihydro-benzo [b] furanyl (2- (2, 3-dihydro-benzo [b] furanyl), 3- (2, 3-dihydro- benzo [b] furan), 4- (2, 3-dihydro-benzo [b] furanyl), 5- (2, 3-dihydro-benzo [b] furan), 6- (2, 3- dihydro-benzo [b] furanyl), 7- (2, 3-dihydro-benzo [b] furanyl), benzo [b] thiophenyl (2- benzo [b] thiophenyl, 3-benzo [b] thiophenyl, 4-benzo [b] thiophenyl, 5-benzo [b] thiophenyl, 6- benzo [b] thiophenyl, 7-benzo [b] thiophenyl), 2,3-dihydro-benzo [b] thiophenyl (2- (2, 3-dihydro- benzo [b] thiophenyl), 3- (2, 3-dihydro-benzo [b] thiophenyl), 4- (2, 3-dihydro-benzo [b] thiophenyl), 5- (2, 3-dihydro-benzo [b] thiophenyl), 6- (2, 3-dihydro-benzo [b] thiophenyl), 7- (2, 3-dihydro- benzo [b] thiophenyl), indolyl (1-indolyl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7- indolyl), indazole (1-indazolyl, 3-indazolyl, 4-indazolyl, 5-indazolyl, 6-indazolyl, 7-indazolyl), benzimidazolyl (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6- benzimidazolyl, 7-benzimidazolyl, 8-benzimidazolyl), benzoxazolyl (1-benzoxazolyl, 2- benzoxazolyl), benzothiazolyl (1-benzothiazolyl, 2-benzothiazolyl, 4-benzothiazolyl, 5- benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl), carbazolyl (1-carbazolyl, 2-carbazolyl, 3- carbazolyl, 4-carbazolyl), 5H-dibenz [b, f] azepine (5H-dibenz [b, f] azepin-1-yl, 5H- dibenz [b, Qazepine-2-yl, 5H-dibenz [b, Qazepine-3-yl, 5H-dibenz [b, Qazepine-4-yl, 5H- dibenz [b, Qazepine-5-yl), 10,11-dihydro-5H-dibenz [b, f] azepine (10,11-dihydro-5H- dibenz [b, Qazepine-1-yl, 10,11-dihydro-5H-dibenz [b, qazepine-2-yl, 10,11-dihydro-5H- dibenz [b, Qazepine-3-yl, 10,11-dihydro-5H-dibenz [b, qazepine-4-yl, 10,11-dihydro-5H- dibenz [b, Qazepine-5-yl), furanyl (e. g. 2-furan, 3-furan, 4-furanyl and 5-furanyl), thienyl (e. g. 2-thienyl, 3-thienyl, 4-thienyi and 5-thienyl) optionally substituted with one or more substituents.

The term"optionally substituted"as used herein means an aryl residue as defined above or a C, 4-alkyl residue as defined above that may be unsubstituted or may have 1 or more pref- erably 1 to 5 substituents, which are the same as or different from one another. Examples of these substituents include, halogen (fluorine, chlorine, bromine, iodine), hydroxyl, cyano, ni- tro, trifluoromethyl, carbamoyl, C, 4-acyl (e. g. acetyl, propionyl, isopropionyl), C, 4-alkoxy (e. g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, and tert. butoxy), C, 4-alkyl as defined above, C, 4-alkoxycarbonyl (e. g. ones having 2 to 6 carbon atoms such as methoxycarbonyl, ethoxycarbonyl, and propoxycarbonyl), C, 4-alkanoyloxy (e. g. ones having 2 to 6 carbon at- oms such as acetoxy, propionyloxy, isopropionyloxy), C, 4-alkylthio (e. g. ones having 1 to 4 carbon atoms such as methylthio, ethylthio, propylthio, and isopropylthio), C, 4-alkylsulphinyl (e. g. ones having 1-4 carbon atoms such as methylsulphinyl and ethylsulphinyl), C, 4- alkylsulphonyl (e. g. ones having 1-4 carbonatoms such as methylsulphonyl and ethyl- sulphonyl), C14-alkylamino (e. g. one having 1 to 4 carbon atoms such as methylamino, eth- ylamino, dimethylamino, and 1-pyrrolidinyl), aminoalkyl (e. g. one having an amino containing group connected to a C, 4-alkyl group as defined above, such as 2-dimethylaminoethyl and 1-pyrrolidinylmethyl), aminoalkoxy (e. g. one having an amino containing group connected via a C, 4-alkyl group as defined above to an oxygen atom, such as 2-dimethylaminoethoxy, 2- (4-morpholinyl) ethoxy and 1-pyrrolidinylmethoxy), aryl as defined above (e. g. phenyl and 4- pyridinyl), aryloxy (e. g. phenyloxy), and aralkyloxy (e. g. benzyloxy).

The term"halogen"as used herein means fluorine, chlorine, bromine or iodine.

The term"perhalomethyl"as used herein means trifluoromethyl, trichloromethyl, tribro- momethyl or triiodomethyl.

The term"perhalomethoxy"as used herein means trifluoromethoxy, trichloromethoxy, tri- bromomethoxy or triiodomethoxy.

The term"aralkyl"as used herein refers to an optionally substituted aryl residue as defined above, connected to an optionally substituted C, 4-alkyl as defined above. Examples of the aralkyl residue include benzyl, 2-phenylethyl, 2-phenylethenyl, 3- (2-pyridyl) propyl, 3- phenylpropyl, 1-naphtylmethyl, 2- (1-naphtyl) ethyl and the like.

The term"C, 4-alkoxy"as used herein, alone or in combination, refers to a straight or branched monovalent substituent comprising a C, 4-alkyl group linked through an ether oxy- gen having its free valence bond from the ether oxygen and having 1 to 6 carbon atoms e. g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, pentoxy.

The term"carbamoyl"as used herein refers to a carbamoyl which can be optionally substi- tuted by one or two residues selected from the list consisting of optionally substituted C, 4- alkyl as defined above, optionally substituted aryl as defined above and optionally substi- tuted aralkyl as defined above.

In a preferred embodiment the invention relates to compounds of general formula (I) in which A is selected from benzene or thiophene.

In another preferred embodiment the invention relates to compounds of general formula (I), wherein R'is optionally substituted phenyl.

In another preferred embodiment the invention relates to compounds of general formula (I), wherein each one of R', R2, and R3 is substituted with one or more substituents.

In another preferred embodiment the invention relates to compounds of general formula (I), wherein the substituents of R'is halogen, perhalomethyi, perhalomethoxy, or C, 4-alkoxy.

In another preferred embodiment the invention relates to compounds of general formula (I), wherein the substituents of R'are selected from the group consisting of hydrogen, halogen, perhalomethyl, perhalomethoxy, or C14-alkoxy.

In another preferred embodiment the invention relates to compounds of general formula (I), wherein the substituents of R'are selected from from the group consisting of chloro, trifluoromethyl, methoxy, trifluoromethoxy.

In another preferred embodiment the invention relates to compounds of general formula (I), wherein R'is selected from the group consisting of phenyl, 4-chlorophenyl, 4- trifluoromethylphenyl, and 4-trifluoromethoxyphenyl.

In another preferred embodiment the invention relates to compounds of general formula (I), wherein R'is 2,3-dihydrobenzofuran or 4-methoxyphenyl.

In another preferred embodiment the invention relates to compounds of general formula (I), wherein R2 is COR'or (CH2) q-aryl, and q is 0,1,2,3,4,5, or 6.

In another preferred embodiment the invention relates to compounds of general formula (I), wherein R3 is selected from the group consisting of phenyl, 3-methoxyphenyl, 4- methoxyphenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, 4- (2-dimethylaminoethoxy) phenyl, or 4-(2-morpholin-4-ylethoxy) phenyl.

In another preferred embodiment the invention relates to compounds of general formula (I), wherein R3 is selected from the group consisting of 4-methylphenyl, 3,4-dimethoxyphenyl, 4- ethoxyphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, dimethylaminophenyl, 4- (2- carboxyethenyl) phenyl, 4- (2-dimethylaminoethoxy) phenyl, 4- (2-morpholin-4-ylethoxy) phenyl, 1 H-indol-5-yl, 3-chloro-4-methoxyphenyl, and 1 H-benzimidazol-5-yl.

In another preferred embodiment the invention relates to compounds of general formula (I), wherein R4 and R5 independently is hydrogen, chloro, or methoxy.

In another preferred embodiment the invention relates to compounds of general formula (I), wherein n is 0 or 1 and m is 0 or 1.

In another preferred embodiment the invention relates to compounds of general formula (I), wherein n is 0 and m is or 1.

In a another preferred embodiment the invention relates to compounds of general formula (la) :

wherein R'is hydrogen, halogen, preferably chloro, methoxy, perhalomethoxy, preferably trifluoromethoxy, perhalomethyl, preferably trifluoromethyl, diloweralkylamino, preferably di- methylamino, or nitro, and R5 and Ra independently are hydrogen, hydroxy, halogen, preferably chloro, bromo or fluoro, methyl, tert-butyl, phenyl, dimethylamino, methoxy, ethoxy, 2-dimethylaminoethoxy, 2-carboxyethenyl, 2-morpholin-4-ylethoxy, perhalomethyl, preferably trifluoromethyl, perha- methoxy, preferably trifluoromethoxy, carboxy, cyano, methylthio, methylsulfonyl, acetamido, nitro, acetyl, acetoxy, or hydroxymethyl.

In another preferred embodiment the invention relates to compounds of general formula (la) : wherein R'is halogen, perhalomethyl, or perhalomethoxy and R5 and R3 independently are hydrogen, methoxy, ethoxy, hydroxy, fluoro, chloro, bromo, iodo, methyl, trifluoromethyl, dimethylamino, 2-carboxyethenyl, 2-dimethylaminoethoxy, or 2- morpholin-4-ylethoxy.

R'is preferably selected from the group consisting of chloro, methoxy and trifluoromethyl, more preferably trifluoromethoxy.

Preferably, R5 and R3 are independently hydrogen, methoxy, chloro, trifluoromethyl, 2- dimethylaminoethoxy, or 2-morpholin-4-ylethoxy.

In another preferred embodiment the invention relates to compounds of general formula (Ib) :

wherein R'is as described above, and RI is hydroxy, halogen, preferably chloro or fluoro, methyl, dimethylamino, methoxy, ethoxy, perhalomethyl, preferably trifluoromethyl, perhalomethoxy, preferably trifluoromethoxy, cyano, methylthio, acetyl, acetoxy, or hydroxymethyl.

In another preferred embodiment the invention relates to compounds of general formula (Ic) :

wherein R'is as defined above, and RI is 4-pyridyl, 5-hydroxypyrazin-2-yl, 5-chloro-6-hydroxypyridin-3-yl, 2-chloropyridin-3-yl, benzofuran-2-yl, benzothiophen-2-yl-, 7-methoxybenzofuran-2-yl, indolyl, preferably 1 H- indol-5-yl, benzimidazol, preferably 1 H-benzimidazol-5-yl or thienyl, preferably 5- chlorothiophen-2-yl.

In another preferred embodiment the invention relates to compounds of general formula (Ic) :

wherein R'is as defined above and R9 is indolyl, preferably 1 H-indol-5-yl or benzimidazol, preferably 1 H-benzimidazol-5-yl.

In the compounds of formula (Ic) RI is preferably benzothiophen-2-yl, indolyl, preferably 1 H- indol-5-yl, or benzimidazol, preferably 1 H-benzimidazol-5-yl.

In another preferred embodiment the invention relates to compounds of general formula (Id) :

wherein R 7is as defined above, and R'° is optionally substituted aralkyl as defined above, preferably 2- (4-methoxyphenyl)-ethenyl, 2- (3-methoxyphenyl)-ethenyl, 2- (4-chlorophenyl)- ethenyl, 2- (4-fluorophenyl)-ethenyl, 2- (4-trifluoromethylphenyl)-ethenyl, 2- (4-methoxy- phenyl)-ethyl, 2- (4-chlorophenyl)-ethyl, 4-chlorobenzyl, 4-methoxybenzyl, 2- (2-furyl)-ethenyl, 2- (4, 5-dimethyl-2-furyl)-ethenyl, 2- (5-methyl-2-furyl)-ethenyl, 2- (3-furyl)-ethenyl, 2- (2-thienyl)- ethenyl, or 2- (3-thienyl)-ethenyl.

In another preferred embodiment the invention relates to compounds of general formula (Id) :

wherein R'is as defined above, and R'° is 4-methoxyphenyl-2-ethenyl.

In the compounds of formula (Id) R'is preferably as defined above and R'° is optionally sub- stituted aralkyl as defined above, preferably 2- (4-methoxyphenyl)-ethenyl, 2- (2-furyl)-ethenyl, 2- (5-methyl-2-furyl)-ethenyl, 2- (3-furyl)-ethenyl, or 2- (3-thienyl)-ethenyl.

In another preferred embodiment the invention relates to compounds of general formula (le) :

wherein R"is pyridyl, preferably 4-pyridyl, and R6 and R8 independently are hydrogen, hydroxy, halogen, preferably chloro, bromo or fluoro, methyl, tert-butyl, phenyl, dimethylamino, methoxy, ethoxy, 2-dimethylaminoethoxy, 2- carboxyethenyl,2-morpholin-4-ylethoxy, perhalomethyl, preferably trifluoromethyl, perhalo-

methoxy, preferably trifluoromethoxy, carboxy, cyano, methylthio, methylsulfonyl, acetamido, nitro, acetyl, acetoxy, or hydroxymethyl.

