IP Library › Granted Patent US 11,453,647
Granted Patent B2
US 11,453,647 · App. 16/640,490 · Granted Sep 27, 2022

Benzimidazole derivatives as adenosine receptor antagonists

Inventors: Eva-Maria Tanzer (Darmstadt, DE); Kai Schiemann (Seeheim-Jugenheim, DE); Markus Klein (Darmstadt, DE)
Assignee: Merck Patent GmbH
C07D235/30A61P35/04C07D401/12C07D403/04C07D403/10C07D403/12C07D405/04C07D405/14C07D413/04C07D413/14C07D417/14C07D471/04C07D471/10C07D491/048C07D491/052C07D491/107C07D491/113C07D498/10A61K45/06
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Quick Facts
Patent No.
US 11,453,647
App. No.
16/640,490
Granted
Sep 27, 2022
Kind
B2
Abstract

The invention relates to benzimidazole derivatives of the general formula I, and the use of the compounds of the present invention for the treatment and/or prevention of hyperproliferative or infectious diseases and disorders in mammals, especially humans, and pharmaceutical compositions containing such compound.

Claims (1011)

1. A compound of formula I,

wherein

Q, Y are CH,

R 1 is Br or one of the following structures:

which is unsubstituted or mono-, di- or trisubstituted with R 4 ,

R 2 is one of the following structures:

which is unsubstituted or mono-, di- or trisubstituted with R 5

R 3 is OCH 3 ,

R 4 is H, R 5 , ═S, ═NR 5 , ═O, OH, COOH, Hal, NH 2 , SO 2 CH 3 , SO 2 NH 2 , CN, CONH 2 , NHCOCH 3 , NHCONH 2 , NO 2 , or linear or branched alkyl having 1-10 C atoms which is unsubstituted or mono-, di- or trisubstituted by R 5 and in which 1-4 C atoms may be replaced, independently of one another, by O, S, SO, SO 2 , NH, NCH 3 , —OCO—, —NHCONH—, —NHCO—, —COO—, —CONH—, —NCH 3 CO—, —CONCH 3 —, —C≡C— groups and/or —CH═CH— groups, and/or, in addition, 1-10 H atoms may be replaced by F and/or CI, or mono-or bicyclic cyclic alkyl having 3-7 C atoms which is unsubstituted or mono-, di- or trisubstituted by R 5 and in which 1-4 C atoms may be replaced, independently of one another, by O, S, SO, SO 2 , NH, NCH 3 , —OCO—, —NHCONH—, —NHCO—, —COO—, —CONH—, —NCH 3 CO—, —CONCH 3 —, —C≡C— groups and/or by —CH═CH— groups and/or, in addition, 1-10 H atoms may be replaced by F and/or CI, or mono- or bicyclic heteroaryl, heterocyclyl, aryl or cyclic alkylaryl, containing 3 to 14 carbon atoms and 0-4 heteroatoms, independently selected from N, O and S, which is unsubstituted or mono-, di- or trisubstituted by R 5 ,

R 5 , R 6 are independently of one another selected from the group consisting of H, ═S, ═NH, ═O, OH, COOH, Hal, NH 2 , SO 2 CH 3 , SO 2 NH 2 , CN, CONH 2 , NHCOCH 3 , NHCONH 2 , NO 2 and linear or branched alkyl having 1-10 C atoms in which 1-4 C atoms may be replaced, independently of one another, by O, S, SO, SO 2 , NH, NCH 3 , —OCO—, —NHCONH—, —NHCO—, —COO—, —CONH—, —NCH 3 CO—, —CONCH 3 —, —C≡C— groups and/or —CH═CH— groups, and/or, in addition, 1-10 H atoms may be replaced by F and/or CI,

Hal is F, C, Br, or I,

or physiologically acceptable salts, solvates, prodrugs or stereoisomers thereof, including mixtures thereof in all ratios.

2. The compound according to claim 1 , wherein R 1 is

3. Compound according to claim 1 , wherein R 1 is Br or one of the following structures:

which is unsubstituted or mono-, di- or trisubstituted with R 5

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

4. A compound selected from the group consisting of:

No.

