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

1. A method for lowering blood glucose level comprising:

administering a pharmaceutical composition which comprises an indole compound of the following formula (1), or pharmaceutically acceptable salt or isomers thereof, as an active ingredient together with a pharmaceutically acceptable carrier:

in which

X represents 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 —(CR4R5) p -A-R6 , wherein p is 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 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.

2. The method of claim 1 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof,

X represents 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 —(CR4R5) p -A-R6, wherein p is 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 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 method of claim 2 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, R1 represents —(CH 2 ) p -A-R6, wherein p denotes a number of 0 to 2, 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 method of claim 3 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, 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 and 4-nitrophenyl.

5. The method of claim 2 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, Y represents a direct bond, —O—, —(CH 2 )O—, —(CH 2 )— or —(CH 2 )SO 2 —.

6. The method of claim 2 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, R2 represents 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 method of claim 6 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, R2 is selected from the group consisting of fluoro, chloro, bromo, methyl, ethyl, propyl, phenyl, methanesulfonylphenyl, pyridine, morpholine, 1,2-imidazole, 1,3-imidazole, pyrrolidine and pyrrole.

8. The method of claim 2 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, 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 method of claim 8 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, 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 method of claim 2 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, X′ represents a direct bond, or is selected from the group consisting of —CO—, —NR4CO—, —SO 2 — and —O—.

11. The method of claim 2 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, 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 method of claim 11 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, 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 method of claim 2 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, 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 method of claim 13 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, 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 method of claim 2 wherein the compound of formula (1) is selected from the group consisting of

[(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;

{(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-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;

{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;

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-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;

[(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-(1-acetyl-pyrrolidin-3-ylamino)-5-methyl-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-(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;

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;

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, and

pharmaceutically acceptable salts or isomers thereof.

16. A method for the treatment of type 2 diabetes or obesity comprising:

administering a pharmaceutical composition which comprises an indole compound of the following Formula (1), or pharmaceutically acceptable salt or isomer thereof, as an active ingredient together with a pharmaceutically acceptable carrier:

in which

X represents 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 —(CR4R5) p -A-R6, wherein p is 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 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.

17. The method of claim 16 wherein said method is for the treatment of obesity.

18. The method of claim 16 wherein said method is for the treatment of type 2 diabetes.