In another preferred embodiment the invention relates to compounds of general formula (If) :

wherein R'° is optionally substituted aralkyl as defined above, preferably 2- (4- methoxyphenyl)-ethenyl, 2- (3-methoxyphenyl)-ethenyl, 2- (4-chlorophenyl)-ethenyl, 2- (4-<BR> fluorophenyl)-ethenyl, 2- (4-trifluoromethylphenyl)-ethenyl, 2- (4-methoxyphenyl)-ethyl, 2- (4-<BR> chlorophenyl)-ethyl, 4-chlorobenzyl, 4-methoxybenzyl, 2- (2-furyl)-ethenyl, 2- (4, 5-dimethyl-2- furyl)-ethenyl, 2- (5-methyl-2-furyl)-ethenyl, 2- (3-furyl)-ethenyl, 2- (2-thienyl)-ethenyl, or 2- (3- thienyl)-ethenyl, and R"is pyridyl, preferably 4-pyridyl.

In another preferred embodiment the invention relates to compounds of general formula (Ig) :

wherein R12 is aryl or aralkyl, and R6 and R8 independently are hydrogen, hydroxy, halogen, preferably chloro, bromo or fluoro, methyl, tert-butyl, phenyl, dimethylamino, methoxy, ethoxy, 2-dimethylaminoethoxy, 2- carboxyethenyl, 2-morpholin-4-ylethoxy, perhalomethyl, preferably trifluoromethyl, perhalo- methoxy, preferably trifluoromethoxy, carboxy, cyano, methylthio, methylsulfonyl, acetamido, nitro, acetyl, acetoxy, or hydroxymethyl.

In another preferred embodiment the invention relates to compounds of general formula (Ih) :

wherein R12 is aryl, preferably 4-trifluoromethoxyphenyl, or aralkyl, preferably benzyl, and R'3 is aralkyl as defined above, preferably 2- (4-methoxyphenyl)-ethenyl, 2- (3- methoxyphenyl)-ethenyl, 2- (4-chlorophenyl)-ethenyl, 2- (4-fluorophenyl)-ethenyl, 2- (4- trifluoromethylphenyl)-ethenyl, 2- (4-methoxyphenyl)-ethyl, 2- (4-chlorophenyl)-ethyl, 4- chlorobenzyl, 4-methoxybenzyl, 2- (2-furyl)-ethenyl, 2- (4, 5-dimethyl-2-furyl)-ethenyl, 2- (5- methyl-2-furyl)-ethenyl, 2- (3-furyl)-ethenyl, 2- (2-thienyl)-ethenyl, or 2- (3-thienyl)-ethenyl.

The most preferred compounds of the invention are: (+)- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-methoxyphenyl)- methanone, (compound No. 1), (-)- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-methoxyphenyl)- methanone, (compound No. 2), (+)- [4- (4-Methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yi]- (4- trifluoromethylphenyl)-methanone, (compound No. 3), (-)- [4- (4-Methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- trifluoromethylphenyl)-methanone, (compound No. 4), [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-methoxyphenyl)- methanone, (compound No. 5), (+)- [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yi]- (4- methoxyphenyl)-methanone, (compound No. 6), (-)- [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- methoxyphenyl)-methanone, (compound No. 7), [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (3-methoxyphenyl)- methanone, (compound No. 8), (+)- [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (3- methoxyphenyl)-methanone, (compound No. 9), (-)- [4- (4-Trifluoromethylphenyl)-4, 5, 6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (3-

methoxyphenyi)-methanone, (compound No. 10), [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl]-phenyl-methanone, (compound No. 11), (+)- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]-phenyl-methanone, (compound No. 12), (-)- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]-phenyl-methanone, (compound No. 13), (4- (2-Dimethylaminoethoxy) phenyl)- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridin-5-yl]-methanone, (compound No. 14), (+)- (4- (2-Dimethylaminoethoxy) phenyl)- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridin-5-yl]-methanone, (compound No. 15), (-)- (4- (2-Dimethylaminoethoxy) phenyl)- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridin-5-yl]-methanone, (compound No. 16), [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- (2- [2-morpholin-4- ylethoxy) phenyl]-methanone, (compound No. 17), (+)- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl]- (4- (2- [2-morpholin-4- ylethoxy) phenyl]-methanone, (compound No. 18), (-)- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- (2- [2-morpholin-4- ylethoxy) phenyl]-methanone, (compound No. 19), [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl]- (4- dimethylaminophenyl)-methanone, (compound No 20), 3- {4- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine-5-carbonyl] phenyl} acrylic acid, (compound No 21), (4-Chlorophenyl)- [4- (4-chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]-methanone, both the racemate, the two pure enantiomers, and mixtures thereof (compound No 22), [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-methoxyphenyl)- methanone, (compound No. 24), [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]-(4-methoxyphenyl)- methanone, (compound No. 25), [4- (2-Dimethylaminoethoxy)-phenyl]- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridin-5-yl]-methanone, (compound No. 26), [4- (2-Dimethylaminoethoxy)-phenyl]- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridin-5-yl]-methanone, (compound No. 27), [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- [4- (2-morpholin-4-

ylethoxy) phenyl]-methanone, (compound No. 28), (4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- [4- (2-morpholin-4- ylethoxy) phenyl]-methanone, (compound No. 29), [4- (4-Trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- methoxyphenyl)-methanone, (compound No. 30), [4- (4-Trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- methoxyphenyl)-methanone, (compound No. 31), [4- (4-Trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]-(4- methoxyphenyl)-methanone, (compound No. 32), [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (1 H-indol-5-yl)-methanone, (compound No. 33), (1 H-indol-5-yl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- methanone, (compound No. 34), (4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-fluorophenyl)-methanone, (compound No. 35), [4- (4-Trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-fluorophenyl)- methanone, (compound No. 36), 4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- [4- (2- dimethylaminoethoxy) phenyl]-methanone, (compound No. 37), [4- (2-Dimethylaminoethoxy) phenyl]- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridin-5-yl]-methanone, (compound No. 38), [7-Chloro-1- (2, 3-dihydrobenzofuran-7-yl)-8-methoxy-1, 2,4,5-tetrahydrobenzo [d] azepin-3-yl]- [4- (2-dimethylaminoethoxy)-phenyl]-methanone, (compound No. 39), [4- (3, 4-Dimethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [2,3-c] pyridin-6-yl]- [4- (2- dimethylaminoethoxy)-phenyl]-methanone, (compound No. 40), (3,4-Dimethoxyphenyl)- [4- (4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno [3,2-c] pyridin- 5-yl] methanone, (compound No. 41), (3-Chloro-4-methoxyphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2- c] pyridin-5-yl] methanone, (compound No. 42), (4-Ethoxyphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5- yl] methanone, (compound No. 43), (4-Methylphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone, (compound No. 44), 3- (4-Methoxyphenyl)-1- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-

5-yl] propenone, (compound No. 45), (1 H-Benzimidazol-5-yl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin- 5-yl] methanone, (compound No. 46), (4-Methoxyphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- methanone [4- (4-Trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- methoxyphenyl)-methanone [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- methylsulfanylphenyl)-methanone 4- [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine-5-carbonyl] benzoic acid methyl ester (4-Hydroxymethylphenyl)- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin- 5-yl] methanone (4-Acetoxyphenyl)- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone (4-Cyanophenyl)- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone 1- {4- [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine-5- carbonyl] phenyl} ethanone 3-Furan-2-yl-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propenone 3- (5-Methylfuran-2-yl)-l- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5- yl] propenone Benzo [b] thiophen-2-yl-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin- 5-yl] methanone 3-Furan-3-yl-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propenone 3-Thiophen-3-yl-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propenone 3-Thiophen-2-yl-1- [4- (4-trifluoromethylphenyl)-4, 5, 6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propenone [4- (4-Methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- methylsulfanylphenyl) methanone 4- [4- (4-Methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine-5-carbonyl] benzonitrile

3-Furan-3-yl-1- [4- (4-methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl] propenone (4-Methoxyphenyl)- [4- (4-methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone (4-Fluorophenyl)- [4- (4-methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5- yl] methanone (4-Chlorophenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone (4-Methylsulfanylphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5, 6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] methanone (4-Dimethylaminophenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] methanone (4-Hydroxymethylphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yi] methanone 3-Furan-3-yl-1- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propenone 4- (4-Chlorophenyl)-5- (4-methoxybenzyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine hydrochlo- ride [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- hydroxyphenyl) methanone 1- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]-2- (4- methoxyphenyl) ethanone [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (3- dimethylaminophenyl) methanone N- {4- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine-5-carbonyl]- phenyl} acetamide [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- methanesulfonylphenyl) methanone 2- (4-Chlorophenyl)-1- [4- (4-chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] ethanone 2- (4-Methoxyphenyl)-1- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin- 5-yl]-ethanone (3-Dimethylaminophenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5, 6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl]-methanone

N- {4- [4- (4-Trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine-5-carbonyl]- phenyl}-acetamide (4-Methanesulfonylphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl]-methanone 2- (4-Chlorophenyl)-1- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl]-ethanone Biphenyl-4-yl- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone (3,4-Dichlorophenyl)- [4- (4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone (4-tert-Butylphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone Pyridin-4-yl- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone (5-Hydroxypyrazin-2-yl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin- 5-yl] methanone (5-Chloro-6-hydroxypyridin-3-yl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yi] methanone 3- (4, 5-Dimethylfuran-2-yl)-l- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] propenone (1-Benzyl-1, 2,3,4-tetrahydro-isoquinolin-2-yl)- (4-methoxyphenyl) methanone (1-Benzyl-1, 2, 3,4-tetrahydro-isoquinolin-2-yl)- (4-chlorophenyl) methanone (1 H-Benzoimidazol-5-yl)- (1-benzyl-1, 2,3,4-tetrahydro-isoquinolin-2-yl) methanone 1-(1-Benzyl-1, 2,3,4-tetrahydro-isoquinolin-2-yl)-3-furan-3-ylpropenone 1- (1-Benzyl-1, 2,3,4-tetrahydro-isoquinolin-2-yl)-3- (4-methoxyphenyl) propenone 1- (1-Benzyl-1, 2,3,4-tetrahydro-isoquinolin-2-yi)-3- (4-methoxyphenyl) propan-l-one 1- (1-Benzyl-1, 2, 3, 4-tetrahydro-isoquinolin-2-yl)-2- (4-methoxyphenyl) ethanone (5-Chlorothiophen-2-yl)- (4-pyridin-4-yl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl) methanone (5-Chlorothiophen-2-yi)- [4- (4-dimethylaminophenyl) 4,5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl)-methanone (5-Chlorothiophen-2-yl)- [4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl) methanone (4-Hydroxymethylphenyl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl) methanone

(4- (4-Dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)- (4- hydroxymethylphenyl)-methanone [4- (4-Nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl)- (4-hydroxymethylphenyl)- methanone (4-Chlorophenyl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl) methanone (4-Chlorophenyl)- (4-pyridin-4-yi-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone (4-Chlorophenyl)- [4- (4-dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)- methanone (4-Chlorophenyl)- [4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone (4-Methoxyphenyl)- [4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone (4-Methoxyphenyl)- (4-pyridin-4-yl-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl)-methanone [4- (4-Dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-methoxyphenyl)- methanone [4- (4-Dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-methoxyphenyl)- methanone 3- (4-Methoxyphenyl)-1- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]-propenone (5-Chlorothiophen-2-yl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone 3-(4-Methoxyphenyl)-1-(4-pyridin-4-yl-4,5,6,7-tetrahydro-thi eno[3,2-c] pyridin-5-yl)-propenone 1- [4- (4-Dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-3- (4- methoxyphenyl)-propenone 3- (4-Methoxyphenyl)-1- (4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)- propenone (4-Dimethylaminophenyl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone (4-Dimethylaminophenyl)- (4-pyridin-4-yl-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl)- methanone (4-Dimethylaminophenyl)- [4- (4-dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin- 5-yl]-methanone (4-Dimethylaminophenyl)- [4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- methanone (1 H-Benzoimidazol-5-yl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone (1 H-Benzoimidazol-5-yl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone (1 H-Benzoimidazol-5-yl)- [4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- methanone (4-Fluorophenyl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone

(4-Fluorophenyl)- (4-pyridin-4-yl-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl)-methanone [4- (4-Dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-fluorophenyl)- methanone (4-Fluorophenyl)- [4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]-methanone (4-Bromophenyl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone (4-Bromophenyl)- (4-pyridin-4-yl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone (4-Bromophenyl)- [4- (4-dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- methanone (4-Bromophenyl)- [4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone 3-Furan-3-yl-1- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-propenone 3- (3-Furan-3-yl)-1- (4-pyridin-4-yl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-propenone 1- [4- (4-Dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-3- (3-furan-3-yl)- propenone 3- (3-Furan-3-yl)-1- [4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-propenone [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-hydroxyphenyl)- methanone, less polar enantiomer, [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl]- (4-hydroxyphenyl)- methanone, more polar enantiomer, (1 H-Benzoimidazol-5-yl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] methanone, less polar enantiomer, (1 H-Benzoimidazol-5-yl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2- c] pyridin-5-yl] methanone, more polar enantiomer, (5-Chlorothiophen-2-yl)- (1- (4-trifluoromethoxyphenyl)-1, 2,3,4-tetrahydroisoquinolin-2-yl]- methanone (4-Chlorophenyl)- [l- (4-trifluoromethoxyphenyl)-1, 2,3,4-tetrahydroisoquinolin-2-yl]-methanone (4-Methoxyphenyl)- [l- (4-trifluoromethoxyphenyl)-1, 2, 3,4-tetrahydroisoquinolin-2-yl]- methanone 3- (4-Methoxyphenyl)-1- [1- (4-trifluoromethoxyphenyl)-1, 2, 3,4-tetrahydroisoquinolin-2- yl] propenone 3-Furan-3-yl-1- (1- (4-trifluoromethoxyphenyl)-1, 2,3,4-tetrahydroisoquinolin-2-yl] propenone (4-Trifluoromethoxyphenyl)- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] methanone (7-Methoxybenzofuran-2-yl)- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] methanone

Benzofuran-2-yl- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone 3- (4-Fluorophenyl)-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- propenone 3- (4-Trifluoromethylphenyl)-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] propenone 3- (3-Methoxyphenyl)-1- [4- (4-trifluoromethylphenyl)-4, 5, 6,7-tetrahydro-thieno [3, 2-c] pyridin-5- yl] propenone 3- (4-Chlorophenyl)-1- [4- (4-trifluoromethylphenyl)-4, 5, 6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propenone 3- (4-Methoxyphenyl)-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propan-1-one 3- (4-Chlorophenyl)-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propan-1-one and salts thereof with a pharmaceutically acceptable acid or base.

