Granted Patent B2

US 12,371,430 · App. 17/274,043 · Granted Jul 29, 2025

Inventors: Lars Burgdorf (Frankfurt am Main, DE); Christos Tsaklakidis (Heidelberg, DE)

Assignee: Merck Patent GmbH

C07D471/04C07D519/00

Abstract

Claims (387)

1. A compound of formula Ia* or Ib*

in which

R 1 denotes H, Het, Ar, (CH 2 ) n OH, 1-methylsulfonyl-cycloprop-1-yl, CONH 2 , CONHA, CONA 2 , Cyc, OA or CH(A)SO 2 A,

R 2 denotes H, A, (CH 2 ) n Ar, (CH 2 ) n Cyc or (CH 2 ) n Het,

R 3 denotes H or A,

Het denotes 1H-pyrrolo[2,3-b]pyridinyl, 1H-pyrrolo[2,3-c]pyridinyl, indolyl, benzimidazolyl, imidazolyl, 1,2,3,4-tetrahydroisoquinolyl, pyridyl, pyrimidinyl, triazolyl, pyrazolyl, quinolyl, isoquinolyl, quinazolinyl, furanyl, tetrahydrofuranyl, pyranyl, 3,6-dihydro-2H-pyranyl, tetrahydropyranyl, 3,6-dihydro-2H-thiopyranyl or hexahydro-thiopyranyl, each of which is unsubstituted or mono-, di- or trisubstituted by A, SOA, SO 2 A, Hal and/or =O,

Ar denotes phenyl, napthyl or biphenyl, each of which is unsubstituted or mono-, di- or trisubstituted by NH 2 , NHA, NA 2 , COOH, COOA, CONH 2 , CONHA, CONA 2 , NHCOA, CHO, COA, SO 3 H, SO 2 NH 2 , O(CH 2 ) p NH 2 , (CH 2 ) n Het 1 , O(CH 2 ) n Het 1 , (CH 2 ) n Ar 1 , O(CH 2 ) n Ar 1 , O(CH 2 ) p CONH 2 , O(CH 2 ) p NHCOA, Hal, SOA, S(═O, ═NH)A, SO 2 A, A, CN and/or (CH 2 ) n OH,

Ar 1 denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OH and/or OA,

Het 1 denotes a mono- or bicyclic aromatic, unsaturated or saturated heterocycle having 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by Hal, A, COOA, NH 2 , NHA and/or NA 2 ,

A denotes unbranched or branched alkyl having 1-6 C-atoms, in which 1-7H atoms may be replaced by OH, F, Cl and/or Br and/or in which one or two non-adjacent CH 2 groups may be replaced by O and/or NH groups,

Cyc denotes cyclic alkyl with 3, 4, 5, 6 or 7 C-atoms,

Hal denotes F, Cl, Br or I,

n denotes 0, 1, 2, 3 or 4, and

p denotes 1, 2, 3 or 4,

with the proviso that R 1 denotes Het and/or R 2 denotes (CH 2 ) n Het,

or a pharmaceutically acceptable salt, tautomer, stereoisomer or racemic mixture thereof, or a non-racemic mixture thereof.

2. A compound of formula Ia* or Ib*

in which

R 1 denotes H, Het, Ar, (CH 2 ) n OH, 1-methylsulfonyl-cycloprop-1-yl, CONH 2 , CONHA, CONA 2 , Cyc, OA or CH(A)SO 2 A,

R 2 denotes H, A, (CH 2 ) n Ar, (CH 2 ) n Cyc or (CH 2 ) n Het,

R 3 denotes H or A,

Het denotes a mono- or bicyclic aromatic, unsaturated or saturated heterocycle having 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by NH 2 , NHA, NA 2 , COOH, COOA, CONH 2 , CONHA, CONA 2 , CONHAr, CN, OH, (CH 2 ) n Ar 1 , O(CH 2 ) n Ar 1 , A, SOA, SO 2 A, Hal, ═NH and/or ═O,

Ar denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by SOA, S(═O, ═NH)A, SO 2 A, A, CN and/or (CH 2 ) n OH,

Ar 1 denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OH and/or OA,

Het 1 denotes a mono- or bicyclic aromatic, unsaturated or saturated heterocycle having 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by Hal, A, COOA, NH 2 , NHA and/or NA 2 ,

