Glucokinase activators and pharmaceutical compositions containing the same as an active ingredient

Abstract

The present invention relates to new compounds of formula (1) exhibiting excellent activity for glucokinase, and pharmaceutical compositions comprising the same as an active ingredient.

1 . Indole compounds of the following formula (1): 
       
         
           
           
               
               
           
         
         in which 
         X represents O or NH, 
         n denotes a number of 0 to 3, 
         Y represents a direct bond, —(CH 2 ) p O—, —(CH 2 ) q —, or —(CH 2 ) q SO 2 —, 
         p denotes a number of 0 to 2, 
         q denotes a number of 1 to 3, 
         R1 represents hydrogen, —(CR4R5) p -A-R6 or —(CR4R5) q —R6, 
         p and q are as defined above, 
         R4 and R5 independently of one another represent hydrogen or C 1 -C 5 -alkyl, 
         A represents 6˜12 membered aryl or optionally oxo-containing C 3 -C 8 -cycloalkyl, or represents 3˜10 membered heterocyclyl or heteroaryl each of which has 1 to 3 hetero atoms selected from O, S, and N, 
         R6 represents hydrogen, hydroxy, halogen, nitro, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylsulfonyl, C 1 -C 6 -alkoxycarbonyl or carboxy, 
         R2 represents hydrogen, nitro, halogen, C 1 -C 6 -alkyl or trifluoromethyl, represents 5˜12 membered heteroaryl or heterocyclyl each of which has 1 to 3 hetero atoms selected from N and O, or represents optionally C 1 -C 6 -alkylsulfonyl-substituted 6˜12 membered aryl, 
         R3 represents R7-X—B—X′—, 
         B represents a direct bond, or represents 3˜10 membered heterocyclyl or heteroaryl each of which optionally contains oxo, is optionally fused, and has 1 to 4 hetero atoms selected from N, O and S, 
         X and X′ independently of one another represent a direct bond, or are selected from the group consisting of —CO—, —(CH 2 ) q —, —NR4C(O)—, —NR4-, —OC(O)—, —O—, —(CH 2 ) p C(O)—, —(CH 2 ) p O—, —(CH 2 ) p NR4-, —C(O)NR4- and —S(O) r —, wherein p and q are as defined above, r denotes a number of 0 to 2, and R4 represents hydrogen or C 1 -C 5 -alkyl, 
         R7 represents hydrogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, halogeno-C 1 -C 6 -alkyl or C 3 -C 6 -cycloalkyl, represents 6˜12 membered aryl, or represents 4˜8 membered heteroaryl or heterocyclyl each of which has 1 to 4 hetero atoms selected from N and O, 
         where alkyl, alkoxy, aryl, cycloalkyl, heterocyclyl and heteroaryl may be optionally substituted, and the substituents are one or more selected from the group consisting of hydroxy, halogen, nitrile, amino, C 1 -C 6 -alkylamino, di(C 1 -C 6 -alkyl)amino, C 1 -C 6 -alkyl, halogeno-C 1 -C 6 -alkyl, C 1 -C 6 -alkylsulfonyl, aryl-C 1 -C 6 -alkoxy and oxo, pharmaceutically acceptable salts or isomers thereof. 
       
     
     