The compounds of the present invention are normoglycaemic agents (i. e. compounds that are able to normalise blood glucose levels from hyper-/hypoglycemic conditions) that interact with the glucose-6-phosphatase catalytic enzyme activity, and hence make them useful in the treatment and prevention of various diseases of the endocrinological system, especially ailments related to carbohydrate metabolism and especially the glucose metabolism, e. g. hyperglycaemia, diabetes mellitus, and especially non-insulin dependent diabetes mellitus (NIDDM) including long-term complications, such as retinopathy, neuropathy, nephropathy, and micro-and macroangiopathy, and hypoglycaemia resulting from, e. g., glycogen storage disease (von Gierke's Disease all types). Moreover, the present compounds are useful in the prophylactic treatment of hyperlipidaemia, hypertension, liver and bile diseases, and athero- sclerosis associated with diabetes. The present compounds are especially useful in the treatment of diseases associated with an increased or reduced activity of the glucose-6- phosphatase complex, e. g. the G-6-Pase catalytic enzyme.

Accordingly, in another aspect the invention relates to a compound of the general formula 1, la, lb, lc or a pharmaceutically acceptable acid addition salt or other salt as defined above thereof for use as a therapeutical acceptable substance, preferably for use as a therapeuti-

cally acceptable substance in the treatment of hyperglycaemia and treatment or prevention of diabetes.

Furthermore, the invention also relates to the use of the inventive compounds of formula 1, la, lb, and Ic as medicaments useful for treating hyperglycaemia and treating or preventing diabetes.

In yet another aspect, the present invention relates to methods of preparing the above men- tioned compounds. Methods of preparing compounds of general formula I comprises: Method A : When R2 is COR3 : Reacting a compound of formula X with a compound of formula Y to form compounds of general formula Ib : Ra p base Ra H L R A a ( 5\\i"y (CH ) R A R Ri R Ri Xi tub wherein R', R3, R4, R5, n, and m are as defined above and L is a leaving group and are se- lected from fluorine, chlorine, bromine, iodine, 1-imidazolyl, 1,2,4-triazolyl, 1- benzotriazolyloxy, 1- (4-aza benzotriazolyl) oxy, pentafluorophenoxy, N-succinyloxy 3,4- dihydro-4-oxo-3- (1, 2,3-benzotriazinyl) oxy, R3COo where R3 is as defined above, or any other leaving group known to act as a leaving group in acylation reactions. The base can be either absent (i. e. compound X acts as a base) or triethylamine, N-ethyl-N, N.- diisopropylamine, N-methylmorpholine, 2, 6-lutidine, 2,2,6,6-tetramethylpiperidine, potassium carbonate, sodium carbonate, caesium carbonate or any other base known to be useful in acylation reactions.

Method B:

When R2 is optionally substituted C, 4 alkyl or aralkyl : a) Reacting a compound of formula X with a compound of formula Z in an alkylation reaction to form compounds of general formula) : 4 buse R (CH2) m 2 NH/R-- A N-R R g (dH2). R 5'11 2). R x z I XZ j

wherein R', R2, R4, R5, n, and m are as defined above, M is a leaving group and is selected from chlorine, bromine, iodine, methanesulfonyloxy, trifluoromethanesulfonyloxy, p- toluenesulfonyloxy or any other group known to act as a leaving group in alkylation reac- tions. The base can be either absent (i. e. compound X acts as a base) or triethylamine, N- ethyl-N, N.-diisopropylamine, N-methylmorpholine, 2,6-lutidine, 2,2,6,6-tetramethylpiperidine, potassium carbonate, sodium carbonate, caesium carbonate or any other base known to be useful in alkylation reactions.

Method C Reacting a compound of formula X with an aldehyde of formula Zz in a reductive alkylation reaction to form compounds of general formula) : R N ° Reducng agent R (CHZ) m PN K 11-A I N- R R" \5 r 2 n R R R R Zu wherein R', R2, R4, R5, n, and m are as defined above, R"is as defined for R2 but one (1) carbon atom shorter. The reducing agent can be selected from the following list : NaCNBH3, NaBH (OAc) 3, diborane, BH3 complexes (eg. with tetrahydrofuran or dimethylsulfide), metallic

sodium, or H2/catalyst or any reductant known to be effective in the reductive alkylation re- action.

Or the compounds of formulae I, la, Ib, and Ic may be prepared by art-recognized procedures from known compounds or readily reparable intermediates.

The starting materials are either known compounds or compounds which may be prepared in analogy with the preparation of known compounds or in analogy with known methods as de- scribed by e. g Tupper D. E. et al., J. Heterocyclic Chem., 33,1123-9 (1996), Stokker G. E., Tetrahedron Lett., 37,5453-6 (1996), Nakagawa, M. et al., Chem. Pharm. Bull., 41,287-91 (1993), Singh H. et al., Heterocycles, 23, 107-10 (1985), Skinner W. A. et al., Can. J. Chem., 43,2251-3 (1965). P. Kumar et al., J. Heterocyclic Chem., 19,677-9 (1982), L. K. Lukanov et al., Synthesis, 1987,204-6, A. L. Stanley & S. P. Stanforth, J. Heterocyclic Chem., 31,1399-1400 (1994), A. K. Bose et al., J. Org. Chem., 56,6968-70 (1991), K. Kementani et al., Heterocycles, 3,311-41 (1975), E. Domonguez et al., Tetrahedron, 43,1943-8 (1987), J. B. Bremner et al., Aust. J. Chem., 41, 1815-26 (1988), M. J. O'Donnel et al., Tetrahedron. Lett., 23,4259-62 (1982).

Pharmacological methods The ability of compounds to inhibit glucose-6-phosphatase (G-6-Pase) catalytic enzyme ac- tivity from pig liver microsomes was tested in the following way: Pig liver microsomes were prepared in a buffer containing 250 mM sucrose, 1 mM EDTA, 25 mM HEPES and 250 mg/l Bacitrazin (pH 7.5) essentially as described by Arion et al., 1980 (Arion, Lange, & Walls. 1980). Microsomes were kept at-80 °C until use.

Prior to measurement microsomes were treated with Triton X-100 (0.04%) ("disrupted micro- somes"). G-6-Pase activity were assayed for 6 min at 30°C in a total volume of 325 uL con- taining 0.5 mM glucose-6-phosphate, 30 mM MES (pH 6.5), test compound and disrupted microsomes (0.05 mg). The reaction was terminated by addition of 100 uL Sigma phospho- rus reagent (cat no 360-3C). This mixture was allowed to stand for 2 min, where the absor- bance (A) was measured at 340 nm. All values were corrected for blank. The inhibitory effect was expressed as percent of control value, i. e. iCso is the concentration of a compound that produces 50% inhibition.

The compounds of the invention are preferably characterized by having a glucose-6- phosphatase inhibitory activity corresponding to an ICgo value of less than 100 ZM, more preferably less than 10 pM, even more preferably less than 1 uM, still more preferably less than 100 nM.

The compounds according to the invention are effective over a wide dosage range. In gen- eral satisfactory results are obtained with dosages from about 0.05 to about 1000 or 5000mg, preferably from about 0.1 to about 500 mg, per day. A most preferable dosage is about 5 mg to about 200 mg per day. The exact dosage will depend upon the mode of ad- ministration, form in which the compound is administered, the subject to be treated and the body weight of the subject to be treated, and the preference and experience of the physician or veterinarian in charge.

The dosage unit of the pharmaceutical compositions according to the invention typically contains from 0.05mg to 1000mg, preferably from 0. 1 mg to 500mg, or, preferably from 5mg to 200mg per day of the active ingredient, which is, preferably, a novel 4,5,6,7-tetrahydro- thieno [3,2-c] pyridine derivative as described herein or a pharmaceutical acceptable salt thereof with a pharmaceutical acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form thereof; or the active ingredient is a previously described 4,5,6,7-tetrahydro-thieno [3,2-c] pyridine derivative or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form thereof.

The route of administration may be any route, which effectively transports the active com- pound to the appropriate or desired site of action, such as oral, nasal, pulmonary, transder- mal or parenteral e. g. rectal, depot, subcutaneous, intravenous, intraurethral, intramuscular, intrapulmonary, intranasal, ophthalmic solution or an ointment, the oral route being pre- ferred.

Optionally, the pharmaceutical composition of the invention may comprise a compound of for- mula I combined with one or more compounds exhibiting a different activity, e. g., a plasma lipid

lowering compounds, sulphonylurea like compounds, or other oral agents useful in the treat- ment of diabetes, or other pharmacologically active material.

Pharmaceutical compositions containing a compound of the present invention may be pre- pared by conventional techniques, e. g. as described in Remington : The Science and Practise of Pharmacy. 19 Ed.. 1995. The compositions may appear in conventional forms, for example capsules, tablets, aerosols, solutions, suspensions or topical applications.

Typical compositions include a compound of formula I or a pharmaceutically acceptable acid addition salt or metal salt thereof, associated with a pharmaceutical acceptable excipient which may be a carrier or a diluent or be diluted by a carrier, or enclosed within a carrier which can be in form of a capsule, sachet, paper or other container. In making the composi- tions, conventional techniques for the preparation of pharmaceutical compositions may be used. For example, the active compound will usually be mixed with a carrier, or diluted by a carrier, or enclosed within a carrier which may be in the form of a ampoule, capsule, sachet, paper, or other container. When the carrier serves as a diluent, it may be solid, semi-solid, or liquid material which acts as a vehicle, excipient, or medium for the active compound. The active compound can be adsorbed on a granular solid container for example in a sachet.

Some examples of suitable carriers are water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, gelatine, lactose, amylose, magnesium stearate, talc, sil- icic acid, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, hy- droxymethylcellulose and polyvinylpyrroiidone. Similarly, the carrier or diluent may include any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. The formulations may also include wetting agents, emulsifying and suspending agents, preserving agents, sweetening agents or flavouring agents. The formulations of the invention may be formulated in any galenic dosage form so as to provide quick, sustained, or delayed release of the active ingredient after ad- ministration to the patient by employing procedures well known in the art. The pharma- ceutical preparations can be sterilized and mixed, if desired, with auxiliary agents, emulsifi- ers, salt for influencing osmotic pressure, buffers and/or coloring substances and the like, which do not deleteriously react with the active compounds.

For administration, preferably nasal administration, the preparation may contain a compound of formula 1, la, lb or Ic dissolved or suspended in a liquid carrier, in particular an aqueous car-

rier, for aerosol application. The carrier may contain additives such as solubilizing agents, e. g. propylene glycol, surfactants, absorption enhancers such as lecithin (phosphatidylcholine) or cyclodextrin, or preservatives such as parabenes. For parenteral application, particularly suit- able are injectable solutions or suspensions, preferably aqueous solutions with the active compound dissolved in polyhydroxylated castor oil. Tablets, dragees, or capsules having talc and/or a carbohydrate carrier or binder or the like are particularly suitable for oral application.

Preferable carriers for tablets, dragees, or capsules include lactose, corn starch, and/or po- tato starch. A syrup or elixir can be used in cases where a sweetened vehicle can be em- ployed.

A typical tablet, appropriate for use in this method, may be prepared by conventional tablet- ting techniques and contains: Core: Active compound (as free compound or salt thereof) 5.0 mg Colloidal silicon dioxide (Aerosil) 1.5 mg Cellulose, microcryst. (Avicel) 70 mg Modified cellulose gum (Ac-Di-Sol) 7.5 mg Magnesium stearate Ad.

Coating: HPMC approx. 9 mg *Mywacett 9-40 T approx. 0.9 mg *Acylated monoglyceride used as plasticizer for film coating.

Due to their high degree of activity, the compounds of the invention may be administered to a mammal in need of such treatment, prevention, elimination, alleviation or amelioration of various diseases as mentioned above and especially of diseases of the endocrinological system such as hyperinsulinaemia and diabetes. Such mammals include both domestic ani- mals, e. g. household pets, and non-domestic animals such as wildlife. Preferably the mam- mal is a human.

EXAMPLES The process for preparing compounds of formula 1, la, lb, and/or Ic and preparations con- taining them is further illustrated in the following examples which, however, are not to be construed as limiting.