A denotes unbranched or branched alkyl having 1-6 C-atoms, in which 1-7H atoms may be replaced by OH, F, Cl and/or Br and/or in which one or two non-adjacent CH 2 groups may be replaced by O and/or NH groups,

Cyc denotes cyclic alkyl with 3, 4, 5, 6 or 7 C-atoms,

Hal denotes F, Cl, Br or I,

n denotes 0, 1, 2, 3 or 4,

p denotes 1, 2, 3 or 4,

with the proviso that R 1 denotes Ar and/or R 2 denotes (CH 2 ) n Ar,

or a pharmaceutically acceptable salt, tautomer, stereoisomer or racemic mixture thereof, or a non-racemic mixture thereof.

3. The compound according to claim 1 , in which

R 1 denotes H, Het, Ar, (CH 2 ) n OH, 1-methylsulfonyl-cycloprop-1-yl, CONH 2 , CONHA, CONA 2 , Cyc, OA or CH(A)SO 2 A,

R 2 denotes H, A, (CH 2 ) n Ar, (CH 2 ) n Cyc or (CH 2 ) n Het,

R 3 denotes H or A,

Ar denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by SOA, S(═O, ═NH)A, SO 2 A, A, CN and/or (CH 2 ) n OH,

A denotes unbranched or branched alkyl having 1-6 C-atoms, in which 1-7H atoms may be replaced by OH, F, C and/or Br and/or in which one or two non-adjacent CH 2 groups may be replaced by O and/or NH groups,

Cyc denotes cyclic alkyl with 3, 4, 5, 6 or 7 C-atoms, Hal denotes F, Cl, Br or I,

n denotes 0, 1, 2, 3 or 4,

with the proviso that R 1 denotes Het and/or R 2 denotes (CH 2 ) n Het,

or a pharmaceutically acceptable salt, tautomer, stereoisomer or racemic mixture thereof, or a non-racemic mixture thereof.

4. A compound, which is one of the following compounds

No.

Structure

 (1)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-7-(6-methyl-pyridin-

3-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

 (2)

5-((R)-3-Methyl-morpholin-4-yl)-7-(6-methyl-pyridin-3-yl)-3-

(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

 (3)

(3R)-3-Methyl-4-[3-(3-methyl-1H-pyrazol-5-yl)-7-(6-

methylpyridin-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine

 (4)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-7-(2-methyl-pyridin-

3-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

 (5)

7-(4-Methanesulfinyl-phenyl)-1-methyl-5-((R)-3-methyl-

morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

 (6)

Imino(methyl)(4-{1-methyl-5-[(3R)-3-methylmorpholin-4-yl]-3-

(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-7-yl}phenyl)-

lambda6-sulfanone

 (7)

7-(4-Methanesulfonyl-phenyl)-1-methyl-5-((R)-3-methyl-

morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

 (8)

7-(6-Methanesulfinyl-2-methyl-pyridin-3-yl)-1-methyl-5-((R)-3-

methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-

pyrazolo[4,3-b]pyridine

 (9)

(3R)-4-(7-{6-[(S)-Methanesulfinyl]-2-methylpyridin-3-yl}-1-

methyl-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-3-

methylmorpholine

(10)

(3R)-4-(7-{6-[(R)-Methanesulfinyl]-2-methylpyridin-3-yl}-1-

methyl-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-3-

methylmorpholine

(11)

(3R)-4-[7-(6-Methanesulfonyl-2-methylpyridin-3-yl)-1-methyl-3-

(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-

methylmorpholine

(12)

7-(6-Methanesulfonyl-2-methyl-pyridin-3-yl)-5-((R)-3-methyl-

morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

(13)

(3R)-4-[7-(6-Methanesulfonyl-2-methylpyridin-3-yl)-3-(3-

methyl-1H-pyrazol-5-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-

methylmorpholine

(14)

2-Methyl-5-((R)-3-methyl-morpholin-4-yl)-7-(6-methyl-pyridin-

3-yl)-3-(1H-pyrazol-3-yl)-2H-pyrazolo[4,3-b]pyridine

(15)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-

7-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazolo[4,3-b]pyridine

(16)