IUPAC-Name

2

4-Fluoro-N-(7-methoxy-4-phenyl-1H-benzoimidazol-2-yl)-

benzamide,

3

2-Bromo-N-(7-methoxy-4-phenyl-1H-benzoimidazol-2-yl)-

isonicotinamide,

4

2-Bromo-N-(4-bromo-7-methoxy-1H-benzoimidazol-2-yl)-

isonicotinamide,

5

6-Bromo-N-(7-methoxy-4-phenyl-1H-benzoimidazol-2-yl)-

nicotinamide,

6

6-Bromo-N-(4-bromo-7-methoxy-1H-benzoimidazol-2-yl)-

nicotinamide,

7

N-(7-Methoxy-4-phenyl-1H-benzoimidazol-2-yl)-2-morpholin-4-yl-

isonicotinamide,

8

N-(7-Methoxy-4-phenyl-1H-benzoimidazol-2-yl)-6-morpholin-4-yl-

nicotinamide,

9

N′-(7-Methoxy-4-phenyl-1H-benzoimidazol-2-yl)-N,N-dimethyl-

formamidine,

10

4-Chloromethyl-N-(7-methoxy-4-phenyl-1H-benzoimidazol-2-yl)-

benzamide,

11

4-Ethylaminomethyl-N-(7-methoxy-4-phenyl-1H-benzoimidazol-2-

yl)-benzamide,

12

4-Hydroxy-4-methyl-piperidine-1-carboxylic acid (7-methoxy-4-

phenyl-1H-benzoimidazol-2-yl)-amide,

13

4-Aminomethyl-N-(7-methoxy-4-phenyl-1H-benzoimidazol-2-yl)-

benzamide,

15

4-Imidazol-1-ylmethyl-N-(7-methoxy-4-phenyl-1H-benzoimidazol-2-

yl)-benzamide,

16

4-Hydroxy-4-methyl-piperidine-1-carboxylic acid (4-cyclohexyl-7-

methoxy-1H-benzoimidazol-2-yl)-amide,

17

N-(4-Cyclohexyl-7-methoxy-1H-benzoimidazol-2-yl)-2-morpholin-4-

yl-isonicotinamide,

21

4-hydroxy-N-(7-methoxy-4-morpholino-1H-benzimidazol-2-yl)-4-

methyl-piperidine-1-carboxamide,

22

4-Hydroxy-4-methyl-piperidine-1-carboxylic acid [7-methoxy-4-(1-

methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

23

N-(7-Methoxy-4-morpholin-4-yl-1H-benzoimidazol-2-yl)-2-

morpholin-4-yl-isonicotinamide,

24

4-Hydroxy-4-methyl-piperidine-1-carboxylic acid [7-methoxy-4-

(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

26

N-[7-Methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-

2-morpholin-4-yl-isonicotinamide,

28

4-Methyl-piperidine-1-carboxylic acid (7-methoxy-4-phenyl-1H-

benzoimidazol-2-yl)-amide,

29

N-[7-Methoxy-4-(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-6-

morpholin-4-yl-nicotinamide,

30

2-(3-Hydroxy-3-methyl-pyrrolidin-1-yl)-N-[7-methoxy-4-(1-methyl-

1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-isonicotinamide,

31

3-Hydroxy-3-methyl-pyrrolidine-1-carboxylic acid [7-methoxy-4-(1-

methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

32

4-Hydroxy-4-trifluoromethyl-piperidine-1-carboxylic acid [7-

methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-

amide,

33

2-Oxa-7-aza-spiro[3.5]nonane-7-carboxylic acid [7-methoxy-4-(1-

methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

34

4-Difluoromethyl-4-hydroxy-piperidine-1-carboxylic acid [7-

methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-

amide,

35

4-Hydroxymethyl-4-methyl-piperidine-1-carboxylic acid [7-methoxy-

4-(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

36

4-Fluoromethyl-4-hydroxy-piperidine-1-carboxylic acid [7-methoxy-

4-(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

37

4-Methoxy-piperidine-1-carboxylic acid [7-methoxy-4-(1-methyl-1H-

pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

38

3-Oxa-9-aza-spiro[5.5]undecane-9-carboxylic acid [7-methoxy-4-

(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

39

4-Methyl-piperidine-1-carboxylic acid [7-methoxy-4-(1-methyl-1H-

pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

40

4-Hydroxy-piperidine-1-carboxylic acid [7-methoxy-4-(1-methyl-1H-

pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

41

4-Benzyl-4-hydroxy-piperidine-1-carboxylic acid [7-methoxy-4-(1-

methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

42

N-[4-methoxy-7-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-

c]pyridin-2-yl]-2-(morpholin-4-yl)pyridine-4-carboxamide,

43

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-2-oxa-6-azaspiro[3.4]octane-6-carboxamide,

44

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxamide,

45

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-1,4-dioxa-8-azaspiro[4.5]decane-8-carboxamide,

46

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]morpholine-4-carboxamide,

47

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-3-oxo-2,8-diazaspiro[4.5]decane-8-carboxamide,

48

4-[(dimethylamino)methyl]-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-

yl)-1H-1,3-benzodiazol-2-yl]benzamide,

49

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-4-(methoxymethyl)benzamide,

50

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-8-carboxamide,

51

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-2-oxo-1,8-diazaspiro[4.5]decane-8-carboxamide,

52

4-(2-hydroxyethyl)-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-

1,3-benzodiazol-2-yl]-1,2,3,6-tetrahydropyridine-1-carboxamide,

53

3-butyl-4-hydroxy-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-

1,3-benzodiazol-2-yl]piperidine-1-carboxamide,

54

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-4-phenoxypiperidine-1-carboxamide,

55

4-hydroxy-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]-4-(pyridin-3-yl)piperidine-1-carboxamide,

56

4-hydroxy-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]-3-(2-methylpropyl)piperidine-1-carboxamide,

57

N-[4-(2,6-dimethylpyridin-4-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]-2-(morpholin-4-yl)pyridine-4-carboxamide,

58

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-4-oxopiperidine-1-carboxamide,

60

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxamide,

62

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-1-methyl-5-oxo-1,4,9-triazaspiro[5.5]undecane-9-carboxamide,

63

4-fluoro-N-[7-methoxy-4-(morpholin-4-yl)-1H-1,3-benzodiazol-2-

yl]benzamide,

64

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-6-oxaspiro[2.5]octane-1-carboxamide,

65

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-5-{3H-[1,2,3]triazolo[4,5-b]pyridin-3-yloxy}pyrazine-2-

carboxamide,

66

(chloromethyl)({2-[(1-{[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-

1,3-benzodiazol-2-yl]carbamoyl}-4-methylpiperidin-4-

yl)oxy]ethyl})dimethylazanium hydrochloride,

67

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-7-oxa-2-azaspiro[4.5]decane-2-carboxamide,

68

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-8-oxa-2-azaspiro[4.5]decane-2-carboxamide,

69

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-2-oxa-7-azaspiro[4.4]nonane-7-carboxamide,

70

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-3-oxabicyclo[3.1.0]hexane-6-carboxamide,

71

4-[(1H-imidazol-1-yl)methyl]-N-[7-methoxy-4-(1-methyl-1H-pyrazol-

4-yl)-1H-1,3-benzodiazol-2-yl]benzamide,

72

(1S,2S)-2-bromo-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-

1,3-benzodiazol-2-yl]cyclopropane-1-carboxamide,

73

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-5-(2-methoxyethoxy)pyrazine-2-carboxamide,