EXAMPLE 1 Preparation of [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-methoxyphenyl)- methanone, (compound No. 5) 4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine (100 mg, 0.35 mmol) was dissolved in dichloromethane (0.5 mL) and triethylamine (0.5 mL) was added. To this solution p-anisoyl chloride (60 mg, 0.35 mmol) dissolved in dichloromethane (0.5 ml) was added in one portion. The mixture was filtered and evaporated to afford 148 mg (100%) of the title compound MS (electrospray) : m/z 418 (M+1) HR-MS: Calculated for C22H'8F3NO2S : 417.1010, Found: 417.0999.

EXAMPLE 2 : Preparation of [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (3-methoxyphenyl)- methanone, (compound No. 8)

4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine (100 mg, 0.35 mmol) was dissolved in dichloromethane (1 mL) and diisopropylethylamine (0.5 mL) was added. To this solution m-anisoyl chloride (50 pL, 0.35 mmol) was added. The mixture was shaken overnight and evaporated to afford the title compound MS (electrospray) : m/z 418 (M+1) HR-MS: Calculated for C22H, 8F3NO2S : 417.1010, Found: 417.1020.

EXAMPLE 3: Preparation of [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]-phenyl-methanone, (compound No 11) Benzoic acid (46 mg, 0.38 mmol) and 1-hydroxybenzotriazole (55 mg, 0.41 mmol) were dis- solved in a mixture of dichloromethane (1 mL) and N, N-dimethylformamide (0.5 mL). N- (3- Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (79 mg, 0.41 mmol) was added and the mixture was shaken 0.5 hour at room temperature. 4- (4-Chlorophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine (100 mg, 0.38 mmol) dissolved in dichloromethane (0.5 ml)

was added and the mixture was shaken at 1000 rpm for 3 hours. Water (1 mL) was added and the mixture was shaken at 1000 rpm overnight at room temperature. The organic phase was evaporated to give 129 mg (97%) of the title compound as an oil.

MS (electrospray) : m/z 354 (M+1) HR-MS: Calculated for CgONCS : 353.0641, Found: 353.0646.

EXAMPLE 4: Preparation of (4- (2-Dimethylaminoethoxy) phenyl)- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridin-5-yl]-methanone, (compound No 14) Methyl 4-hydroxybenzoate (10 g, 66 mmoles) was dissolved in N, N-dimethylformamide (200 mL). Potassium carbonate (45 g, 0.33 moles) and 2-chloro-N, N-dimethylethylamine hydro- chloride (14.2 g, 99 mmoles) were added and the resulting mixture was stirred vigorously at room temperature for 7 days. More 2-chloro-N, N-dimethylethylamine hydrochloride (3 g, 20 mmoles) was added and stirring at room temperature was continued for 2 days. The reaction mixture was poured into water (600 mL) and extraction with ethyl acetate (2 x 200 mL), washing of the combined organic phases with water (200 mL), drying over MgSO4 and evaporation afforded 11.9 g (81 %) of methyl 4- (2-dimethylaminoethoxy) benzoate as an oil.

The above benzoate (11.9 g, 53 mmoles) was dissolved in 5 N hydrochloric acid and the mixture was heated at reflux temperature for 2 days. Cooling, filtration and washing with water afforded 8.63 g (66%) of 4- (2-dimethylaminoethoxy) benzoic acid hydrochloride as crystals.

The above benzoic acid (93 mg, 0.38 mmoles) was suspended in N, N-dimethylformamide (1 mL). 1-Hydroxybenzotriazole (55 mg, 0.42 mmotes), N- (3-dimethylaminopropyl)-N'- ethylcarbodiimide hydrochloride (79 mg, 0.42 mmoles), and triethylamine (106 pL, 0.76 mmoles) were added and the resulting mixture was shaken at 1000 rpm for 1.5 hour. 4- (4- Trifluoromethyiphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridine (108 mg, 0.38 mmoles) were added and the resulting mixture was shaken at 1000 rpm for 3 hours. Water (2 mL) and ethyl acetate (1 mL) were added and the resulting mixture was shaken at 1000 rpm for 15 min- utes. The organic phase was evaporated to afford 144 mg (80%) of the title compound as an oil.

MS (eiectrospray) : m/z 475.0 (M+1) HR-MS: Calculated for C2sH25F3N202S : 474.1588, Found: 474.1580.

EXAMPLE 5: Preparation of (4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- [4- (2-morpholin-4- ylethoxy) phenyl]-methanone, (compound No 17) Methyl 4-hydroxybenzoate (10 g, 66 mmoles) was dissolved in N, N-dimethylformamide (200 mL). Potassium carbonate (45 g, 0.33 moles) and 4- (2-chloroethyl) morpholine hydrochloride (18.3 g, 99 mmoles) were added and the resulting mixture was stirred vigorously at room temperature for 5 days. The reaction mixture was poured into water (500 mL) and extraction with ethyl acetate (2 x 250 mL), washing of the combined organic phases with water (200 mL), drying over MgS04 and evaporation afforded 16.8 g (96%) of methyl 4- (2-morpholin-4- ylethoxy) benzoate as an oil.

The above benzoate (16.8 g, 63 mmoles) was dissolved in 5 N hydrochloric acid and the mixture was heated at reflux temperature for 16 hours. Cooling, filtration and washing with water afforded 15.6 g (86%) of 4- (2-morpholin-4-ylethoxy) benzoic acid hydrochloride as crystals.

The above benzoic acid (111 mg, 0.38 mmoles) was suspended in N, N-dimethylformamide (1 mL). 1-Hydroxybenzotriazole (55 mg, 0.42 mmoles), N- (3-dimethylaminopropyl)-N'- ethylcarbodiimide hydrochloride (79 mg, 0.42 mmoles), and triethylamine (106 uL, 0.76 mmoles) were added and the resulting mixture was shaken at 1000 rpm for 1.5 hour. 4- (4- Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine (100 mg, 0.38 mmoles) was added and the resulting mixture was shaken at 1000 rpm for 3 hours. Water (2 mL) and ethyl ace- tate (1 mL) were added and the resulting mixture was shaken at 1000 rpm for 15 minutes.

The organic phase was evaporated to afford 122 mg (66%) of the title compound as an oil.

MS (electrospray) : m/z 483.0 (M+1) HR-MS: Calculated for C26H27CIN203S : 482.1431, Found: 482.1430.

EXAMPLE 6 : Preparation of (+)- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yi]- (4-methoxyphenyl)- methanone, (compound No 1) [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-methoxyphenyl)- methanone (30 mg) was dissolved in a 1: 1 mixture of n-heptane and 2-propanoi (5 mL) and fractionated by HPLC (2 runs) using a 21.1 x 250 mm (R, R)-Whelk-O column (Regis). The

column was eluted isocratically with a 1: 1 mixture of n-heptane and 2-propanol at a flow rate of 12 mL/min and fractions collected corresponding to 0.8 min/fraction. The eluting enanti- omers were detected spectroscopically by measuring absorbance at a wavelength of 225 nm. Two eluting peaks were detected, one corresponding to TR 44-50 min and one corre- sponding to TR 62-72 min. Fractions from the two runs corresponding to TR 44-50 min were separately pooled and evaporated to yield 12.1 mg of the title compound.

100% ee (Determined by HPLC using a 4.6 x 250 mm (R, R)-Whelk-O column eluted with a 1: 1 mixture of n-heptane and 2-propanol, the flow rate was 1 ml/min, eluting sample was monitored spectroscopically at 225 and 245 nm, TR 15.5 min).

EXAMPLE 7 : Preparation of (-)- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yi]- (4-methoxyphenyl)- methanone, (compound No 2) Fractions from the two runs of example 6 corresponding to TR 62-72 min were separately pooled and evaporated to yield 12.5 mg of the title compound 98% ee (Conditions as described in example 6, TR 20.8 min).

Optical rotation, using a Perkin Elmer Polarimeter (Model 241): [aJ2°D=-170. 0 (c=0.25, ethyl acetate).

EXAMPLE 8 : Preparation of (+)- [4- (4-Methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl]- (4- trifluoromethylphenyl)-methanone, (compound No 3)

[4- (4-Methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yi]- (4-trifluoromethylphenyl)- methanone (17 mg) was dissolved in a 1: 2: 2 mixture of ethyl acetate, n-heptane and 2- propanol (2.5 mL) and fractionated by HPLC using a 21.1 x 250 mm (R, R)-Whelk-O column (Regis). The column was eluted isocratically with a 1: 1 mixture of n-heptane and 2-propanol at a flow rate of 10 mUmin and fractions collected corresponding to 1 min/fraction. The eluting enantiomers were detected spectroscopically by measuring absorbance at a wave- length of 225 nm. Two eluting peaks were detected, one corresponding to TR 27-32 min and one corresponding to TR 62-74 min. Fractions corresponding to TR 27-32 min were pooled and evaporated to yield 7.1 mg of the title compound 100% ee (Determined by HPLC using a 4.6 x 250 mm (R, R)-Whelk-O column eluted with a 1: 1 mixture of n-heptane and 2-propanol, the flow rate was 1 mL/min, eluting sample was monitored spectroscopically at 225 and 245 nm, TR 9. 2 min) Optical rotation, using a Perkin Eimer Polarimeter (Model 241), [a] 20D= + 175.4 (c=0.142, ethyl acetate).

EXAMPLE 9 : Preparation of (-)- [4- (4-Methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- trifluoromethylphenyl)-methanone, (compound No 4)

Fractions from the two runs of example 8 corresponding to TR 62-74 min were separately pooled and evaporated to yield 6.8 mg of the title compound.

>99.5% ee (Conditions as described in example 8, TR 17.0 min).

[a] 20D=-170. 6 (c=0.136, ethyl acetate).

EXAMPLE 10: [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl]- (4- dimethylaminophenyl)-methanone, (compound No 20) 4-Dimethylaminobenzoic acid (0.20 g, 1.2 mmol) was dissolved in N, N-dimethylformamide (3 ml) and 1-hydroxybenzotriazole (0. 20 g, 1.5 mmol) was added. To the resulting mixture N- (3- dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.28 g, 1.5 mmol) was added and the mixture was stirred at room temperature for 15 minutes. 4- (4-Trifluoromethylphenyl)- 4,5,6,7-tetrahydro-thieno [3,2-c] pyridine (0.41 g, 1.5 mmol) followed by diisopropylethylamine (0.42 ml, 2.4 mmol) were added and the mixture was stirred at room temperature for 16 hours. water (2 ml) was added and the mixture was extracted with ethyl acetate (2 x 5 ml).

The combined organic extracts were washed with saturated aqueous sodium chloride solu- tion (4 ml), dried (MgSO4) and concentrated in vacuo to afford the title compound MS (electrospray) : m/z 431 (M+1) HPLC (Method B): Rt = 29 min.

EXAMPLE 11: 3- {4- [4- (4-Chlorophenyl)-4, 5, 6,7-tetrahydro-thieno [3,2-c] pyridine-5-carbonyl] phenyl} acrylic acid, (compound No 21) (E)-4- (2-tert-Butoxycarbonylvinyl) benzoic acid (0.36 g, 1.4 mmol) was dissolved in N, N- dimethylformamide (50 ml) and 1-hydroxybenzoetriazole (0.20 g, 1.4 mmol) and N- (3- dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.28 g, 1.4 mmol) were added and the mixture was stirred at room temperature for 20 minutes. 4- (4-Chlorophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine (0.30 g, 1.2 mmol) and N-ethyl-N, N-diisopropylamine (420 ul, 2.4 mmol) were added to the mixture and stirring at room temperature was continued for 16 hours. The mixture was diluted with water (50 ml) and extracted with ethyl acetate (3 x 50 ml). The combined organic extracts were washed with saturated sodium chloride (80 ml), dried over MgS04 and concentrated in vacuo. The residue was purified by coloumn chro- matography over silica gel (60 ml) eluting with a mixture of ethyl acetate and heptane (1: 2).

This afforded 0.56 g (97%) of 3- {4- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c]- pyridine-5-carbonyl] phenyl} acrylic acid tert butyl ester as an oil.

'H-NMR (300 MHz, DMSO-dg) : 8 = 1.50 (9H, s), 2.8-3.1 (2H, m), 3.25 (1H, m), 3.65 (1H, m), 6.58! 1H, d), 6.78 (1H, bs), 6.87 (1H, d), 7.3-7.45 (7H, m), 7.60 (1H, d), 7.77 (2H, d).

The above ter-butyl ester (0.30 g, 0.62 mmol) was dissolved in dichloromethane (3 ml) and the mixture was cooled to 0 °C. At 0 °C trifluoroacetic acid (3 ml) was added and the mixture was stirred at 0 °C for 30 minutes. The mixture was concentrated in vacuo. The residue was dissolved in dichloromethane (5 ml), concentrated in vacuo dissolved again in methanol (5 ml) and concentrated in vacuo. 10.6 mg of the residue was dissolved in 750 ; J methane) and purified by preparative HPLC using a Gilson binary gradient HPLC system equipped with 305/306 master/slave pumps, 117 UV detector and fraction collector. The eluting sample was detected at 210 and 225 nm. Flow rate was 15 minute. The column was 20*250 mm ODS 10 um (YMC) eluted with a gradient of acetonitrile (solvent B) and de-ionised water added 0.05% TFA (solvent A), 45% B to 100% B over 30 minutes. Fractions corresponding to TR 12-14 minutes were pooled to yield 8.3 mg of the title compound.

MS: m/z 424 (M+1).

