Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1

A compound of the general formula (II):

• wherein:
• X is S or O;
• R5 is selected from hydrogen, C1-C8 alkyl, C3-10-cycloalkyl, C3-10-cycloalkyl-C1-8-alkyl, aryl, aryl-C1-8-alkyl, heterocyclyl, heterocyclyl-C1-8-alkyl and haloalkyl;
• wherein any aryl, cycloalkyl, or heterocyclyl residue is optionally independently substituted by one or more C1-8-alkyl, aryl, halogen, halo-C1-C8-alkyl, HO—C1-C8-alkyl, R8R9N—C1-C8-alkyl, C1-C8-alkyl-OR10, —OR10, (C3-C10)-cycloalkyl or C1-C8-alkyl-sulfonyl;
• R6 is selected from C1-8-alkyl, C1-8-alkoxy, C3-10-cycloalkyl, heterocyclyl, C3-10-cycloalkyl-C1-8-alkyl, CN—C1-8-alkyl, aryl, aryl-C1-8-alkyl, heterocyclyl-C1-8-alkyl and haloalkyl;
• R7 is selected from —NR8R9, halo, C1-8-alkyl, —(CR8R9)n—OR8, —S—C1-C8-alkyl, C3-10-cycloalkyl, heterocyclyl, C3-10-cycloalkyl-C1-8-alkyl, cyano-C1-8-alkyl, aryl, aryl-C1-8-alkyl, heterocyclyl-C1-8-alkyl, heterocyclyl-C(O)—C1-8-alkyl, heterocyclyl-SO2—C1-8-alkyl, C1-8-haloalkyl, R8R9N—C1-8-alkyl, HO—C1-8-alkyl, —C(O)—C3-C10-cycloalkyl, —C(O)—C1-C8-haloalkyl, —(CR8R9)n—Y—(CR8R9)n-heterocyclyl and —(CR8R9)n—Y—(CR8R9)n—C(O)—R8 (wherein n is 0-5, Y is NR10, O or S);
• wherein any aryl, alkyl, heterocyclyl or cycloalkyl residue is optionally substituted by one or more of
• —C1-C8-alkyl,
• -halo,
• —OH,
• —OR10,
• C1-C8-alkyl-SO2—,
• —SO2-aryl,
• —C(O)—(CR8R9)n-carbamate,
• —C(O)—O—C1-C8-alkyl,
• —C(O)—C1-C8-alkyl,
• —C(O)—(CR8R9)n—C(O)—NR8R9,
• —C(O)—(CR8R9)n—NR8—C(O)—C1-C8-alkyl
• —C(O)—(CR8R9)n—NR8R9,
• —C(O)—C3-C10-cycloalkyl,
• —C(O)-aryl,
• —C(O)—(CR8R9)n-heterocyclyl,
• —C1-C8 alkyl-OR8,
• —C(O)-halo-C1-C8-alkyl or
• —C(O)—(CR8R9)n-aryl,
• wherein any aryl, alkyl, cycloalkyl, or heterocyclyl residue is optionally independently substituted by one or more C1-8-alkyl, aryl, halogen, —NR10R10, C1-C8-haloalkyl, HO—C1-C8-alkyl, R8R9N—C1-C8-alkyl, C1-C8-alkyl-OR10, —OR10, (C3-C10)-cycloalkyl or C1-C8-alkyl-sulfonyl, —O—(CR8R9)n-heterocyclyl, —O—(CR8R9)n—C(O)—NR8R9, —O—(CR8R9)n—NR8R9, —Y—(CR8R9)n—NR8—C(O)—C1-C8-alkyl, —Y—(CR8R9)n-heterocyclyl, —O—(CR8R9)n—NR8R9, C1-C8-alkyl-SO2, or —O—(CR8R9)n—N—C(O)-heterocyclyl;
• wherein R8 and R9 are each independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkoxy, —NR10R10, —S—(C1-C8)alkyl, aryl and heterocyclyl;
• any alkyl, alkoxy, heterocyclyl or aryl may be substituted with one to three substituents selected from -halo, unsubstituted C1-C8 alkyl, unsubstituted C1-C8 alkoxy, unsubstituted C1-C8 thioalkoxy and unsubstituted aryl(C1-C4)alkyl;
