NZ729136B2

NZ729136B2 - Compounds active towards bromodomains

Info

Publication number: NZ729136B2
Application number: NZ729136A
Authority: NZ
Inventors: Gitte Friberg; Seitzberg Jimmi Gerner; Visnja Poljak; Lene Teuber; Akinleminu Kronborg Tine Titilola
Original assignee: Nuevolution A/S
Priority date: 2014-08-01
Filing date: 2015-07-29
Publication date: 2021-04-30

Abstract

Disclosed are compounds towards bromodomains, pharmaceutical compositions containing the compounds and use of the compounds in therapy.

Description

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25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc 25348474:gcc The table shows that compounds disclosed herein may be selective compounds, such as compounds having less than 30-fold selectivity, between 30 and 100-fold selectivity and more than 100-fold selectivity for BRD4_1 over BRD4_2. The compounds disclosed herein may also be non-selective.

The cell viability assay is used to demonstrate the compounds ability to kill cancer cells.

The LPS induced cytokine release assay demonstrates the compounds ability to inhibit the production of IL12p40 following an inflammatory stimulus (LPS), and as can be seen compounds disclosed herein are able to inhibit the production of IL12p40.

In summary, compounds disclosed herein, have been found to likely bind and thereby modulate or inhibit the function of bromodomains, and compounds disclosed herein may be selective as well as non-selective, and usefulness to treat a wide range of diseases, disorders, or conditions have been demonstrated, for example by the cell viability assay and the LPS induced cytokine release assay.

Definitions of the specific embodiments of the invention as claimed herein follow.

According to a first embodiment of the invention there is provided a compound having the general Formula (XI): (XI), wherein R is hydrogen or methyl; R3a is hydrogen or methyl; R is hydrogen; R , R , R and R independently of each other are selected from the group consisting 4 5 6 8b of hydrogen, halogen, C alkyl, C alkoxy, C cycloalkyl, -CN, -OH, -CF , and -OCF ; 1-4 1-4 3-5 3 3 X and X independently of each other are selected from the group consisting of N and C; (25692687_1):GCC when X is N, R is absent, when X is C, R is selected from the group consisting of 4 9b 4 9b hydrogen, halogen, C alkyl, C alkoxy, C cycloalkyl, -CN, -OH, -CF , and -OCF 1-4 1-4 3-5 3 3; when X is N, R is absent, when X is C, R is selected from the group consisting 3 10b 3 10b of hydrogen, halogen, C alkyl, C alkoxy, C cycloalkyl, -CN, -OH, -CF , and -OCF ; 1-4 1-4 3-5 3 3 R is selected from the group consisting of hydrogen, halogen, unsubstituted or substituted C alkyl, unsubstituted or substituted C alkenyl, unsubstituted or substituted C 1-6 1-6 1-6 alkynyl, unsubstituted or substituted C alkoxy, -OH, -CN, -NO , unsubstituted or substituted 1-6 2 C cycloalkyl, unsubstituted or substituted C cycloalkenyl, unsubstituted or substituted C 3-8 3-8 2-9 heteroalicyclyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, - NR R , -NR C(=O)R , -NR C(=O)NR R , -NR C(=O)OR , -C(=O)R , -C(=O)OR , - 12 13 14 15 16 17 18 28 19 20 21 OC(=O)R , -C(=O)NR R , -S(=O)R , -SO R , -SO NR R , and -OR ; 21 22 23 24 2 25 2 26 27 31 R12, R13, R14, R15, R16, R17, R18, R19, R21, and R28 independently are absent or selected from the group consisting of hydrogen, unsubstituted or substituted C alkyl, unsubstituted or substituted C alkenyl, unsubstituted or substituted C alkynyl, unsubstituted 2-6 2-6 or substituted C alkoxy, unsubstituted or substituted C cycloalkyl, unsubstituted or 1-6 3-8 substituted C cycloalkenyl, unsubstituted or substituted C heteroalicyclyl, unsubstituted or 3-8 2-9 substituted aryl, and unsubstituted or substituted heteroaryl, or R and R , R and R taken together with the nitrogen atom to which they are 12 13 17 18 attached form a ring selected from the group consisting of unsubstituted or substituted C heteroalicyclyl and unsubstituted or substituted heteroaryl; R , R , R , and R are independently absent or selected from the group consisting 22 23 26 27 of hydrogen, unsubstituted or substituted C1-6 alkyl, unsubstituted or substituted C2-6 alkenyl, unsubstituted or substituted C alkynyl, unsubstituted or substituted C alkoxy, unsubstituted 2-6 1-6 or substituted C cycloalkyl, unsubstituted or substituted C cycloalkenyl, unsubstituted or 3-8 3-8 substituted C heteroalicyclyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl, or R and R , R and R are taken together with the atom to which they are attached 22 23 26 27 form a ring selected from the group consisting of unsubstituted or substituted C heteroalicyclyl and unsubstituted or substituted heteroaryl; R , R and R are independently absent or selected from hydrogen, 24 25 unsubstituted or substituted C alkyl, unsubstituted or substituted C alkenyl, unsubstituted or 1-6 2-6 substituted C alkynyl, unsubstituted or substituted C alkoxy, unsubstituted or substituted C 2-6 1-6 3- cycloalkyl, unsubstituted or substituted C cycloalkenyl, unsubstituted or substituted C 8 3-8 2-9 heteroalicyclyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; (25692687_1):GCC R is absent or selected from the group consisting of hydrogen, unsubstituted or substituted C alkyl, unsubstituted or substituted C alkenyl, unsubstituted or substituted C 1-6 2-6 2-6 alkynyl, unsubstituted or substituted C alkoxy, unsubstituted or substituted C cycloalkyl, 1-6 3-8 unsubstituted or substituted C cycloalkenyl, unsubstituted or substituted C heteroalicyclyl, 3-8 2-9 unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; A is N; R and R are independently of each other selected from hydrogen, unsubstituted or substituted C alkyl, unsubstituted or substituted C alkenyl, substituted or unsubstituted C 1-6 1-6 1-6 alkoxy, unsubstituted or substituted C cycloalkyl, unsubstituted or substituted C 3-8 3-8 cycloalkenyl, unsubstituted or substituted C heteroalicyclyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, -C(=O)R and -SO R ; or 2 25 Rx and Ry are both taken together with A to form a ring system selected from the group consisting of unsubstituted or substituted C heteroalicyclyl, and unsubstituted or substituted heteroaryl, or one of R or R is taken together with A to form a ring system selected from the group consisting of unsubstituted or substituted C heteroalicyclyl, and unsubstituted or substituted heteroaryl; and whenever R and R independently of each other are selected from hydrogen, unsubstituted or substituted C alkyl, unsubstituted or substituted C alkenyl, substituted or 1-6 1-6 unsubstituted C alkoxy, unsubstituted or substituted C cycloalkyl, unsubstituted or 1-6 3-8 substituted C cycloalkenyl, unsubstituted or substituted C heteroalicyclyl, unsubstituted or 3-8 2-9 substituted aryl, unsubstituted or substituted heteroaryl, -C(=O)R20 and -SO2R25, then R11b cannot be hydrogen; whenever one or more heteroatom(s) is/are present it is/they are selected from O, N and S; wherein, when any of C alkyl, C alkenyl, C alkynyl, C alkoxy, C cycloalkyl 1-6 1-6 1-6 1-6 3-8 and C cycloalkenyl is substituted, the substituent group(s) is(are) one (or more) group(s) individually and independently selected from alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, oxo, alkoxy, aryloxy, acyl, ester, O-carboxy, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, (25692687_1):GCC trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof; wherein, when C heteroalicyclyl is substituted, the substituent(s) is(are) one (or more) group(s) independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, oxo, alkoxy, aryloxy, acyl, ester, O-carboxy, mercapto, alkylthio, arylthio, cyano, halogen, C-amido, N-amido, S-sulfonamido, N-sulfonamido, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof, including substituents forming an aromatic ring, including aryl and heteroaryl, when fused to the heteroalicyclyl group; and wherein, when any of aryl and heteroaryl is substituted, hydrogen atoms are replaced by substituent group(s) that is(are) one (or more) group(s) independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, oxo, alkoxy, aryloxy, acyl, ester, O- carboxy, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and protected derivatives thereof, including cycloalkyl, cycloalkenyl, cycloalkynyl, and heterocyclyl substituents on the aryl or heteroaryl forming a non-aromatic ring when fused to the aryl or heteroaryl.