EXAMPLE 12: (4-Chlorophenyl)- [4- (4-chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]-methanone, (compound No 22), less polar enantiomer (4-Chlorophenyl)- [4- (4-chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]-methanone (4.1 mg) was dissolved in a 1: 2: 4 mixture of ethyl acetate, heptane and 2-propanol (3.5 ml) and fractionated by HPLC using a 21.1 x 250 mm (R, R)-Whetk-O column (Regis). The col- umn was eluted isocratically with a 1: 1 mixture of heptane and 2-propanol at a flow rate of 10 ml/min and fractions collected corresponding to 1 min/fraction. The eluting enantiomers were detected spectroscopically by measuring absorbance at a wavelength of 225 nm. Two eluting peaks were detected, one corresponding to TR 28-32 mininutes and one correspond-

ing to TR 51-58 minutes. Fractions corresponding TR 28-32 minutes were pooled and evapo- rated to yield 1.8 mg of the title compound 100% ee (Determined by HPLC using a 4.6 x 250 mm (R, R)-Whelk-O column eluted with n- heptane: 2-propanol (1: 1), the flow rate was 1 ml/min, eluting sample was monitored spectro- scopically at 225 nm, TR9. 9 min) EXAMPLE 13: (4-Chlorophenyl)- [4- (4-chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]-methanone, (compound No 23), more polar enantiomer Fractions from example 12 corresponding to TR 51-58 minutes were pooled and evaporated to yield 2.6 mg of the title compound.

99.5% ee (Conditions as described in example 12, TR 15. 5 min).

EXAMPLE 14: [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-methoxyphenyl)- methanone, (compound No. 24), less polar enantiomer

[4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yi]- (4-methoxyphenyl)- methanone (11.2 mg) was dissolved in a 1: 1 mixture of heptane and 2-propanol (2 ml) and fractionated by HPLC using a 21.1 x 250 mm (R, R)-Whelk-O column (Regis). The column was eluted isocratically with a 1: 1 mixture of heptane and 2-propanol at a flow rate of 10 ml/min and fractions collected corresponding to 1 minute/fraction. The eluting enantiomers were detected spectroscopically by measuring absorbance at a wavelength of 225 nm. Two eluting peaks were detected, one corresponding to TR 40-43 minutes and one corresponding to TR 55-59 minutes. Fractions corresponding to TR 40-43 minutes were pooled and evapo- rated to yield 4.0 mg of the title compound >99% ee (Determined by HPLC using a 4.6 x 250 mm (R, R)-Whelk-O column eluted with a 1: 1 mixture of heptane and 2-propanol, the flow rate was 1 ml/min, eluting sample was monitored spectroscopically at 225 and 245 nm, TR 12.6 min).

EXAMPLE 15: [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-methoxyphenyl)- methanone, (compound No. 25), more polar enantiomer

Fractions from example 14 corresponding to TR 55-59 minutes were pooled and evaporated to yield 4.0 mg of the title compound 99% ee (Conditions as described in example 14, TR 16.4 min).

EXAMPLE 16: [4- (2-Dimethylaminoethoxy)-phenyl]- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridin-5-yl]-methanone, (compound No. 26), less polar enantiomer [4- (2-Dimethylaminoethoxy)-phenyl]- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridin-5-yl]-methanone (ca. 20 mg) was dissolved in a 1: 1 mixture of heptane and 2-propanol (1 ml) and fractionated by HPLC using a 20 x 250 mm Chiralcel OD column.

The column was eluted isocratically with a 7: 3: 0.01 mixture of heptane, 2-propanol and di- ethylamin at a flow rate of 6 ml/min and fractions collected corresponding to 1 min/fraction.

The eluting enantiomers were detected spectroscopically by measuring absorbance at a wavelength of 225 nm. Two eluting peaks were detected, one corresponding to TR 20-25 minutes and one corresponding to TR 27-33 minutes. Fractions corresponding to TR 20-25 minutes were pooled and evaporated to yield 8.4 mg of the title compound >99.9% ee (Determined by HPLC using a 4.6 x 250 mm Chiralcel OD column eluted with a 70: 30: 0.07 mixture of heptane, 2-propanol and diethylamine, the flow rate was 0.4 ml/min, eluting sample was monitored spectroscopically at 225 and 245 nm, TR 15. 4 min).

EXAMPLE 17: [4- (2-Dimethylaminoethoxy)-phenyl]- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridin-5-yl]-methanone, (compound No. 27), more polar enantiomer

Fractions from example 16 corresponding to TR 27-33 minutes were pooled and evaporated to yield 8.9 mg of the title compound.

>99% ee (Conditions as described in example 16, TR 20.1 min).

EXAMPLE 18: [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- [4- (2-morpholin-4- ylethoxy) phenyl]-methanone, (compound No. 28), less polar enantiomer [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yi]- [4- (2-morpholin-4- ylethoxy) phenyl]-methanone (ca. 10 mg) was dissolved in 3 ml a 15: 15: 1: 0.2 mixture of heptane, 2-propanol, ethyl acetate and diethylamine (3 ml) and fractionated by HPLC using a 20 x 250 mm Chiralcel OD column. The column was eluted isocratically with a 70: 30: 0.1 mixture of heptane, 2-propanol and diethylamine at a flow rate of 6 ml/min and fractions col-

lected corresponding to 1 minute/fraction. The eluting enantiomers were detected spectro- scopically by measuring absorbance at a wavelength of 225 nm. Two eluting peaks were detected, one corresponding to TR 40-47 minutes and one corresponding to TR 50-59 min- utes. Fractions corresponding to TR 40-47 minutes were pooled and evaporated to yield 4.1 mg of the title compound.

>99.9% ee (Determined by HPLC using a 4.6 x 250 mm Chiralcel OD column eluted with a 70: 30: 0.07 mixture of heptane, 2-propanol and diethylamine, the flow rate was 0.4 ml/min, eluting sample was monitored spectroscopically at 225 nm, TR22. 9 min).

EXAMPLE 19: [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- [4- (2-morpholin-4- ylethoxy) phenyl]-methanone, (compound No. 29), more polar enantiomer Fractions from example 18 corresponding to TR 50-59 minutes were pooled and evaporated to yield 4.0 mg of the title compound 98% ee (Conditions as described in example 18, TR 28. 5 min).

EXAMPLE 20: [4- (4-Trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- methoxyphenyl)-methanone, (compound No. 30), less polar enantiomer

[4- (4-Trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-methoxy- phenyl)-methanone (10 mg) was dissolved in 2-propanol (0.5 ml) and fractionated by HPLC using a 21.1 x 250 mm (R, R)-Whelk-O column (Regis). The column was eluted isocratically with a 1: 1 mixture of heptane and 2-propanol at a flow rate of 10 ml/min and fractions col- lected corresponding to 1 minute/fraction. The eiuting enantiomers were detected spectro- scopically by measuring absorbance at a wavelength of 225 nm. Two eluting peaks were detected, one corresponding to TR 24-30 minutes and one corresponding to TR 41-47 min- utes. Fractions corresponding to TR 24-30 minutes were pooled and evaporated to yield 2.5 mg of the title compound.

>99.8% ee (Determined by HPLC using a 4.6 x 250 mm (R, R)-Whelk-O column eluted with a 1: 1 mixture of n-heptane and 2-propanol, the flow rate was 1 ml/minute, eluting sample was monitored spectroscopically at 225 and 254 nm, TR 12.0 min) EXAMPLE 21: [4- (4-Trifluoromethoxyphenyl)-4, 5, 6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- methoxyphenyl)-methanone, (compound No. 31), more polar enantiomer

Fractions from example 20 corresponding to TR 41-47 minutes were pooled and evaporated to yield 2.3 mg of the title compound 99.1% ee (Conditions as described in example 20, TR 15.8 min).

The compounds of this invention can also be prepared by parallel syntheses, for example by a method essentially as described above, e. g. as described in example 3. The 1- hydroxybenzotriazole or another hydroxy azole known to be effective as alcohol component in active ester mediated amide coupling reactions can either be present in the reaction or it can be omitted depending on the substitution on the carboxylic acid part. This will be recog- nised by those skilled in the art.

A general procedure for parallel preparation of compounds of the invention is given in exam- ple 22: EXAMPLE 22: [4- (4-Trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- methoxyphenyl)-methanone, (compound No. 32) A solution of 4- (4-Trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridine in N, N- dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) was added to a solution of 4- methoxybenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 mt, 0.15 mmol). To this solu- tion 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) was added. The mixture was shaken overnight at

room temperature at 1000 rpm, added saturated NaCI (2 ml), and extracted with ethyl ace- tate (2 x 1 ml). The combined organic extracts were evaporated to afford the title compound MS (electrospray) : m/z 434 (M+1) HPLC (Method B): Rt = 33.2 min.

EXAMPLE 23: [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (1 H-indol-5-yl)-methanone, (compound No. 33) Similarly as described in example 22 using a solution of 4- (4-chlorophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of indole-5-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 mi) affords the title compound.

MS (electrospray) : m/z 393 (M+1) HPLC (Method B): Rt = 30.7 min.

EXAMPLE 24: (1 H-Indol-5-yl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- methanone, (compound No. 34)

Similarly as described in example 22 using a solution of 4- (4-Trifluoromethoxyphenyl)- 4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of indole-5-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 mi) affords the title compound.

MS (eiectrospray) : m/z 443 (M+1) HPLC (Method B): Rt = 31.5 min.

EXAMPLE 25: [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-fluorophenyl)-methanone, (compound No. 35) Similarly as described in example 22 using a solution of 4- (4-chlorophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-fluorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound

MS (electrospray) : m/z 372 (M+1) HPLC (Method B): Rt = 32.6 min.

EXAMPLE 26: [4- (4-Trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-fluorophenyl)- methanone, (compound No. 36) Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3, 2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-fluorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z 422 (M+1) HPLC (Method B): Rt = 32.2 min.

EXAMPLE 27: [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl]- [4- (2- dimethylaminoethoxy) phenyl]-methanone, (compound No. 37)

Similarly as described in example 22 using a solution of 4- (4-chlorophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a suspension of 4- (2-dimethylaminoethoxy) benzoic acid hydrochloride in N, N- dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), triethylamine (42 pi), and 0.25 ml of a sus- pension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z 441 (M+1) HPLC (Method B): Rt = 23.4 min.

EXAMPLE 28: [4- (2-Dimethylaminoethoxy) phenyl]- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridin-5-yl]-methanone, (compound No. 38) Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a suspension of 4- (2-dimethylaminoethoxy) benzoic acid hydrochloride in N, N-dimethyl- formamide (0.375 M, 0.4 ml, 0.15 mmol), triethylamine (42 NI), and 0.25 ml of a suspension

of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound MS (electrospray) : m/z 491 (M+1) HPLC (Method B): Rt = 24.9 min.

EXAMPLE 29: [7-Chloro-1- (2, 3-dihydrobenzofuran-7-yl)-8-methoxy-1, 2,4,5-tetrahydrobenzo [d] azepin-3-yl]- [4- (2-dimethylaminoethoxy)-phenyl]-methanone, (compound No. 39) Similarly as described in example 22 using a solution of 7-chloro-1-(2, 3-dihydrobenzofuran- 7-yl)-8-methoxy-1, 2,4,5-tetrahydrobenzo [d] azepine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a suspension of 4- (2-dimethylaminoethoxy) benzoic acid hydrochloride in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), triethylamine (42 NI), and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound MS (electrospray) : m/z 521 (M+1) HPLC (Method B): R, = 22.9 min.

EXAMPLE 30: [4- (3, 4-Dimethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [2,3-c] pyridin-6-yi]- [4- (2- dimethylaminoethoxy)-phenyl]-methanone, (compound No. 40)

Similarly as described in example 22 using a solution of 4- (3, 4-Dimethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [2,3-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a suspension of 4- (2-dimethylaminoethoxy) benzoic acid hydrochloride in N, N- dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), triethylamine (42 pI), and 0.25 mi of a sus- pension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z 467 (M+1) HPLC (Method B): Rt = 18.1 min.

EXAMPLE 31: (3,4-Dimethoxyphenyl)- [4- (4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno [3,2-c] pyridin- 5-yl] methanone, (compound No. 41) Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 3,4-dimethoxybenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15

mmol), and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound MS (electrospray) : m/z 464 (M+1) HPLC (Method B): Rt = 32.1 min EXAMPLE 32: (3-Chloro-4-methoxyphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2- c] pyridin-5-yl] methanone, (compound No. 42) Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3-chloro-4-methoxybenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z 468 (M+1) HPLC (Method B): Rt = 34.4 min EXAMPLE 33: (4-Ethoxyphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5- yl] methanone, (compound No. 43)

Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-ethoxybenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 mi) affords the title compound.

MS (electrospray) : m/z 448 (M+1) HPLC (Method B): Rt = 35.1 min EXAMPLE 34: (4-Methylphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5- yl] methanone, (compound No. 44) Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-methylbenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethyicarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound

MS (electrospray) : m/z 418 (M+1) HPLC (Method B): Rt = 35.2 min EXAMPLE 35: 3- (4-Methoxyphenyl)-1- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin- 5-yl] propenone, (compound No. 45) Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxy-phenyl)- 4,5,6,7-tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-methoxycinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 mi) affords the title compound MS (electrospray) : m/z 460 (M+1) HPLC (Method B): Rt = 35.0 min EXAMPLE 36: (1 H-Benzimidazol-5-yl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin- 5-yl] methanone, (compound No. 46)

Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of benzimidazole-5-carboxylic acid in N, N-dimethytformamide (0.375 M, 0.4 ml, 0.15 mmol), and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z 444 (M+1) HPLC (Method B): Rt = 23.1 min EXAMPLE 37: (4-Methoxyphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- methanone 4-Methoxybenzoic acid (0.64 g, 4.2 mmol) was dissolved in N, N-dimethylformamide (25 ml) and 1-hydroxybenzotriazole (0.71 g, 5 mmol) was added followed by N- (3- dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.96 g, 5 mmol). The resulting mixture was stirred at room temperature for 30 minutes. 4- (4-Trifluoromethoxyphenyl)- 4,5,6,7-tetrahydro-thieno [3,2-c] pyridine (1.5 g, 5 mmol) followed by N, N-

diisopropylethylamine (1.4 ml, 8.4 mmol) were added and the resulting mixture was stirred at room temperature for 16 hours. Water (10 ml) was added and the mixture was extracted with diethyl ether (3 x 20 ml). The combined organic extracts were washed with saturated aque- ous ammonium chloride (20 ml), dried over MgS04 and concentrated in vacuo. The residue was purified by column chromatography over silica gel eluting with a mixture of ethyl acetate and heptane (1: 2). The pure fractions were pooled and concentrated in vacuo. The residue was crystallised from a mixture of methyl ter-butyl ether and heptane to afford 2.13 g (98%) of the title compound.

