Heterocyclic Carbonyl Compounds

• US 20080090882A1
• Filed: 04/04/2005
• Published: 04/17/2008
• Est. Priority Date: 10/21/2004
• Status: Active Grant

• Current Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Original Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Inventors: Beier, Norbert, Gericke, Rolf, Lang, Florian, Mederski, Werner, Dorsch, Dieter
• Granted Patent: US 8,815,924 B2
• Time in Patent Office: Days
• US Class Current: 514/365
• CPC Class Codes: A61K 31/341 not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• CPC Class Codes: A61K 31/416 condensed with carbocyclic ring systems, e.g. indazole
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/421 1,3-Oxazoles, e.g. pemoline, trimethadione
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/12 for cataracts
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 231/56 : Benzopyrazoles; Hydrogenated benzopyrazoles
• CPC Class Codes: C07D 233/54 : having two double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 233/68 : Halogen atoms
• CPC Class Codes: C07D 263/34 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 277/56 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 307/34 : having two or three double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 307/68 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 333/38 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 413/00 : Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
• CPC Class Codes: C07D 413/02 : containing two hetero rings

Abstract

Novel heterocyclic compounds of the formula (I), in which R¹, D, W, T and T′ have the meanings indicated in Claim 1, are SGK inhibitors and can be used for the treatment of SGK-induced diseases and conditions, such as diabetes, obesity, metabolic syndrome (dyslipidaemia), systemic and pulmonary hypertonia, cardiovascular diseases and kidney diseases, generally in fibroses and inflammatory processes of any type.

Claims

1. Compounds of the formula I

2. Compounds according to claim 1 in which

R¹, R^1a each, independently of one another, denote a mono- or bicyclic saturated, unsaturated or aromatic carbo- or heterocycle having 0 to 4 N, O and/or S atoms, which is unsubstituted or is mono-, di- or trisubstituted by A, Hal, NO₂, CN, —

[C(R³)₂]_n—

Ar′

, —

O—

[C(R³)₂]_n—

Ar′

, —

[C(R³)₂]_n-Het′

, —

[C(R³)₂]_n-cycloalkyl, —

[C(R³)₂]_n—

OR³, —

[C(R³)₂]_nN(R³)₂, —

[C(R³)₂]_nCOOR³, —

[C(R³)₂]_nCON(R³)₂, —

[C(R³)₂]_nCONHAr′

, —

[C(R³)₂]_nCONR³N(R³)₂, O—

[C(R³)₂]_oCON(R³)₂, O—

[C(R³)₂]_oCONR³N(R³)₂, NR³COA, NR³CON(R³)₂, NR³SO₂A, COR³, SO₂NR³, S(O)_mA, ═

S, ═

NR³ and/or ═

O (carbonyl oxygen),

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

3. Compounds according to claim 1 in which

R¹, R^1a each, independently of one another, denote a mono- or bicyclic saturated, unsaturated or aromatic carbo- or heterocycle having 0 to 4 N, O and/or S atoms, which is unsubstituted or is mono-, di- or trisubstituted by A, Hal, CN, —

[C(R³)₂]_n—

Ar′

, —

O—

[C(R³)₂]_n—

Ar′

, —

[C(R³)₂]_n—

OR³, —

[C(R³)₂]_nCONHAr′

, —

[C(R³)₂]_nN(R³)₂ or —

[C(R³)₂]_nCOOR³,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

4. Compounds according to claim 1 in which

R¹, R^1a each, independently of one another, denote a mono- or bicyclic saturated, unsaturated or aromatic carbo- or heterocycle having 0 to 4 N, O and/or S atoms, which is unsubstituted or is mono-, di- or trisubstituted by A, Hal, CN, —

[C(R³)₂]_n—

Ar′

, —

O—

[C(R³)₂]_n—

Ar′

, —

C(R³)₂]_nCONHAr′

, —

[C(R³)₂]_n—

OR³, —

[C(R³)₂]_nN(R³)₂ or —

[C(R³)₂]_nCOOR³,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

5. Compounds according to claim 1 in which

R¹ denotes a mono- or bicyclic unsaturated or aromatic carbo- or heterocycle having 0 to 4 N, O and/or S atoms, which is unsubstituted or is mono-, di- or trisubstituted by A, Hal, —