• wherein R10 is independently selected from hydrogen, C1-C8 alkyl, aryl-C1-C8 alkyl, C1-C8 alkoxy, —S—(C1-C8)alkyl, heterocyclyl and aryl;
• any alkyl, heterocyclyl or aryl may be substituted with one to three substituents selected from -halo, unsubstituted C1-C8 alkyl, unsubstituted C1-C8 alkoxy, unsubstituted C1-C8 thioalkoxy and unsubstituted aryl(C1-C4)alkyl;
• or R6 and R7 form, together with the carbon atom bonded thereto, a saturated, partially unsaturated or unsaturated C3-10-cycloalkyl or a saturated, partially unsaturated or unsaturated C4-C14 heterocyclyl;
• wherein the cycloalkyl or the heterocyclyl may be optionally substituted by one or more of C1-C8-alkyl, aryl, C1-C8-haloalkyl, aryl-C1-C8-alkyl, C3-C10-cycloalkyl, —OR8, ═O, ═NR8, ═N—OR8, —NR8R9, —SR8, -halo, —OC(O)R8, —C(O)R8, —CO2R8, —CONR8R9, —OC(O)NR8R9, —NR9C(O)R8, —NR8C(O)NR8R9, NR SO2NR8R9, —NR8CO2R9—NHC(NH2)═NH, —NR8C(NH2)═NH, —NHC(NH2)═NR8, —S(O)R8, —SO2R8, —SO2NR8R9, —NR8SO2R9, —CN and —NO2;
• and pharmaceutically acceptable salts, solvates, hydrates, geometrical isomers, tautomers, optical isomers, N-oxides and prodrug forms thereof, with the proviso that:
• when
• X is S, R6=R7=methyl, then R5 is not phenyl or 4-iodophenyl,
• X is S, R6=R7=phenyl, then R5 is not phenyl, and
• X is S, R6 and R7 combine to form a cyclopropyl ring, then R5 is not n-butyl, cyclohexyl, benzyl, phenyl or naphthyl.

A compound of the general formula (III):

• wherein:
• R5 is selected from hydrogen, C1-C8 alkyl, C3-10-cycloalkyl, C3-10-cycloalkyl-C1-8-alkyl, aryl, aryl-C1-8-alkyl, heterocyclyl, heterocyclyl-C1-8-alkyl and haloalkyl;
• wherein any aryl, cycloalkyl, or heterocyclyl residue is optionally independently substituted by one or more C1-8-alkyl, aryl, halogen, halo-C1-C8-alkyl, HO—C1-C8-alkyl, R8R9N—C1-C8-alkyl, C1-C8-alkyl-OR10, —OR10, (C3-C10)-cycloalkyl or C1-C8-alkyl-sulfonyl;
• R6 is selected from C1-8-alkyl, C1-8-alkoxy, C3-10-cycloalkyl, heterocyclyl, C3-10-cycloalkyl-C1-8-alkyl, CN—C1-8-alkyl, aryl, aryl-C1-8-alkyl, heterocyclyl-C1-8-alkyl and haloalkyl;
• R7 is selected from —NR8R9, halo, C1-8-alkyl, —(CR8R9)n—OR8, —S-C1-C8-alkyl, C3-10-cycloalkyl, heterocyclyl, C3-10-cycloalkyl-C1-8-alkyl, cyano-C1-8-alkyl, aryl, aryl-C1-8-alkyl, heterocyclyl-C1-8-alkyl, heterocyclyl-C(O)—C1-8-alkyl, heterocyclyl-SO2—C1-8-alkyl, C1-8-haloalkyl, R8R9N—C1-8-alkyl, HO—C1-8-alkyl, —C(O)—C3-C10-cycloalkyl, —C(O)—C1-C8-haloalkyl, —(CR8R9)n—Y—(CR8R9)n-heterocyclyl and —(CR8R9)n—Y—(CR8R9)n—C(O)—R8 (wherein n is 0-5, Y is NR10, O or S);
• wherein any aryl, alkyl, heterocyclyl or cycloalkyl residue is optionally substituted by one or more of
• —C1-C8-alkyl,