74

4-hydroxy-N-[7-methoxy-4-(pyridin-4-yl)-1H-1,3-benzodiazol-2-yl]-

4-methylpiperidine-1-carboxamide,

75

4-benzyl-4-hydroxy-N-[7-methoxy-4-(morpholin-4-yl)-1H-1,3-

benzodiazol-2-yl]piperidine-1-carboxamide,

76

4-[(1H-imidazol-1-yl)methyl]-N-[7-methoxy-4-(morpholin-4-yl)-1H-

1,3-benzodiazol-2-yl]benzamide,

77

N-[7-methoxy-4-(morpholin-4-yl)-1H-1,3-benzodiazol-2-yl]-1-

benzofuran-5-carboxamide,

78

4-hydroxy-N-{7-methoxy-4-[1-(oxan-2-yl)-1H-pyrazol-4-yl]-1H-1,3-

benzodiazol-2-yl}-4-methylpiperidine-1-carboxamide,

79

4-hydroxy-N-[7-methoxy-4-(1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-4-methylpiperidine-1-carboxamide,

80

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-1-benzofuran-5-carboxamide,

81

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-5-(morpholin-4-yl)pyrazine-2-carboxamide,

82

4-hydroxy-N-[4-methoxy-7-(1-methyl-1H-pyrazol-4-yl)-3H-

imidazo[4,5-c]pyridin-2-yl]-4-methylpiperidine-1-carboxamide,

83

4-benzyl-4-hydroxy-N-[4-methoxy-7-(1-methyl-1H-pyrazol-4-yl)-3H-

imidazo[4,5-c]pyridin-2-yl]piperidine-1-carboxamide,

84

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-1,2-oxazole-3-carboxamide,

85

N-[7-methoxy-4-(pyridin-4-yl)-1H-1,3-benzodiazol-2-yl]-2-oxa-6-

azaspiro[3.4]octane-6-carboxamide,

86

1-(1-chloro-3-hydroxypropan-2-yl)-N-[7-methoxy-4-(morpholin-4-

yl)-1H-1,3-benzodiazol-2-yl]-1H-pyrazole-4-carboxamide,

87

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-6-(morpholin-4-yl)pyridazine-3-carboxamide,

88

4-[(dimethylamino)methyl]-N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-

benzodiazol-2-yl]benzamide,

89

4-[(dimethylamino)methyl]-N-[7-methoxy-4-(pyridin-4-yl)-1H-1,3-

benzodiazol-2-yl]benzamide,

90

4-[(dimethylamino)methyl]-N-[7-methoxy-4-(morpholin-4-yl)-1H-1,3-

benzodiazol-2-yl]benzamide,

91

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-6-(morpholin-

4-yl)pyridazine-3-carboxamide,

92

4-hydroxy-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]-4-(prop-2-yn-1-yl)piperidine-1-carboxamide,

93

N4-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-N1,N1-dimethylbenzene-1,4-dicarboxamide,

94

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-4-(trifluoromethoxy)benzamide,

95

2-bromo-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]pyridine-4-carboxamide,

96

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-2-methyl-1,3-oxazole-4-carboxamide,

97

4-[(1H-imidazol-1-yl)methyl]-N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-

benzodiazol-2-yl]benzamide,

98

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-1,3-benzoxazole-5-carboxamide,

99

3-amino-4-hydroxy-N-[7-methoxy-4-(morpholin-4-yl)-1H-1,3-

benzodiazol-2-yl]benzamide,

100

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-4-[(2-oxopyrrolidin-1-yl)methyl]benzamide,

101

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-2,3-dihydro-1-benzofuran-5-carboxamide,

102

4-hydroxy-N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-4-

(prop-2-yn-1-yl)piperidine-1-carboxamide,

103

4-benzyl-4-hydroxy-N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-

benzodiazol-2-yl]piperidine-1-carboxamide,

104

2-[(3S)-3-hydroxy-3-methylpyrrolidin-1-yl]-N-[7-methoxy-4-(1-

methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-yl]pyridine-4-

carboxamide,

105

2-(4-hydroxy-4-methylpiperidin-1-yl)-N-[7-methoxy-4-(1-methyl-1H-

pyrazol-4-yl)-1H-1,3-benzodiazol-2-yl]pyridine-4-carboxamide,

106

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-2-{2-oxa-7-azaspiro[4.4]nonan-7-yl}pyridine-4-carboxamide,

107

2-[(3R)-3-hydroxy-3-methylpyrrolidin-1-yl]-N-[7-methoxy-4-(1-

methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-yl]pyridine-4-

carboxamide,

108

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-2,3-dihydro-

1-benzofuran-5-carboxamide,

109

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-3-(methoxymethyl)pyrrolidine-1-carboxamide,

110

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-2-oxa-7-

azaspiro[4.4]nonane-7-carboxamide,

111

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-8-oxa-2-

azaspiro[4.5]decane-2-carboxamide,

112

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-hexahydro-

1H-furo[3,4-c]pyrrole-5-carboxamide,

113

(5R)-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]-7-oxa-2-azaspiro[4.5]decane-2-carboxamide,

114

(5S)-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]-7-oxa-2-azaspiro[4.5]decane-2-carboxamide,

115

(5S)-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]-2-oxa-7-azaspiro[4.4]nonane-7-carboxamide,

116

(5R)-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]-2-oxa-7-azaspiro[4.4]nonane-7-carboxamide,

117

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-3-

(methoxymethyl)pyrrolidine-1-carboxamide,

118

2-(4-hydroxy-4-methylpiperidin-1-yl)-N-[7-methoxy-4-(oxan-4-yl)-

1H-1,3-benzodiazol-2-yl]pyridine-4-carboxamide,

119

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-2-{2-oxa-7-

azaspiro[4.4]nonan-7-yl}pyridine-4-carboxamide,

120

2-(4-fluorophenoxy)-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-

1H-1,3-benzodiazol-2-yl]-2-methylpropanamide,

121

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-hexahydro-1H-furo[3,4-c]pyrrole-5-carboxamide,