M. p. 68-70 °C.

Calculated for C22H, 8F3NO3S. 0. 25H2O : C, 60.34%; H, 4.26%; N, 3.20%. Found: C, 60.35%; H, 4.38%; N, 3.07%; C, 60.34%; H, 4.33%; N, 3.09%.

EXAMPLE 38: [4- (4-Trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- methoxyphenyl)-methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-methoxy-3-nitrobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 mi) affords the title compound

MS (electrospray) : m/e: 479 (M+1) HPLC (method B): Rt = 32.5 min.

EXAMPLE 39: [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- methylsulfanylphenyl)-methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5, 6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-methylsulfanylbenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 434 (M+1) HPLC (method B): Rt = 33.5 min.

EXAMPLE 40: 4- [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine-5-carbonyl] benzoic acid methyl ester

Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of mono methyl terephthalic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 446 (M+1) HPLC (method B): Rt = 31.9 min.

EXAMPLE 41: (4-Hydroxymethylphenyl)- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin- 5-yl] methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-hydroxymethylbenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound

MS (electrospray) : m/z: 418 (M+1) HPLC (method B): Rt = 27.2 min.

EXAMPLE 42: (4-Acetoxyphenyl)- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-acetoxybenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound MS (electrospray) : m/z: 446 (M+1) HPLC (method B): Rt = 30.7 min.

EXAMPLE 43: (4-Cyanophenyl)- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone

Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5, 6,7- tetrahydro-thieno [3, 2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 4-cyanobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound MS (electrospray) : m/z: 413 (M+1) HPLC (method B): Rt = 30.6 min.

EXAMPLE 44: 1- {4- [4- (4-Trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridine-5- carbonyl] phenyl} ethanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 4-acetylbenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound

MS (electrospray) : m/z: 430 (M+1) HPLC (method B): Rt = 30.5 min.

EXAMPLE 45: 3-Furan-2-yl-l- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5- yl] propenone Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3- (furan-2-yl) acrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound MS (electrospray) : m/z: 404 (M+1) HPLC (method B): Rt = 32.2 min.

EXAMPLE 46: 3- (5-Methylfuran-2-yl)-l- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5- yl] propenone

Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3- (5-methylfuran-2-yl) acrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 418 (M+1) HPLC (method B): R, = 33.7 min.

EXAMPLE 47: Benzo [b] thiophen-2-yl-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin- 5-yl] methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of benzo [b] thiophen-2-yl-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound

MS (electrospray) : m/z: 444 (M+1) HPLC (method B): Rt = 35.1 min.

EXAMPLE 48: 3-Furan-3-yl-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propenone Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3-furan-3-ylacrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z : 404 (M+1) HPLC (method B): Rt = 31.4 min.

EXAMPLE 49: 3-Thiophen-3-yl-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propenone

Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3-thiophen-3-ylacrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 420 (M+1) HPLC (method B): Rt = 32.8 min.

EXAMPLE 50: 3-Thiophen-2-yl-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propenone Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 3-thiophen-3-ylacrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound

MS (electrospray) : m/z: 420 (M+1) HPLC (method B): Rt = 33.3 min.

EXAMPLE 51: [4- (4-Methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yi]- (4- methylsulfanylphenyl) methanone Similarly as described in example 22 using a solution of 4- (4-methoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-methylsulfanylbenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 396 (M+1) HPLC (method B): Rt = 29.5 min.

EXAMPLE 52: 4- [4- (4-Methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridine-5-carbonyl] benzonitrile

Similarly as described in example 22 using a solution of 4- (4-methoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 4-cyanobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z : 375 (M+1) HPLC (method B): Rt = 26.2 min.

EXAMPLE 53: 3-Furan-3-yl-1- [4- (4-methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl] propenone Similarly as described in example 22 using a solution of 4- (4-methoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3- (furan-3-yl) acrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound

MS (electrospray) : m/z: 366 (M+1) HPLC (method B): Rt = 26.9 min.

EXAMPLE 54: (4-Methoxyphenyl)- [4- (4-methoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone Similarly as described in example 22 using a solution of 4- (4-methoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-methoxybenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound MS (electrospray) : m/z: 380 (M+1) HPLC (method B): Rt = 27.6 min.

EXAMPLE 55: (4-Fluorophenyl)- [4- (4-methoxyphenyl)-4, 5, 6,7-tetrahydro-thieno [3, 2-c] pyridin-5- yl] methanone

Similarly as described in example 22 using a solution of 4- (4-methoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 4-fluorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound MS (eiectrospray) : m/z: 368 (M+1) HPLC (method B): Rt = 27.7 min.

EXAMPLE 56: (4-Chlorophenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-chlorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 mt) affords the title compound MS (electrospray) : m/z: 438 (M+1) HPLC (method B): Rt = 32.8 min.

EXAMPLE 57: (4-Methylsulfanylphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] methanone

Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3, 2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-methylsulfanylbenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound MS (electrospray) : m/z : 450 (M+1) HPLC (method B): Rt = 32.6 min.

EXAMPLE 58: (4-Dimethylaminophenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] methanone

Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-dimethyiaminobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound MS (electrospray) : m/z: 447 (M+1) HPLC (method B): Rt = 27.1 min.

EXAMPLE 59: (4-Hydroxymethylphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2- c] pyridin-5-yl] methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-hydroxymethylbenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound MS (electrospray) : m/z: 434 (M+1) HPLC (method B): Rt = 26.6 min.

EXAMPLE 60: 3-Furan-3-yl-1- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5- yi] propenone

Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 3- (3-furan-3-yl) acrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 420 (M+1) HPLC (method B): Rt = 30.4 min.

EXAMPLE 61: 4- (4-Chlorophenyl)-5- (4-methoxybenzyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine hydrochlo- ride 4- (4-Chlorophenyl)- 4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine (0.10 g, 0.38 mmol) was dis- solved in N, N-dimethylformamide (0.5 ml) and triethylamine (110 ul, 0.76 mmol) and 4- methoxybenzyl chloride (51 NI, 0.38 mmol) were added and the resulting mixture was

shaken at 1000 rpm for 3 days. Water (2 ml) was added and the mixture was extracted with ethyl acetate (2 x 1 ml). The combined organic extracts were concentrated in vacuo. The residue was purified by preparative thin layer chromatography eluting with a mixture of ethyl acetate and heptane (1: 4) to afford the free base. This was dissolved in diethyl ether and 1 N HCI in diethyl ether was added drop wise to complete precipitation to afford 52 mg (34%) of the title compound.

HPLC-MS: Rt = 9.57 min. m/z = 370 (M+1).

EXAMPLE 62: [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl]- (4- hydroxyphenyl) methanone 4-Hydroxybenzoic acid (1.3 g, 9.6 mmol) was dissolved in N, N-dimethylformamide (25 ml) and 1-hydroxybenzotriazole (1.3 g, 9.6 mmol) was added followed by N- (3- dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (1.8 g, 9.6 mmol), 4- (4- chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine (2.0 g, 8 mmol) and N, N- diisopropylethylamine (2.5 ml, 16 mmol). The resulting mixture was stirred at room tem- perature for 16 hours. Water (200 ml) was added and the mixture was extracted with diethyl ether (3 x 100 ml). The combined organic extracts were washed with saturated aqueous so- dium chloride (150 ml), dried over MgSO4 and concentrated in vacuo. The residue was puri- fied by column chromatography over silica gel eluting with a mixture of ethyl acetate and heptane (1: 1). The pure fractions were pooled and concentrated in vacuo to afford 3.14 g (100%) of the title compound

M. p. 202-207 °C.

Calculated for C20H, 6CINO2S : C, 64.95%; H, 4.36%; N, 3.79%. Found: C, 64.54%; H, 4.74%; N, 4.29%; C, 64.63%; H, 4.76%; N, 4.28%.

HPLC-MS: Rt = 14. 18 min. m/z : 370 (M+1) EXAMPLE 63: 1- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]-2- (4- methoxyphenyl) ethanone Similarly as described in example 22 using a solution of 4- (4-chlorophenyl)-4, 5,6,7- tetrahydro-thieno [3, 2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-methoxyphenylacetic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 398 (M+1) HPLC (method B): Rt = 32.2 min.

EXAMPLE 64: [4- (4-Chlorophenyl)-4, 5, 6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (3- dimethylaminophenyl) methanone

Similarly as described in example 22 using a solution of 4- (4-chlorophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3-dimethylaminobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 397 (M+1) HPLC (method B): Rt = 25.9 min.

EXAMPLE 65: N- {4- [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridine-5-carbonyl]- phenyl} acetamide Similarly as described in example 22 using a solution of 4- (4-chlorophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-acetamidobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 411 (M+1) HPLC (method B): Rt = 27. 2 min.

EXAMPLE 66: [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4- methanesulfonylphenyl) methanone Similarly as described in example 22 using a solution of 4- (4-chlorophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-methanesulfonylbenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 432 (M+1) HPLC (method B): Rt = 28.1 min.

EXAMPLE 67: 2- (4-Chlorophenyl)-1- [4- (4-chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] ethanone

Similarly as described in example 22 using a solution of 4- (4-chlorophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-chlorophenylacetic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 402 (M+1) HPLC (method B): R, = 34.5 min.

EXAMPLE 68: 2- (4-Methoxyphenyl)-1- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin- 5-yl]-ethanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-chlorophenylacetic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound

MS (electrospray) : m/z: 448 (M+1) HPLC (method B): R, = 32.9 min.

EXAMPLE 69: (3-Dimethylaminophenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5, 6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl]-methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3-dimethylaminobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 447 (M+1) HPLC (method B): R, = 27.2 min.

EXAMPLE 70: N- {4- [4- (4-Trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine-5-carbonyl]- phenyl}-acetamide

Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 4-acetamidobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 461 (M+1) HPLC (method B): Rt = 28.2 min.

EXAMPLE 71: (4-Methanesulfonylphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl]-methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-methanesulfonylbenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15

mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 482 (M+1) HPLC (method B): Rt = 29.1 min.

EXAMPLE 72: 2- (4-Chlorophenyl)-1- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yi]-ethanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-chlorophenylacetic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 452 (M+1) HPLC (method B): Rt = 34.9 min.

EXAMPLE 73: Biphenyl-4-yl- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone

Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-biphenylcarboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichioromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 480 (M+1) HPLC (method B): Rt = 36.7 min.

EXAMPLE 74: (3,4-Dichlorophenyl)- [4- (4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 3,4-dichlorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol)

and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound MS (electrospray) : m/z: 472 (M+1) HPLC (method B): Rt = 36.2 min.

EXAMPLE 75: (4-tert-Butylphenyl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-tert-butylbenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 460 (M+1) HPLC (method B): Rt = 37.0 min.

EXAMPLE 76: Pyridin-4-yl- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone

Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of pyridine-4-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 405 (M+1) HPLC (method B): Rt = 23.9 min.

EXAMPLE 77: (5-Hydroxypyrazin-2-yl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin- 5-yl] methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethytformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 5-hydroxypyrazine-2-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml,

0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound MS (electrospray) : m/z: 422 (M+1) HPLC (method B): Rt = 26.0 min.

EXAMPLE 78: (5-Chloro-6-hydroxypyridin-3-yl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2- c] pyridin-5-yl] methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethoxyphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 2-hydroxy-3-chloropyridine-5-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'- ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title com- pound.

MS (electrospray) : m/z: 455 (M+1) HPLC (method B): Rt = 26.8 min.

EXAMPLE 79: 3- (4, 5-Dimethylfuran-2-yl)-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] propenone

Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3- (4, 5-dimethylfuran-2-yl) acrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

MS (electrospray) : m/z: 432 (M+1) HPLC (method B): Rt = 35.2 min.