[C(R³)₂]_n—

OR³, —

[C(R³)₂]_nN(R³)₂ or —

[C(R³)₂]_nCOOR³,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

6. Compounds according to claim 1 in which

R¹ denotes a mono- or bicyclic aromatic carbocycle, which is un-substituted or is mono-, di- or trisubstituted by A, Hal, —

[C(R³)₂]_n—

OR³—

[C(R³)₂]_nN(R³)₂ or —

[C(R³)₂]_nCOOR³,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

7. Compounds according to claim 1 in which

R¹ denotes a mono- or bicyclic unsaturated or aromatic heterocycle having 1 to 4 N, O and/or S atoms, which is unsubstituted or is mono-, di- or trisubstituted by A, Hal, —

C(R³)₂]_nCONHAr′

, —

[C(R³)₂]_n—

OR³, —

[C(R³)₂]_nN(R³)₂ or —

[C(R³)₂]_nCOOR³,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

8. Compounds according to claim 1 in which

R¹ denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by A, Hal, OH or OA, or

a mono- or bicyclic unsaturated or aromatic heterocycle having 1-2 nitrogen atoms, which is unsubstituted or monosubstituted by NH₂,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

9. Compounds according to claim 1 in which

R^1a denotes a monocyclic saturated, unsaturated or aromatic carbocycle, which is unsubstituted or mono-, di- or trisubstituted by A, Hal, CN, —

[C(R³)₂]_n—

Ar′

, —

O—

[C(R³)₂]_n—

Ar′

, —

[C(R³)₂]_n—

OR³, —

[C(R³)₂]_nN(R³)₂ or —

[C(R³)₂]_nCOOR³,

and pharmaceutically-usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

10. Compounds according to claim 1 in which

R^1a denotes phenyl, which is unsubstituted or is mono-, di- or trisubstituted by A, Hal, benzyloxy, OH or OA,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

11. Compounds according to claim 1 in which

R^1a denotes phenyl, which is unsubstituted or is mono-, di- or trisubstituted by A, Hal, benzyloxy, OH or OA, or 2,1,3-benzothiadiazole,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

12. Compounds according to claim 1 in which

Ar′

denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by Hal and/or A,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

13. Compounds according to claim 1 in which

Het′

denotes a monocyclic saturated, unsaturated or aromatic heterocycle having 1 to 2 N and/or O atoms, which may be un-substituted or mono-, di- or trisubstituted by A, Hal, OH and/or OA,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

14. Compounds according to claim 1 in which

Het′

denotes furyl, thienyl, pyrrolyl, imidazolyl, pyridyl, pyrimidinyl, pyrazolyl, thiazolyl, indolyl, pyrrolidinyl, piperidinyl, morpholinyl or piperazinyl, each of which is unsubstituted or mono-, di- or trisubstituted by A, Hal, OH and/or OA,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

15. Compounds according to claim 1 in which

A denotes unbranched or branched alkyl having 1-6 C atoms, in which 1-7H atoms may be replaced by F,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

16. Compounds according to claim 1 in which

X denotes H,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

17. Compounds according to claim 1 in which

R denotes —

C(═

O)—

N(R³)[C(R³)₂]_nR^1a,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

18. Compounds according to claim 1 in which

R denotes —

C(═

O)—

NHCH₂R^1a,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

19. Compounds according to claim 1 in which

R¹, R^1a each, independently of one another, denote a mono- or bicyclic saturated, unsaturated or aromatic carbo- or heterocycle having 0 to 4 N, O and/or S atoms, which is unsubstituted or is mono-, di- or trisubstituted by A, Hal, CN, —