According to a second embodiment of the invention there is provided a compound or pharmaceutically acceptable salt, hydrate, solvate, polymorph, stereoisomer, or tautomer thereof, the compound selected from the group consisting of: N-(2-hydroxymethylquinolyl)[(4-methylpiperazinyl)methyl]pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)(piperazinylmethyl)pyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)pyrrolidinyl-benzamide, 5-[(4-acetylpiperazinyl)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)(4-methylpiperazinyl)sulfonylmorpholino- benzamide, (25692687_1):GCC -[3-(dimethylamino)pyrrolidinyl]sulfonyl-N-(2-hydroxymethylquinolyl) morpholino-benzamide, -[3-(dimethylamino)azetidinyl]sulfonyl-N-(2-hydroxymethylquinolyl)morpholino- benzamide, 5-(3-aminoazetidinyl)sulfonyl-N-(2-hydroxymethylquinolyl)morpholino- benzamide, N3-(2-hydroxymethylquinolyl)-N1,N1-dimethylmorpholino-benzene-1,3- dicarboxamide, N-(2-hydroxymethylquinolyl)(4-methylpiperazinecarbonyl)morpholino- benzamide, N-(2-hydroxymethylquinolyl)(morpholinecarbonyl)morpholino-benzamide, N-(2-hydroxymethylquinolyl)(methoxymethyl)pyrrolidinyl-benzamide, -(hydroxymethyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(4-methylpiperazin yl)benzamide, 2-[3-(dimethylamino)pyrrolidinyl](dimethylsulfamoyl)-N-(2-hydroxymethyl quinolyl)benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-hydroxypyrrolidin yl)benzamide, 2-(2-dimethylaminoethylamino)(dimethylsulfamoyl)-N-(2-hydroxymethyl quinolyl)benzamide, -(dimethylsulfamoyl)(2-hydroxyethylamino)-N-(2-hydroxymethyl quinolyl)benzamide, 2-[3-(dimethylamino)azetidinyl](dimethylsulfamoyl)-N-(2-hydroxymethyl quinolyl)benzamide, N-(2-hydroxymethylquinolyl)nitropyrrolidinyl-pyridinecarboxamide, -amino-N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridinecarboxamide, -[(2-aminooxo-ethyl)amino]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- pyridinecarboxamide, N-(2-hydroxymethylquinolyl)[2-(methoxymethyl)pyrrolidinyl] (morpholinomethyl)benzamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)[2-(1H-pyrazolyl)pyrrolidin yl]benzamide, (25692687_1):GCC N-[2-hydroxy(trifluoromethyl)quinolyl](morpholinomethyl)pyrrolidinyl- benzamide, N-(2-hydroxy-4,7-dimethylquinolyl)(morpholinomethyl)pyrrolidinyl-benzamide, 2-[2-(hydroxymethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl) (morpholinomethyl)benzamide, N-(2-hydroxymethylquinolyl)(3-hydroxypyrrolidinyl) (morpholinomethyl)benzamide, 2-[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl) (morpholinomethyl)benzamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)(2-oxopyrrolidinyl)benzamide, 2-cyano-N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridinecarboxamide, 2-acetyl-N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridinecarboxamide, 2-(1-hydroxyethyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridine carboxamide, N4-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridine-2,4-dicarboxamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl(1H-tetrazolyl)pyridine carboxamide, -(1-hydroxyethyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)(1-methoxyethyl)pyrrolidinyl-benzamide, 2-[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl) (methoxymethyl)benzamide, N-(2-hydroxymethylquinolyl)(methoxymethyl)[2-(1H-pyrazolyl)pyrrolidin yl]benzamide, N-(2-hydroxymethylquinolyl)(isopropoxymethyl)pyrrolidinyl-benzamide, 2-[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl) (trifluoromethoxy)benzamide, -amino-N-(2-hydroxymethylquinolyl)morpholino-benzamide, -[(2-aminooxo-ethyl)amino]-N-(2-hydroxymethylquinolyl)morpholino-benzamide, -fluoro-N-(2-hydroxymethylquinolyl)morpholino-benzamide, N-(2-hydroxymethylquinolyl)morpholino(1-piperidylsulfonyl) benzamide, N-(2-hydroxymethylquinolyl)morpholinomorpholinosulfonyl-benzamide, N-(2-hydroxymethylquinolyl)morpholinosulfamoyl-benzamide, -acetamido-N-(2-hydroxymethylquinolyl)morpholino-benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, (25692687_1):GCC -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)morpholino-benzamide, N-(2-hydroxymethylquinolyl)morpholinosulfonylpyrrolidinyl-benzamide, -(dimethylsulfamoyl)morpholino-N-[2-oxo(trifluoromethyl)-1H-quinolin yl]benzamide, 5-(dimethylsulfamoyl)-N-(4-hydroxyoxo-1H-quinolinyl)morpholino-benzamide, N-(2-hydroxymethylquinolyl)nitropyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)pyrrolidinyl-pyridine carboxamide, 2-(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)(morpholinomethyl)pyridine- 3-carboxamide, N-(2-hydroxymethylquinolyl)(3-hydroxypyrrolidinyl) (morpholinomethyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)morpholino(morpholinomethyl)pyridine carboxamide, N-(4-chlorohydroxyquinolyl)morpholino(morpholinomethyl)pyridine carboxamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridinecarboxamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridinecarboxamide, 2-[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl)pyridine carboxamide, N-(4-methoxyoxo-1H-quinolinyl)[(4-methylpiperazinyl)methyl]pyrrolidinyl- benzamide, -(dimethylsulfamoyl)-N-(2-hydroxy-4,7-dimethylquinolyl)morpholino-benzamide, -amino-N-(2-hydroxymethylquinolyl)pyrazolyl-benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxy-4,8-dimethylquinolyl)pyrrolidinyl-benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethoxymethylquinolyl)pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl(trifluoromethyl)benzamide, N-(2-hydroxymethylquinolyl)(3-hydroxypyrrolidinyl)morpholinosulfonyl- benzamide, N-(2-hydroxymethylquinolyl)(3-methoxypyrrolidinyl)morpholinosulfonyl- benzamide, -(cyanomethyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)(1-morpholinocyclopropyl)pyrrolidinyl-benzamide, (25692687_1):GCC 2-[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl)(1- morpholinocyclopropyl)benzamide, 2-cyano(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridine carboxamide, 2-cyano-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, N-(4-methoxyoxo-1H-quinolinyl)[(4-methylpiperazinyl)methyl]pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(3-methylmorpholinyl)pyridinecarboxamide, 2-[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl)pyridine carboxamide, -(dimethylsulfamoyl)-N-(2-hydroxy-4,7-dimethylquinolyl)morpholino-benzamide, N-(2-hydroxy-4,7-dimethylquinolyl)morpholino-pyridinecarboxamide, 2-(3-fluoropyrrolidinyl)-N-(2-hydroxy-4,7-dimethylquinolyl)pyridinecarboxamide, 2-(3,3-difluoropyrrolidinyl)-N-(2-hydroxy-4,7-dimethylquinolyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, N-(2-hydroxyisopropylquinolyl)morpholino-pyridinecarboxamide, 2-(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridinecarboxamide, 2-(3,3-difluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl(trifluoromethyl)pyridine carboxamide, N-(2-hydroxymethylquinolyl)morpholino(trifluoromethyl)pyridinecarboxamide, N-(2-hydroxy-4,8-dimethylquinolyl)morpholino-pyridinecarboxamide, N-(2-hydroxy-4,7-dimethylquinolyl)methylmorpholino-pyridinecarboxamide, N-(2-hydroxymethylquinolyl)methylmorpholino-pyridinecarboxamide, N-(2-hydroxymethylquinolyl)morpholino(trifluoromethyl)pyridinecarboxamide, -chloro-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, 2-(3,4a,5,6,7,7a-hexahydro-2H-pyrrolo[3,4-b][1,4]oxazinyl)-N-(2-hydroxymethyl quinolyl)pyridinecarboxamide, 2-(2,3,4a,5,7,7a-hexahydrofuro[3,4-b][1,4]oxazinyl)-N-(2-hydroxymethyl quinolyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(3-oxaazabicyclo[3.2.1]octanyl)pyridine carboxamide, (25692687_1):GCC 2-[3-(hydroxymethyl)morpholinyl]-N-(2-hydroxymethylquinolyl)pyridine carboxamide, 2-(4,4-difluoropiperidyl)-N-(2-hydroxymethylquinolyl)pyridinecarboxamide, 2-(6,8-dihydro-5H-imidazo[1,2-a]pyrazinyl)-N-(2-hydroxymethylquinolyl)pyridine carboxamide, N-(2-hydroxymethylquinolyl)(3-oxopiperazinyl)pyridinecarboxamide, N-(2-hydroxymethoxyquinolyl)morpholino-pyridinecarboxamide, N-(2-hydroxymethylquinolyl)iodomorpholino-benzamide, N-(2-hydroxymethylquinolyl)isoxazolylmorpholino-benzamide, 5-(3,5-dimethylisoxazolyl)-N-(2-hydroxymethylquinolyl)morpholino-benzamide, N-(2-hydroxy-4,7-dimethylquinolyl)iodomorpholino-benzamide, N-(2-hydroxy-4,7-dimethylquinolyl)(1-methylpyrazolyl)morpholino-benzamide, -(3,5-dimethylisoxazolyl)-N-(2-hydroxy-4,7-dimethylquinolyl)morpholino- benzamide, N-(2-hydroxy-4,8-dimethylquinolyl)iodomorpholino-benzamide, -(3-furyl)-N-(2-hydroxy-4, 8-dimethylquinolyl)morpholino-benzamide, N-(2-hydroxymethoxymethylquinolyl)(1-methylpyrazolyl)morpholino- benzamide, -(3-furyl)-N-(2-hydroxymethoxymethylquinolyl)morpholino-benzamide, 5-(3,5-dimethylisoxazolyl)-N-(2-hydroxymethoxymethylquinolyl)morpholino- benzamide, 2-(3-fluoropyrrolidinyl)(3-furyl)-N-(2-hydroxymethylquinolyl)pyridine carboxamide, N-(2-hydroxy-4,7-dimethylquinolyl)isoxazolylmorpholino-benzamide, 2-cyano-N-(2-hydroxy-4,7-dimethylquinolyl)morpholino-pyridinecarboxamide, -(dimethylsulfamoyl)-N-(2-hydroxyisopropylquinolyl)pyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)(1-methylpyrazolyl)morpholino-benzamide, -(3-furyl)-N-(2-hydroxymethylquinolyl)morpholino-benzamide, -(1-hydroxyethyl)-N-(2-hydroxymethylquinolyl)morpholino-benzamide, N-(2-hydroxymethoxymethylquinolyl)(1-methylpyrazolyl)morpholino- pyridinecarboxamide, N-(2-hydroxymethoxymethylquinolyl)(1-methylpyrazolyl)morpholino- pyridinecarboxamide, (25692687_1):GCC N-(2-hydroxy-4,7-dimethylquinolyl)(1-methylpyrazolyl)morpholino-pyridine carboxamide, -(dimethylsulfamoyl)[(3R)fluoropyrrolidinyl]-N-(2-hydroxymethyl quinolyl)benzamide, 5-(dimethylsulfamoyl)[(3S)fluoropyrrolidinyl]-N-(2-hydroxymethyl quinolyl)benzamide, -(3-furyl)-N-(2-hydroxymethylquinolyl)morphpholino-pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(1-methylpyrazolyl)morpholino-pyridine carboxamide, N-(2-hydroxymethylquinolyl)isoxazolylmorpholino-pyridinecarboxamide, -(3,5-dimethylisoxazolyl)-N-(2-hydroxymethylquinolyl)morpholino-pyridine carboxamide, -(3-furyl)-N-(2-hydroxymethylquinolyl)(6-oxaazaspiro[3.3]heptanyl)pyridine- 3-carboxamide, 5-(3-furyl)-N-(2-hydroxy-4,8-dimethylquinolyl)morpholino-pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(5-methyl-1,3,4-oxadiazolyl)morpholino- benzamide, N-(2-hydroxymethylquinolyl)morpholino(1H-tetrazolyl)benzamide, 3-[(2-hydroxymethylquinolyl)carbamoyl]morpholino-benzoic acid, 