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, \u2014(CH2)pO\u2014, \u2014(CH2)q\u2014, or \u2014(CH2)qSO2\u2014,
p denotes a number of 0 to 2,
q denotes a number of 1 to 3,
R1 represents \u2014(CR4R5)p-A-R6 , wherein p is as defined above,
R4 and R5 independently of one another represent hydrogen or C1-C5-alkyl,
A represents 6\u02dc12 membered aryl or optionally oxo-containing C3-C8-cycloalkyl, or represents 3\u02dc10 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, C1-C6-alkylcarbonyl, C1-C6-alkylsulfonyl, C1-C6-alkoxycarbonyl or carboxy,
R2 represents nitro, halogen, C1-C6-alkyl or trifluoromethyl, represents 5\u02dc12 membered heteroaryl or heterocyclyl each of which has 1 to 3 hetero atoms selected from N and O, or represents optionally C1-C6-alkylsulfonyl-substituted 6\u02dc12 membered aryl,
R3 represents R7-X\u2014B\u2014X\u2032\u2014,
B represents a direct bond, or represents 3\u02dc10 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\u2032 independently of one another represent a direct bond, or are selected from the group consisting of \u2014CO\u2014, \u2014(CH2)q\u2014, \u2014NR4C(O)\u2014, \u2014NR4-, \u2014OC(O)\u2014, \u2014O\u2014, \u2014(CH2)pC(O)\u2014, \u2014(CH2)pO\u2014, \u2014(CH2)pNR4-, \u2014C(O)NR4- and \u2014S(O)r\u2014, wherein p and q are as defined above, r denotes a number of 0 to 2, and R4 represents hydrogen or C1-C5-alkyl,
R7 represents hydrogen, hydroxy, C1-C6-alkyl, C1-C6-alkoxy, halogeno-C1-C6-alkyl or C3-C6-cycloalkyl, represents 6\u02dc12 membered aryl, or represents 4\u02dc8 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, C1-C6-alkylamino, di(C1-C6-alkyl)amino, C1-C6-alkyl, halogeno-C1-C6-alkyl, C1-C6-alkylsulfonyl, aryl-C1-C6-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, \u2014(CH2)pO\u2014, \u2014(CH2)q\u2014, or \u2014(CH2)qSO2\u2014,
P denotes a number of 0 to 2,
q denotes a number of 1 to 3,
R1 represents \u2014(CR4R5)p-A-R6, wherein p is as defined above,
R4 and R5 independently of one another represent hydrogen or C1-C5-alkyl,
A represents 6\u02dc12 membered aryl or optionally oxo-containing C3-C7-cycloalkyl, or represents 4\u02dc8 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, C1-C6-alkylcarbonyl, C1-C6-alkylsulfonyl, C1-C6-alkoxycarbonyl or carboxy,
R2 represents halogen, C1-C6-alkyl or trifluoromethyl, represents 5\u02dc8 membered heteroaryl or heterocyclyl each of which has 1 to 3 hetero atoms selected from N and O, or represents optionally C1-C6-alkylsulfonyl-substituted 6\u02dc10 membered aryl,
R3 represents R7-X\u2014B\u2014X\u2032\u2014,
B represents a direct bond, or represents 4\u02dc10 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\u2032 independently of one another represent a direct bond, or are selected from the group consisting of \u2014CO\u2014, \u2014(CH2)q\u2014, \u2014NR4C(O)\u2014, \u2014NR4-, \u2014OC(O)\u2014, \u2014O\u2014, \u2014(CH2)pC(O)\u2014, \u2014C(O)NR4- and \u2014S(O)r\u2014, wherein p and q are as defined above, r denotes a number of 0 to 2, and R4 represents hydrogen or C1-C5-alkyl, and
R7 represents hydrogen, hydroxy, C1-C6-alkyl, halogeno-C1-C6-alkyl or C3-C6-cycloalkyl, represents 6\u02dc12 membered aryl, or represents 4\u02dc8 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 \u2014(CH2)p-A-R6, wherein p denotes a number of 0 to 2, R4 and R5 independently of one another represent hydrogen or C1-C5-alkyl, A represents 6\u02dc12 membered aryl or optionally oxo-containing C3-C6-cycloalkyl or represents 5\u02dc6 membered heterocyclyl which has 1 to 2 hetero atoms selected from O, S, and N, and R6 represents hydrogen, halogen, nitro, C1-C6-alkylcarbonyl, C1-C6-alkylsulfonyl, C1-C6-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, \u2014O\u2014, \u2014(CH2)O\u2014, \u2014(CH2)\u2014 or \u2014(CH2)SO2\u2014.