[C(R³)₂]_n—

Ar′

, —

O—

[C(R³)₂]_n—

Ar′

, —

[C(R³)₂]_n—

OR³, —

C(R³)₂]_nCONHAr′

, —

[C(R³)₂]_nN(R³)₂ or —

[C(R³)₂]_nCOOR³,

D denotes O, NH or S,

W denotes CX or N,

T denotes CX, N or CR,

T′

denotes CX, N or CR,

with the proviso that one of the radicals T or T′

denotes CR and the other is not equal to CR,

R denotes —

C(═

O)—

N(R³)[C(R³)₂]_nR^1a,

X denotes H,

R³ denotes H or A,

A denotes unbranched or branched alkyl having 1-10 C atoms, in which one or two CH₂ groups may be replaced by O or S atoms and/or by —

CH═

CH—

groups and/or in addition 1-7H atoms may be replaced by F,

Ar′

denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by Hal and/or A,

Hal denotes F, Cl, Br or I,

n denotes 0, 1, 2 or 3,

and pharmaceutically usable derivatives;

salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

20. Compounds according to claim 1 in which

R¹ denotes a mono- or bicyclic unsaturated or aromatic heterocycle having 1 to 4 N, O and/or S atoms, which is unsubstituted or is mono-, di- or trisubstituted by A, Hal, —

C(R³)₂]_nCONHAr′

, —

[C(R³)₂]_n—

OR³, —

[C(R³)₂]_nN(R³)₂ or —

[C(R³)₂]_nCOOR³,

R^1a denotes phenyl, which is unsubstituted or is mono-, di- or trisubstituted by A, Hal, benzyloxy, OH or OA,

or 2,1,3-benzothiadiazole,

D denotes O, NH or S,

W denotes CX or N,

T denotes CX, N or CR,

T′

denotes CX, N or CR,

with the proviso that one of the radicals T or T′

denotes CR and the other is not equal to CR,

R denotes —

C(═

O)—

NH—

CHA-R^1a,

X denotes H,

R³ denotes H or A,

Ar′

denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by Hal and/or A,

A denotes unbranched or branched alkyl having 1-10 C atoms, in which one or two CH₂ groups may be replaced by O or S atoms and/or by —

CH═

CH—

groups and/or in addition 1-7H atoms may be replaced by F,

Hal denotes F, Cl, Br or I,

n denotes 0, 1, 2 or 3,

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

21. Compounds according to claim 1 selected from the group

N-3-hydroxybenzyl-2-(4-hydroxyphenyl)-3H-imidazole-4-carboxamide (“

1”

),

N-3-hydroxybenzyl-2-(3-hydroxyphenyl)oxazole-4-carboxamide (“

2”

),

N-3-hydroxybenzyl-5-(4-hydroxyphenyl)furan-2-carboxamide (“

3”

),

N-3-hydroxybenzyl-2-(4-hydroxyphenyl)thioazole-5-carboxamide (“

4”

),

N-3-chlorobenzyl-2-(3-amino-1H-indazol-5-yl)-3H-imidazole-4-carboxamide (“

5”

),

N-3-hydroxybenzyl-2-(2,4-dihydroxyphenyl)-3H-imidazole-4-carboxamide (“

6”

),

N-3-hydroxybenzyl-2-(4-hydroxyphenyl)oxazole-4-carboxamide (“

7”

),

N—

[(R)-1-(3-hydroxyphenyl)ethyl]-2-(3-hydroxyphenyl)oxazole-4-carboxamide (“

8”

),

N-4-hydroxyphenyl-2-(4-hydroxyphenyl)-3H-imidazole-4-carboxamide (“

9”

),

N-3-hydroxyphenyl-2-(3-hydroxyphenyl)-3H-imidazole-4-carboxamide (“

10”

),

N-4-hydroxyphenyl-2-(3-hydroxyphenyl)-3H-imidazole-4-carboxamide (“

11”

),

N-3-hydroxyphenyl-2-(4-hydroxyphenyl)-3H-imidazole-4-carboxamide (“

12”

),

N-3-hydroxyphenyl-2-(3-hydroxyphenyl)oxazole-4-carboxamide (“

13”