5-cyano-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, -bromo(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridine carboxamide, N-(2-hydroxymethylquinolyl)(4-methylpiperazinyl)morpholino-pyridine carboxamide, N-(2-hydroxymethylquinolyl)-2,5-dimorpholino-pyridinecarboxamide, -[4-(dimethylamino)piperidyl]-N-(2-hydroxymethylquinolyl)morpholino-pyridine- 3-carboxamide, -(3,5-dimethylisoxazolyl)-N-(2-hydroxy-4,7-dimethylquinolyl)morpholino-pyridine- 3-carboxamide, 5-(3-furyl)-N-(2-hydroxymethoxymethylquinolyl)morpholino-pyridine carboxamide, -(3-furyl)-N-(2-hydroxymethoxymethylquinolyl)morpholino-pyridine carboxamide, -(3-furyl)-N-(2-hydroxy-4,7-dimethylquinolyl)morpholino-pyridinecarboxamide, (25692687_1):GCC -(azetidinyl)-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, -[(3S)fluoropyrrolidinyl]-N-(2-hydroxymethylquinolyl)morpholino-pyridine carboxamide, N-(2-hydroxy-4,7-dimethylquinolyl)(2-methyltetrazolyl)morpholino-pyridine carboxamide, N-(2-hydroxy-4,7-dimethylquinolyl)(1-methyltetrazolyl)morpholino-pyridine carboxamide, 2-cyano(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridine carboxamide, 2-cyano-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, -(dimethylsulfamoyl)(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridine- 3-carboxamide, N-(2-hydroxy-4,7-dimethylquinolyl)(3-methylisoxazolyl)morpholino-pyridine carboxamide, N-(2-hydroxymethoxymethylquinolyl)(5-methyl-1,3,4-oxadiazolyl) morpholino-benzamide, N4-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridine-2,4-dicarboxamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl(1H-tetrazolyl)pyridine carboxamide, 5-(cyanomethyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)(1-morpholinocyclopropyl)pyrrolidinyl-benzamide, -(1-hydroxyethyl)-N-(2-hydroxymethylquinolyl)[2-(2-pyridyl)pyrrolidin yl]benzamide, 2-acetyl-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, 2-(1-hydroxyethyl)-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, 2-acetyl(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridine carboxamide, -(3-fluoropyrrolidinyl)(1-hydroxyethyl)-N-(2-hydroxymethylquinolyl)pyridine carboxamide, 2-cyano[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethyl quinolyl)pyridinecarboxamide, 2-acetyl[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethyl quinolyl)pyridinecarboxamide, (25692687_1):GCC -[2-(dimethylaminomethyl)pyrrolidinyl](1-hydroxyethyl)-N-(2-hydroxymethyl quinolyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)morpholino-benzamide, N-(2-hydroxymethylquinolyl)(4-methylpiperazinyl)benzamide, N-(2-hydroxymethylquinolyl)(4-pyrazinylpiperazinyl)benzamide, N-(2-hydroxymethylquinolyl)morpholinosulfamoyl-benzamide, -(2,5-dioxopyrrolidinyl)-N-(2-hydroxymethylquinolyl)morpholino-benzamide, -(benzenesulfonamido)-N-(2-hydroxymethylquinolyl)(4-methylpiperazin yl)benzamide, 5-(ethylsulfonylamino)-N-(2-hydroxymethylquinolyl)(4-methylpiperazin yl)benzamide, N-(2-hydroxymethylquinolyl)morpholinonitro-benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)morpholino-benzamide, N-(2-hydroxymethylquinolyl)morpholino(1-piperidylsulfonyl)benzamide, N-(2-hydroxymethylquinolyl)morpholinomorpholinosulfonyl-benzamide, 2-(dimethylamino)-N-(2-hydroxymethylquinolyl)nitro-benzamide, N-(2-hydroxymethylquinolyl)nitropyrrolidinyl-benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, N-(4-hydroxyoxo-1H-quinolinyl)morpholinomorpholinosulfonyl-benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-methylpyrrolidin yl)benzamide, -(dimethylsulfamoyl)(3-fluoropyrrolidinyl)-N-(2-hydroxymethyl quinolyl)benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-methoxypyrrolidin yl)benzamide, 1-[4-(dimethylsulfamoyl)[(2-hydroxymethylquinolyl)carbamoyl]phenyl]pyrrolidine carboxamide, 2-[3-(dimethylamino)pyrrolidinyl](dimethylsulfamoyl)-N-(2-hydroxymethyl quinolyl)benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-isobutylpyrrolidin yl)benzamide, 2-[3-(dimethylaminomethyl)pyrrolidinyl](dimethylsulfamoyl)-N-(2-hydroxymethyl quinolyl)benzamide, (25692687_1):GCC -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-ureidopyrrolidin yl)benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-pyrrolidinylpyrrolidin yl)benzamide, 2-[3-(2-aminooxo-ethoxy)pyrrolidinyl](dimethylsulfamoyl)-N-(2-hydroxymethyl quinolyl)benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-phenylpyrrolidin yl)benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(2-methylpyrrolidin yl)benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)[2-(methoxymethyl)pyrrolidin yl]benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(5-methyl-2,3,3a,4,6,6a- hexahydropyrrolo[3,4-b]pyrrolyl)benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(2-isobutylpyrrolidin yl)benzamide, 2-[2-(dimethylaminomethyl)pyrrolidinyl](dimethylsulfamoyl)-N-(2-hydroxymethyl quinolyl)benzamide, -(dimethylsulfamoyl)[2-(1-hydroxymethyl-ethyl)pyrrolidinyl]-N-(2-hydroxy methylquinolyl)benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)[2-(1H-pyrazolyl)pyrrolidin yl]benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)[2-(1H-tetrazolyl)pyrrolidin yl]benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(4-methyl-3,3a,5,6,7,7a- hexahydro-2H-pyrrolo[3,2-b]pyridinyl)benzamide, 1-[4-(dimethylsulfamoyl)[(2-hydroxymethylquinolyl)carbamoyl]phenyl]-N,N- dimethyl-pyrrolidinecarboxamide, -(dimethylsulfamoyl)(3-hydroxymethylazabicyclo[3.2.1]octanyl)-N-(2-hydroxy methylquinolyl)benzamide, -(dimethylsulfamoyl)(4-hydroxy-2,5-dimethylpiperidyl)-N-(2-hydroxymethyl quinolyl)benzamide, -(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(2-phenylpiperidyl)benzamide, -(diethylsulfamoyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, (25692687_1):GCC -(diethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(1-piperidyl)benzamide, N-(2-hydroxymethylquinolyl)(2-methylpiperidyl)nitro-pyridinecarboxamide, -[[2-hydroxyethyl(methyl)amino]methyl]-N-(2-hydroxymethylquinolyl)pyrrolidin yl-benzamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl[(tetrahydrofuran ylmethylamino)methyl]benzamide, -[[3-(dimethylamino)pyrrolidinyl]methyl]-N-(2-hydroxymethylquinolyl) pyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)[(3-hydroxypyrrolidinyl)methyl]pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)[[(2S)(methoxymethyl)pyrrolidinyl]methyl] pyrrolidinyl-benzamide, -[[4-(2-hydroxyethyl)piperazinyl]methyl]-N-(2-hydroxymethylquinolyl)pyrrolidin- 1-yl-benzamide, N-(2-hydroxymethylquinolyl)[(4-methyl-1,4-diazepanyl)methyl]pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)[(3-methoxypyrrolidinyl)methyl]pyrrolidinyl- benzamide, -[(3-hydroxyazetidinyl)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)[[3-(methoxymethyl)azetidinyl]methyl]pyrrolidin- 1-yl-benzamide, N-(2-hydroxymethylquinolyl)[[3-(methoxymethyl)piperidyl]methyl]pyrrolidin yl-benzamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)pyrrolidinyl-pyridine carboxamide, N-(2-hydroxymethylquinolyl)(3-methylpyrrolidinyl) (morpholinomethyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(2-methylpyrrolidinyl) (morpholinomethyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(3-hydroxypyrrolidinyl) (morpholinomethyl)pyridinecarboxamide, 2-(3-fluoromethyl-pyrrolidinyl)-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, (25692687_1):GCC 2-(3-carbamoylpyrrolidinyl)-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(3-isobutylpyrrolidinyl) (morpholinomethyl)pyridinecarboxamide, 2-(2-carbamoylhydroxy-pyrrolidinyl)-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)[2-(1H-pyrazolyl)pyrrolidin yl]pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)(3-pyrrolidinylpyrrolidin yl)pyridinecarboxamide, 2-[2-(dimethylcarbamoyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(4-methyl-2,3,4a,5,7,7a-hexahydropyrrolo[3,4- b][1,4]oxazinyl)(morpholinomethyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)[3-(4-pyridyl)pyrrolidin yl]pyridinecarboxamide, 2-[2-(hydroxymethyl)morpholinyl]-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, 2-[2-(hydroxymethyl)methyl-morpholinyl]-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, 2-[2-(dimethylaminomethyl)morpholinyl]-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, 2-[3-(hydroxymethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, 5-[(2-furylmethylamino)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)[(isobutylamino)methyl]pyrrolidinyl-benzamide, -[(cyclopropylamino)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)[(3-pyridylmethylamino)methyl]pyrrolidinyl- benzamide, -[(cyanomethylamino)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- benzamide, (25692687_1):GCC N-(2-hydroxymethylquinolyl)[[isopropyl(methyl)amino]methyl]pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl[(2,2,2- trifluoroethylamino)methyl]benzamide, N-(2-hydroxymethylquinolyl)[(3-methoxypiperidyl)methyl]pyrrolidinyl- benzamide, -[[3-(dimethylamino)azetidinyl]methyl]-N-(2-hydroxymethylquinolyl)pyrrolidin- 1-yl-benzamide, N-(2-hydroxymethylquinolyl)[(1H-imidazolylmethylamino)methyl]pyrrolidin yl-benzamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl[[1-(1H-tetrazol yl)ethylamino]methyl]benzamide, -(dimethylaminomethyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)[[(2-methoxypyridyl)methylamino]methyl] pyrrolidinyl-benzamide, -[(3-cyanopiperidyl)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- benzamide, 1-[[3-[(2-hydroxymethylquinolyl)carbamoyl]pyrrolidinyl-phenyl]methyl]-N- methyl-pyrrolidinecarboxamide, N-(2-hydroxymethylquinolyl)[[1-(1H-imidazolyl)ethylamino]methyl]pyrrolidin- 1-yl-benzamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl[(tetrahydrofuran ylamino)methyl]benzamide, N-(2-hydroxymethylquinolyl)[(isoxazolylamino)methyl]pyrrolidinyl- benzamide, -[(3-fluoropyrrolidinyl)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)[[(1-methylpyrazolyl)amino]methyl]pyrrolidin yl-benzamide, N-(2-hydroxymethylquinolyl)(1,4-oxazepanylmethyl)pyrrolidinyl-benzamide, 2-(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)(morpholinomethyl)pyridine- 3-carboxamide, and N-(2-hydroxymethylquinolyl)morpholino(morpholinomethyl)pyridine carboxamide. (25692687_1):GCC According to a third embodiment of the invention there is provided a pharmaceutical composition comprising a compound according to the first or second embodiment and at least one pharmaceutical acceptable excipient.