2-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-

7-(1H-pyrrolo[2,3-b]pyridin-4-yl)-2H-pyrazolo[4,3-b]pyridine

(17)

7-(6-Methanesulfonyl-4-methyl-pyridin-3-yl)-1-methyl-5-((R)-3-

methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-

b]pyridine

(18)

7-(1-Isopropyl-1H-pyrazol-4-yl)-1-methyl-5-((R)-3-methyl-

morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

(19)

7-(1,3-Dimethyl-1H-pyrazol-4-yl)-1-methyl-5-((R)-3-methyl-

morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

(20)

7-(3-Fluoro-pyridin-4-yl)-1-methyl-5-((R)-3-methyl-morpholin-4-

yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

(21)

7-(6-Methanesulfonyl-4-methyl-pyridin-3-yl)-2-methyl-5-((R)-3-

methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-2H-

pyrazolo[4,3-b]pyridine

(22)

7-(2,4-Dimethyl-pyridin-3-yl)-1-methyl-5-((R)-3-methyl-

morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

(23)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-7-(3-methyl-pyridin-

4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

(24)

[1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-

1H-pyrazolo[4,3-b]pyridin-7-yl]-methanol

(25)

2-[1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-

yl)-1H-pyrazolo[4,3-b]pyridin-7-yl]-propan-2-ol

(26)

7-(1-Methanesulfonyl-cyclopropyl)-1-methyl-5-((R)-3-methyl-

morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

(27)

5-((R)-3-Methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-

pyrazolo[4,3-b]pyridine-7-carboxylic acid dimethylamide

(28)

5-((R)-3-Methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-

pyrazolo[4,3-b]pyridine-7-carboxylic acid methylamide

(29)

5-((R)-3-Methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-

pyrazolo[4,3-b]pyridine-7-carboxylic acid amide

(30)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-

1H-pyrazolo[4,3-b]pyridine-7-carboxylic acid dimethylamide

(31)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-

1H-pyrazolo[4,3-b]pyridine-7-carboxylic acid methylamide

(32)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-

1H-pyrazolo[4,3-b]pyridine-7-carboxylic acid amide

(33)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-7-(6-methyl-pyridin-

2-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

(34)

7-[1-(2-Fluoro-ethyl)-1H-pyrazol-3-yl]-1-methyl-5-((R)-3-

methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-

pyrazolo[4,3-b]pyridine

(35)

(3R)-3-Methyl-4-[7-(2-methylphenyl)-3-(1H-pyrazol-3-yl)-1H-

pyrazolo[4,3-b]pyridin-5-yl]morpholine

(36)

7-[2-(2-Fluoro-ethyl)-2H-pyrazol-3-yl]-1-methyl-5-((R)-3-

methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-

pyrazolo[4,3-b]pyridine

(37)

2-{3-[1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-

3-yl)-1H-pyrazolo[4,3-b]pyridin-7-yl]-pyrazol-1-yl}-ethanol

(38)

(3R)-3-Methyl-4-[3-(1H-pyrazol-3-yl)-7-(pyridin-2-yl)-1H-

pyrazolo[4,3-b]pyridin-5-yl]morpholine

(39)

(3R)-3-Methyl-4-[7-(3-methylpyridin-2-yl)-3-(1H-pyrazol-3-yl)-

1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine

(40)

(3R)-3-Methyl-4-[1-methyl-3-(1H-pyrazol-5-yl)-1H-

pyrazolo[4,3-b]pyridin-5-yl]morpholine

(41)

(3R)-4-[7-(4-Methanesulfonylphenyl)-1-(propan-2-yl)-3-(1H-

pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-

methylmorpholine

(42)

1-Methyl-7-(3-methyl-3H-imidazol-4-yl)-5-((R)-3-methyl-

morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

(43)

7-Cyclopropyl-1-methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(2H-

pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

(44)

7-lsopropoxy-1-methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(2H-

pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

(45)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(2H-pyrazol-3-yl)-

1H-pyrazolo[4,3-b]pyridin-7-ol

(46)

1-(4-Methanesulfonyl-phenyl)-5-((R)-3-methyl-morpholin-4-yl)-

3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

(47)