• -halo,
• —OH,
• —OR10,
• C1-C8-alkyl-SO2—,
• —SO2-aryl,
• —C(O)—(CR8R9)n-carbamate,
• —C(O)—O—C1-C8-alkyl,
• —C(O)—C1-C8-alkyl,
• —C(O)—(CR8R9)n—C(O)—NR8R9,
• —C(O)—(CR8R9)n—NR8—C(O)—C1-C8-alkyl
• —C(O)—(CR8R9)n—NR8R9,
• —C(O)—C3-C10-cycloalkyl,
• —C(O)-aryl,
• —C(O)—(CR8R9)n-heterocyclyl,
• —C1-C8 alkyl-OR8,
• —C(O)-halo-C1-C8-alkyl or
• —C(O)—(CR8R9)n-aryl,
• wherein any aryl, alkyl, cycloalkyl, or heterocyclyl residue is optionally independently substituted by one or more C1-8-alkyl, aryl, halogen, —NR10R10, C1-C8-haloalkyl, HO—C1-C8-alkyl, R8R9N—C1-C8-alkyl, C1-C8-alkyl-OR10, —OR10, (C3-C10)-cycloalkyl or C1-C8-alkyl-sulfonyl, —O—(CR8R9)n-heterocyclyl, —O—(CR R9)n—C(O)—NR3R9—O—(CR R9)n—NR8R9, —Y—(CR8R9)n—NR8—C(O)—C1-C8-alkyl, —Y—(CR8R9)n-heterocyclyl, —O—(CR8R9)n—NR8R9, C1-C8-alkyl-SO2, or —O—(CR8R9)n—N—C(O)-heterocyclyl;
• wherein R8 and R9 are each independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkoxy, —NR10, —S—(C1-C8)alkyl, aryl and heterocyclyl;
• any alkyl, alkoxy, heterocyclyl or aryl may be substituted with one to three substituents selected from -halo, unsubstituted C1-C8 alkyl, unsubstituted C1-C8 alkoxy, unsubstituted C1-C8 thioalkoxy and unsubstituted aryl(C1-C4)alkyl;
• wherein R10 is independently selected from hydrogen, C1-C8 alkyl, aryl-C1-C8 alkyl, C1-C8 alkoxy, —S—(C1-C8)alkyl, heterocyclyl and aryl;
• any alkyl, heterocyclyl or aryl may be substituted with one to three substituents selected from -halo, unsubstituted C1-C8 alkyl, unsubstituted C1-C8 alkoxy, unsubstituted C1-C8 thioalkoxy and unsubstituted aryl(C1-C4)alkyl;
• or R6 and R7 form, together with the carbon atom bonded thereto, a saturated, partially unsaturated or unsaturated C3-10-cycloalkyl or a saturated, partially unsaturated or unsaturated C4-C14 heterocyclyl;
• wherein the cycloalkyl or the heterocyclyl may be optionally substituted by one or more of C1-C8-alkyl, aryl, C1-C8-haloalkyl, aryl-C1-C8-alkyl, C3-C10-cycloalkyl, —OR8, ═O, ═NR8, ═N—OR8, —NR8R9, —SR8, -halo, —OC(O)R8, —C(O)R8, —CO2R8, —CONR8R9, —OC(O)NR8R9, —NR9C(O)R3, —NR8C(O)NR8R9, —NR8SO2NR8R9, —NR8CO2R9, —NHC(NH2)═NH, —NR8C(NH2)═NH, —NHC(NH2)═NR8, —S(O)R8, —SO2R8, —SO2NR8R9, —NR8SO2R9, —CN and —NO2;
• and pharmaceutically acceptable salts, solvates, hydrates, geometrical isomers, tautomers, optical isomers, N-oxides and prodrug forms thereof, with the proviso that:
• when
• R6=R7=methyl, then R5 is not phenyl or 4-iodophenyl,
• R6=R7=phenyl, then R5 is not phenyl, and
• R6 and R7 combine to form a cyclopropyl ring, then R5 is not n-butyl, cyclohexyl, benzyl, phenyl or naphthyl.