According to a fourth embodiment of the invention there is provided the use of a compound according to the first or second embodiment or a pharmaceutical composition according to the third embodiment in the manufacture of a medicament for modulating the activity of at least one bromodomain, when contacting the bromodomain with the compound or the pharmaceutical composition. (25692687_1):GCC

Claims

WHAT IS CLAIMED IS:

1. A compound having the general Formula (XI): (XI), 5 wherein R is hydrogen or methyl; R is hydrogen or methyl; R is hydrogen; R , R , R and R independently of each other are selected from the group consisting 4 5 6 8b of hydrogen, halogen, C alkyl, C alkoxy, C cycloalkyl, -CN, -OH, -CF , and -OCF ; 1-4 1-4 3-5 3 3 10 X and X independently of each other are selected from the group consisting of N and when X is N, R is absent, when X is C, R is selected from the group consisting of 4 9b 4 9b hydrogen, halogen, C alkyl, C alkoxy, C cycloalkyl, -CN, -OH, -CF , and -OCF 1-4 1-4 3-5 3 3; when X is N, R is absent, when X is C, R is selected from the group consisting 3 10b 3 10b 15 of hydrogen, halogen, C alkyl, C alkoxy, C cycloalkyl, -CN, -OH, -CF , and -OCF ; 1-4 1-4 3-5 3 3 R is selected from the group consisting of hydrogen, halogen, unsubstituted or substituted C1-6 alkyl, unsubstituted or substituted C1-6 alkenyl, unsubstituted or substituted C1-6 alkynyl, unsubstituted or substituted C alkoxy, -OH, -CN, -NO , unsubstituted or substituted 1-6 2 C cycloalkyl, unsubstituted or substituted C cycloalkenyl, unsubstituted or substituted C 3-8 3-8 2-9 20 heteroalicyclyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, - NR R , -NR C(=O)R , -NR C(=O)NR R , -NR C(=O)OR , -C(=O)R , -C(=O)OR , - 12 13 14 15 16 17 18 28 19 20 21 OC(=O)R , -C(=O)NR R , -S(=O)R , -SO R , -SO NR R , and -OR ; 21 22 23 24 2 25 2 26 27 31 R , R , R , R , R , R , R , R , R , and R independently are absent or 12 13 14 15 16 17 18 19 21 28 selected from the group consisting of hydrogen, unsubstituted or substituted C alkyl, 25 unsubstituted or substituted C alkenyl, unsubstituted or substituted C alkynyl, unsubstituted 2-6 2-6 or substituted C alkoxy, unsubstituted or substituted C cycloalkyl, unsubstituted or 1-6 3-8 (25692687_1):GCC substituted C cycloalkenyl, unsubstituted or substituted C heteroalicyclyl, unsubstituted or 3-8 2-9 substituted aryl, and unsubstituted or substituted heteroaryl, or R and R , R and R taken together with the nitrogen atom to which they are 12 13 17 18 attached form a ring selected from the group consisting of unsubstituted or substituted C 5 heteroalicyclyl and unsubstituted or substituted heteroaryl; R , R , R , and R are independently absent or selected from the group consisting 22 23 26 27 of hydrogen, unsubstituted or substituted C alkyl, unsubstituted or substituted C alkenyl, 1-6 2-6 unsubstituted or substituted C alkynyl, unsubstituted or substituted C alkoxy, unsubstituted 2-6 1-6 or substituted C cycloalkyl, unsubstituted or substituted C cycloalkenyl, unsubstituted or 3-8 3-8 10 substituted C heteroalicyclyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl, or R22 and R23, R26 and R27 are taken together with the atom to which they are attached form a ring selected from the group consisting of unsubstituted or substituted C heteroalicyclyl and unsubstituted or substituted heteroaryl; 15 R , R and R are independently absent or selected from hydrogen, 20 24 25 unsubstituted or substituted C alkyl, unsubstituted or substituted C alkenyl, unsubstituted or 1-6 2-6 substituted C alkynyl, unsubstituted or substituted C alkoxy, unsubstituted or substituted C 2-6 1-6 3- cycloalkyl, unsubstituted or substituted C cycloalkenyl, unsubstituted or substituted C 8 3-8 2-9 heteroalicyclyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; 20 R is absent or selected from the group consisting of hydrogen, unsubstituted or substituted C alkyl, unsubstituted or substituted C alkenyl, unsubstituted or substituted C 1-6 2-6 2-6 alkynyl, unsubstituted or substituted C1-6 alkoxy, unsubstituted or substituted C3-8 cycloalkyl, unsubstituted or substituted C cycloalkenyl, unsubstituted or substituted C heteroalicyclyl, 3-8 2-9 unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; 25 A is N; R and R are independently of each other selected from hydrogen, unsubstituted or substituted C alkyl, unsubstituted or substituted C alkenyl, substituted or unsubstituted C 1-6 1-6 1-6 alkoxy, unsubstituted or substituted C cycloalkyl, unsubstituted or substituted C 3-8 3-8 cycloalkenyl, unsubstituted or substituted C heteroalicyclyl, unsubstituted or substituted aryl, 30 unsubstituted or substituted heteroaryl, -C(=O)R and -SO R ; or 20 2 25 R and R are both taken together with A to form a ring system selected from the group consisting of unsubstituted or substituted C heteroalicyclyl, and unsubstituted or substituted heteroaryl, or (25692687_1):GCC one of R or R is taken together with A to form a ring system selected from the group consisting of unsubstituted or substituted C heteroalicyclyl, and unsubstituted or substituted heteroaryl; and whenever R and R independently of each other are selected from hydrogen, 5 unsubstituted or substituted C alkyl, unsubstituted or substituted C alkenyl, substituted or 1-6 1-6 unsubstituted C alkoxy, unsubstituted or substituted C cycloalkyl, unsubstituted or 1-6 3-8 substituted C cycloalkenyl, unsubstituted or substituted C heteroalicyclyl, unsubstituted or 3-8 2-9 substituted aryl, unsubstituted or substituted heteroaryl, -C(=O)R and -SO R , then R 20 2 25 11b cannot be hydrogen; 10 whenever one or more heteroatom(s) is/are present it is/they are selected from O, N and S; wherein, when any of C1-6 alkyl, C1-6 alkenyl, C1-6 alkynyl, C1-6 alkoxy, C3-8 cycloalkyl and C cycloalkenyl is substituted, the substituent group(s) is(are) one (or more) group(s) individually and independently selected from alkenyl, alkynyl, cycloalkyl, cycloalkenyl, 15 cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, oxo, alkoxy, aryloxy, acyl, ester, O-carboxy, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and 20 the protected derivatives thereof; wherein, when C heteroalicyclyl is substituted, the substituent(s) is(are) one (or more) group(s) independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, oxo, alkoxy, aryloxy, acyl, ester, O-carboxy, mercapto, 25 alkylthio, arylthio, cyano, halogen, C-amido, N-amido, S-sulfonamido, N-sulfonamido, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof, including substituents forming an aromatic ring, including aryl and heteroaryl, when fused to the heteroalicyclyl 30 group; and wherein, when any of aryl and heteroaryl is substituted, hydrogen atoms are replaced by substituent group(s) that is(are) one (or more) group(s) independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, (25692687_1):GCC aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, oxo, alkoxy, aryloxy, acyl, ester, O- carboxy, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including 5 mono- and di-substituted amino groups, and protected derivatives thereof, including cycloalkyl, cycloalkenyl, cycloalkynyl, and heterocyclyl substituents on the aryl or heteroaryl forming a non-aromatic ring when fused to the aryl or heteroaryl.