1-(3-Methanesulfonyl-phenyl)-5-((R)-3-methyl-morpholin-4-yl)-

3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine

(48)

3-{1-Methyl-5-[(3R)-3-methylmorpholin-4-yl]-3-(1H-pyrazol-3-

yl)-1H-pyrazolo[4,3-b]pyridin-7-yl}benzonitrile

(49)

(3R)-3-Methyl-4-[1-methyl-7-(2-methylphenyl)-3-(1H-pyrazol-5-

yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine

(50)

(3R)-4-[7-(4-Methanesulfonyl-2-methylphenyl)-1-methyl-3-(1H-

pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-

methylmorpholine

(51)

(3R)-4-{7-[4-(Methoxymethyl)phenyl]-1-methyl-3-(1H-pyrazol-

3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl}-3-methylmorpholine

(52)

(4-{1-Methyl-5-[(3R)-3-methylmorpholin-4-yl]-3-(1H-pyrazol-3-

yl)-1H-pyrazolo[4,3-b]pyridin-7-yl}phenyl)methanol

(53)

3-[5-((3R)-3-Methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-

pyrazolo[4,3-b]pyridin-1-yl]-benzonitrile

(54)

(3R)-4-[7-(3,6-Dihydro-2H-pyran-4-yl)-1-methyl-3-(1H-pyrazol-

3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-methylmorpholine

(55)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(2H-pyrazol-3-yl)-

7-(tetrahydro-pyran-4-yl)-1H-pyrazolo[4,3-b]pyridine

(57)

(3R)-4-{1-[(3-Methanesulfonylphenyl)methyl]-3-(1H-pyrazol-3-

yl)-1H-pyrazolo[4,3-b]pyridin-5-yl}-3-methylmorpholine

(58)

(3R)-3-Methyl-4-[1-methyl-3-(1H-pyrazol-3-yl)-7-(pyridin-2-yl)-

1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine

(59)

(3R)-4-[1-Benzyl-3-(1H-pyrazol-5-yl)-1H-

pyrazolo[4,3-b]pyridin-5-yl]-3-methylmorpholine

(60)

4-[5-[(3R)-3-Methylmorpholin-4-yl]-3-(1H-pyrazol-3-yl)-1H-

pyrazolo[4,3-b]pyridin-1-yl]benzonitrile

(61)

(3R)-3-Methyl-4-[1-methyl-7-(1-methyl-1H-pyrazol-5-yl)-3-(1H-

pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine

(62)

(3R)-3-Methyl-4-[1-methyl-7-(3-methylpyridin-2-yl)-3-(1H-

pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine

(63)

(3R)-4-[1-(Cyclopropylmethyl)-3-(1H-pyrazol-3-yl)-1H-

pyrazolo[4,3-b]pyridin-5-yl]-3-methylmorpholine

(64)

5-((R)-3-Methyl-morpholin-4-yl)-1-phenethyl-3-(1H-pyrazol-3-

yl)-1H-pyrazolo[4,3-b]pyridine

(65)

(3R)-3-Methyl-4-[1-methyl-3-(1H-pyrazol-3-yl)-7-[6-(trifluoro-

methyl)pyridin-3-yl]-1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine

(66)

(3R)-3-Methyl-4-[1-methyl-3-(1H-pyrazol-3-yl)-7-[2-(trifluoro-

methyl)pyridin-3-yl]-1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine

(67)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(2H-pyrazol-3-yl)-

7-(tetrahydro-pyran-3-yl)-1H-pyrazolo[4,3-b]pyridine

(68)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(2H-pyrazol-3-yl)-

7-(R)-tetrahydro-pyran-3-yl-1H-pyrazolo[4,3-b]pyridine

(69)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(2H-pyrazol-3-yl)-

7-(S)-tetrahydro-pyran-3-yl-1H-pyrazolo[4,3-b]pyridine

(70)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(2H-pyrazol-3-yl)-

7-(tetrahydro-furan-3-yl)-1H-pyrazolo[4,3-b]pyridine

(71)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(2H-pyrazol-3-yl)-

7-(S)-tetrahydro-furan-3-yl-1H-pyrazolo[4,3-b]pyridine

(72)