122

2-(3-hydroxy-3-methylpyrrolidin-1-yl)-N-[7-methoxy-4-(oxan-4-yl)-

1H-1,3-benzodiazol-2-yl]pyridine-4-carboxamide,

123

N-[7-methoxy-4-(morpholin-4-yl)-1H-1,3-benzodiazol-2-yl]-2-oxa-7-

azaspiro[4.4]nonane-7-carboxamide,

124

1-{[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]carbamoyl}piperidine-4-carboxylic acid,

125

N-[7-methoxy-4-(morpholin-4-yl)-1H-1,3-benzodiazol-2-yl]-8-oxa-2-

azaspiro[4.5]decane-2-carboxamide,

126

N1-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]piperidine-1,4-dicarboxamide,

127

4-(diethylamino)-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-

1,3-benzodiazol-2-yl]benzamide,

128

4-hydroxy-N-{7-methoxy-4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-1H-

1,3-benzodiazol-2-yl}-4-methylpiperidine-1-carboxamide,

129

N-[7-methoxy-4-(pyridin-4-yl)-1H-1,3-benzodiazol-2-yl]-8-oxa-2-

azaspiro[4.5]decane-2-carboxamide,

130

2-(1-{[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-

yl]carbamoyl}piperidin-4-yl)acetic acid,

131

4-hydroxy-N-[7-methoxy-4-(2-methylphenyl)-1H-1,3-benzodiazol-2-

yl]-4-methylpiperidine-1-carboxamide,

132

2-(1-{[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-

2-yl]carbamoyl}piperidin-4-yl)acetic acid,

133

N4-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-N1,N1-

dimethylbenzene-1,4-dicarboxamide,

134

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-3-(2-methoxyethyl)pyrrolidine-1-carboxamide,

135

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-5-(morpholin-4-yl)pyridine-2-carboxamide,

136

N-[7-methoxy-4-(morpholin-4-yl)-1H-1,3-benzodiazol-2-yl]-1-

methyl-1H-pyrazole-4-carboxamide,

137

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-3-(2-

methoxyethyl)pyrrolidine-1-carboxamide,

138

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-4-[(2-

oxopyrrolidin-1-yl)methyl]benzamide,

139

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-5-(morpholin-

4-yl)pyridine-2-carboxamide,

140

(3R)-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]-3-(2-methoxyethyl)pyrrolidine-1-carboxamide,

141

(3S)-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]-3-(2-methoxyethyl)pyrrolidine-1-carboxamide,

142

2-[(3R)-3-hydroxy-3-methylpyrrolidin-1-yl]-N-[7-methoxy-4-(oxan-4-

yl)-1H-1,3-benzodiazol-2-yl]acetamide,

143

2-[(3S)-3-hydroxy-3-methylpyrrolidin-1-yl]-N-[7-methoxy-4-(oxan-4-

yl)-1H-1,3-benzodiazol-2-yl]acetamide,

144

N-[4-(4-fluorophenyl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-4-

hydroxy-4-methylpiperidine-1-carboxamide,

145

tert-butyl 4-(4-{2-[(4-hydroxy-4-methylpiperidine-1-carbonyl)amino]-

4-methoxy-1H-1,3-benzodiazol-7-yl}-1H-pyrazol-1-yl)piperidine-1-

carboxylate,

146

4-{[2-amino-7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-1-yl]methyl}benzoic acid,

147

(3S)-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]-3-(methoxymethyl)pyrrolidine-1-carboxamide,

148

(3R)-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]-3-(methoxymethyl)pyrrolidine-1-carboxamide,

149

(5S)-N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-2-oxa-7-

azaspiro[4.4]nonane-7-carboxamide,

150

(5R)-N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-2-oxa-7-

azaspiro[4.4]nonane-7-carboxamide,

151

4-hydroxy-N-{7-methoxy-4-[1-(3-methylbutyl)-1H-pyrazol-4-yl]-1H-

1,3-benzodiazol-2-yl}-4-methylpiperidine-1-carboxamide,

152

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-4-[(morpholin-4-yl)methyl]benzamide,

153

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-2-[(5R)-2-

oxa-7-azaspiro[4.4]nonan-7-yl]pyridine-4-carboxamide,

154

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-2-[(5S)-2-

oxa-7-azaspiro[4.4]nonan-7-yl]pyridine-4-carboxamide,

155

N-[4-(3,6-dihydro-2H-pyran-4-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]-4-hydroxy-4-methylpiperidine-1-carboxamide,

156

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-1-methyl-1H-1,2,3-triazole-4-carboxamide,

157

4-hydroxy-N-{4-methoxy-7-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]-1H-

1,3-benzodiazol-2-yl}-4-methylpiperidine-1-carboxamide,

158

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-5-(2-methoxyethoxy)pyridine-2-carboxamide,

159

2-(1-{[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-

2-yl]carbamoyl}piperidin-3-yl)acetic acid,

160

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-1-methyl-1H-pyrazole-4-carboxamide,

161

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-1-(2-methoxyethyl)-1H-pyrazole-4-carboxamide,

162

N5-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-N2,N2-dimethylpyridine-2,5-dicarboxamide,

163

4-hydroxy-N-[4-methoxy-1-methyl-7-(1-methyl-1H-pyrazol-4-yl)-1H-

1,3-benzodiazol-2-yl]-4-methylpiperidine-1-carboxamide,

164

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-1-(2-methoxyethyl)-1H-1,2,3-triazole-4-carboxamide,