         2 . The compounds of  claim 1  wherein
 X represents O or NH,   n denotes a number of 0 to 3,   Y represents a direct bond, —(CH 2 ) p O—, —(CH 2 ) q —, or —(CH 2 ) g SO 2 —,   p denotes a number of 0 to 2,   q denotes a number of 1 to 3,   R1 represents —(CR4R5) p -A-R6 or —(CR4R5) q —R6,   p and q are as defined above,   R4 and R5 independently of one another represent hydrogen or C 1 -C 5 -alkyl,   A represents 6˜12 membered aryl or optionally oxo-containing C 3 -C 7 -cycloalkyl, or represents 4˜8 membered heterocyclyl or heteroaryl each of which has 1 to 3 hetero atoms selected from O, S, and N,   R6 represents hydrogen, hydroxy, halogen, nitro, C 1 -C 6 -alkylcarbonyl C 1 -C 6 -alkylsulfonyl, C 1 -C 6 -alkoxycarbonyl or carboxy,   R2 represents hydrogen, halogen, C 1 -C 6 -alkyl or trifluoromethyl, represents 5˜8 membered heteroaryl or heterocyclyl each of which has 1 to 3 hetero atoms selected from N and O, or represents optionally C 1 -C 6 -alkylsulfonyl-substituted 6˜10 membered aryl,   R3 represents R7-X—B—X′—,   B represents a direct bond, or represents 4˜10 membered heterocyclyl or heteroaryl each of which optionally contains oxo, is optionally fused, and has 1 to 4 hetero atoms selected from N, O and S,   X and X′ independently of one another represent a direct bond, or are selected from the group consisting of —CO—, —(CH 2 ) q —, —NR4C(O)—, —NR4-, —OC(O)—, —O—, —(CH 2 ) p C(O)—, —C(O)NR4- and —S(O) r —, wherein p and q are as defined above, r denotes a number of 0 to 2, and R4 represents hydrogen or C 1 -C 5 -alkyl, and   R7 represents hydrogen, hydroxy, C 1 -C 6 -alkyl, halogeno-C 1 -C 6 -alkyl or C 3 -C 6 -cycloalkyl, represents 6˜12 membered aryl, or represents 4˜8 membered heteroaryl or heterocyclyl each of which has 1 to 4 hetero atoms selected from N and O.   
     
     
         3 . The compounds of  claim 2  wherein R1 represents —(CH 2 ) p -A-R6 or —(CR4R5) q —R6, wherein p denotes a number of 0 to 2, q denotes a number of 1 to 3, R4 and R5 independently of one another represent hydrogen or C 1 -C 5 -alkyl, A represents 6˜12 membered aryl or optionally oxo-containing C 3 -C 6 -cycloalkyl or represents 5˜6 membered heterocyclyl which has 1 to 2 hetero atoms selected from O, S, and N, and R6 represents hydrogen, halogen, nitro, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylsulfonyl, C 1 -C 6 -alkoxycarbonyl or carboxy. 
     
     
         4 . The compounds of  claim 3  wherein R1 is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, difluorocyclohexyl, tetrahydrofuran, tetrahydropyran, (tetrahydropyran-4-yl)methyl, tetrahydrothiopyran, 4-oxo-cyclohexyl, (1-methanesulfonyl)pyrrolidine, (1-acetyl)piperidine, 4-nitrophenyl and methylpropiolate. 
     
     
         5 . The compounds of  claim 2  wherein Y represents a direct bond, —O—, —(CH 2 )O—, —(CH 2 )— or —(CH 2 )SO 2 —. 
     
     
         6 . The compounds of  claim 2  wherein R2 represents hydrogen, halogen, C 1 -C 3 -alkyl or trifluoromethyl, represents 5˜6 membered heteroaryl or heterocyclyl each of which has 1 to 3 hetero atoms selected from N and O, or represents optionally methanesulfonyl-substituted 6˜10 membered aryl. 
     
     
         7 . The compounds of  claim 6  wherein R2 is selected from the group consisting of hydrogen, fluoro, chloro, bromo, methyl, ethyl, propyl, phenyl, methanesulfonylphenyl, pyridine, morpholine, 1,2-imidazole, 1,3-imidazole, pyrrolidine and pyrrole. 
     
     
         8 . The compounds of  claim 2  wherein B represents a direct bond, represents pyrazole, imidazole or oxadiazole each of which is optionally substituted by C 1 -C 6 -alkyl, or represents 5˜9 membered heterocyclyl which optionally contains oxo, is optionally fused, and has 1 to 4 hetero atoms selected from N, S and O. 
     
     
         9 . The compounds of  claim 8  wherein B represents a direct bond, or is selected from the following formulae (i) to (xi) 
       
         
           
           
               
               
           
         
         in which R7 is as defined in  claim 1  or  2 . 
       
     
     
         10 . The compounds of  claim 2  wherein X′ represents a direct bond, or is selected from the group consisting of —CO—, —NR4CO—, —SO 2 — and —O—. 
     