1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(2H-pyrazol-3-yl)-

7-(R)-tetrahydro-furan-3-yl-1H-pyrazolo[4,3-b]pyridine

(73)

(3R)-3-Methyl-4-[1-(propan-2-yl)-3-(1H-pyrazol-3-yl)-1H-

pyrazolo[4,3-b]pyridin-5-yl]morpholine

(74)

(3R)-4-[7-(6-Methanesulfonyl-2-methylpyridin-3-yl)-1-methyl-3-

[3-(trifluoromethyl)-1H-pyrazol-5-yl]-1H-pyrazolo[4,3-b]pyridin-

5-yl]-3-methylmorpholine

(75)

(3R)-4-[7-(5-Methanesulfonyl-2-methylphenyl)-1-methyl-3-(1H-

pyrazol-5-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-

methylmorpholine

(76)

(3R)-4-[7-(3-Methanesulfonylphenyl)-1-methyl-3-(1H-pyrazol-

5-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-methylmorpholine

(77)

(3R)-3-Methyl-4-[3-(1H-pyrazol-3-yl)-1-[2-(pyridin-4-yl)ethyl]-

1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine

(78)

(3R)-4-{7-[1-(Difluoromethyl)-1H-pyrazol-5-yl]-1-methyl-3-(1H-

pyrazol-5-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl}-3-

methylmorpholine

(79)

(3R)-4-[7-(3,6-Dihydro-2H-thiopyran-4-yl)-1-methyl-3-(1H-

pyrazol-5-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-

methylmorpholine

(80)

4-[1-Methyl-5-[(3R)-3-methylmorpholin-4-yl]-3-(1H-pyrazol-5-

yl)-1H-pyrazolo[4,3-b]pyridin-7-yl]-3,6-dihydro-2H-1lamdba4-

thiopyran-1-one

(81)

4-[1-Methyl-5-[(3R)-3-methylmorpholin-4-yl]-3-(1H-pyrazol-5-

yl)-1H-pyrazolo[4,3-b]pyridin-7-yl]-3,6-dihydro-2H-1lamdba6-

thiopyran-1,1-dione

(82)

4-[1-Methyl-5-[(3R)-3-methylmorpholin-4-yl]-3-(1H-pyrazol-5-

yl)-1H-pyrazolo[4,3-b]pyridin-7-yl]-2H-1lambda6-thiopyran-1,1-

dione

(83)

(3R)-3-Methyl-4-[3-(1H-pyrazol-3-yl)-1-[(pyridin-3-yl)methyl]-

1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine

(84)

(3R)-4-[7-(1,5-Dimethyl-1H-1,2,3-triazol-4-yl)-1-methyl-3-(1H-

pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-

methylmorpholine

(85)

2-Methyl-1-{5-[(3R)-3-methylmorpholin-4-yl]-3-(1H-pyrazol-3-

yl)-1H-pyrazolo[4,3-b]pyridin-1-yl}propan-2-ol

(86)

2-Methyl-2-{5-[(3R)-3-methylmorpholin-4-yl]-3-(1H-pyrazol-3-

yl)-1H-pyrazolo[4,3-b]pyridin-1-yl}propan-1-ol

(87)

(3R)-3-Methyl-4-[1-methyl-7-(4-methylpyrimidin-5-yl)-3-(1H-

pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine

(88)

(3R)-3-Methyl-4-[3-(1H-pyrazol-3-yl)-1-[(pyridin-2-yl)methyl]-

1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine

(89)

(3R)-4-[7-(1-Methanesulfonylethyl)-1-methyl-3-(1H-pyrazol-3-

yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-methylmorpholine

or a pharmaceutically acceptable salt, tautomer, stereoisomer or racemic mixture thereof, or a non-racemic mixture thereof.

5. A pharmaceutical composition comprising at least one compound of formula Ia* or Ib*according to claim 1 and/or a pharmaceutically acceptable salt, tautomer, stereoisomer or racemic mixture thereof, or a non-racemic mixture thereof, and a pharmaceutically acceptable carrier, excipient or vehicle.

6. A method for the treatment of cancer selected from the group consisting of lung cancer, breast cancer, ovarian cancer, colon cancer, cancer of the blood, cancer of the bone and blood-borne tumors, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to claim 5 .