),

N-4-hydroxybenzyl-2-(3-hydroxyphenyl)oxazole-4-carboxamide (“

14”

),

N-4-hydroxyphenyl-2-(3-hydroxyphenyl)oxazole-4-carboxamide

N-3-hydroxybenzyl-2-(4-hydroxy-2-methylphenyl)-3H-imidazole-4-carboxamide (“

16”

),

N-3-hydroxybenzyl-5-(3-chlorophenyl)furan-2-carboxamide (“

17”

),

N-4-hydroxybenzyl-5-(3-chlorophenyl)furan-2-carboxamide (“

18”

),

N-(benzo-2,1,3-thiadiazol-5-ylmethyl)-5-(3-chlorophenyl)furan-2-carboxamide (“

19”

),

N-3-fluorobenzyl-2-(4-hydroxyphenyl)-3H-imidazole-4-carboxamide (“

20”

),

N-4-hydroxybenzyl-2-(4-hydroxyphenyl)-3H-imidazole-4-carboxamide (“

21”

),

N-4-hydroxybenzyl-2-(3-hydroxyphenyl)-3H-imidazole-4-carboxamide (“

23”

),

N-3-hydroxybenzyl-2-(3-hydroxyphenyl)-3H-imidazole-4-carboxamide (“

26”

),

N-3-fluorobenzyl-2-(3-hydroxyphenyl)-3H-imidazole-4-carboxamide (“

27”

),

N-3-fluorobenzyl-2-(4-fluorophenyl)-3H-imidazole-4-carboxamide (“

28”

),

N-3-hydroxybenzyl-2-(4-fluorophenyl)-3H-imidazole-4-carboxamide (“

29”

),

N-3-fluorobenzyl-2-(4-hydroxyphenyl)oxazole-4-carboxamide (“

30”

),

N-2-methoxybenzyl-2-(4-hydroxyphenyl)-3H-imidazole-4-carboxamide (“

31”

),

N-2-methoxybenzyl-5-(3-chlorophenyl)furan-2-carboxamide (“

32”

),

N-2-hydroxybenzyl-5-(3-chlorophenyl)furan-2-carboxamide (“

33”

),

N-3-fluorobenzyl-2-(3-chloro-6-methoxyphenyl)oxazole-4-carboxamide (“

34”

),

N-3-hydroxybenzyl-2-(3-amino-1H-indazol-5-yl)-3H-imidazole-4-carboxamide (“

35”

),

N-3-methoxybenzyl-2-(3-amino-1H-indazol-5-yl)-3H-imidazole-4-carboxamide (“

36”

),

N-[(R)-1-(3-methoxyphenyl)ethyl]-2-(3-amino-1H-indazol-5-yl)-3H-imidazole-4-carboxamide (“

37”

),

N-3,5-difluorobenzyl-2-(3-amino-1H-indazol-5-yl)-3H-imidazole-4-carboxamide (“

38”

),

N-[(R)-1-(3-hydroxyphenyl)ethyl]-2-(3-amino-1H-indazol-5-yl)-3H-imidazole-4-carboxamide (“

39”

),

N-3-hydroxybenzyl-2-(3-amino-1H-indazol-5-yl)oxazole-4-carboxamide (“

40”

),

N-[(R)-1-(3-methoxyphenyl)ethyl]-2-(3-amino-1H-indazol-5-yl)oxazole-4-carboxamide (“

41”

),

N-3-hydroxybenzyl-5-(3-amino-1H-indazol-5-yl)furan-2-carboxamide (“

42”

),

N-3-chlorobenzyl-5-(3-amino-1H-indazol-5-yl)furan-2-carboxamide (“

43”

),

N-3,5-difluorobenzyl-2-(3-hydroxyphenyl)oxazole-4-carboxamide (“

44”

),

N-2-methoxybenzyl-2-(4-hydroxyphenyl)oxazole-4-carboxamide (“

45”

),

N-3-hydroxybenzyl-2-(3-chloro-6-methoxyphenyl)oxazole-4-carboxamide (“

46”