A compound of the general formula (IV):

• wherein:
• R5 is selected from hydrogen, C1-C8 alkyl, C3-10-cycloalkyl, C3-10-cycloalkyl-C1-8-alkyl, aryl, aryl-C1-8-alkyl, heterocyclyl, heterocyclyl-C1-8-alkyl and haloalkyl;
• wherein any aryl, cycloalkyl, or heterocyclyl residue is optionally independently substituted by one or more C1-8-alkyl, aryl, halogen, halo-C1-C8-alkyl, HO—C1-C8-alkyl, R3R9N—C1-C8-alkyl, C1-C8-alkyl-OR10, —OR”, (C3-C10)-cycloalkyl or C1-C8-alkyl-sulfonyl;
• R6 is selected from C1-8-alkyl, C1-8-alkoxy, C3-10-cycloalkyl, heterocyclyl, C3-10-cycloalkyl-C1-8-alkyl, CN—C1-8-alkyl, aryl, aryl-C1-8-alkyl, heterocyclyl-C1-8-alkyl and haloalkyl;
• R7 is selected from —NR8R9, halo, C1-8-alkyl, —(CR8R9)n—OR8, —S—C1-C8-alkyl, C3-10-cycloalkyl, heterocyclyl, C3-10-cycloalkyl-C1-8-alkyl, cyano-C1-8-alkyl, aryl, aryl-C1-8-alkyl, heterocyclyl-C1-8-alkyl, heterocyclyl-C(O)—C1-8-alkyl, heterocyclyl-SO2—C1-8-alkyl, C1-8-haloalkyl, R8R9N—C1-8-alkyl, HO—C1-8-alkyl, —C(O)—C3-C10-cycloalkyl, —C(O)—C1-C8-haloalkyl, —(CR8R9)n—Y—(CR8R9)n-heterocyclyl and —(CR8R9)n—Y—(CR8R9)n—C(O)—R8 (wherein n is 0-5, Y is NR10, O or S);
• wherein any aryl, alkyl, heterocyclyl or cycloalkyl residue is optionally substituted by one or more of
• —C1-C8-alkyl,
• -halo,
• —OH,
• —OR10,
• C1-C8-alkyl-SO2—,
• —SO2-aryl,
• —C(O)—(CR8R9)n-carbamate,
• —C(O)—O—C1-C8-alkyl,
• —C(O)—C1-C8-alkyl,
• —C(O)—(CR8R9)n—C(O)n—NR8R9,
• —C(O)—(CR8R9)n—NR8—C(O)n—C1-C8-alkyl
• —C(O)—(CR8R9)n—NR8R9,
• —C(O)—C3-C10-cycloalkyl,
• —C(O)-aryl,
• —C(O)—(CR8R9)n-heterocyclyl,
• —C1-C8 alkyl-OR8,
• —C(O)-halo-C1-C8-alkyl or
• —C(O)—(CR8R9)n-aryl,
• wherein any aryl, alkyl, cycloalkyl, or heterocyclyl residue is optionally independently substituted by one or more C1-8-alkyl, aryl, halogen, —NR10R10, C1-C8-haloalkyl, HO—C1-C8-alkyl, R8R9N—C1-C8-alkyl, C1-C8-alkyl-OR10, —OR10, (C3-C10)-cycloalkyl or C1-C8-alkyl-sulfonyl, —O—(CR8R9)n-heterocyclyl, —O—(CR8R9)n—C(O)—NR8R9, —O—(CR8R9)n—NR8R9, —Y—(CR8R9), —NR8—C(O)—C1-C8-alkyl, —Y—(CR8R9)n-heterocyclyl, —O—(CR8R9)n—NR8R9, C1-C8-alkyl-SO2, or —O—(CR8R9)n—N—C(O)-heterocyclyl;
• wherein R8 and R9 are each independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkoxy, —NR10R10, —S—(C1-C8)alkyl, aryl and heterocyclyl;
• any alkyl, alkoxy, heterocyclyl or aryl may be substituted with one to three substituents selected from -halo, unsubstituted C1-C8 alkyl, unsubstituted C1-C8 alkoxy, unsubstituted C1-C8 thioalkoxy and unsubstituted aryl(C1-C4)alkyl;
• wherein R10 is independently selected from hydrogen, C1-C8 alkyl, aryl-C1-C8 alkyl, C1-C8 alkoxy, —S—(C1-C8)alkyl, heterocyclyl and aryl;
• any alkyl, heterocyclyl or aryl may be substituted with one to three substituents selected from -halo, unsubstituted C1-C8 alkyl, unsubstituted C1-C8 alkoxy, unsubstituted C1-C8 thioalkoxy and unsubstituted aryl(C1-C4)alkyl;
• or R6 and R7 form, together with the carbon atom bonded thereto, a saturated, partially unsaturated or unsaturated C3-10-cycloalkyl or a saturated, partially unsaturated or unsaturated C4-C14 heterocyclyl;
• wherein the cycloalkyl or the heterocyclyl may be optionally substituted by one or more of C1-C8-alkyl, aryl, C1-C8-haloalkyl, aryl-C1-C8-alkyl, C3-C10-cycloalkyl, —OR8═O, ═NR8, ═N—OR8, —NR8R9, —SR8, -halo, —OC(O)R8, —C(O)R8, —CO2R8, —CONR8R9, —OC(O)NR8R9, —NR9C(O)R8, —NR8C(O)NR8R9, —NR8SO2NR8R9, —NR8CO2R9, —NHC(NH2)═NH, —NR8C(NH2)═NH, —NHC(NH2)═NR8, —S(O)R8, —SO2R8, —SO2NR8R9, —NR8SO2R9, —CN and —NO2;
• and pharmaceutically acceptable salts, solvates, hydrates, geometrical isomers, tautomers, optical isomers, N-oxides and prodrug forms thereof.