165

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-2-methyl-1,3-thiazole-5-carboxamide,

167

1-(2-Hydroxy-ethyl)-1H-pyrazole-4-carboxylic acid [7-methoxy-4-(1-

methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

168

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-4-[(4-methylpiperazin-1-yl)methyl]benzamide,

169

1-Methyl-1H-pyrazole-4-carboxylic acid [7-methoxy-4-(1-methyl-

1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

170

5-Methyl-isoxazole-4-carboxylic acid [7-methoxy-4-(1-methyl-1H-

pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

171

5-Cyclopropyl-isoxazole-4-carboxylic acid [7-methoxy-4-(1-methyl-

1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

172

1-Cyano-cyclopropanecarboxylic acid [7-methoxy-4-(1-methyl-1H-

pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

173

Thiazole-5-carboxylic acid [7-methoxy-4-(1-methyl-1H-pyrazol-4-

yl)-1H-benzoimidazol-2-yl]-amide,

174

5,6,7,8-Tetrahydro-imidazo[1,2-a]pyridine-3-carboxylic acid [7-

methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-

amide,

175

4-(4-Methyl-piperazin-1-yl)-but-2-ynoic acid [7-methoxy-4-(1-

methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

179

(S)-3-Methanesulfonyl-pyrrolidine-1-carboxylic acid [7-methoxy-4-

(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

180

(S)-3-Fluoro-pyrrolidine-1-carboxylic acid [7-methoxy-4-(1-methyl-

1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

181

(S)-3-Cyano-pyrrolidine-1-carboxylic acid [7-methoxy-4-(1-methyl-

1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-amide,

182

(R)-3-Dimethylaminomethyl-pyrrolidine-1-carboxylic acid [7-

methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]-

amide,

183

5-Methyl-isoxazole-4-carboxylic acid (7-methoxy-4-morpholin-4-yl-

1H-benzoimidazol-2-yl)-amide,

184

N-[7-methoxy-4-(morpholin-4-yl)-1H-1,3-benzodiazol-2-yl]-1-(2-

methoxyethyl)-1H-1,2,3-triazole-4-carboxamide,

185

1-Methyl-1H-[1,2,3]triazole-4-carboxyylic acid (7-methoxy-4-

morpholin-4-yl-1H-benzoimidazol-2-yl)-amide,

186

Pyridine-2,5-dicarboxylic acid 2-dimethylamide 5-{[7-methoxy-4-

(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-amide},

187

1-(2-Methoxy-ethyl)-1H-pyrazole-4-carboxylic acid [7-methoxy-4-

(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

188

N-[7-Methoxy-4-(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-4-

morpholin-4-ylmethyl-benzamide,

189

N-[7-Methoxy-4-(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-4-

(4-methyl-piperazin-1-ylmethyl)-benzamide,

190

1-Methyl-1H-pyrazole-4-carboxylic acid [7-methoxy-4-(tetrahydro-

pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

191

5-Methyl-isoxazole-4-carboxylic acid [7-methoxy-4-(tetrahydro-

pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

192

5-Cyclopropyl-isoxazole-4-carboxylic acid [7-methoxy-4-

(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

193

1-(2-Methoxy-ethyl)-1H-[1,2,3]triazole-4-carboylic acid [7-

methoxy-4-(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

194

1-Methyl-1H-[1,2,3]triazole-4-carboylic acid [7-methoxy-4-

(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

195

1-Cyano-cyclopropanecarboxylic acid [7-methoxy-4-(tetrahydro-

pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

196

Thiazole-5-carboxylic acid [7-methoxy-4-(tetrahydro-pyran-4-yl)-

1H-benzoimidazol-2-yl]-amide,

197

2-Methyl-oxazole-5-carboxylic acid [7-methoxy-4-(tetrahydro-

pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

198

2-Methyl-thiazole-5-carboxylic acid [7-methoxy-4-(tetrahydro-

pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

199

Imidazo[1,2-a]pyridine-3-carboxylic acid [7-methoxy-4-(tetrahydro-

pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

200

5-Amino-2H-[1,2,4]triazole-3-carboxylic acid [7-methoxy-4-

(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

201

(S)-3-Methanesulfonyl-pyrrolidine-1-carboxylic acid [7-methoxy-4-

(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

202

(S)-3-Fluoro-pyrrolidine-1-carboxylic acid [7-methoxy-4-(tetrahydro-

pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

203

(S)-3-Cyano-pyrrolidine-1-carboxylic acid [7-methoxy-4-

(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

204

(R)-3-Dimethylaminomethyl-pyrrolidine-1-carboxylic acid [7-

methoxy-4-(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

205

Pyrazolo[1,5-a]pyridine-3-carboxylic acid [7-methoxy-4-(tetrahydro-

pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

206

1H-[1,2,4]Triazole-3-carboxylic acid [7-methoxy-4-(tetrahydro-

pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

207

5,6,7,8-Tetrahydro-imidazo[1,2-a]pyridine-3-carboxylic acid [7-

methoxy-4-(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

208

2,3-Dimethyl-3H-imidazole-4-sulfonic acid [7-methoxy-4-

(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-amide,

209

1-[7-Methoxy-4-(tetrahydro-pyran-4-yl)-1H-benzoimidazol-2-yl]-3-

thiazol-2-ylmethyl-urea,

210

N-[7-methoxy-4-(morpholin-4-yl)-1H-1,3-benzodiazol-2-yl]-1-

methyl-1H-1,2,3-triazole-4-carboxamide,

211

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-1-(2-

methoxyethyl)-1H-1,2,3-triazole-4-carboxamide,

212

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-1-methyl-1H-

1,2,3-triazole-4-carboxamide,

213

1-cyano-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]cyclopropane-1-carboxamide,

214

N5-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-N2,N2-

dimethylpyridine-2,5-dicarboxamide,

215

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-2-methyl-1,3-oxazole-5-carboxamide,