     
         11 . The compounds of  claim 2  wherein X represents a direct bond, or is selected from the group consisting of —C(O)NR4-, —NR4-, —OC(O)—, —NR4C(O)—, —(CH 2 )C(O)—, —S(O) 2 — and —C(O)—. 
     
     
         12 . The compounds of  claim 11  wherein X represents a direct bond, or is selected from the group consisting of —C(O)NH—, —C(O)N(Me)-, —NH—, —N(Me)-, —OC(O)—, —N(Me)C(O)—, —(CH 2 )C(O)—, —S(O) 2 — and —C(O)—. 
     
     
         13 . The compounds of  claim 2  wherein R7 represents hydrogen, hydroxy, C 1 -C 6 -alkyl, halogeno-C 1 -C 6 -alkyl or C 4 -C 6 -cycloalkyl, represents optionally halogen-substituted 6˜10 membered aryl, or represents 5˜6 membered heteroaryl or heterocyclyl each of which has 1 to 4 hetero atoms selected from N and O. 
     
     
         14 . The compounds of  claim 13  wherein R7 is selected from the group consisting of hydrogen, hydroxy, methyl, trifluoromethyl, ethyl, t-butyl, cyclohexyl, pyrrolidine, phenyl, 2-fluorophenyl, piperidine, pyridine, 1,3-pyrazine, 1,4-pyrazine, furan, trifluoromethyl, 1,2,3,4-tetrazole and tetrahydrofuran. 
     