2. A compound according to claim 1, wherein R is selected from the group consisting of unsubstituted or substituted C heteroalicyclyl and unsubstituted or substituted 10 heteroaryl.

3. A compound according to claim 1, wherein R is selected from the group consisting of: (25692687_1):GCC (25692687_1):GCC wherein R and R are independently of each other selected from the group 83a 83b consisting of hydrogen, fluoro, C alkyl, or R and R taken together with the carbon atom 1-6 83a 83b 5 to which they are attached form a C cycloalkyl; R and R independently of each other are selected from the group consisting of 80 81 hydrogen, halogen, -CN, -OH, C alkyl, C haloalkyl, C hydroxyalkyl, C aminoalkyl, 1-4 1-4 1-4 1-4 -CF , C alkoxy, C alkoxy-C alkyl, -OCF , -NR R , -C(=O)NR R , -C(=O)OR ; 3 1-4 1-4 1-4 3 52 53 52 53 52 r and s are integers selected from 0, 1 or 2; 10 R , R , R , and R independently of each other are selected from the group 47 48 49 50 consisting of hydrogen, C alkyl, C alkoxy-C alkyl, -NR R , C aminoalkyl, -OH, - 1-6 1-6 1-6 52 53 1-6 C(=O)NR R ; 55 56 R is selected from the group consisting of C alkyl, C alkoxy, -NR R , and -OH; 82 1-6 1-6 85 86 R , R , and R independently of each other are selected from the group consisting of 52 53 54 15 hydrogen, C alkyl, C haloalkyl, C hydroxyalkyl, C aminoalkyl, C alkoxy, C 1-6 1-6 1-6 1-6 1-6 1-4 alkoxy-C alkyl, C cycloalkyl, and -C(=O)R ; 1-4 3-8 82 R and R independently of each other are selected from the group consisting of C 55 56 1-6 alkyl, unsubstituted or substituted C cycloalkyl, unsubstituted or substituted C 3-8 2-9 heteroalicyclyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and (25692687_1):GCC R and R independently of each other are selected from the group consisting of 85 86 hydrogen, C alkyl, and C cycloalkyl or R and R taken together with the nitrogen atom 1-6 3-8 85 86 form a ring system selected from unsubstituted or substituted heteroalicyclyl.

4. A compound according to claim 3, wherein R and R are hydrogen. 80 81

5.5. A compound according to any one of claims 1 to 3, wherein said unsubstituted or substituted C cycloalkyl is selected from unsubstituted or substituted cyclopropyl, unsubstituted or substituted cyclobutyl and unsubstituted or substituted cyclopentyl; said unsubstituted or substituted C heteroalicyclyl is selected from unsubstituted or 10 substituted morpholinyl, unsubstituted or substituted pyrrolidinyl, unsubstituted or substituted pyrrolidinonyl, unsubstituted or substituted piperidinyl, unsubstituted or substituted piperazinyl, unsubstituted or substituted azetidinyl, unsubstituted or substituted oxazepanyl, and unsubstituted or substituted diazepanyl; said unsubstituted or substituted aryl is unsubstituted or substituted phenyl; and 15 said unsubstituted or substituted heteroaryl is selected from the group consisting of unsubstituted or substituted pyridinyl, unsubstituted or substituted imidazolyl, unsubstituted or substituted isoxazolyl, unsubstituted or substituted pyrazolyl, unsubstituted or substituted furanyl and unsubstituted or substituted tetrazolyl.

6. A compound according to any one of claims 1 to 4, wherein said substituted C 20 cycloalkyl, substituted C heteroalicyclyl , substituted aryl and substituted heteroaryl is substituted by a substituent selected from the group consisting of halogen, -CN, -OH, oxo, C alkyl, C haloalkyl, C hydroxyalkyl, C alkoxy, C haloalkoxy-C alkyl, C alkoxy-C 1-4 1-4 1-4 1-4 1-4 1-4 1-4 alkyl, -NR R , -C(=O)NR R , -C(=O)OR , -C(=O)R , and C aminoalkyl. 52 53 52 53 52 82 1-4

7. A compound according to any one of claims 1 to 6, wherein R and R 25 independently of each other are selected from the group consisting of hydrogen, unsubstituted or substituted C alkyl, unsubstituted or substituted C cycloalkyl, unsubstituted or 1-6 3-8 substituted C heteroalicyclyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, -C(=O)-C alkyl, and wherein at least one of R and R is not hydrogen. 1-6 x y

8. A compound according to claim 7, wherein C alkyl is substituted by a 30 substituent selected from the group consisting of -OH, unsubstituted or substituted C (25692687_1):GCC cycloalkyl, unsubstituted or substituted C heteroalicyclyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl.

9. A compound according to any one of claims 1 to 6, wherein R and R taken together with A form a ring system selected from the group consisting of: which ring system is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from the group consisting of unsubstituted or substituted C alkyl, unsubstituted or substituted C alkoxy, unsubstituted or substituted C haloalkyl, unsubstituted or substituted C 1-6 1-6 1-6 10 hydroxyalkyl, unsubstituted or substituted C aminoalkyl, halogen, -OH, -CN, unsubstituted or substituted C cycloalkyl, unsubstituted or substituted C cycloalkenyl, unsubstituted or 3-8 3-8 substituted C2-9 heteroalicyclyl, unsubstituted or substituted C2-9 heteroalicyclyl-C1-6 alkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heteroaryl-C alkyl, - (CR R ) NR R , -NR C(=O)NR R , -C(=O)NR R , and -C(=O)OR ; 64 65 t 62 63 64 65 66 67 68 69 (25692687_1):GCC wherein R , R , R , R , R , R , R , R , R and R are independently of each 60 61 62 63 64 65 66 67 68 69 other selected from the group consisting of hydrogen, unsubstituted or substituted C alkyl; or the ring system is part of a bicyclic ring system; and t is selected from an integer selected from 0, 1, 2 and 3. 5 10. A compound according to claim 9, wherein said unsubstituted or substituted C alkyl is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, C haloalkyl, C aminoalkyl, -CH NR R , C hydroxyalkyl, C alkoxy-C alkyl, aryl- 1-6 1-6 2 70 71 1-6 1-6 1-6 C alkyl, wherein R and R independently of each other are selected from hydrogen or C 1-6 70 71 1-4 alkyl, and;

10.said unsubstituted or substituted C heteroalicyclyl is selected from unsubstituted or substituted pyrrolidinyl, and unsubstituted or substituted pyrrolidinylone; said unsubstituted or substituted heteroaryl is selected from unsubstituted or substituted imidazolyl, unsubstituted or substituted pyrrolyl, unsubstituted or substituted pyrazolyl, unsubstituted or substituted tetrazolyl, and unsubstituted or substituted pyridyl; and 15 said unsubstituted or substituted aryl is selected from unsubstituted or substituted phenyl.

11. A compound according to claim 1, wherein R is selected from the group consisting of halogen, unsubstituted or substituted C alkoxy, -OH, -CN, -NO , unsubstituted 1-6 2 or substituted C heteroalicyclyl, unsubstituted or substituted aryl, unsubstituted or substituted 20 heteroaryl, -NR R , -C(=O)NR R , -SO R , and -SO NR R , and 12 13 22 23 2 25 2 26 27 wherein R , R , R , R , R , R , and R , independently of each other are selected 12 13 22 23 25 26 27 from the group consisting of hydrogen, unsubstituted or substituted C alkyl, unsubstituted or substituted C alkoxy, unsubstituted or substituted C cycloalkyl, unsubstituted or substituted 1-6 3-8 C heteroalicyclyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl; or 25 R and R R and R , R and R , taken together with the nitrogen atom to which they are 12 13, 22 23 26 27 simultaneously attached form a ring selected from the group consisting of unsubstituted or substituted C heteroalicyclyl, and unsubstituted or substituted heteroaryl.