216

N-[4-(azepan-1-yl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-4-hydroxy-

4-methylpiperidine-1-carboxamide,

217

N-[4-(3-fluorophenyl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-4-

hydroxy-4-methylpiperidine-1-carboxamide,

218

N-[4-(2-fluorophenyl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-4-

hydroxy-4-methylpiperidine-1-carboxamide,

219

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-1,3-thiazole-5-carboxamide,

220

(3R)-3-methanesulfonyl-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-

yl)-1H-1,3-benzodiazol-2-yl]pyrrolidine-1-carboxamide,

221

(3S)-3-fluoro-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]pyrrolidine-1-carboxamide,

222

4-hydroxy-N-[7-methoxy-4-(1-methyl-6-oxo-1,6-dihydropyridin-3-

yl)-1H-1,3-benzodiazol-2-yl]-4-methylpiperidine-1-carboxamide,

223

(3S)-3-(aminomethyl)-N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-

1H-1,3-benzodiazol-2-yl]pyrrolidine-1-carboxamide,

224

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-1-methyl-1H-

pyrazole-4-carboxamide,

225

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-1-(2-

methoxyethyl)-1H-pyrazole-4-carboxamide,

226

1-cyano-N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-

yl]cyclopropane-1-carboxamide,

227

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-2-methyl-1,3-

thiazole-5-carboxamide,

228

3-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-1-[(1,3-

thiazol-2-yl)methyl]urea,

229

N-{7-[1-(difluoromethyl)-1H-pyrazol-4-yl]-4-methoxy-1H-1,3-

benzodiazol-2-yl}-4-hydroxy-4-methylpiperidine-1-carboxamide,

230

4-hydroxy-N-(4-methoxy-7-{1-[2-(2-methoxyethoxy)ethyl]-1H-

pyrazol-4-yl}-1H-1,3-benzodiazol-2-yl)-4-methylpiperidine-1-

carboxamide,

231

4-hydroxy-N-{4-methoxy-7-[1-(pyridin-2-yl)-1H-pyrazol-4-yl]-1H-

1,3-benzodiazol-2-yl}-4-methylpiperidine-1-carboxamide,

232

N-[7-methoxy-4-(1-propylcyclopropyl)-1H-1,3-benzodiazol-2-yl]-1-

methyl-1H-pyrazole-4-carboxamide,

233

N-[4-(hexan-3-yl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-1-methyl-

1H-pyrazole-4-carboxamide,

234

N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-2-methyl-1,3-

oxazole-5-carboxamide,

235

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-4-[(4-methylpiperazin-1-yl)methyl]benzamide,

236

4-hydroxy-N-{4-methoxy-7-[3-(2-methoxyethoxy)phenyl]-1H-1,3-

benzodiazol-2-yl}-4-methylpiperidine-1-carboxamide,

237

4-hydroxy-N-(4-methoxy-7-{1-[(pyridin-3-yl)methyl]-1H-pyrazol-4-

yl}-1H-1,3-benzodiazol-2-yl)-4-methylpiperidine-1-carboxamide,

238

4-hydroxy-N-{7-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]-4-

methoxy-1H-1,3-benzodiazol-2-yl}-4-methylpiperidine-1-

carboxamide,

239

N-[4-(3-fluorophenyl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-1-

methyl-1H-pyrazole-4-carboxamide,

240

N4-[4-(3-fluorophenyl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-N1,N1-

dimethylbenzene-1,4-dicarboxamide,

241

4-hydroxy-N-{4-methoxy-7-[1-(oxolan-3-yl)-1H-pyrazol-4-yl]-1H-

1,3-benzodiazol-2-yl}-4-methylpiperidine-1-carboxamide,

242

N4-[4-(2-fluorophenyl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-N1,N1-

dimethylbenzene-1,4-dicarboxamide,

243

N-[4-(2-fluorophenyl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-1-

methyl-1H-pyrazole-4-carboxamide,

244

N-[4-methoxy-1-methyl-7-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-

benzodiazol-2-yl]-1-methyl-1H-pyrazole-4-carboxamide,

245

tert-butyl 3-(4-{2-[(4-hydroxy-4-methylpiperidine-1-carbonyl)amino]-

4-methoxy-1H-1,3-benzodiazol-7-yl}-1H-pyrazol-1-yl)azetidine-1-

carboxylate,

246

N-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-5-oxopyrrolidine-3-carboxamide,

247

3-[7-methoxy-4-(1-methyl-1H-pyrazol-4-yl)-1H-1,3-benzodiazol-2-

yl]-1-[(1,3-thiazol-2-yl)methyl]urea,

248

4-(2,5-dioxopyrrolidin-1-yl)-N-[7-methoxy-4-(1-methyl-1H-pyrazol-

4-yl)-1H-1,3-benzodiazol-2-yl]benzamide,

249

1-[(3R,4S)-4-fluoropyrrolidin-3-yl]-3-[7-methoxy-4-(1-methyl-1H-

pyrazol-4-yl)-1H-1,3-benzodiazol-2-yl]urea,

250

4-(2,5-dioxopyrrolidin-1-yl)-N-[7-methoxy-4-(oxan-4-yl)-1H-1,3-

benzodiazol-2-yl]benzamide,

251

tert-butyl (3S,4R)-3-fluoro-4-({[7-methoxy-4-(1-methyl-1H-pyrazol-

4-yl)-1H-1,3-benzodiazol-2-yl]carbamoyl}amino)pyrrolidine-1-

carboxylate,

252

N4-[7-methoxy-4-(1,2,3,6-tetrahydropyridin-4-yl)-1H-1,3-

benzodiazol-2-yl]-N1,N1-dimethylbenzene-1,4-dicarboxamide,

253

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-1H-imidazole-4-

carboxamide,

254

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-1-methyl-1H-

imidazole-5-carboxamide,

255

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-2-methyl-1H-

imidazole-4-carboxamide,

256

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-1,3-thiazole-5-

carboxamide,

257

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-2-methyl-1,3-

thiazole-5-carboxamide,

258

2-amino-N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-1,3-

thiazole-5-carboxamide,

259

N4-[7-methoxy-4-(pyridin-3-yl)-1H-1,3-benzodiazol-2-yl]-N1,N1-

dimethylbenzene-1,4-dicarboxamide,

260

N-[7-methoxy-4-(pyridin-3-yl)-1H-1,3-benzodiazol-2-yl]-1-methyl-

1H-pyrazole-4-carboxamide,

261

N4-[4-(2,5-dihydrofuran-3-yl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-