A compound selected from:

• 2-(bicyclo[2.2.1]hept-2-ylamino)-5-isopropyl-1,3-thiazol-4(5H)-one;
• 2-(bicyclo[2.2.1]hept-2-ylamino)-5-ethyl-1,3-thiazol-4(5H)-one;
• 2-(bicyclo[2.2.1]hept-2-ylamino)-5-phenyl-1,3-thiazol-4(5H)-one;
• 2-(cyclohexylamino)-5-ethyl-1,3-thiazol-4(5H)-one;
• 2-(bicyclo[2.2.1]hept-2-ylamino)-5,5-dimethyl-1,3-thiazol-4(5H)-one;
• 5-Isopropyl-2-(tricyclo[3.3.1.0˜3,7˜]non-3-ylamino)-1,3-thiazol-4(5H)-one;
• 6-(tricyclo[3.3.1.0˜3,7˜]non-3-ylamino)-5-thia-7-azaspiro[3.4]oct-6-en-8-one;
• 2-(Tricyclo[3.3.1.0˜3,7˜]non-3-ylamino)-1,3-thiazol-4(5H)-one;
• 6-(Cyclooctylamino)-5-thia-7-azaspiro[3.4]oct-6-en-8-one;
• 6-(Cycloheptylamino)-5-thia-7-azaspiro[3.4]oct-6-en-8-one;
• 6-(Bicyclo[2.2.1]hept-2-ylamino)-5-thia-7-azaspiro[3.4]oct-6-en-8-one;
• 6-[(2,2,3,3-Tetramethylcyclopropyl)amino]-5-thia-7-azaspiro[3.4]oct-6-en-8-one;
• 6-[(2-Methylphenyl)amino]-5-thia-7-azaspiro[3.4]oct-6-en-8-one;
• 2-[(cyclohexylmethyl)amino]-5,5-dimethyl-1,3-thiazol-4(5H)-one;
• 2-[(2-fluorophenyl)amino]-5-isopropyl-1,3-thiazol-4(5H)-one;
• 2-[(cyclohexylmethyl)amino]-5-(2-hydroxyphenyl)-1,3-thiazol-4(5H)-one;
• (5S)-2-(cycloheptylamino)-5-methyl-1,3-thiazol-4(5H)-one;
• (5R)-2-(cycloheptylamino)-5-methyl-1,3-thiazol-4(5H)-one;
• 2-(cycloheptylamino)-5-ethyl-1,3-thiazol-4(5H)-one;
• 2-(cycloheptylamino)-5-isopropyl-1,3-thiazol-4(5H)-one;
• 5-tert-butyl-2-(cycloheptylamino)-1,3-thiazol-4(5H)-one;
• 2-(cyclooctylamino)-5-ethyl-1,3-thiazol-4(5H)-one;
• 5-isopropyl-2-[(2-isopropylphenyl)amino]-1,3-thiazol-4(5H)-one;
• 5-ethyl-2-[(2-isopropylphenyl)amino]-1,3-thiazol-4(5H)-one;
• 2-[(2-chlorophenyl)amino]-5-ethyl-1,3-thiazol-4(5H)-one;
• 5-ethyl-2-[(2-methylphenyl)amino]-1,3-thiazol-4(5H)-one;
• 5-isopropyl-2-[(2,2,3,3-tetramethylcyclopropyl)amino]-1,3-thiazol-4(5H)-one;
• 2-(bicyclo[2.2.1]hept-2-ylamino)-5-(4-hydroxybenzyl)-1,3-thiazol-4(5H)-one;
• 5-[(cyclohexylmethyl)amino]-4-thia-6-azaspiro[2.4]hept-5-en-7-one;
• 2-(cycloheptylamino)-5-(3,4-dihydroxybenzyl)-1,3-thiazol-4(5H)-one;
• 2-(cycloheptylamino)-5-(1H-imidazol-4-ylmethyl)-1,3-thiazol-4(5H)-one;
• 2-(cycloheptylamino)-5-isobutyl-1,3-thiazol-4(5H)-one;
• 2-(cycloheptylamino)-5-(1H-indol-3-ylmethyl)-1,3-thiazol-4(5H)-one;
• 2-(cycloheptylamino)-5-(4-hydroxybenzyl)-1,3-thiazol-4(5H)-one;
• (5R)-2-(cycloheptylamino)-5-(cyclohexylmethyl)-1,3-thiazol-4(5H)-one;
• 2-(cyclooctylamino)-5-(4-hydroxybenzyl)-1,3-thiazol-4(5H)-one;
• (5S)-2-(cycloheptylamino)-5-(cyclohexylmethyl)-1,3-thiazol-4(5H)-one;