     
         15 . The compounds of  claim 2  which are selected from the group consisting of
 [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl]-methanol;   {(R)-2-[7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-methanol;   {(R)-2-[7-(tetrahydro-furan-3-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-methanol;   {(R)-2-[7-(1-methanesulfonyl-pyrrolidin-3-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-methanol;   [(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;   {(R)-2-[5-fluoro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-methanol;   [(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;   {(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-methanol;   {(R)-2-[5-chloro-7-(tetrahydro-thiopyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-methanol;   [(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;   {(R)-2-[5-bromo-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-methanol;   [(R)-2-(7-cyclopentylamino-5-methoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;   {(R)-2-[7-cyclopentylamino-5-(pyridin-3-yloxy)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-methanol;   {(R)-2-[5-(pyridin-3-yloxy)-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-methanol;   Cyclopentyl-[2-((R)-4-pyrrolidin-1-ylmethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-amine;   Cyclopentyl-[2-((R)-4-morpholin-4-ylmethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-amine;   Cyclopentyl-[2-((R)-4-dimethylaminomethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-amine;   {(R)-2-[5-morpholin-4-ylmethyl-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-methanol;   [(R)-2-[7-cyclopentylamino-5-pyrazol-1-ylmethyl-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl]-methanol;   [(R)-2-(7-cyclopentylamino-5-imidazol-1-ylmethyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;   {(R)-2-[7-cyclopentylamino-5-(1H-pyrrol-3-ylmethyl)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-methanol;   [(R)-2-(7-cyclopentylamino-5-methanesulfonylmethyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;   [7-Cyclopentylamino-2-((R)-4-hydroxymethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-5-yl]-methanol;   [(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;   [(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   [(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid ethyl ester;   2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl]-ethanol;   {(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid methyl ester;   {(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethanol;   [(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   2-[(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl]-ethanol;   {(R)-2-[5-bromo-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   2-{(R)-2-[5-bromo-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethanol;   [(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   [(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid ethyl ester;   2-[(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;   {(R)-2-[5-fluoro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   2-{(R)-2-[5-fluoro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethanol;   [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid ethyl ester;   2-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;   {(R)-2-[7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   2-{(R)-2-[7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethanol;   [(R)-2-(7-cyclopentylamino-5-methoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;   [(R)-2-(7-cyclopentylamino-5-methoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   [(R)-2-(7-cyclopentylamino-5-methoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid ethyl ester;   {(R)-2-[5-methoxy-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid methyl ester;   {(R)-2-[5-methoxy-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   [(R)-2-(7-cyclopentylamino-5-ethoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   [(R)-2-(7-cyclopentylamino-5-propoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   [(R)-2-(7-cyclopentylamino-5-phenoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   {(R)-2-[5-phenoxy-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   {(R)-2-[7-cyclopentylamino-5-(pyridin-3-yloxy)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid methyl ester;   {(R)-2-[7-cyclopentylamino-5-(pyridin-3-yloxy)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   {(R)-2-[5-(pyridin-3-yloxy)-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid methyl ester;   {(R)-2-[5-(pyridin-3-yloxy)-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   [(R)-2-(7-cyclopentylamino-5-methyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;   [(R)-2-(7-cyclopentylamino-5-methyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   {(R)-2-[5-methyl-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   {(R)-2-[5-methyl-7-(4-oxo-cyclohexylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   {(R)-2-[7-cyclopentylamino-5-(4-methanesulfonyl-phenoxy)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   [(R)-2-(7-cyclopentylamino-5-phenoxymethyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;   [(R)-2-(7-cyclopentylamino-5-phenoxymethyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   [(R)-2-(7-cyclopentylamino-5-pyrrolidin-1-ylmethyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]acetic