N1,N1-dimethylbenzene-1,4-dicarboxamide,

262

N4-[4-(3,6-dihydro-2H-pyran-4-yl)-5-fluoro-7-methoxy-1H-1,3-

benzodiazol-2-yl]N1,N1-dimethylbenzene-1,4-dicarboxamide,

263

3-{[dimethyl(oxo)-lambda6-sulfanylidene]amino}-N-[7-methoxy-4-

(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]benzamide,

264

N-[4-(3,6-dihydro-2H-pyran-4-yl)-5-fluoro-7-methoxy-1H-1,3-

benzodiazol-2-yl]-1-methyl-1H-pyrazole-4-carboxamide,

265

N-[7-(3-fluorophenyl)-4-methoxy-1H-1,3-benzodiazol-2-yl]-1H-

imidazole-4-carboxamide,

266

N-[4-methoxy-7-(pyridin-4-yl)-1H-1,3-benzodiazol-2-yl]-1H-

imidazole-4-carboxamide,

267

N-{4-methoxy-7-[3-(2-methoxyethoxy)phenyl]-1H-1,3-benzodiazol-

2-yl}-1H-imidazole-4-carboxamide,

268

N-[4-methoxy-7-(pyridin-3-yl)-1H-1,3-benzodiazol-2-yl]-1H-

imidazole-4-carboxamide,

269

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-1,3-dimethyl-1H-

pyrazole-4-carboxamide,

270

4-hydroxy-N-(7-methoxy-4-{1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-1,3-

benzodiazol-2-yl)-4-methylpiperidine-1-carboxamide,

271

4-hydroxy-N-[4-(1H-indazol-4-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]-4-methylpiperidine-1-carboxamide,

272

4-hydroxy-N-[4-(1H-indol-6-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]-4-methylpiperidine-1-carboxamide,

273

4-hydroxy-N-[7-methoxy-4-(1-methyl-1H-indazol-5-yl)-1H-1,3-

benzodiazol-2-yl]-4-methylpiperidine-1-carboxamide,

274

4-hydroxy-N-[7-methoxy-4-(3-methyl-1H-indazol-5-yl)-1H-1,3-

benzodiazol-2-yl]-4-methylpiperidine-1-carboxamide,

275

4-hydroxy-N-(4-{imidazo[1,2-a]pyridin-7-yl}-7-methoxy-1H-1,3-

benzodiazol-2-yl)-4-methylpiperidine-1-carboxamide,

277

N4-[5-fluoro-7-methoxy-4-(oxan-4-yl)-1H-1,3-benzodiazol-2-yl]-

N1,N1-dimethylbenzene-1,4-dicarboxamide,

278

N-(7-methoxy-4-{1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-1,3-benzodiazol-

2-yl)-1-(2-methoxyethyl)-1H-pyrazole-4-carboxamide,

279

N-[4-(1H-indazol-4-yl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-1-(2-

methoxyethyl)-1H-pyrazole-4-carboxamide,

280

N-[4-(1H-indo1-6-yl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-1-(2-

methoxyethyl)-1H-pyrazole-4-carboxamide,

281

N-[7-methoxy-4-(1-methyl-1H-indazol-5-yl)-1H-1,3-benzodiazol-2-

yl]-1-(2-methoxyethyl)-1H-pyrazole-4-carboxamide,

282

N-[7-methoxy-4-(3-methyl-1H-indazol-5-yl)-1H-1,3-benzodiazol-2-

yl]-1-(2-methoxyethyl)-1H-pyrazole-4-carboxamide,

283

N-[4-(2,3-dihydro-1H-indo1-4-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]-1-(2-methoxyethyl)-1H-pyrazole-4-carboxamide,

284

N2-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-N5,N5-

dimethylpyridine-2,5-dicarboxamide,

285

4-(2,5-dioxopyrrolidin-1-yl)-N-(7-methoxy-4-phenyl-1H-1,3-

benzodiazol-2-yl)benzamide,

286

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)imidazo[1,2-

a]pyridine-3-carboxamide,

287

4,4-difluoro-N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-

yl)pipendine-1-carboxamide,

288

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)imidazo[1,2-

b]pyridazine-3-carboxamide,

289

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)imidazo[1,2-

a]pyrimidine-3-carboxamide,

290

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-2-(pyridin-4-yl)-

1H-imidazole-4-carboxamide,

291

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-5H,6H,7H,8H-

imidazo[1,2-a]pyridine-3-carboxamide,

292

N-[4-(2,3-dihydro-1H-indo1-4-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]-4-hydroxy-4-methylpiperidine-1-carboxamide,