EXAMPLE 80: (1-Benzyl-1, 2,3,4-tetrahydro-isoquinolin-2-yl)- (4-methoxyphenyl) methanone Similarly as described in example 22 using a solution of 1-benzyl-1, 2,3,4-tetrahydro- isoquinoline in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 4- methoxybenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound

HPLC-MS: Rt = 15.0 min. m/z: 358 (M+1) EXAMPLE 81: (1-Benzyl-1, 2,3,4-tetrahydro-isoquinolin-2-yl)- (4-chlorophenyl) methanone

Similarly as described in example 22 using a solution of 1-benzyl-1, 2,3,4-tetrahydro- isoquinoline in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- chlorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 16.1 min. m/z: 362 (M+1) EXAMPLE 82: (1 H-Benzoimidazol-5-yl)- (1-benzyl-1, 2,3,4-tetrahydro-isoquinolin-2-yl) methanone

Similarly as described in example 22 using a solution of 1-benzyl-1, 2,3,4-tetrahydro- isoquinoline in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of benzimi- dazole-5-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 9.55 min. m/z: 368 (M+1) EXAMPLE 83: 1- (1-Benzyl-1, 2,3,4-tetrahydro-isoquinolin-2-yl)-3-furan-3-ylpropenone Similarly as described in example 22 using a solution of 1-benzyl-1, 2,3,4-tetrahydro- isoquinoline in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3- (3- furan-3-yl) acrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 14.7 min. m/z: 344 (M+1) EXAMPLE 84: 1- (1-Benzyl-1, 2,3,4-tetrahydro-isoquinolin-2-yi)-3- (4-methoxyphenyl) propenone

Similarly as described in example 22 using a solution of 1-benzyl-1, 2,3,4-tetrahydro- isoquinoline in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- methoxycinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 15.7 min. m/z: 384 (M+1) EXAMPLE 85: 1- (1-Benzyl-1, 2,3,4-tetrahydro-isoquinolin-2-yl)-3- (4-methoxyphenyt) propan-1-one Similarly as described in example 22 using a solution of 1-benzyl-1, 2, 3,4-tetrahydro- isoquinoline in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- methoxyhydrocinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 15.7 min. m/z: 386 (M+1) EXAMPLE 86: 1- (1-Benzyl-1, 2,3,4-tetrahydro-isoquinolin-2-yi)-2- (4-methoxyphenyl) ethanone

Similarly as described in example 22 using a solution of 1-benzyl-1, 2,3,4-tetrahydro- isoquinoline in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- methoxyphenylacetic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 15.2 min. m/z: 372 (M+1) Preparation of 4- (4-nitro-phenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridine trifluoroacetate : 2- (2-Thienyl)-ethylamine (5 g, 39.4 mmol), 4-nitrobenzaldehyde and triethylamine (10 ml) were dissolved in ethanol (100 ml). The reaction mixture was stirred at room temperature for 48 hours. The solid formed was filtered and dried to afford 7.75 g (76%) (4- nitrobenzylidene)- (2-thiophen-2-yl-ethyl)-amine.

M. p.: 83.9-84.4°C.

The above (4-nitrobenzylidene)-(2-thiophen-2-yl-ethyl)-amine (1 g, 3.8 mmol) was added trifluoroacetic acid (100 ml) at once (strongly exothermic reaction). The reaction mixture was stirred at room temperature for 72 hours, then evaporated in vacuo. Crystallisation from a mixture of diethyl ether and dichloromethane afforded 1.2 g (85%) of the title compound.

M. p.: 128-129.5°C.

Preparation of dimethyl- [4- (4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-4-yl)-phenyl]-amine : 2- (2-Thienyl)-ethylamine (5 g, 39.4 mmol), 4-dimethylaminobenzaldehyde (5.9 g, 94 mmol) triethylamine (6 ml) and ethanol (150moi) were mixed at room temperature. The reaction mixture was stirred at room temperature for 15 hours. The reaction mixture was concen- trated to 75 ml by evaporation in vacuo and the solid formed was filtered and dried to afford 6.82 g (67%) dimethyl-{4-[(2-thiophen-2-yl-ethylimino)-methyl]-phenyl}-am ine.

M. p.: 76.8-77 °C.

The above dimethyl-{4-[(2-thiophen-2-yl-ethylimino)-methyl]-phenyl}-am ine (1 g, 3.9 mmol) was added TFA (20 mL) at once (strongly exothermic reaction). The reaction mixture was stirred at room temperature for 72 hours, then evaporated in vacuo. The crude oil was sus- pended in dichloromethane (75 ml) and extracted with 1 N hydrochloric acid (50 ml). The aqueous phase was added 2 N sodium hydroxide to pH=10, then extracted with di- chloromethane (3x125 ml). The organic phase was dried with MgS04, filtered, evaporated in vacuo to afford 0.96 g (95%) of the title compound M. p.: 95-98 °C.

Preparation of 4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine:

2- (2-Thienyl)-ethylamine (2 g, 15.7 mmol) and benzaldehyde (1.67 g, 15.7 mmol) were dis- solved in toluene (50 ml) and the reaction mixture was heated at reflux until 20 ml of toluene and water was distilled of in a Dean Stark trap. The remaining mixture was evaporated in vacuo to give the crude imine (3.44 g). The crude imine was added trifluoroacetic acid (50 ml) at once (strongly exothermic reaction). The reaction mixture was stirred at room tem- perature for 72 hours, then evaporated in vacuo. The crude oil was dissolved in di- chloromethane (50 ml) and washed with 2 N sodium hydroxide (30 ml). The aqueous phase was extracted with dichloromethane (3x30ml). The combined organic phases were dried with MgSO4, filtered and evaporated in vacuo. The residue was purified by column chromatogra- phy on silica gel eluting with a mixture of dichloromethane and methanol (19: 1). This af- forded 0.823 g (24%) of the title compound M. p.: 79.8-80.7°C Preparation of 4-(pyridin-4-yl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridine, NNC 60-0372.

2- (2-Thienyl)-ethylamine (2 g, 15.7 mmol) 4-pyridylaldehyde (1.68 g, 15.7 mmol), triethy- lamine (1 ml) and ethanol (15 ml) were mixed and the reaction mixture was stirred at room temperature for 15 hours, then evaporated in vacuo. The crude oil was added trifluoroacetic acid (75 m) at once (strongly exothermic reaction). The reaction mixture was stirred at room temperature for 0.5 hour, then evaporated in vacuo. The residue was dissolved in di- chloromethane (150 ml) and washed with 2 N sodium hydroxide (100 ml). The aqueous phase was extracted with dichloromethane (3 x 50 ml). The combined organic phases were

dried with MgS04, filtered and evaporated in vacuo to give an oil (3.21 g) which was crystal- lised from a mixture of dichloromethane and hexane to afford 2.4 g (71%) of the title com- pound.

M. p.: 81.8-83.8 °C.

Preparation of 1- (4-trifluoromethoxyphenyl)-1, 2,3,4-tetrahydro-isoquinoline: Phenethylamine (0.59 g, 4.9 mmol), 4-trifluoromethoxybenzoic acid (1.0 g, 4.9 mmol) and N- (3-dimethylaminopropyl)-N-ethylcarbodimide, HCI (1.39 g, 7.3 mmol) were mixed in N, N- dimethylformamide (50 mL) at room temperature and the reaction mixture was stirred for 16 hours. Water (50 mL) was added and the mixture was extracted with ethyl acetate (2 x 50 mL). The combined organic phases were dried (MgSO4), filtered and evaporated in vacuo giving 1.5 g crude product which was purified by column chromatography on silica gel eluting with a mixture of dichloromethane and methanol (9: 1). This afforded 0.67 g (45%) of N- phenethyl-4-trifluoromethoxybenzamide.

M. p.: 143.2-143.9 °C.

The above N-phenethyl-4-trifluoromethoxybenzamide (0.67 g, 2.2 mmol) was added to a mixture of phosphorous pentoxide (0.92 g, 6.5 mmol) and phosphorous oxychloride (1.03 g, 6.7 mmol) in xylene (50 mL). The reaction mixture was stirred at 140 °C for 16 hours. After cooling, water (50 mL) was added and the mixture was basified with 1 N NaOH. The aque- ous phase was extracted with xylene (3 x 50 mL). The combined organic phases were dried (MgS04), filtered and evaporated in vacuo giving 0.96 g crude product which was purified by column chromatography on silica gel eluting with a mixture of dichloromethane and methanol (9: 1). This afforded 0.40 g (62%) of 1- (4-Trifluoromethoxy-phenyl)-3, 4-dihydro-isoquinoline as an oil.

The above 1- (4-trifluoromethoxyphenyl)-3, 4-dihydro-isoquinoline (0.40 g, 1.4 mmol) was dis- solved in methanol (20 mL) and sodium borohydride (0.08 g, 2.1 mmol) was added slowly.

The reaction mixture was stirred at room temperature for 2.5 hours. The mixture was evapo- rated in vacuo, redissolved in 1 N NaOH (20 mL) and extracted with dichloromethane (50 mL). The organic phase was dried (MgSO4), filtered and evaporated in vacuo. The remain- ing oil (0.35 g) was purified by column chromatography on silica gel eluting with a mixture of dichloromethane and methanol (9: 1). This afforded 0.56 g (56%) of the title compound.

M. p.: 56.6-57. 1 °C.

EXAMPLE 87: (5-Chlorothiophen-2-yl)- (4-pyridin-4-yi-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl) methanone Similarly as described in example 22 using a solution of 4-pyridin-4-yl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 5- chlorothiophene-2-carboxylic acid acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 9.27 min. m/z: 361 (M+1) EXAMPLE 88: (5-Chlorothiophen-2-yl)- [4- (4-dimethylaminophenyl) 4,5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl)-methanone

Similarly as described in example 22 using a solution of 4-dimethylaminophenyl) 4,5,6,7- tetrahydro-thieno [3, 2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 5-chlorothiophene-2-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mt of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: R, = 10.70 min. m/z: 403 (M+1) EXAMPLE 89: (5-Chlorothiophen-2-yl)- [4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl) methanone Similarly as described in example 22 using a solution of 4- (4-nitrophenyl)-4, 5,6,7-tetrahydro- thieno [3, 2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 5- chlorothiophene-2-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol)

and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 16.18 min. m/z: 405 (M+1) EXAMPLE 90: (4-Hydroxymethylphenyl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl) methanone Similarly as described in example 22 using a solution of 4-phenyl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- hydroxymethylbenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 mi) affords the title compound HPLC-MS: Rt = 12.33 min. m/z: 350 (M+1) EXAMPLE 91: [4- (4-Dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)- (4- hydroxymethylphenyl)-methanone

Similarly as described in example 22 using a solution of 4- (4-dimethylaminophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-hydroxymethylbenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: R, = 8.07 min. m/z: 393 (M+1) EXAMPLE 92: [4- (4-Nitrophenyl)-4, 5, 6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)- (4-hydroxymethylphenyl)- methanone Similarly as described in example 22 using a solution of 4- (4-nitrophenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- hydroxymethylbenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound

HPLC-MS: Rt = 12.44 min. m/z: 395 (M+1) EXAMPLE 93: (4-Chlorophenyl)- (4-phenyl-4, 5, 6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl) methanone

Similarly as described in example 22 using a solution of 4-phenyl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethyiformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- chlorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 15.90 min. m/z: 355 (M+1) EXAMPLE 94: (4-Chlorophenyl)- (4-pyridin-4-yl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone

Similarly as described in example 22 using a solution of 4-pyridin-4-yl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-

chlorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 9.18 min. m/z: 355 (M+1) EXAMPLE 95: (4-Chlorophenyl)- [4- (4-dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)- methanone Similarly as described in example 22 using a solution of 4- (4-dimethylaminophenyl)-4, 5, 6, 7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-chlorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 mi) affords the title compound.

HPLC-MS: Rt = 10.43 min. m/z: 397 (M+1) EXAMPLE 96: (4-Chlorophenyl)- [4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone

Similarly as described in example 22 using a solution of 4- (4-nitrophenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- chlorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 15.81 min. m/z: 399 (M+1) EXAMPLE 97: (4-Methoxyphenyl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone Similarly as described in example 22 using a solution of 4-phenyl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- methoxybenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 mi) affords the title compound HPLC-MS: Rt = 14.83 min. m/z: 350 (M+1)

EXAMPLE 98: (4-Methoxyphenyl)- (4-pyridin-4-yi-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone

Similarly as described in example 22 using a solution of 4-pyridin-4-yl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- methoxybenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 8.50 min. m/z: 351 (M+1) EXAMPLE 99: [4- (4-Dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yi]- (4-methoxyphenyl)- methanone

Similarly as described in example 22 using a solution of 4-pyridin-4-yl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-

methoxybenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 9.55 min. m/z: 393 (M+1) EXAMPLE 100: [4- (4-Dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-methoxyphenyl)- methanone Similarly as described in example 22 using a solution of 4- (4-nitrophenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- methoxybenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 mi) affords the title compound HPLC-MS: Rt = 14.80 min. m/z: 395 (M+1) EXAMPLE 101: 3- (4-Methoxyphenyl)-1- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl]-propenone

Similarly as described in example 22 using a solution of 4-phenyl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- methoxycinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 15.45 min. m/z: 376 (M+1) EXAMPLE 102: (5-Chlorothiophen-2-yl)- (4-phenyl-4, 5, 6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone Similarly as described in example 22 using a solution of 4-phenyl-4, 5,6,7-tetrahydro- thieno [3, 2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 5- chlorothiophene-2-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 16.42 min. m/z: 360 (M+1)

EXAMPLE 103: 3- (4-Methoxyphenyl)-1- (4-pyridin-4-yl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-propenone

Similarly as described in example 22 using a solution of 4-pyridin-4-yl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- methoxycinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 9.42 min. m/z: 377 (M+1) EXAMPLE 104: 1- [4- (4-Dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-3- (4- methoxyphenyl)-propenone

Similarly as described in example 22 using a solution of 4- (4-dimethylaminophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a

solution of 4-methoxycinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 10.32 min. m/z: 418 (M+1) EXAMPLE 105: 3- (4-Methoxyphenyl)-1- (4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)- propenone Similarly as described in example 22 using a solution of 4- (4-nitrophenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 4- methoxycinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 15.47 min. m/z: 421 (M+1) EXAMPLE 106: (4-Dimethylaminophenyl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yi)-methanone