6. The method of claim 2 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, R2 represents halogen, C1-C3-alkyl or trifluoromethyl, represents 5\u02dc6 membered heteroaryl or heterocyclyl each of which has 1 to 3 hetero atoms selected from N and O, or represents optionally methanesulfonyl-substituted 6\u02dc10 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 C1-C6-alkyl, or represents 5\u02dc9 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\u2032 represents a direct bond, or is selected from the group consisting of \u2014CO\u2014, \u2014NR4CO\u2014, \u2014SO2\u2014 and \u2014O\u2014.
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 \u2014C(O)NR4-, \u2014NR4-, \u2014OC(O)\u2014, \u2014NR4C(O)\u2014, \u2014(CH2)C(O)\u2014, \u2014S(O)2\u2014 and \u2014C(O)\u2014.
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 \u2014C(O)NH\u2014, \u2014C(O)N(Me)-, \u2014NH\u2014, \u2014N(Me)-, \u2014OC(O)\u2014, \u2014N(Me)C(O)\u2014, \u2014(CH2)C(O)\u2014, \u2014S(O)2\u2014 and \u2014C(O)\u2014.
13. The method of claim 2 wherein in the compound of formula (1), or pharmaceutically acceptable salt or isomer thereof, R7 represents hydrogen, hydroxy, C1-C6-alkyl, halogeno-C1-C6-alkyl or C4-C6-cycloalkyl, represents optionally halogen-substituted 6\u02dc10 membered aryl, or represents 5\u02dc6 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\u2014(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\u2032bipyrazinyl-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-1,2,4triazolo4,3-apyrazin-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\u2014((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-1,2,4triazolo4,3-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, \u2014(CH2)pO\u2014, \u2014(CH2)q\u2014, or \u2014(CH2)qSO2\u2014,
p denotes a number of 0 to 2,
q denotes a number of 1 to 3,
R1 represents \u2014(CR4R5)p-A-R6, wherein p is as defined above,
R4 and R5 independently of one another represent hydrogen or C1-C5-alkyl,
A represents 6\u02dc12 membered aryl or optionally oxo-containing C3-C8-cycloalkyl, or represents 3\u02dc10 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, C1-C6-alkylcarbonyl, C1-C6-alkylsulfonyl, C1-C6-alkoxycarbonyl or carboxy,
R2 represents nitro, halogen, C1-C6-alkyl or trifluoromethyl, represents 5\u02dc12 membered heteroaryl or heterocyclyl each of which has 1 to 3 hetero atoms selected from N and O, or represents optionally C1-C6-alkylsulfonyl-substituted 6\u02dc12 membered aryl,
R3 represents R7-X\u2014B\u2014X\u2032\u2014,
B represents a direct bond, or represents 3\u02dc10 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\u2032 independently of one another represent a direct bond, or are selected from the group consisting of \u2014CO\u2014, \u2014(CH2)q\u2014, \u2014NR4C(O)\u2014, \u2014NR4-, \u2014OC(O)\u2014, \u2014O\u2014, \u2014(CH2)pC(O)\u2014, \u2014(CH2)pO\u2014, \u2014(CH2)pNR4-, \u2014C(O)NR4- and \u2014S(O)r\u2014, wherein p and q are as defined above, r denotes a number of 0 to 2, and R4 represents hydrogen or C1-C5-alkyl,
R7 represents hydrogen, hydroxy, C1-C6-alkyl, C1-C6-alkoxy, halogeno-C1-C6-alkyl or C3-C6-cycloalkyl, represents 6\u02dc12 membered aryl, or represents 4\u02dc8 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, C1-C6-alkylamino, di(C1-C6-alkyl)amino, C1-C6-alkyl, halogeno-C1-C6-alkyl, C1-C6-alkylsulfonyl, aryl-C1-C6-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.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A sparging device including:
(a) an inlet chamber;
(b) a number of sparger passages, each sparger passage extending from a respective passage inlet in communication with the inlet chamber to a respective passage outlet;
(c) a first fluid chamber defining a first chamber area through which at least one respective sparger passage extends;
(d) a first fluid communication device associated with each sparger passage extending through the first chamber area, the respective first fluid communication device enabling fluid communication between the first fluid chamber and an interior of the respective sparger passage;
(e) a scraper plate adjacent to the inlet chamber, the scraper plate having a number of plate openings, each plate opening aligning with a different one of the sparger passages; and
(f) a scraper blade mounted in the inlet chamber in position to scrape across plate openings of the scraper plate.