acid methyl ester;   [(R)-2-(7-cyclopentylamino-5-methanesulfonylmethyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;   [(R)-2-(7-cyclopentylamino-5-methanesulfonylmethyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   2-[(R)-2-(7-cyclopentylamino-5-methanesulfonylmethyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;   Cyclopentyl-{5-methanesulfonylmethyl-2-[(R)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;   1-(4-{2-[(R)-2-(7-cyclopentylamino-5-methanesulfonylmethyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;   2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-morpholin-4-yl-ethanone;   2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-N-(2-morpholin-4-yl-ethyl)-acetamide;   2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-N-(3-morpholin-4-yl-propyl)-acetamide;   2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-N-methyl-acetamide;   2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-N,N-dimethyl-acetamide;   2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(4-methyl-piperazin-1-yl)-ethanone;   2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(3-dimethylamino-pyrrolidin-1-yl)-ethanone;   2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(3-hydroxy-pyrrolidin-1-yl)-ethanone;   2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-piperidin-1-yl-ethanone;   2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-N-methyl-acetamide;   2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-1-morpholin-4-yl-ethanone;   2-[(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(4-methyl-piperazin-1-yl)-ethanone;   2-[(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-N-(2-morpholin-4-yl-ethyl)-acetamide;   1-(4-Acetyl-piperazin-1-yl)-2-[(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanone;   2-[(R)-2-(7-cyclopentylamino-5-methoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-N-methyl-acetamide;   2-[(R)-2-(7-cyclopentylamino-5-methoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-morpholin-4-yl-ethanone;   2-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-N-ethyl-acetamide;   2-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-N-methyl-acetamide;   2-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-morpholin-4-yl-ethanone;   N-methyl-2-{(R)-2-[7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetamide;   1-Morpholin-4-yl-2-{(R)-2-[7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethanone;   {5-Chloro-2-[(R)-4-(2-dimethylamino-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;   {5-Chloro-2-[(R)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;   {5-Chloro-2-[(R)-4-(2-piperazin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;   1-(4-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;   (5-Chloro-2-{(R)-4-[2-(4-ethanesulfonyl-piperazin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;   1-(4-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;   (5-Chloro-2-{(R)-4-[2-(4-methyl-piperazin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;   1-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperidin-4-ol;   (4-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-2-one;   (5-Chloro-2-{(R)-4-[2-(3-dimethylamino-pyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;   {5-Chloro-2-[(R)-4-(2-piperidin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;   (5-Chloro-2-{(R)-4-[2-(1,1-dioxo-thiomorpholin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;   {5-Chloro-2-[(R)-4-(2-pyrazol-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;   (S)-1-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-pyrrolidine-2-carboxylic acid;   {5-Chloro-2-[(R)-4-(2-methanesulfonyl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;   3-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-5-methyl-3H-imidazole-4-carboxylic acid ethyl ester;   3-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-5-methyl-3H-imidazole-4-carboxylic acid;   1-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-pyrrolidin-2-one;   1-(2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-piperidine-3-carboxylic acid;   1-(2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-piperidine-3-carboxylic acid dimethylamide;   [(S)-1-(2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-pyrrolidin-3-yl]-carbamic acid t-butyl ester;   (2-{(R)-4-[2-((S)-3-amino-pyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-5-chloro-1H-indol-7-yl)-(tetrahydro-pyran-4-yl)-amine;   N—[(S)-1-(2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-pyrrolidin-3-yl]-acetamide;   {5-Chloro-2-[(R)-4-(2-piperazin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-(tetrahydro-pyran-4-yl)-amine;   1-[4-(2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-piperazin-1-yl]-2-hydroxy-ethanone;   1-[4-(2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-piperazin-1-yl]-2-tetrazol-1-yl-ethanone;   1-[4-(2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-piperazin-1-yl]-3,3,3-trifluoro-propan-1-one;   [4-(2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-piperazin-1-yl]-furan-2-yl-methanone;   (5-Chloro-2-{(R)-4-[2-(2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-(tetrahydro-pyran-4-yl)-amine;   (5-Chloro-2-{(R)-4-[2-(4-pyrimidin-2-yl-piperazin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-(tetrahydro-pyran-4-yl)-amine;   {2-[(R)-4-(2-amino-ethyl)-4,5-dihydro-thiazol-2-yl]-5-fluoro-1H-indol-7-yl}-cyclopentyl-amine;   