12. A compound or pharmaceutically acceptable salt, hydrate, solvate, polymorph, stereoisomer, or tautomer thereof, the compound selected from the group consisting of: 30 N-(2-hydroxymethylquinolyl)[(4-methylpiperazinyl)methyl]pyrrolidinyl- benzamide, (25692687_1):GCC N-(2-hydroxymethylquinolyl)(piperazinylmethyl)pyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)pyrrolidinyl-benzamide, 5-[(4-acetylpiperazinyl)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- benzamide, 5 N-(2-hydroxymethylquinolyl)(4-methylpiperazinyl)sulfonylmorpholino- benzamide, 5-[3-(dimethylamino)pyrrolidinyl]sulfonyl-N-(2-hydroxymethylquinolyl) morpholino-benzamide, 5-[3-(dimethylamino)azetidinyl]sulfonyl-N-(2-hydroxymethylquinolyl)morpholino- 10 benzamide, 5-(3-aminoazetidinyl)sulfonyl-N-(2-hydroxymethylquinolyl)morpholino- benzamide, N3-(2-hydroxymethylquinolyl)-N1,N1-dimethylmorpholino-benzene-1,3- dicarboxamide, 15 N-(2-hydroxymethylquinolyl)(4-methylpiperazinecarbonyl)morpholino- benzamide, N-(2-hydroxymethylquinolyl)(morpholinecarbonyl)morpholino-benzamide, N-(2-hydroxymethylquinolyl)(methoxymethyl)pyrrolidinyl-benzamide, 5-(hydroxymethyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, 20 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(4-methylpiperazin yl)benzamide, 2-[3-(dimethylamino)pyrrolidinyl](dimethylsulfamoyl)-N-(2-hydroxymethyl quinolyl)benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-hydroxypyrrolidin 25 yl)benzamide, 2-(2-dimethylaminoethylamino)(dimethylsulfamoyl)-N-(2-hydroxymethyl quinolyl)benzamide, 5-(dimethylsulfamoyl)(2-hydroxyethylamino)-N-(2-hydroxymethyl quinolyl)benzamide, 30 2-[3-(dimethylamino)azetidinyl](dimethylsulfamoyl)-N-(2-hydroxymethyl quinolyl)benzamide, N-(2-hydroxymethylquinolyl)nitropyrrolidinyl-pyridinecarboxamide, 5-amino-N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridinecarboxamide, (25692687_1):GCC 5-[(2-aminooxo-ethyl)amino]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- pyridinecarboxamide, N-(2-hydroxymethylquinolyl)[2-(methoxymethyl)pyrrolidinyl] (morpholinomethyl)benzamide, 5 N-(2-hydroxymethylquinolyl)(morpholinomethyl)[2-(1H-pyrazolyl)pyrrolidin yl]benzamide, N-[2-hydroxy(trifluoromethyl)quinolyl](morpholinomethyl)pyrrolidinyl- benzamide, N-(2-hydroxy-4,7-dimethylquinolyl)(morpholinomethyl)pyrrolidinyl-benzamide, 10 2-[2-(hydroxymethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl) (morpholinomethyl)benzamide, N-(2-hydroxymethylquinolyl)(3-hydroxypyrrolidinyl) (morpholinomethyl)benzamide, 2-[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl) 15 (morpholinomethyl)benzamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)(2-oxopyrrolidinyl)benzamide, 2-cyano-N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridinecarboxamide, 2-acetyl-N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridinecarboxamide, 2-(1-hydroxyethyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridine 20 carboxamide, N4-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridine-2,4-dicarboxamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl(1H-tetrazolyl)pyridine carboxamide, 5-(1-hydroxyethyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, 25 N-(2-hydroxymethylquinolyl)(1-methoxyethyl)pyrrolidinyl-benzamide, 2-[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl) (methoxymethyl)benzamide, N-(2-hydroxymethylquinolyl)(methoxymethyl)[2-(1H-pyrazolyl)pyrrolidin yl]benzamide, 30 N-(2-hydroxymethylquinolyl)(isopropoxymethyl)pyrrolidinyl-benzamide, 2-[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl) (trifluoromethoxy)benzamide, 5-amino-N-(2-hydroxymethylquinolyl)morpholino-benzamide, 5-[(2-aminooxo-ethyl)amino]-N-(2-hydroxymethylquinolyl)morpholino-benzamide, (25692687_1):GCC 5-fluoro-N-(2-hydroxymethylquinolyl)morpholino-benzamide, N-(2-hydroxymethylquinolyl)morpholino(1-piperidylsulfonyl) benzamide, N-(2-hydroxymethylquinolyl)morpholinomorpholinosulfonyl-benzamide, N-(2-hydroxymethylquinolyl)morpholinosulfamoyl-benzamide, 5 5-acetamido-N-(2-hydroxymethylquinolyl)morpholino-benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)morpholino-benzamide, N-(2-hydroxymethylquinolyl)morpholinosulfonylpyrrolidinyl-benzamide, 5-(dimethylsulfamoyl)morpholino-N-[2-oxo(trifluoromethyl)-1H-quinolin 10 yl]benzamide, 5-(dimethylsulfamoyl)-N-(4-hydroxyoxo-1H-quinolinyl)morpholino-benzamide, N-(2-hydroxymethylquinolyl)nitropyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)pyrrolidinyl-pyridine carboxamide, 15 2-(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)(morpholinomethyl)pyridine- 3-carboxamide, N-(2-hydroxymethylquinolyl)(3-hydroxypyrrolidinyl) (morpholinomethyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)morpholino(morpholinomethyl)pyridine 20 carboxamide, N-(4-chlorohydroxyquinolyl)morpholino(morpholinomethyl)pyridine carboxamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridinecarboxamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridinecarboxamide, 25 2-[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl)pyridine carboxamide, N-(4-methoxyoxo-1H-quinolinyl)[(4-methylpiperazinyl)methyl]pyrrolidinyl- benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxy-4,7-dimethylquinolyl)morpholino-benzamide, 30 5-amino-N-(2-hydroxymethylquinolyl)pyrazolyl-benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxy-4,8-dimethylquinolyl)pyrrolidinyl-benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethoxymethylquinolyl)pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl(trifluoromethyl)benzamide, (25692687_1):GCC N-(2-hydroxymethylquinolyl)(3-hydroxypyrrolidinyl)morpholinosulfonyl- benzamide, N-(2-hydroxymethylquinolyl)(3-methoxypyrrolidinyl)morpholinosulfonyl- benzamide, 5 5-(cyanomethyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)(1-morpholinocyclopropyl)pyrrolidinyl-benzamide, 2-[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl)(1- morpholinocyclopropyl)benzamide, 2-cyano(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridine 10 carboxamide, 2-cyano-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, N-(4-methoxyoxo-1H-quinolinyl)[(4-methylpiperazinyl)methyl]pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridinecarboxamide, 15 N-(2-hydroxymethylquinolyl)(3-methylmorpholinyl)pyridinecarboxamide, 2-[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl)pyridine carboxamide, 5-(dimethylsulfamoyl)-N-(2-hydroxy-4,7-dimethylquinolyl)morpholino-benzamide, N-(2-hydroxy-4,7-dimethylquinolyl)morpholino-pyridinecarboxamide, 20 2-(3-fluoropyrrolidinyl)-N-(2-hydroxy-4,7-dimethylquinolyl)pyridinecarboxamide, 2-(3,3-difluoropyrrolidinyl)-N-(2-hydroxy-4,7-dimethylquinolyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, N-(2-hydroxyisopropylquinolyl)morpholino-pyridinecarboxamide, 2-(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridinecarboxamide, 25 2-(3,3-difluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl(trifluoromethyl)pyridine carboxamide, N-(2-hydroxymethylquinolyl)morpholino(trifluoromethyl)pyridinecarboxamide, N-(2-hydroxy-4,8-dimethylquinolyl)morpholino-pyridinecarboxamide, 30 N-(2-hydroxy-4,7-dimethylquinolyl)methylmorpholino-pyridinecarboxamide, N-(2-hydroxymethylquinolyl)methylmorpholino-pyridinecarboxamide, N-(2-hydroxymethylquinolyl)morpholino(trifluoromethyl)pyridinecarboxamide, 5-chloro-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, (25692687_1):GCC 2-(3,4a,5,6,7,7a-hexahydro-2H-pyrrolo[3,4-b][1,4]oxazinyl)-N-(2-hydroxymethyl quinolyl)pyridinecarboxamide, 2-(2,3,4a,5,7,7a-hexahydrofuro[3,4-b][1,4]oxazinyl)-N-(2-hydroxymethyl quinolyl)pyridinecarboxamide, 5 N-(2-hydroxymethylquinolyl)(3-oxaazabicyclo[3.2.1]octanyl)pyridine carboxamide, 2-[3-(hydroxymethyl)morpholinyl]-N-(2-hydroxymethylquinolyl)pyridine carboxamide, 2-(4,4-difluoropiperidyl)-N-(2-hydroxymethylquinolyl)pyridinecarboxamide, 10 2-(6,8-dihydro-5H-imidazo[1,2-a]pyrazinyl)-N-(2-hydroxymethylquinolyl)pyridine carboxamide, N-(2-hydroxymethylquinolyl)(3-oxopiperazinyl)pyridinecarboxamide, N-(2-hydroxymethoxyquinolyl)morpholino-pyridinecarboxamide, N-(2-hydroxymethylquinolyl)iodomorpholino-benzamide, 15 N-(2-hydroxymethylquinolyl)isoxazolylmorpholino-benzamide, 5-(3,5-dimethylisoxazolyl)-N-(2-hydroxymethylquinolyl)morpholino-benzamide, N-(2-hydroxy-4,7-dimethylquinolyl)iodomorpholino-benzamide, N-(2-hydroxy-4,7-dimethylquinolyl)(1-methylpyrazolyl)morpholino-benzamide, 5-(3,5-dimethylisoxazolyl)-N-(2-hydroxy-4,7-dimethylquinolyl)morpholino- 20 benzamide, N-(2-hydroxy-4,8-dimethylquinolyl)iodomorpholino-benzamide, 5-(3-furyl)-N-(2-hydroxy-4, 8-dimethylquinolyl)morpholino-benzamide, N-(2-hydroxymethoxymethylquinolyl)(1-methylpyrazolyl)morpholino- benzamide, 25 5-(3-furyl)-N-(2-hydroxymethoxymethylquinolyl)morpholino-benzamide, 5-(3,5-dimethylisoxazolyl)-N-(2-hydroxymethoxymethylquinolyl)morpholino- benzamide, 2-(3-fluoropyrrolidinyl)(3-furyl)-N-(2-hydroxymethylquinolyl)pyridine carboxamide, 30 N-(2-hydroxy-4,7-dimethylquinolyl)isoxazolylmorpholino-benzamide, 2-cyano-N-(2-hydroxy-4,7-dimethylquinolyl)morpholino-pyridinecarboxamide, 5-(dimethylsulfamoyl)-N-(2-hydroxyisopropylquinolyl)pyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)(1-methylpyrazolyl)morpholino-benzamide, 5-(3-furyl)-N-(2-hydroxymethylquinolyl)morpholino-benzamide, (25692687_1):GCC 5-(1-hydroxyethyl)-N-(2-hydroxymethylquinolyl)morpholino-benzamide, N-(2-hydroxymethoxymethylquinolyl)(1-methylpyrazolyl)morpholino- pyridinecarboxamide, N-(2-hydroxymethoxymethylquinolyl)(1-methylpyrazolyl)morpholino- 5 pyridinecarboxamide, N-(2-hydroxy-4,7-dimethylquinolyl)(1-methylpyrazolyl)morpholino-pyridine carboxamide, 5-(dimethylsulfamoyl)[(3R)fluoropyrrolidinyl]-N-(2-hydroxymethyl quinolyl)benzamide, 10 5-(dimethylsulfamoyl)[(3S)fluoropyrrolidinyl]-N-(2-hydroxymethyl quinolyl)benzamide, 5-(3-furyl)-N-(2-hydroxymethylquinolyl)morphpholino-pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(1-methylpyrazolyl)morpholino-pyridine carboxamide, 15 N-(2-hydroxymethylquinolyl)isoxazolylmorpholino-pyridinecarboxamide, 5-(3,5-dimethylisoxazolyl)-N-(2-hydroxymethylquinolyl)morpholino-pyridine carboxamide, 5-(3-furyl)-N-(2-hydroxymethylquinolyl)(6-oxaazaspiro[3.3]heptanyl)pyridine- 3-carboxamide, 20 5-(3-furyl)-N-(2-hydroxy-4,8-dimethylquinolyl)morpholino-pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(5-methyl-1,3,4-oxadiazolyl)morpholino- benzamide, N-(2-hydroxymethylquinolyl)morpholino(1H-tetrazolyl)benzamide, 3-[(2-hydroxymethylquinolyl)carbamoyl]morpholino-benzoic acid, 25 5-cyano-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, 