),

N-[(S)-1-(3-hydroxyphenyl)ethyl]-2-(3-chloro-6-methoxyphenyl)oxazole-4-carboxamide (“

47”

),

N-[(R)-1-(3-hydroxyphenyl)ethyl]-2-(3-chloro-6-methoxyphenyl)oxazole-4-carboxamide (“

48”

),

N-3-methoxybenzyl-2-(3-chloro-6-methoxyphenyl)oxazole-4-carboxamide (“

49”

),

N-3-chlorobenzyl-2-(3-amino-1H-indazol-5-yl)oxazole-4-carboxamide (“

50”

),

N-3-hydroxybenzyl-2-(3-bromophenyl)-3H-imidazole-4-carboxamide, (“

52”

),

N-3-methoxybenzyl-2-(3-bromophenyl)-3H-imidazole-4-carboxamide (“

53”

),

N-3-chlorobenzyl-2-(3-bromophenyl)-3H-imidazole-4-carboxamide (“

54”

),

N-3-hydroxybenzyl-2-(3-chlorophenyl)-3H-imidazole-4-carboxamide (“

55”

),

N-3-methoxybenzyl-2-(3-chlorophenyl)-3H-imidazole-4-carboxamide (“

56”

),

N-3-chlorobenzyl-2-(3-chlorophenyl)-3H-imidazole-4-carboxamide (“

57”

),

N-3-hydroxybenzyl-5-(3-amino-1H-indazol-6-yl)furan-2-carboxamide (“

61”

),

N-3-hydroxybenzyl-5-(3-amino-1H-indazol-5-yl)furan-2-carboxamide (“

62”

),

N-3-chlorobenzyl-5-(3-amino-1H-indazol-5-yl)thiophene-2-carboxamide (“

63”

),

N-3-methoxybenzyl-5-(3-amino-1H-indazol-5-yl)furan-2-carboxamide (“

64”

),

N-3-chlorobenzyl-5-(3-amino-1H-indazol-5-yl)furan-2-carboxamide (“

65”

),

N-3-hydroxybenzyl-5-(3-amino-1H-indazol-5-yl)thiophene-2-carboxamide (“

66”

),

N-3-methoxybenzyl-5-(3-amino-1H-indazol-5-yl)thiophene-2-carboxamide (“

67”

),

N-[(R)-1-(3-methoxyphenyl)ethyl]-5-(3-amino-1H-indazol-5-yl)thiophene-2-carboxamide (“

68”

),

N-3-methoxybenzyl-5-(3-amino-1H-indazol-6-yl)furan-2-carboxamide (“

69”

),

N-[(R)-1-(3-methoxyphenyl)ethyl]-5-(3-amino-1H-indazol-5-yl)furan-2-carboxamide (“

70”

),

N-[(S)-1-(3-methoxyphenyl)ethyl]-5-(3-amino-1H-indazol-5-yl)furan-2-carboxamide (“

71”

);

N-3-trifluoromethoxybenzyl-5-(3-amino-1H-indazol-5-yl)furan-2-carboxamide (“

72”

),

N-[1-(3-methoxyphenyl)pentyl]-5-(3-amino-1H-indazol-5-yl)furan-2-carboxamide (“

73”

),

N-(3-trifluoromethoxyphenyl)-5-(3-amino-1H-indazol-5-yl)furan-2-carboxamide (“

74”

),

N-p-tolyl-3-amino-5-[5-(3-hydroxybenzylcarbamoyl)furan-2-yl]-indazole-1-carboxamide (“

75”

),

N-3-hydroxybenzyl-5-(3-amino-1-methyl-1H-indazol-5-yl)furan-2-carboxamide (“

76”

),

N-2-hydroxybenzyl-5-(4-hydroxyphenyl)furan-2-carboxamide (“

77”

),

N-3-fluorobenzyl-5-(4-hydroxyphenyl)furan-2-carboxamide (“

78”

),

N-[(S)-1-(3-hydroxyphenyl)ethyl]-5-(4-hydroxyphenyl)furan-2-carboxamide (“

79”