1-(4-{2-[(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;   Cyclopentyl-{5-fluoro-2-[(R)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;   Cyclopentyl-{2-[(R)-4-(2-dimethylamino-ethyl)-4,5-dihydro-thiazol-2-yl]-5-fluoro-1H-indol-7-yl}-amine;   Cyclopentyl-{5-fluoro-2-[(R)-4-(2-pyrrolidin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;   Cyclopentyl-(2-{(R)-4-[2-(1,1-dioxo-thiomorpholin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-5-fluoro-1H-indol-7-yl)-amine;   4-{2-[(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-2-one;   1-(4-{2-[(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;   Cyclopentyl-{5-fluoro-2-[(R)-4-(2-methanesulfonyl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;   {2-[(R)-4-(2-dimethylamino-ethyl)-4,5-dihydro-thiazol-2-yl]-5-fluoro-1H-indol-7-yl}-(tetrahydro-pyran-4-yl)-amine;   {5-Fluoro-2-[(R)-4-(2-pyrrolidin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-(tetrahydro-pyran-4-yl)-amine;   {5-Fluoro-2-[(R)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-(tetrahydro-pyran-4-yl)-amine;   1-[4-(2-{(R)-2-[5-fluoro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl-piperazin-1-yl)-ethanone;   (2-{(R)-4-[2-(1,1-dioxo-thiomorpholin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-5-fluoro-1H-indol-7-yl)-(tetrahydropyran-4-yl)-amine;   (5-Fluoro-2-[(R)-4-(2-methanesulfonyl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl)-(tetrahydro-pyran-4-yl)-amine;   4-(2-{(R)-2-[5-fluoro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-piperazin-2-one;   1-[4-(2-{(R)-2-[5-fluoro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-piperazin-1-yl]-2-hydroxy-ethanone;   Cyclopentyl-{2-[(R)-4-(2-methoxy-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;   Cyclopentyl-{2-[(R)-4-(2-dimethylamino-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;   Cyclopentyl-{2-[(R)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;   Cyclopentyl-{2-[(R)-4-(2-piperidin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;   {2-[(R)-4-(2-methanesulfonyl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-(tetrahydro-pyran-4-yl)-amine;   1-(4-{2-[(R)-2-(7-cyclopentylamino-5-methoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;   2-Hydroxy-1-[4-(2-{(R)-2-[5-methoxy-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-piperazin-1-yl]-ethanone;   3-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;   3-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;   3-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propan-1-ol;   3-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-propionic acid;   3-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-propan-1-ol;   3-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-N-(2-morpholin-4-yl-ethyl)-propionamide;   3-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(4-methyl-piperazin-1-yl)-propan-1-one;   1-(4-{3-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propyl}-piperazin-1-yl)-ethanone;   {5-Chloro-2-[(R)-4-(3-morpholin-4-yl-propyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;   3-[(R)-2-(7-cyclopentylamino-5-methyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;   3-[(R)-2-(7-cyclopentylamino-5-methyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;   3-[(R)-2-(7-cyclopentylamino-5-phenoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;   3-[(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;   3-[(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;   3-[(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;   3-[(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;   3-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;   3-[(R)-2-(7-cyclopentylamino-5-methoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;   3-[(R)-2-(7-cyclopentylamino-5-ethoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;   3-[(R)-2-(7-cyclopentylamino-5-ethoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;   3-[(R)-2-(7-cyclopentylamino-5-trifluoromethoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;   3-[(R)-2-(7-cyclopentylamino-5-trifluoromethoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;   [(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-ylmethoxy]-acetic acid ethyl ester;   [(R)-2-(7-cyclopentylamino-5-fluoro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-ylmethoxy]-acetic acid;   Cyclopentyl-{2-[(R)-4-(3-cyclopentyl-[1,2,4]oxadiazol-5-ylmethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;   Cyclopentyl-{2-[(R)-4-(3-piperidin-1-yl-[1,2,4]oxadiazol-5-ylmethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;   [(R)-2-(7-phenoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   1-(4-{2-[(R)-2-(7-phenoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;   2-[(R)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-7-phenoxy-1H-indole;   7-Phenoxy-2-[(R)-4-(2-pyrrolidin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indole;   Dimethyl-{2-[(R)-2-(7-phenoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-amine;   [(S)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   {(S)-2-[7-(1-acetyl-piperidin-4-ylamino)-5-methyl-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   ((S)-2-{7-[(tetrahydro-pyran-2-ylmethyl)-amino]-1H-indol-2-yl}-4,5-dihydro-thiazol-4-yl)-acetic acid;   ((S)-2-{7-[(tetrahydro-pyran-4-ylmethyl)-amino]-1H-indol-2-yl}-4,5-dihydro-thiazol-4-yl)-acetic acid;   {(S)-2-[7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   {(S)-2-[7-(1-acetyl-pyrrolidin-3-ylamino)-5-methyl-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   [(S)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   ((S)-2-{5-phenoxy-7-[(tetrahydro-pyran-4-ylmethyl)-amino]-1H-indol-2-yl}-4,5-dihydro-thiazol-4-yl)-acetic acid;   {(S)-2-[5-phenoxy-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   {(S)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   [(S)-2-(7-cyclobutylamino-5-methyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   {(S)-2-[5-methyl-7-(tetrahydro-furan-3-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   {(S)-2-[7-(cyclopropylmethyl-amino)-5-methyl-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   ((S)-2-{5-methyl-7-[(tetrahydro-pyran-4-ylmethyl)-amino]-1H-indol-2-yl}-4,5-dihydro-thiazol-4-yl)-acetic acid;   {(S)-2-[5-methyl-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   [(S)-2-(7-cyclopentylamino-5-methyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methylester;   [(S)-2-(7-cyclopentylamino-5-phenoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;   {(S)-2-[7-(4,4-difluoro-cyclohexylamino)-5-methyl-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid;   (2-{(S)-4-[2-((R)-3-amino-pyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-5-chloro-1H-indol-7-yl)-cyclopentyl-amine;   (5-Chloro-2-{(S)-4-[2-((R)-3-dimethylamino-pyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;   1-(4-{2-[(S)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;   1-(4-{2-[(S)-2-(7-amino-5-chloro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;   1-(4-{2-[(S)-2-(5-methyl-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;   {5-Methyl-2-[(S)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-(tetrahydro-pyran-4-yl)-amine;   1-(4-{2-[(S)-2-(7-cyclopentylamino-5-phenoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;   Cyclopentyl-{5-phenoxy-2-[(S)-4-(2-piperazin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;   4-{2-[(S)-2-(7-cyclopentylamino-5-phenoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazine-1-carboxylic acid t-butyl ester;   Cyclopentyl-(2-{(S)-4-[2-(3-methyl-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-5-phenoxy-1H-indol-7-yl)-amine;   4-{2-[(S)-2-(7-cyclopentylamino-5-phenoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-2-one;   (4-{2-[(S)-2-(7-cyclopentylamino-5-phenoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-(tetrahydro-furan-2-yl)-methanone;   Cyclopentyl-(5-phenoxy-2-{(S)-4-[2-(4-pyridin-2-yl-piperazin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-amine;   Cyclopentyl-[2-((S)-4-{2-[4-(2-fluoro-phenyl)-piperazin-1-yl]-ethyl}-4,5-dihydro-thiazol-2-yl)-5-phenoxy-1H-indol-7-yl)-amine;   1-(4-{2-[(S)-2-(7-cyclopentylamino-5-phenoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;   {(R)-1-[2-[(S)-2-{5-methyl-7-[(tetrahydro-pyran-4-ylmethyl)-amino]-1H-indol-2-yl}-4,5-dihydro-thiazol-4-yl]-ethyl]-pyrrolidin-2-yl}-methanol;   N—((R)-1-{2-[(S)-2-(7-cyclopentylamino-5-phenoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-pyrrolidin-3-yl)-acetamide;   (2-{(S)-4-[2-(4-benzyl-piperazin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-5-phenoxy-1H-indol-7-yl)-cyclopentyl-amine;   {5-Methyl-2-[(S)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-(tetrahydro-pyran-4-ylmethyl)methyl-amine;   {2-[(S)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-5-phenoxy-1H-indol-7-yl}-(tetrahydro-pyran-4-ylmethyl)-amine;   4-[2-((S)-2-{5-phenoxy-7-[(tetrahydro-pyran-4-ylmethyl)-amino]-1H-indol-2-yl}-4,5-dihydro-thiazol-4-yl)-ethyl]-piperazin-2-one;   Cyclopentyl-{5-phenoxy-2-[(S)-4-(2-pyrrolidin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl)-amine;   (4,4-Difluoro-cyclohexyl)-{2-[(S)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl)-amine;   (2-{(S)-4-[2-(3-methyl-5,6-dihydro-8H-[1,2,4]triazolo[4,3-pyrazin-7-yl]-ethyl)-4,5-dihydro-thiazol-2-yl}-5-phenoxy-1H-indol-7-yl)-(tetrahydro-pyran-4-ylmethyl)-amine;   4-[2-((S)-2-{5-phenoxy-7-[(tetrahydro-pyran-4-ylmethyl)-amino]-1H-indol-2-yl}-4,5-dihydro-thiazol-4-yl)-ethyl]-piperazin-2-one; and   4-(2-{(S)-2-[7-(4,4-difluoro-cyclohexylamino)-5-phenoxy-7-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-piperazin-2-one.   
     
     
         16 . A pharmaceutical composition for the activation of glucokinase, which comprises the compounds of formula (1) as defined in  claim 1 , pharmaceutically acceptable salts or isomers thereof as an active ingredient together with pharmaceutically acceptable carriers. 
     
     
         17 . The composition of  claim 16  for the prevention or treatment of diabetes, complications of diabetes, diabetes related diseases, or obesity. 
     
     
         18 . The composition of  claim 17  wherein diabetes is type 1 diabetes. 
     
     
         19 . The composition of  claim 17  wherein diabetes is type 2 diabetes. 
     
     
         20 . The composition of  claim 17  wherein complications of diabetes are neurogenic disease, hyperlipidemia, hypertension, retinosis, or renal failure. 
     
     
         21 . The composition of  claim 16  which is a hypoglycemic composition. 
     
     
         22 . A process for preparing a pharmaceutical composition for the prevention or treatment of the diseases caused by deactivation of glucokinase, which comprises the step of mixing the compounds of formula (1) as defined in  claim 1 , pharmaceutically acceptable salts or isomers thereof as an active ingredient together with pharmaceutically acceptable carriers.