• [2-(cycloheptylamino)-4-oxo-4,5-dihydro-1,3-thiazol-5-yl]acetonitrile;
• 2-(cycloheptylamino)-5-(pyridin-3-ylmethyl)-1,3-thiazol-4(5H)-one;
• 5-Isopropyl-2-[(2-methylphenyl)amino]-1,3-thiazol-4(5H)-one;
• 2-(Cyclooctylamino)-5,5-dimethyl-1,3-thiazol-4(5H)-one;
• 2-(Cyclooctylamino)-5-isopropyl-1,3-thiazol-4(5H)-one;
• 2-(Bicyclo[2.2.1]hept-2-ylamino)-1-thia-3-azaspiro[4.5]dec-2-en-4-one;
• 2-(Tricyclo[3.3.1.0˜3,7˜]non-3-ylamino)-1-thia-3-azaspiro[4.5]dec-2-en-4-one;
• 2-(Cycloheptylamino)-1-thia-3-azaspiro[4.5]dec-2-en-4-one;
• 2-(Cyclooctylamino)-1-thia-3-azaspiro[4.5]dec-2-en-4-one;
• 2-{[1-(4-Chlorophenyl)cyclobutyl]amino}-5-isopropyl-1,3-thiazol-4(5H)-one;
• 6-{[1-(4-Chlorophenyl)cyclobutyl]amino}-5-thia-7-azaspiro[3.4]oct-6-en-8-one;
• 2-(cycloheptylamino)-5,5-diethyl-1,3-thiazol-4(5H)-one;
• (5S)-5-isopropyl-2-{[(2S)-2-phenylpropyl]amino}-1,3-thiazol-4(5H)-one;
• (5R)-5-ethyl-2-{[(2S)-2-phenylpropyl]amino}-1,3-thiazol-4(5H)-one;
• (5S)-5-ethyl-2-{[(2S)-2-phenylpropyl]amino}-1,3-thiazol-4(5H)-one;
• (5R)-5-isopropyl-2-{[(2R)-2-phenylpropyl]amino}-1,3-thiazol-4(5H)-one;
• (5S)-5-isopropyl-2-{[(2R)-2-phenylpropyl]amino}-1,3-thiazol-4(5H)-one;
• (5R)-5-ethyl-2-{[(2R)-2-phenylpropyl]amino}-1,3-thiazol-4(5H)-one;
• (5S)-5-ethyl-2-{[(2R)-2-phenylpropyl]amino}-1,3-thiazol-4(5H)-one;
• 2-Anilino-5-isopropyl-1,3-thiazol-4(5H)-one;
• 5-Isopropyl-2-[(2-morpholin-4-ylethyl)amino]-1,3-thiazol-4(5H)-one;
• 2-(Bicyclo[2.2.1]hept-2-ylamino)-1-thia-3-azaspiro[4.4]non-2-en-4-one;
• 2-(Cycloheptylamino)-1-thia-3-azaspiro[4.4]non-2-en-4-one;
• 2-(Cyclooctylamino)-1-thia-3-azaspiro[4.4]non-2-en-4-one;
• 2-[(2,2,3,3-Tetramethylcyclopropyl)amino]-1-thia-3-azaspiro[4.4]non-2-en-4-one;
• 2-[(2-chlorobenzyl)amino]-5-isopropyl-1,3-oxazol-4(5H)-one;
• 2-[(4-chlorobenzyl)amino]-5-isopropyl-1,3-oxazol-4(5H)-one;
• 5-isopropyl-2-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,3-oxazol-4(5H)-one;
• 5-isopropyl-2-[(2-morpholin-4-ylethyl)amino]-1,3-oxazol-4(5H)-one;
• 5-benzyl-2-[(cyclohexylmethyl)amino]-1,3-oxazol-4(5H)-one;
• 2-(cycloheptylamino)-5-isopropyl-1,3-oxazol-4(5H)-one;
• 2-(bicyclo[2.2.1]hept-2-ylamino)-5-isopropyl-1,3-oxazol-4(5H)-one;
• 2-(bicyclo[2.2.1]hept-2-ylamino)-5-isobutyl-1,3-oxazol-4(5H)-one;
• 2-(cycloheptylamino)-5-isobutyl-1,3-oxazol-4(5H)-one;
• 5-isobutyl-2-[(2-methylphenyl)amino]-1,3-oxazol-4(5H)-one, and
• pharmaceutically acceptable salts, solvates, hydrates, geometrical isomers, tautomers, optical isomers, N-oxides and prodrug forms thereof.