),

N-[(R)-1-(3-hydroxyphenyl)ethyl]-5-(4-hydroxyphenyl)furan-2-carboxamide (“

80”

),

N-3-chlorobenzyl-2-(3-amino-1H-indazol-6-yl)oxazole-4-carboxamide (“

81”

),

N-3-hydroxybenzyl-5-(3-hydroxyphenyl)furan-2-carboxamide (“

82”

),

N-3-chlorobenzyl-5-(3-hydroxyphenyl)furan-2-carboxamide (“

83”

),

N-3-benzyloxybenzyl-5-(2-methyl-4-methoxyphenyl)furan-2-carboxamide (“

84”

),

N-3-methoxybenzyl-5-(2-methyl-4-methoxyphenyl)furan-2-carboxamide (“

85”

),

and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

22. Process for the preparation of compounds of the formula I according to claim 1 and pharmaceutically usable derivatives, solvates, salts and stereoisomers thereof, characterised in that

a) a compound of the formula I

in which

T denotes CX, N or CR,

T′

denotes CX, N or CR,

with the proviso that one of the radicals T or T′

denotes CR and the other is not equal to CR,

R denotes —

C(═

O)-L,

R¹, W, D and X have the meanings indicated in claim 1, and

L denotes Cl, Br, I or a free or reactively functionally modified OH group,

is reacted with a compound of the formula III

HN(R²)[C(R²)₂]_nR^1a 

 

III

in which

R^1a, R² and n have the meanings indicated in claim 1,

or

b) a radical R¹ in a compound of the formula I is converted into another radical R¹ by cleaving an ether,

and/or a base or acid of the formula I is converted into one of its salts.

23. Medicaments comprising at least one compound according to claim 1 and/or pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios, and optionally excipients and/or adjuvants.

24. Use of compounds according to claim 1, and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios, for the preparation of a medicament for the treatment and/or prophylaxis of diseases in which the inhibition, regulation and/or modulation of kinase signal transduction plays a role.

25. Use according to claim 24, where the kinase is SGK.

26. Use of compounds according to claim 1, and pharmaceutically usable derivatives, solvates and stereoisomers thereof, including mixtures thereof in all ratios, for the preparation of a medicament for the treatment of diseases which are influenced by inhibition of SGKs by the compounds according to claim 1.

27. Use of compounds according to claim 1, and pharmaceutically usable derivatives, solvates and stereoisomers thereof, including mixtures thereof in all ratios, for the preparation of a medicament for the treatment or prevention of diabetes, obesity, metabolic syndrome (dyslipidaemia), systemic and pulmonary hypertonia, cardiovascular diseases and renal diseases, generally in fibroses and inflammatory processes of all types, cancer, tumour cells, tumour metastases, coagulopathies, neuronal excitability, glaucoma, cataracts, bacterial infections and in anti-infectious therapy, for increasing learning ability and attention, for the treatment and prophylaxis of cell ageing and stress, and for the treatment of tinitus.

28. Use according to claim 27, where diabetes is diabetes mellitus, diabetic nephropathy, diabetic neuropathy, diabetic angiopathy and microangiopathy.

29. Use according to claim 27, where cardiovascular diseases are cardiac fibroses after myocardial infarction, cardiac hypertrophy, cardiac insufficiency and arteriosclerosis.

30. Use according to claim 27, where renal diseases are glomerulosclerosis, nephrosclerosis, nephritis, nephropathy and electrolyte excretion disorder.

31. Use according to claim 27, where fibroses and inflammatory processes are liver cirrhosis, lung fibrosis, fibrosing pancreatitis, rheumatism and arthritis, Crohn'"'"'s disease, chronic bronchitis, radiation fibrosis, sclerormatitis, cystic fibrosis, scarring and Alzheimer'"'"'s disease.

32. Medicaments comprising at least one compound according to claim 1 and/or pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios, and at least one further medicament active ingredient.

33. Set (kit) consisting of separate packs of

(a) an effective amount of a compound according to claim 1 and/or pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios, and

(b) an effective amount of a further medicament active ingredient.