2. The sparging device of claim 1 further including:
(a) a second fluid chamber defining a second chamber area through which at least one respective sparger passage extends, the second chamber area being separate from the first chamber area; and
(b) a second fluid communication device associated with each sparger passage extending through the second chamber area, the respective second fluid communication device enabling fluid communication between the second fluid chamber and an interior of the respective sparger passage.
3. The sparging device of claim 2 further including:
(a) an inlet side component having a number of openings formed therein;
(b) an intermediate component having a number of openings formed therein, the intermediate component openings aligning with the openings formed in the inlet side component when the intermediate component is placed with the inlet side component in an operating position; and
(c) an outlet side component having a number of openings formed therein, the outlet side component openings aligning with the openings formed in the intermediate component when the intermediate component is placed with the outlet side component in an operating position, and
(d) wherein the first fluid chamber is defined at an interface between the inlet side component and the intermediate component, and the second fluid chamber is defined at an interface between the intermediate component and the outlet side component.
4. The sparging device of claim 3 wherein each sparger passage is defined by a respective sparger sleeve mounted in a respective sleeve receiving opening, each sleeve receiving opening being made up of a respective inlet side component opening, a respective intermediate component opening, and a respective outlet side component opening.
5. The sparging device of claim 4 wherein each first fluid communication device associated with a respective sparger passage and each second fluid communication device associated with a respective sparger passage is formed in the respective sparger sleeve.
6. The sparging device of claim 5 wherein each sparger sleeve includes:
(a) a first porous and permeable material section aligning with the first fluid chamber, and
(b) a second porous and permeable material section aligning with the second fluid chamber.
7. The sparging device of claim 1 further including a pressure application device associated with the inlet chamber for forcing material from the inlet chamber through the sparger passages.
8. A sparging device including:
(a) a number of screen passages extending transversely through a screen body from a first side of the screen body to a second side of the screen body, the first side of the screen body including a scraper surface facing an inlet chamber;
(b) a first fluid chamber within the screen body;
(c) a first fluid communication device positioned in the screen body between the first fluid chamber and a respective one of the screen passages at a location between the first side of the screen body and the second side of the screen body, the first fluid communication device providing fluid communication from the first fluid chamber to the area defined by the respective screen passage; and
(d) a scraper blade mounted in the inlet chamber in position to be driven so as to scrape across the scraper surface.
9. The sparging device of claim 8 further including a fluid inlet passage formed in the screen body and extending from an exterior surface of the screen body to the first fluid chamber.
10. The sparging device of claim 8 wherein the screen body includes a first side component and a second side component, the first side component including a first portion of each screen passage and the second side component including a second portion of each screen passage, the first side component also including the scraper surface and aligning with the second side component so that the first portion of each respective screen passage aligns with the second portion of each screen passage.
11. The sparging device of claim 10 wherein the first fluid chamber is formed at an interface between the first side component and the second side component.
12. The sparging device of claim 11 wherein the first fluid communication device is defined in a sleeve positioned between the first side component and the second side component, the sleeve having an inner surface defining a middle portion of the respective screen passage between the first portion and second portion of the respective screen passage.
13. The sparging device of claim 8 further including:
(a) a second fluid chamber within the screen body separate from the first fluid chamber; and
(b) a second fluid communication device positioned in the screen body between the second fluid chamber and the respective one of the screen passages at a location between the first side of the screen body and the second side of the screen body, the second fluid communication device providing fluid communication from the second fluid chamber to the area defined by the respective screen passage.
14. The sparging device of claim 8 further including for each screen passage a respective first fluid communication device positioned in the screen body between the first fluid chamber and the respective screen passage at a location between the first side of the screen body and the second side of the screen body, each first fluid communication device comprising a respective section of porous and permeable material interposed between the respective screen passage and the first fluid chamber, and providing fluid communication from the first fluid chamber to the area defined by the respective screen passage.