7. The pharmaceutical composition according to claim 5 , further comprising an additional pharmaceutically active ingredient.

8. A kit, comprising separate packs of

(a) an effective amount of the compound of formula Ia* or Ib* according to claim 1 and/or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer or racemate thereof, or a mixture thereof,

and

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

9. A method for the treatment of cancer selected from the group consisting of lung cancer, breast cancer, ovarian cancer and colon cancer, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to claim 5 .

10. A pharmaceutical composition comprising at least one compound of the formula Ia* or Ib*according to claim 2 and/or a pharmaceutically acceptable salt, tautomer, stereoisomer or racemic mixture thereof, or a non-racemic mixture thereof, and a pharmaceutically acceptable carrier, excipient or vehicle.

11. A method for the treatment of cancer selected from the group consisting of lung cancer, breast cancer, ovarian cancer, colon cancer, cancer of the blood, cancer of the bone and blood-borne tumors, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to claim 10 .

12. A pharmaceutical composition comprising at least one compound of claim 4 and/or a pharmaceutically acceptable salt, tautomer, stereoisomer or racemic mixture thereof, or a non-racemic mixture thereof, and a pharmaceutically acceptable carrier, excipient or vehicle.

13. A method for the treatment of cancer selected from the group consisting of lung cancer, breast cancer, ovarian cancer, colon cancer, cancer of the blood, cancer of the bone and blood-borne tumors, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to claim 12 .

14. The compound according to claim 2 , in which

R 1 denotes H, Het, Ar, (CH 2 ) n OH, 1-methylsulfonyl-cycloprop-1-yl, CONH 2 , CONHA, CONA 2 , Cyc, OA or CH(A)SO 2 A,

R 2 denotes H, A, (CH 2 ) n Ar, (CH 2 ) n Cyc or (CH 2 ) n Het,

R 3 denotes H or A,

Het denotes 1H-pyrrolo[2,3-b]pyridinyl, 1H-pyrrolo[2,3-c]pyridinyl, indolyl, benzimidazolyl, imidazolyl, 1,2,3,4-tetrahydroisoquinolyl, pyridyl, pyrimidinyl, triazolyl, pyrazolyl, quinolyl, isoquinolyl, quinazolinyl, furanyl, tetrahydrofuranyl, pyranyl, 3,6-dihydro-2H-pyranyl, tetrahydropyranyl, 3,6-dihydro-2H-thiopyranyl or hexahydro-thiopyranyl, each of which is unsubstituted or mono-, di- or trisubstituted by A, SOA, SO 2 A, Hal and/or ═O,

A denotes unbranched or branched alkyl having 1-6 C-atoms, in which 1-7H atoms may be replaced by OH, F, Cl and/or Br and/or in which one or two non-adjacent CH 2 groups may be replaced by O and/or NH groups,

Cyc denotes cyclic alkyl with 3, 4, 5, 6 or 7 C-atoms,

Hal denotes F, Cl, Br or I,

n denotes 0, 1, 2, 3 or 4,

with the proviso that R 1 denotes Ar and/or R 2 denotes (CH 2 ) n Ar,

or a pharmaceutically acceptable salt, tautomer, stereoisomer or racemic mixture thereof, or a non-racemic mixture thereof.

15. The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 2 a pharmaceutically acceptable salt thereof.

17. The compound according to claim 4 a pharmaceutically acceptable salt thereof.

18. A compound of formula Ia* or Ib* according to claim 1 , which are respectively of formula Ia or Ib

in which

R 1 denotes H, Het, Ar, (CH 2 ) n OH, 1-methylsulfonyl-cycloprop-1-yl, CONH 2 , CONHA, CONA 2 , Cyc, OA or CH(A)SO 2 A,

R 2 denotes H, A, (CH 2 ) n Ar, (CH 2 ) n Cyc or (CH 2 ) n Het,

R 3 denotes H or A,

Het denotes 1H-pyrrolo[2,3-b]pyridinyl, 1H-pyrrolo[2,3-c]pyridinyl, indolyl, benzimidazolyl, imidazolyl, 1,2,3,4-tetrahydroisoquinolyl, pyridyl, pyrimidinyl, triazolyl, pyrazolyl, quinolyl, isoquinolyl, quinazolinyl, furanyl, tetrahydrofuranyl, pyranyl, 3,6-dihydro-2H-pyranyl, tetrahydropyranyl, 3,6-dihydro-2H-thiopyranyl or hexahydro-thiopyranyl, each of which is unsubstituted or mono-, di- or trisubstituted by A, SOA, SO 2 A, Hal and/or ═O,