5-bromo(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridine carboxamide, N-(2-hydroxymethylquinolyl)(4-methylpiperazinyl)morpholino-pyridine carboxamide, 30 N-(2-hydroxymethylquinolyl)-2,5-dimorpholino-pyridinecarboxamide, 5-[4-(dimethylamino)piperidyl]-N-(2-hydroxymethylquinolyl)morpholino-pyridine- 3-carboxamide, 5-(3,5-dimethylisoxazolyl)-N-(2-hydroxy-4,7-dimethylquinolyl)morpholino-pyridine- 3-carboxamide, (25692687_1):GCC 5-(3-furyl)-N-(2-hydroxymethoxymethylquinolyl)morpholino-pyridine carboxamide, 5-(3-furyl)-N-(2-hydroxymethoxymethylquinolyl)morpholino-pyridine carboxamide, 5 5-(3-furyl)-N-(2-hydroxy-4,7-dimethylquinolyl)morpholino-pyridinecarboxamide, 5-(azetidinyl)-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, 5-[(3S)fluoropyrrolidinyl]-N-(2-hydroxymethylquinolyl)morpholino-pyridine carboxamide, N-(2-hydroxy-4,7-dimethylquinolyl)(2-methyltetrazolyl)morpholino-pyridine 10 carboxamide, N-(2-hydroxy-4,7-dimethylquinolyl)(1-methyltetrazolyl)morpholino-pyridine carboxamide, 2-cyano(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridine carboxamide, 15 2-cyano-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, 5-(dimethylsulfamoyl)(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridine- 3-carboxamide, N-(2-hydroxy-4,7-dimethylquinolyl)(3-methylisoxazolyl)morpholino-pyridine carboxamide, 20 N-(2-hydroxymethoxymethylquinolyl)(5-methyl-1,3,4-oxadiazolyl) morpholino-benzamide, N4-(2-hydroxymethylquinolyl)pyrrolidinyl-pyridine-2,4-dicarboxamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl(1H-tetrazolyl)pyridine carboxamide, 25 5-(cyanomethyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)(1-morpholinocyclopropyl)pyrrolidinyl-benzamide, 5-(1-hydroxyethyl)-N-(2-hydroxymethylquinolyl)[2-(2-pyridyl)pyrrolidin yl]benzamide, 2-acetyl-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, 30 2-(1-hydroxyethyl)-N-(2-hydroxymethylquinolyl)morpholino-pyridinecarboxamide, 2-acetyl(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)pyridine carboxamide, 5-(3-fluoropyrrolidinyl)(1-hydroxyethyl)-N-(2-hydroxymethylquinolyl)pyridine carboxamide, (25692687_1):GCC 2-cyano[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethyl quinolyl)pyridinecarboxamide, 2-acetyl[2-(dimethylaminomethyl)pyrrolidinyl]-N-(2-hydroxymethyl quinolyl)pyridinecarboxamide, 5 5-[2-(dimethylaminomethyl)pyrrolidinyl](1-hydroxyethyl)-N-(2-hydroxymethyl quinolyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)morpholino-benzamide, N-(2-hydroxymethylquinolyl)(4-methylpiperazinyl)benzamide, N-(2-hydroxymethylquinolyl)(4-pyrazinylpiperazinyl)benzamide, 10 N-(2-hydroxymethylquinolyl)morpholinosulfamoyl-benzamide, 5-(2,5-dioxopyrrolidinyl)-N-(2-hydroxymethylquinolyl)morpholino-benzamide, 5-(benzenesulfonamido)-N-(2-hydroxymethylquinolyl)(4-methylpiperazin yl)benzamide, 5-(ethylsulfonylamino)-N-(2-hydroxymethylquinolyl)(4-methylpiperazin 15 yl)benzamide, N-(2-hydroxymethylquinolyl)morpholinonitro-benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)morpholino-benzamide, N-(2-hydroxymethylquinolyl)morpholino(1-piperidylsulfonyl)benzamide, N-(2-hydroxymethylquinolyl)morpholinomorpholinosulfonyl-benzamide, 20 2-(dimethylamino)-N-(2-hydroxymethylquinolyl)nitro-benzamide, N-(2-hydroxymethylquinolyl)nitropyrrolidinyl-benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, N-(4-hydroxyoxo-1H-quinolinyl)morpholinomorpholinosulfonyl-benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-methylpyrrolidin 25 yl)benzamide, 5-(dimethylsulfamoyl)(3-fluoropyrrolidinyl)-N-(2-hydroxymethyl quinolyl)benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-methoxypyrrolidin yl)benzamide, 30 1-[4-(dimethylsulfamoyl)[(2-hydroxymethylquinolyl)carbamoyl]phenyl]pyrrolidine carboxamide, 2-[3-(dimethylamino)pyrrolidinyl](dimethylsulfamoyl)-N-(2-hydroxymethyl quinolyl)benzamide, (25692687_1):GCC 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-isobutylpyrrolidin yl)benzamide, 2-[3-(dimethylaminomethyl)pyrrolidinyl](dimethylsulfamoyl)-N-(2-hydroxymethyl quinolyl)benzamide, 5 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-ureidopyrrolidin yl)benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-pyrrolidinylpyrrolidin yl)benzamide, 2-[3-(2-aminooxo-ethoxy)pyrrolidinyl](dimethylsulfamoyl)-N-(2-hydroxymethyl 10 quinolyl)benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(3-phenylpyrrolidin yl)benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(2-methylpyrrolidin yl)benzamide, 15 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)[2-(methoxymethyl)pyrrolidin yl]benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(5-methyl-2,3,3a,4,6,6a- hexahydropyrrolo[3,4-b]pyrrolyl)benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(2-isobutylpyrrolidin 20 yl)benzamide, 2-[2-(dimethylaminomethyl)pyrrolidinyl](dimethylsulfamoyl)-N-(2-hydroxymethyl quinolyl)benzamide, 5-(dimethylsulfamoyl)[2-(1-hydroxymethyl-ethyl)pyrrolidinyl]-N-(2-hydroxy methylquinolyl)benzamide, 25 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)[2-(1H-pyrazolyl)pyrrolidin yl]benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)[2-(1H-tetrazolyl)pyrrolidin yl]benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(4-methyl-3,3a,5,6,7,7a- 30 hexahydro-2H-pyrrolo[3,2-b]pyridinyl)benzamide, 1-[4-(dimethylsulfamoyl)[(2-hydroxymethylquinolyl)carbamoyl]phenyl]-N,N- dimethyl-pyrrolidinecarboxamide, 5-(dimethylsulfamoyl)(3-hydroxymethylazabicyclo[3.2.1]octanyl)-N-(2-hydroxy methylquinolyl)benzamide, (25692687_1):GCC 5-(dimethylsulfamoyl)(4-hydroxy-2,5-dimethylpiperidyl)-N-(2-hydroxymethyl quinolyl)benzamide, 5-(dimethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(2-phenylpiperidyl)benzamide, 5-(diethylsulfamoyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, 5 5-(diethylsulfamoyl)-N-(2-hydroxymethylquinolyl)(1-piperidyl)benzamide, N-(2-hydroxymethylquinolyl)(2-methylpiperidyl)nitro-pyridinecarboxamide, 5-[[2-hydroxyethyl(methyl)amino]methyl]-N-(2-hydroxymethylquinolyl)pyrrolidin yl-benzamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl[(tetrahydrofuran 10 ylmethylamino)methyl]benzamide, 5-[[3-(dimethylamino)pyrrolidinyl]methyl]-N-(2-hydroxymethylquinolyl) pyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)[(3-hydroxypyrrolidinyl)methyl]pyrrolidinyl- benzamide, 15 N-(2-hydroxymethylquinolyl)[[(2S)(methoxymethyl)pyrrolidinyl]methyl] pyrrolidinyl-benzamide, 5-[[4-(2-hydroxyethyl)piperazinyl]methyl]-N-(2-hydroxymethylquinolyl)pyrrolidin- 1-yl-benzamide, N-(2-hydroxymethylquinolyl)[(4-methyl-1,4-diazepanyl)methyl]pyrrolidinyl- 20 benzamide, N-(2-hydroxymethylquinolyl)[(3-methoxypyrrolidinyl)methyl]pyrrolidinyl- benzamide, 5-[(3-hydroxyazetidinyl)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- benzamide, 25 N-(2-hydroxymethylquinolyl)[[3-(methoxymethyl)azetidinyl]methyl]pyrrolidin- 1-yl-benzamide, N-(2-hydroxymethylquinolyl)[[3-(methoxymethyl)piperidyl]methyl]pyrrolidin yl-benzamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)pyrrolidinyl-pyridine 30 carboxamide, N-(2-hydroxymethylquinolyl)(3-methylpyrrolidinyl) (morpholinomethyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(2-methylpyrrolidinyl) (morpholinomethyl)pyridinecarboxamide, (25692687_1):GCC N-(2-hydroxymethylquinolyl)(3-hydroxypyrrolidinyl) (morpholinomethyl)pyridinecarboxamide, 2-(3-fluoromethyl-pyrrolidinyl)-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, 5 2-(3-carbamoylpyrrolidinyl)-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(3-isobutylpyrrolidinyl) (morpholinomethyl)pyridinecarboxamide, 2-(2-carbamoylhydroxy-pyrrolidinyl)-N-(2-hydroxymethylquinolyl) 10 (morpholinomethyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)[2-(1H-pyrazolyl)pyrrolidin yl]pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)(3-pyrrolidinylpyrrolidin yl)pyridinecarboxamide, 15 2-[2-(dimethylcarbamoyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(4-methyl-2,3,4a,5,7,7a-hexahydropyrrolo[3,4- b][1,4]oxazinyl)(morpholinomethyl)pyridinecarboxamide, N-(2-hydroxymethylquinolyl)(morpholinomethyl)[3-(4-pyridyl)pyrrolidin 20 yl]pyridinecarboxamide, 2-[2-(hydroxymethyl)morpholinyl]-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, 2-[2-(hydroxymethyl)methyl-morpholinyl]-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, 25 2-[2-(dimethylaminomethyl)morpholinyl]-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, 2-[3-(hydroxymethyl)pyrrolidinyl]-N-(2-hydroxymethylquinolyl) (morpholinomethyl)pyridinecarboxamide, 5-[(2-furylmethylamino)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- 30 benzamide, N-(2-hydroxymethylquinolyl)[(isobutylamino)methyl]pyrrolidinyl-benzamide, 5-[(cyclopropylamino)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- benzamide, (25692687_1):GCC N-(2-hydroxymethylquinolyl)[(3-pyridylmethylamino)methyl]pyrrolidinyl- benzamide, 5-[(cyanomethylamino)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- benzamide, 5 N-(2-hydroxymethylquinolyl)[[isopropyl(methyl)amino]methyl]pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl[(2,2,2- trifluoroethylamino)methyl]benzamide, N-(2-hydroxymethylquinolyl)[(3-methoxypiperidyl)methyl]pyrrolidinyl- 10 benzamide, 5-[[3-(dimethylamino)azetidinyl]methyl]-N-(2-hydroxymethylquinolyl)pyrrolidin- 1-yl-benzamide, N-(2-hydroxymethylquinolyl)[(1H-imidazolylmethylamino)methyl]pyrrolidin yl-benzamide, 15 N-(2-hydroxymethylquinolyl)pyrrolidinyl[[1-(1H-tetrazol yl)ethylamino]methyl]benzamide, 5-(dimethylaminomethyl)-N-(2-hydroxymethylquinolyl)pyrrolidinyl-benzamide, N-(2-hydroxymethylquinolyl)[[(2-methoxypyridyl)methylamino]methyl] pyrrolidinyl-benzamide, 20 5-[(3-cyanopiperidyl)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- benzamide, 1-[[3-[(2-hydroxymethylquinolyl)carbamoyl]pyrrolidinyl-phenyl]methyl]-N- methyl-pyrrolidinecarboxamide, N-(2-hydroxymethylquinolyl)[[1-(1H-imidazolyl)ethylamino]methyl]pyrrolidin- 25 1-yl-benzamide, N-(2-hydroxymethylquinolyl)pyrrolidinyl[(tetrahydrofuran ylamino)methyl]benzamide, N-(2-hydroxymethylquinolyl)[(isoxazolylamino)methyl]pyrrolidinyl- benzamide, 30 5-[(3-fluoropyrrolidinyl)methyl]-N-(2-hydroxymethylquinolyl)pyrrolidinyl- benzamide, N-(2-hydroxymethylquinolyl)[[(1-methylpyrazolyl)amino]methyl]pyrrolidin yl-benzamide, N-(2-hydroxymethylquinolyl)(1,4-oxazepanylmethyl)pyrrolidinyl-benzamide, (25692687_1):GCC 2-(3-fluoropyrrolidinyl)-N-(2-hydroxymethylquinolyl)(morpholinomethyl)pyridine- 3-carboxamide, and N-(2-hydroxymethylquinolyl)morpholino(morpholinomethyl)pyridine carboxamide. 5