A compound selected from

• 2-[1-(4-Fluoro-phenyl)-ethylamino]-5-methyl-5-(tetrahydro-pyran-4-ylmethyl)-thiazol-4-one;
• (5S)-5-((1-acetyl-4-piperidinyl)methyl)-2-((1S,4R)-bicyclo[2.2.1]hept-2-ylamino)-5-methyl-1,3-thiazol-4(5H)-one;
• (5R)-2-((1S,4R)-bicyclo[2.2.1]hept-2-ylamino)-5-methyl-5-(tetrahydro-2H-pyran-4-ylmethyl)-1,3-thiazol-4(5H)-one;
• (5S)-2-((1S,4R)-bicyclo[2.2.1]hept-2-ylamino)-5-methyl-5-tetrahydro-2H-pyran-4-yl-1,3-thiazol-4(5H)-one;
• 2-((1R,2R,4S)-bicyclo[2.2.1]hept-2-ylamino)-8-oxa-1-thia-3-azaspiro[4.5]dec-2-en-4-one;
• (5S)-2-((1S,4R)-bicyclo[2.2.1]hept-2-ylamino)-5-((1-(3-furanylcarbonyl)-4-piperidinyl)methyl)-5-methyl-1,3-thiazol-4(5H)-one;
• 2-(1-Cyclohexyl-ethylamino)-5-isopropyl-5-methyl-thiazol-4-one;
• 2-(5,5-Difluoro-bicyclo[2.2.1]hept-2-ylamino)-5-isopropyl-5-methyl-thiazol-4-one;
• 2-(bicyclo[2.2.1]hept-2-ylamino)-5-isopropyl-5-methyl-thiazol-4-one;
• 2-[1-(2-Trifluoromethyl-phenyl)-ethylamino]-8-oxa-1-thia-3-aza-spiro[4.5]dec-2-en-4-one;
• (5R)-2-((1S,2S,4R)-bicyclo[2.2.1]hept-2-ylamino)-5-methyl-5-(trifluoromethyl)-1,3-thiazol-4(5H)-one;
• 2-(Bicyclo[2.2.1]hept-2-ylamino)-5-(1-fluoro-1-methyl-ethyl)-5-methyl-thiazol-4-one;
• 2-[1-(4-Fluoro-phenyl)-ethylamino]-5-methyl-5-pyridin-4-yl-thiazol-4-one;
• 5-Methyl-5-pyridin-4-yl-2-[1-(2-trifluoromethyl-phenyl)-ethylamino]-thiazol-4-one;
• 2-[1-(2-Fluoro-phenyl)-ethylamino]-5-methyl-5-pyridin-4-yl-thiazol-4-one;
• 5-(1-Fluoro-1-methyl-ethyl)-2-[1-(2-fluoro-phenyl)-ethylamino]-5-methyl-thiazol-4-one;
• 2-[1-(2-Fluoro-phenyl)-ethylamino]-5-methyl-5-trifluoromethyl-thiazol-4-one;
• 5-(1,1-Difluoro-ethyl)-2-[1-(4-fluoro-phenyl)-ethylamino]-5-methyl-thiazol-4-one;
• 2-[1-(2-Chloro-phenyl)-ethylamino]-5-methyl-5-trifluoromethyl-thiazol-4-one;
• 2-[1-(4-Fluoro-phenyl)-ethylamino]-5-methyl-5-trifluoromethyl-thiazol-4-one;
• 2-[1-(2-Chloro-phenyl)-ethylamino]-5-methyl-5-trifluoromethyl-thiazol-4-one;
• 2-[1-(4-Fluoro-phenyl)-ethylamino]-5-(2-methoxy-pyridin-4-yl)-5-methyl-thiazol-4-one;
• 5-(1,1-Difluoro-ethyl)-2-[1-(4-fluoro-phenyl)-ethylamino]-5-methyl-thiazol-4-one;
• and
• 5-(1-Fluoro-1-methyl-ethyl)-2-[1-(4-fluoro-phenyl)-ethylamino]-5-methyl-thiazol-4-one, and
• pharmaceutically acceptable salts, solvates, hydrates, geometrical isomers, tautomers, optical isomers, N-oxides and prodrug forms thereof.