Ar denotes phenyl, napthyl or biphenyl, each of which is unsubstituted or mono-, di- or trisubstituted by NH 2 , NHA, NA 2 , COOH, COOA, CONH 2 , CONHA, CONA 2 , NHCOA, CHO, COA, SO 3 H, SO 2 NH 2 , O(CH 2 ) p NH 2 , (CH 2 ) n Het 1 , O(CH 2 ) n Het 1 , (CH 2 ) n Ar 1 , O(CH 2 ) n Ar 1 , O(CH 2 ) p CONH 2 , O(CH 2 ) p NHCOA, Hal, SOA, S(═O, ═NH)A, SO 2 A, A, CN and/or (CH 2 ) n OH,

Ar 1 denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OH and/or OA,

Het 1 denotes a mono- or bicyclic aromatic, unsaturated or saturated heterocycle having 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by Hal, A, COOA, NH 2 , NHA and/or NA 2 ,

A denotes unbranched or branched alkyl having 1-6 C-atoms, in which 1-7H atoms may be replaced by OH, F, Cl and/or Br and/or in which one or two non-adjacent CH 2 groups may be replaced by O and/or NH groups,

Cyc denotes cyclic alkyl with 3, 4, 5, 6 or 7 C-atoms,

Hal denotes F, Cl, Br or I,

n denotes 0, 1, 2, 3 or 4, and

p denotes 1, 2, 3 or 4,

with the proviso that R 1 denotes Het and/or R 2 denotes (CH 2 ) n Het, or a pharmaceutically acceptable salt thereof.

19. A compound of formula Ia* or Ib* according to claim 2 , which are respectively of formula Ia or Ib

in which

R 1 denotes H, Het, Ar, (CH 2 ) n OH, 1-methylsulfonyl-cycloprop-1-yl, CONH 2 , CONHA, CONA 2 , Cyc, OA or CH(A)SO 2 A,

R 2 denotes H, A, (CH 2 ) n Ar, (CH 2 ) n Cyc or (CH 2 ) n Het,

R 3 denotes H or A,

Het denotes a mono- or bicyclic aromatic, unsaturated or saturated heterocycle having 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by NH 2 , NHA, NA 2 , COOH, COOA, CONH 2 , CONHA, CONA 2 , CONHAr, CN, OH, (CH 2 ) n Ar 1 , O(CH 2 ) n Ar 1 , A, SOA, SO 2 A, Hal, ═NH and/or ═O,

Ar denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by SOA, S(═O, ═NH)A, SO 2 A, A, CN and/or (CH 2 ) n OH,

Ar 1 denotes phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OH and/or OA,

Het 1 denotes a mono- or bicyclic aromatic, unsaturated or saturated heterocycle having 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by Hal, A, COOA, NH 2 , NHA and/or NA 2 ,

A denotes unbranched or branched alkyl having 1-6 C-atoms, in which 1-7H atoms may be replaced by OH, F, Cl and/or Br and/or in which one or two non-adjacent CH 2 groups may be replaced by 0 and/or NH groups,

Cyc denotes cyclic alkyl with 3, 4, 5, 6 or 7 C-atoms,

Hal denotes F, Cl, Br or I,

n denotes 0, 1, 2, 3 or 4,

p denotes 1, 2, 3 or 4,

with the proviso that R 1 denotes Ar and/or R 2 denotes (CH 2 ) n Ar, or a pharmaceutically acceptable salt thereof.

20. A method for the treatment of cancer selected from the group consisting of lung cancer, breast cancer, ovarian cancer, colon cancer, cancer of the blood, cancer of the bone and blood-borne tumors, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition comprising at least one compound of claim 18 and/or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, excipient or vehicle.

Assignments (3)

Priority Claims (1)

Continuity (1)

References Cited (13)