13. A pharmaceutical composition comprising a compound according to any one of the preceding claims and at least one pharmaceutical acceptable excipient.

14. Use of a compound according to any one of claims 1 to 12 or a pharmaceutical composition according to claim 13 in the manufacture of a medicament for modulating the activity of at least one bromodomain, when contacting the bromodomain with the compound or 10 the pharmaceutical composition.

15. The use according to claim 14, wherein modulating the activity comprises inhibiting the bromodomain.

16. The use according to claim 14 or 15, wherein the bromodomain is a member of the BET (bromodomain and extraterminal) family. 15

17. The use according to any one of claims 14 to 16, wherein modulating the activity of at least one bromodomain occurs when treating a disease or condition related to systemic or tissue inflammation, inflammatory responses to infection or hypoxia, cellular activation and proliferation, lipid metabolism, fibrosis, or in the prevention and treatment of viral infections.

18. The use according to any one of claims 14 to 16, wherein modulating the activity 20 of at least one bromodomain occurs when treating a disease or condition such as rheumatoid arthritis, osteoarthritis, acute gout, psoriasis, psoriatric arthritis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, inflammatory bowel syndrome, Crohn's disease, ulcerative colitis, colitis, asthma, chronic obstructive airways disease, pneumonitis, myocarditis, pericarditis, myositis, eczema, dermatitis, atopic dermatitis, allergy, ankylosing 25 spondylitis, lupus erythematosus, Hashimoto’s disease, pancreatitis, autoimmune ocular disease, Sjögren’s disease, optic neuritis, neuromyelitis optica, Myasthenia Gravis, Guillain Barre syndrome, Graves’ disease, alopecia, vitiligo, bullous skin diseases, nephritis, vasculitis, atherosclerosis, Alzheimer's disease, depression, retinitis, uveitis, scleritis, hepatitis, pancreatitis, primary biliary cirrhosis, sclerosing cholangitis, hypophysitis, thyroiditis, 30 Addison's disease, type I diabetes and acute rejection of transplanted organs; or treating an acute inflammatory disease or condition such as acute gout, giant cell arteritis, nephritis including lupus nephritis, vasculitis with organ involvement such as (25692687_1):GCC glomerulonephritis, vasculitis including giant cell arteritis, Polyarteritis nodosa, Behcet's disease, Wegener's granulomatosis, Kawasaki disease, Takayasu's Arteritis, vasculitis with organ involvement and acute rejection of transplanted organs; or treating an inflammatory response to infection caused by bacteria, viruses, fungi, 5 parasites or their toxins, such as sepsis, sepsis syndrome, septic shock, endotoxaemia, systemic inflammatory response syndrome (SIRS), multi-organ dysfunction syndrome, toxic shock syndrome, acute lung injury, ARDS (adult respiratory distress syndrome), acute renal failure, fulminant hepatitis, burns, acute pancreatitis, post-surgical syndromes, sarcoidosis, Herxheimer reactions, encephalitis, myelitis, meningitis, malaria and SIRS associated with viral infections 10 such as influenza, herpes zoster, herpes simplex and coronavirus; or treating ischaemia-reperfusion injury such as myocardial infarction, cerebrovascular ischaemia (stroke), acute coronary syndromes, renal reperfusion injury, organ transplantation, coronary artery bypass grafting, cardio-pulmonary bypass procedures, pulmonary, renal, hepatic, gastro-intestinal or peripheral limb embolism; or 15 treating a disorder or condition of lipid metabolism such as hypercholesterolemia, atherosclerosis and Alzheimer's disease; or treating a fibrotic disorder or condition such as idiopathic pulmonary fibrosis, renal fibrosis, post-operative stricture, keloid formation, scleroderma and cardiac fibrosis; or treating or preventing a viral infection such as herpes virus, human papilloma virus, 20 human immunodeficiency virus (HIV), adenovirus and poxvirus; or treating cancer, including hematological, epithelial including lung, breast and colon carcinomas, midline carcinomas, sarcomas, mesenchymal, hepatic, renal and neurological tumours; such as adenocarcinoma, acute lymphoblastic leukemia, acute myelogenous leukemia, adult T-cell leukemia/lymphoma, bladder cancer, blastoma, bone cancer, breast cancer, brain 25 cancer, burkitts lymphoma, carcinoma, myeloid sarcoma, cervical cancer, chronic lymphocytic leukemia, chronic myelogenous leukemia, colorectal cancer, diffuse large B-cell lymphoma, endometrial cancer, esophageal cancer, follicular lymphoma, gastrointestinal cancer, glioblastoma multiforme, glioma, gallbladder cancer, gastric cancer, head and neck cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, intestinal cancer, kidney cancer, laryngeal 30 cancer, leukemia, lung cancer, lymphoma, liver cancer, small cell lung cancer, non-small cell lung cancer, melanoma, mesothelioma, multiple myeloma, ocular cancer, optic nerve tumor, oral cancer, ovarian cancer, pituitary tumor, primary central nervous system lymphoma, (25692687_1):GCC prostate cancer, pancreatic cancer, pharyngeal cancer, renal cell carcinoma, rectal cancer, sarcoma, skin cancer, spinal tumor, small intestine cancer, stomach cancer, T-cell lymphoma, testicular cancer, thyroid cancer, throat cancer, urogenital cancer, urothelial carcinoma, uterine cancer, vaginal cancer, or Wilms' tumor; or 5 treating obesity, such as obesity associated with cancer treatment or obesity associated with diabetes and cardiac hypertrophy. NUEVOLUTION A/S 10 By the Attorneys for the Applicant SPRUSON & FERGUSON Per: (25692687_1):GCC