Similarly as described in example 22 using a solution of 4-phenyl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 4- dimethylaminobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 11.83 min. m/z: 363 (M+1) EXAMPLE 107: (4-Dimethylaminophenyl)- (4-pyridin-4-yl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)- methanone Similarly as described in example 22 using a solution of 4-pyridin-4-yl-4, 5,6,7-tetrahydro- thieno [3, 2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- dimethylaminobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound

HPLC-MS: R, = 7.5 min. m/z: 364 (M+1) EXAMPLE 108: (4-Dimethylaminophenyl)- [4- (4-dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin- 5-yl]-methanone Similarly as described in example 22 using a solution of 4- (4-dimethylaminophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-dimethylaminobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 8.15 min. m/z: 406 (M+1) EXAMPLE 109: (4-Dimethylaminophenyl)- [4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- methanone

Similarly as described in example 22 using a solution of 4- (4-nitrophenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- dimethylaminobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmot) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 12.68 min. m/z: 408 (M+1) EXAMPLE 110: (1 H-Benzoimidazol-5-yl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone Similarly as described in example 22 using a solution of 4-phenyl-4, 5,6,7-tetrahydro- thieno [3, 2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of benzimidazole-5-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: R, = 9.27 min. m/z: 360 (M+1)

EXAMPLE 111: (1 H-Benzoimidazol-5-yl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl)-methanone

Similarly as described in example 22 using a solution of 4- (4-dimethylaminophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of benzimidazole-5-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 7.17 min. m/z: 403 (M+1) EXAMPLE 112: (1 H-Benzoimidazol-5-yl)- [4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- methanone

Similarly as described in example 22 using a solution of 4- (4-nitrophenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of benzimidazole-5-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 9.50 min. m/z: 405 (M+1) EXAMPLE 113: (4-Fluorophenyl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone Similarly as described in example 22 using a solution of 4-phenyl-4, 5,6,7-tetrahydro- thieno [3, 2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- fluorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 15.07 min. m/z: 339 (M+1) EXAMPLE 114: (4-Fluorophenyl)- (4-pyridin-4-yl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone

Similarly as described in example 22 using a solution of 4-pyridin-4-yl-4, 5,6,7-tetrahydro- thieno [3, 2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- fluorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 8.62 min. m/z: 339 (M+1) EXAMPLE 115: [4- (4-Dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-fiuorophenyl)- methanone Similarly as described in example 22 using a solution of 4- (4-dimethylaminophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-fluorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: R, = 9.68 min. m/z: 381 (M+1)

EXAMPLE 116: (4-Fluorophenyl)- [4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl]-methanone

Similarly as described in example 22 using a solution of 4- (4-nitrophenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- fluorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 14.95 min. m/z: 383 (M+1) EXAMPLE 117: (4-Bromophenyl)- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone

Similarly as described in example 22 using a solution of 4-phenyl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-

bromobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 16.07 min. m/z: 398 + 400 (M+1) EXAMPLE 118: (4-Bromophenyl)- (4-pyridin-4-yl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone Similarly as described in example 22 using a solution of 4-pyridin-4-yl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- bromobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 9.30 min. m/z : 399 + 401 (M+1) EXAMPLE 119: (4-Bromophenyl)- [4- (4-dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- methanone

Similarly as described in example 22 using a solution of 4- (4-dimethylaminophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-bromobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 mi) affords the title compound HPLC-MS: R, = 10.72 min. m/z: 441 + 443 (M+1) EXAMPLE 120: (4-Bromophenyl)- [4- (4-nitrophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-methanone Similarly as described in example 22 using a solution of 4- (4-nitrophenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4- bromobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 mi) affords the title compound.

HPLC-MS: Rt = 15.84 min. m/z: 442 + 444 (M+1)

EXAMPLE 121: 3-Furan-3-yl-l- (4-phenyl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-propenone

Similarly as described in example 22 using a solution of 4-phenyl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3- furan-3-ylacrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 14.77 min. m/z: 336 (M+1) EXAMPLE 122: 3- (3-Furan-3-yl)-1- (4-pyridin-4-yl-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-propenone

Similarly as described in example 22 using a solution of 4-pyridin-4-yl-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3- furan-3-ylacrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of

a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 8.58 min. m/z: 337 (M+1) EXAMPLE 123: 1- [4- (4-Dimethylaminophenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl)-3- (3-furan-3-yl)- propenone Similarly as described in example 22 using a solution of 4- (4-dimethylaminophenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3-furan-3-ylacrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 9.38 min. m/z: 379 (M+1) EXAMPLE 124: 3- (3-Furan-3-yt)-1- [4- (4-nitropheny))-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl)-propenone

Similarly as described in example 22 using a solution of 4- (4-nitrophenyl)-4, 5,6,7-tetrahydro- thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 3- furan-3-ylacrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 14.57 min. m/z: 381 (M+1) EXAMPLE 125: [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-hydroxyphenyl)- methanone, less polar enantiomer, [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3, 2-c] pyridin-5-yl]- (4-hydroxyphenyl)- methanone (21 mg) was dissolved in a 1: 1: 1 mixture of ethyl acetate, 2-propanol and n- heptane (3 ml) and fractionated by HPLC using a 21.1 x 250 mm (R, R)-Whelk-O column (Regis). The column was eluted isocratically with a mixture of n-heptane and 2-propanol (1: 1) at a flow rate of 10 ml/min and fractions were collected corresponding to 1 min/fraction.

The eluting enantiomers were detected spectroscopically by measuring absorbance at a wavelength of 225 nm. Two eluting peaks were detected, corresponding to TR 24-29 minutes

and TR 42-50 minutes, respectively. Fractions corresponding to TR 24-29 minutes were pooled and evaporated to yield 8.8 mg of the title compound 100% ee (Determined by HPLC using a 4.6 x 250 mm (R, R)-Whelk-O column eluted with n- heptane: 2-propanol (1: 1), the flow rate was 1 ml/min, eluting sample was monitored spectro- scopically at 225 and 280 nm, TR 8. 9 min).

EXAMPLE 126: [4- (4-Chlorophenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- (4-hydroxyphenyl)- methanone, more polar enantiomer, Fractions from example 125 corresponding to TR 42-50 minutes were pooled and evaporated to yield 9.1 mg of the title compound 99.4 % ee (Conditions as described in example 125, TR 12. 5 min).

EXAMPLE 127: (1 H-Benzoimidazol-5-yl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] methanone, less polar enantiomer,

(1 H-Benzoimidazol-5-yl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] methanone (15 mg) was dissolved in a 1: 1 mixture of n-heptane: 2-propanol (2 ml) and fractionated by HPLC using a 20 x 250 mm Chiralpak AS column. The column was eluted isocratically with a mixture of n-heptane, ethanol and diethylamine (70: 30: 0.1) at a flow rate of 6 ml/min and fractions collected corresponding to 1 min/fraction. The eluting enantiomers were detected spectroscopically by measuring absorbance at a wavelength of 225 nm. Two eluting peaks were detected, corresponding to TR 16-19 minutes and TR 27-35 minutes, respectively. Fractions corresponding to TR 16-19 minutes were pooled and evapo- rated to yield 7.2 mg of the title compound 100% ee (Determined by HPLC using a 4.6 x 250 mm Chiralpak AS column eluted with a mixture of n-heptane, ethanol and diethylamine (70: 30: 0.07), the flow rate was 0.6 mi/min, eluting sample was monitored spectroscopically at 225 and 245 nm, TR 8.4 min).

EXAMPLE 128: (1 H-Benzoimidazol-5-yl)- [4- (4-trifluoromethoxyphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] methanone, more polar enantiomer, Fractions from example 127 corresponding to TR 27-35 minutes were pooled and evaporated to yield 8.0 mg of the title compound >99% ee (Conditions as described in example 127, TR 14.7 min).

EXAMPLE 129: (5-Chlorothiophen-2-yl)- [l- (4-trifluoromethoxyphenyl)-1, 2,3,4-tetrahydroisoquinolin-2-yl]- methanone

Similarly as described in example 22 using a solution of 1- (4-trifluoromethoxyphenyl)-1, 2,3,4- tetrahydroisoquinoline in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 5-chlorothiophene-2-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 17.75 min. m/z: 438 (M+1) EXAMPLE 130: (4-Chlorophenyl)- [1- (4-trifluoromethoxyphenyl)-1, 2,3,4-tetrahydroisoquinolin-2-yl]-methanone

Similarly as described in example 22 using a solution of 1- (4-trifluoromethoxyphenyl)-1, 2,3,4- tetrahydroisoquinoline in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-chlorobenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 17.42 min. m/z: 432 (M+1) EXAMPLE 131: (4-Methoxyphenyl)- [1- (4-trifluoromethoxyphenyl)-1, 2,3,4-tetrahydroisoquinolin-2-yl]- methanone Similarly as described in example 22 using a solution of 1- (4-trifluoromethoxyphenyl)-1, 2,3,4- tetrahydroisoquinoline in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-methoxybenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 mi) affords the title compound HPLC-MS: Rt = 16.42 min. m/z: 428 (M+1) EXAMPLE 132: 3- (4-Methoxyphenyl)-1- [1- (4-trifluoromethoxyphenyl)-1, 2,3,4-tetrahydroisoquinolin-2- yl] propenone

Similarly as described in example 22 using a solution of 1- (4-trifluoromethoxyphenyl)-1, 2,3,4- tetrahydroisoquinoline in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-methoxycinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: R, = 17.02 min. m/z: 454 (M+1) EXAMPLE 133: 3-Furan-3-yl-1- [1- (4-trifluoromethoxyphenyl)-1, 2,3,4-tetrahydroisoquinolin-2-yl] propenone Similarly as described in example 22 using a solution of 1- (4-trifluoromethoxyphenyl)-1, 2,3,4- tetrahydroisoquinoline in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3-furan-3-ylacrylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in di- chloromethane (1.73 g in 8.3 mi) affords the title compound HPLC-MS: Rt = 16.12 min. m/z: 414 (M+1)

EXAMPLE 134: (4-Trifluoromethoxyphenyl)- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3, 2- c] pyridin-5-yl] methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-trifluoromethoxybenzoic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 17.01 min. m/z: 472 (M+1) EXAMPLE 135: (7-Methoxybenzofuran-2-yl)- [4- (4-trifluoromethylphenyl)-4, 5, 6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] methanone

Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5, 6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 7-methoxybenzofuran-2-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'- ethylcarbodiimide hydrochloride in dichloromethane (1.73 g in 8.3 ml) affords the title com- pound.

HPLC-MS: Rt = 16.98 min. m/z: 458 (M+1) EXAMPLE 136: Benzofuran-2-yl- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] methanone Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of benzofuran-2-carboxylic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 17.01 min. m/z: 428 (M+1) EXAMPLE 137: 3- (4-Fluorophenyl)-l- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5-yl]- propenone

Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-fluorocinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 16.58 min. m/z: 432 (M+1) EXAMPLE 138: 3- (4-Trifluoromethylphenyl)-l- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2- c] pyridin-5-yl] propenone Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 mi, 0.15 mmol), a solution of 4-trifluoromethylcinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: R, = 17.38 min. m/z : 482 (M+1)

EXAMPLE 139: 3- (3-Methoxyphenyl)-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propenone

Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 3-methoxycinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound.

HPLC-MS: Rt = 16.54 min. m/z: 444 (M+1) EXAMPLE 140: 3- (4-Chlorophenyl)-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propenone

Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-chlorocinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 mi of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochlo- ride in dichloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 17.41 min. m/z: 448 (M+1) EXAMPLE 141: 3- (4-Methoxyphenyl)-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propan-1-one Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3, 2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-methoxyhydrocinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 16.41 min. m/z: 446 (M+1) EXAMPLE 142: 3- (4-Chlorophenyl)-1- [4- (4-trifluoromethylphenyl)-4, 5,6,7-tetrahydro-thieno [3,2-c] pyridin-5- yl] propan-1-one

Similarly as described in example 22 using a solution of 4- (4-trifluoromethylphenyl)-4, 5,6,7- tetrahydro-thieno [3,2-c] pyridine in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol), a solution of 4-chlorohydrocinnamic acid in N, N-dimethylformamide (0.375 M, 0.4 ml, 0.15 mmol) and 0.25 ml of a suspension of N- (3-dimethylaminopropyl)-N'-ethylcarbodiimide hy- drochloride in dichloromethane (1.73 g in 8.3 ml) affords the title compound HPLC-MS: Rt = 17.38 min. m/z: 450 (M+1) General : The HPLC-MS analyses were performed on a PE Sciex API 100 LC/MS System using a WatersTM 3 mm x 150 mm 3.5 p C-18 Symmetry column and positive ionspray with a flow rate at 20 minute. The column was eluted with a linear gradient of 5-90% A, 85-0% B and 10% C in 15 minutes at a flow rate of 1 ml/min (solvent A = acetonitrile, solvent B = water and solvent C = 0.1 % trifluoroacetic acid in water).

The given HPLC (method B) refers to the following system: The used HPLC-system was comprised of a Merck Hitachi L-4000 UV Detector (detection at 254 nm), a Merck Hitachi L-6200A Intelligent Pump, a Merck Hitachi AS-2000A Autosam- pler, and a 4 mm * 250 mm 5 u Licrosorp RP-18 column. The compounds were eluted using a gradient of 20% to 80% acetonitrile/0. 1% trifluoroacetic acid/water during 30 minutes at 1 ml/minute, followed by a gradient of 80% to 100% acetonitrile/0. 1 % trifluoroacetic acid/water during 5 minutes at 1 ml/minute then with 100% acetonitrile/0. 1% trifluoroacetic acid during 1 minute at 1 mi/minute and 4 minutes at 2 ml/minute.