A process for the preparation of compounds of Formula (II), (III) or (IV):

• comprising the following reaction scheme:
• wherein:
• X is S or O;
• R5 is selected from hydrogen, C1-C8 alkyl, C3-10-cycloalkyl, C3-10-cycloalkyl-C1-8-alkyl, aryl, aryl-C1-8-alkyl, heterocyclyl, heterocyclyl-C1-8-alkyl and haloalkyl;
• wherein any aryl, cycloalkyl, or heterocyclyl residue is optionally independently substituted by one or more C1-8-alkyl, aryl, halogen, halo-C1-C8-alkyl, HO—C1-C8-alkyl, R8R9N—C1-C8-alkyl, C1-C8-alkyl-OR10, —OR10, (C3-C10)-cycloalkyl or C1-C8-alkyl-sulfonyl;
• R6 is selected from C1-8-alkyl, C1-8-alkoxy, C3-10-cycloalkyl, heterocyclyl, C3-10-cycloalkyl-C1-8-alkyl, CN—C1-8-alkyl, aryl, aryl-C1-8-alkyl, heterocyclyl-C1-8-alkyl and haloalkyl;
• R7 is selected from —NR8R9, halo, C1-8-alkyl, —(CR8R9)n—OR8, —S—C1-C8-alkyl, C3-10-cycloalkyl, heterocyclyl, C3-10-cycloalkyl-C1-8-alkyl, cyano-C1-8-alkyl, aryl, aryl-C1-8-alkyl, heterocyclyl-C1-8-alkyl, heterocyclyl-C(O)—C1-8-alkyl, heterocyclyl-SO2—C1-8-alkyl, C1-8-haloalkyl, R8R9N—C1-8-alkyl, HO—C1-8-alkyl, —C(O)—C3-C10-cycloalkyl, —C(O)—C1-C8-haloalkyl, —(CR8R9)n—Y—(CR8R9)n-heterocyclyl and —(CR8R9)n—Y—(CR8R9)n—C(O)—R8 (wherein n is 0-5, Y is NR10, O or S);
• wherein any aryl, alkyl, heterocyclyl or cycloalkyl residue is optionally substituted by one or more of
• —C1-C8-alkyl,
• -halo,
• —OH,
• —OR10,
• C1-C8-alkyl-SO2—,
• —SO2-aryl,
• —C(O)—(CR8R9)n-carbamate,
• —C(O)—O—C1-C8-alkyl,
• —C(O)—C1-C8-alkyl,
• —C(O)—(CR8R9)n—C(O)n—NR8R9,
• —C(O)—(CR8R9)n—NR8—C(O)—C1-C8-alkyl
• —C(O)—(CR8R9)n—NR8R9,
• —C(O)—C3-C10-cycloalkyl,
• —C(O)-aryl,
• —C(O)—(CR8R9)n-heterocyclyl,
• —C1-C8 alkyl-OR8,
• —C(O)-halo-C1-C8-alkyl or
• —C(O)—(CR8R9)n-aryl,
• wherein any aryl, alkyl, cycloalkyl, or heterocyclyl residue is optionally independently substituted by one or more C1-8-alkyl, aryl, halogen, —NR10R10, C1-C8-haloalkyl, HO—C1-C8-alkyl, R8R9N—C1-C8-alkyl, C1-C8-alkyl-OR10, —OR10, (C3-C10)-cycloalkyl or C1-C8-alkyl-sulfonyl, —O—(CR8R9)n-heterocyclyl, —O—(CR8R9)n—C(O)—NR8R9, —O—(CR8R9)n—NR8R9, —Y—(CR8R9)n—NR8—C(O)—C1-C8-alkyl, —Y—(CR8R9)n-heterocyclyl, —O—(CR8R9)n—NR8R9, C1-C8-alkyl-SO2, or —O—(CR8R9)n—N—C(O)-heterocyclyl;
• wherein R8 and R9 are each independently selected from hydrogen, C1-C8 alkyl, C1-C8 alkoxy, —NR10R10, —S—(C1-C8)alkyl, aryl and heterocyclyl;
• any alkyl, alkoxy, heterocyclyl or aryl may be substituted with one to three substituents selected from -halo, unsubstituted C1-C8 alkyl, unsubstituted C1-C8 alkoxy, unsubstituted C1-C8 thioalkoxy and unsubstituted aryl(C1-C4)alkyl;
• wherein R10 is independently selected from hydrogen, C1-C8 alkyl, aryl-C1-C8 alkyl, C1-C8 alkoxy, —S—(C1-C8)alkyl, heterocyclyl and aryl;
• any alkyl, heterocyclyl or aryl may be substituted with one to three substituents selected from -halo, unsubstituted C1-C8 alkyl, unsubstituted C1-C8 alkoxy, unsubstituted C1-C8 thioalkoxy and unsubstituted aryl(C1-C4)alkyl;
• LG is a leaving group;
• and pharmaceutically acceptable salts, solvates, hydrates, geometrical isomers, tautomers, optical isomers, N-oxides and prodrug forms thereof.