41. Use according to claim 10 of compounds according to claim 34, and pharmaceutically usable derivatives, solvates and stereoisomers thereof, including mixtures thereof in all ratios, for the preparation of a medicament for the treatment of diseases which are influenced by inhibition of SGK by the compounds according to claim 34.

43. A method of treating diabetes comprising administering a compound of claim 1.

34. Intermediate compounds of the formula I-I

35. Intermediate compounds according to claim 34 in which

D denotes O, NH or S,

W denotes CX or N,

T denotes CX, N or CR,

T′

denotes CX, N or CR,

with the proviso that one of the radicals T or T′

denotes CR and the other is not equal to CR,

R denotes COOH,

X denotes H,

R⁴ denotes R², —

[C(R³)₂]_nCON(R²)₂, COR² or S(O)_mA,

R² denotes H, A, —

[C(R³)₂]_n—

Ar′

, —

[C(R³)₂]_n—

OR³, —

[C(R³)₂]_n—

COOA or —

[C(R³)₂]_nN(R³)₂,

R³ denotes H or A,

A denotes unbranched or branched alkyl having 1-10 C atoms, and in addition 1-7H atoms may be replaced by F,

Ar′

denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by Hal and/or A,

Hal denotes F, Cl, Br or I,

m denotes 0, 1 or 2,

n denotes 0, 1, 2 or 3,

and/or pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

36. Intermediate compounds according to claim 35 in which

D denotes O, NH or S,

W denotes CX or N,

T denotes CX, N or CR,

T′

denotes CX, N or CR,

with the proviso that one of the radicals T or T′

denotes CR and the other is not equal to CR,

R denotes COOH,

X denotes H,

R⁴ denotes R² or —

(CH₂)_nCONHR²,

R² denotes H, A or —

(CH₂)_n—

Ar′

,

A denotes unbranched or branched alkyl having 1-10 C atoms, and in addition 1-7H atoms may be replaced by F,

Ar′

denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by Hal and/or A,

Hal denotes F, Cl, Br or I,

n denotes 0, 1, 2 or 3,

and/or pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

38. Medicaments comprising at least one compound according to claim 34 and/or pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios, and optionally excipients and/or adjuvants.

39. Use of compounds according to claim 34, and pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios, for the preparation of a medicament for the treatment and/or prophylaxis of diseases in which the inhibition, regulation and/or modulation of kinase signal transduction plays a role.

40. Use according to claim 39, where the kinase is SGK.

42. Use of compounds according to claim 34, and pharmaceutically usable derivatives, solvates and stereoisomers thereof, including mixtures thereof in all ratios, for the preparation of a medicament for the treatment or prevention of diabetes, obesity, metabolic syndrome (dyslipidaemia), systemic and pulmonary hypertonia, cardiovascular diseases and kidney diseases, generally in fibroses and inflammatory processes of all types, cancer, tumour cells, tumour metastases, coagulopathies, neuronal excitability, glaucoma, cataracts, bacterial infections and in anti-infectious therapy, for increasing learning ability and attention, and the for the treatment and prophylaxis of cell ageing and stress, and for the treatment of tinitus.

37. Intermediate compounds selected from the group

2-(3-amino-1H-indazol-5-yl)-3H-imidazole-4-carboxylic acid (“

58”

),

2-(3-amino-1H-indazol-5-yl)oxazole-4-carboxylic acid (“

59”

),

5-(3-amino-1H-indazol-5-yl)furan-2-carboxylic acid (“

60”

),

5-(3-amino-1-p-tolylcarbamoyl-1H-indazol-5-yl)furan-2-carboxylic acid (“

86”

),

5-(3-amino-1-benzyl-1H-indazol-5-yl)furan-2-carboxylic acid (“

87”

),

5-(3-amino-1-methyl-1H-indazol-5-yl)furan-2-carboxylic acid (“

88”

),

and/or pharmaceutically usable derivatives, salts, solvates and stereoisomers thereof, including mixtures thereof in all ratios.