293

N1-(4-methoxy-7-phenyl-1H-1,3-benzodiazol-2-yl)-N4-

propylbenzene-1,4-dicarboxamide,

294

N-(4-methoxy-7-phenyl-1H-1,3-benzodiazol-2-yl)-4-(4-

methylpiperazine-1-carbonyl)benzamide,

295

N4-(4-methoxy-7-phenyl-1H-1,3-benzodiazol-2-yl)-N1-(2-

methoxyethyl)-N1-methylbenzene-1,4-dicarboxamide,

296

N1-[2-(dimethylamino)ethyl]-N4-(4-methoxy-7-phenyl-1H-1,3-

benzodiazol-2-yl)-N1-methylbenzene-1,4-dicarboxamide,

297

N4-(4-methoxy-7-phenyl-1H-1,3-benzodiazol-2-yl)-N1-methyl-N1-

propylbenzene-1,4-dicarboxamide,

298

N-(4-methoxy-7-phenyl-1H-1,3-benzodiazol-2-yl)-4-(morpholine-4-

carbonyl)benzamide,

299

N-[4-methoxy-7-(2-methylpyridin-4-yl)-1H-1,3-benzodiazol-2-yl]-

1H-imidazole-4-carboxamide,

300

N-(5-cyano-7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-1-

methyl-1H-pyrazole-4-carboxamide,

301

N-(4-{imidazo[1,2-a]pyridin-7-yl}-7-methoxy-1H-1,3-benzodiazol-2-

yl)-1-(2-methoxyethyl)-1H-pyrazole-4-carboxamide,

302

N-[4-(1H-indo1-5-yl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-1-(2-

methoxyethyl)-1H-pyrazole-4-carboxamide,

303

4-hydroxy-N-[4-(1H-indo1-5-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]-4-methylpiperidine-1-carboxamide,

304

N-[4-(1H-indo1-7-yl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-1-(2-

methoxyethyl)-1H-pyrazole-4-carboxamide,

305

4-hydroxy-N-[4-(1H-indo1-7-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]-4-methylpiperidine-1-carboxamide,

306

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-1-methyl-1H-

pyrazole-4-carboxamide,

307

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-1-(2-

methoxyethyl)-1H-pyrazole-4-carboxamide,

308

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-2-methyl-1,3-

oxazole-5-carboxamide,

309

N4-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-N1,N1-

dimethylbenzene-1,4-dicarboxamide,

310

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-8-oxa-2-

azaspiro[4.5]decane-2-carboxamide,

311

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-4-[(2-

oxopyrrolidin-1-yl)methyl]benzamide,

312

N1-(2-hydroxyethyl)-N4-(4-methoxy-7-phenyl-1H-1,3-benzodiazol-

2-yl)benzene-1,4-dicarboxamide,

313

N4-[7-methoxy-4-(1,4-oxazepan-4-yl)-1H-1,3-benzodiazol-2-yl]-

N1,N1-dimethylbenzene-1,4-dicarboxamide,

314

N-[4-(3,6-dihydro-2H-pyran-4-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]cyclopropanecarboxamide,

315

N-[7-methoxy-4-(pyridin-3-yl)-1H-1,3-benzodiazol-2-

yl]cyclopropanecarboxamide,

316

N4-[4-(4-fluorophenyl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-N1,N1-

dimethylbenzene-1,4-dicarboxamide,

317

4-(2,5-dioxopyrrolidin-1-yl)-N-[4-(4-fluorophenyl)-7-methoxy-1H-

1,3-benzodiazol-2-yl]benzamide,

318

N-[4-(4-fluorophenyl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-1-

methyl-1H-pyrazole-4-carboxamide,

319

N4-[4-(2,6-dimethoxypyridin-3-yl)-7-methoxy-1H-1,3-benzodiazol-

2-yl]-N1,N1-dimethylbenzene-1,4-dicarboxamide,

320

N-[4-(2,6-dimethoxypyridin-3-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]cyclopropanecarboxamide,

321

N-[7-methoxy-4-(pyridin-3-yl)-1H-1,3-benzodiazol-2-yl]-2-methyl-

1,3-oxazole-5-carboxamide,

322

N-[4-(2,5-dihydrofuran-3-yl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-2-

methyl-1,3-oxazole-5-carboxamide,

323

N-[4-(4-fluorophenyl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-2-

methyl-1,3-oxazole-5-carboxamide,

324

N4-[4-(3,6-dihydro-2H-pyran-4-yl)-7-methoxy-1H-1,3-benzodiazol-

2-yl]-N1,N1-dimethylbenzene-1,4-dicarboxamide,

325

N-[4-(3,6-dihydro-2H-pyran-4-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]-1-methyl-1H-pyrazole-4-carboxamide,

326

(4-{2-[(4-hydroxy-4-methylpiperidine-1-carbonyl)amino]-7-methoxy-

1H-1,3-benzodiazol-4-yl}morpholin-2-yl)methyl carbamate,

327

(1-{2-[(4-hydroxy-4-methylpiperidine-1-carbonyl)amino]-7-methoxy-

1H-1,3-benzodiazol-4-yl}piperidin-3-yl)methyl cyanate,

328

(1-{2-[(4-hydroxy-4-methylpiperidine-1-carbonyl)amino]-7-methoxy-

1H-1,3-benzodiazol-4-yl}piperidin-3-yl)methyl carbamate,

329

N-(7-methoxy-4-phenyl-1H-1,3-benzodiazol-2-yl)-2-oxa-8-

azaspiro[4.5]decane-8-carboxamide,

330

N-[4-(1H-indo1-6-yl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-1H-

imidazole-4-carboxamide,

331

N-[4-(1H-indo1-6-yl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-1-methyl-

1H-pyrazole-4-carboxamide,

332

N-[4-(4-fluorophenyl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-8-oxa-2-

azaspiro[4.5]decane-2-carboxamide,

333

N-[4-(3,6-dihydro-2H-pyran-4-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]-8-oxa-2-azaspiro[4.5]decane-2-carboxamide,

334

N-[4-(3,6-dihydro-2H-pyran-4-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]-4-[(2-oxopyrrolidin-1-yl)methyl]benzamide,

335

N-[4-(4-fluorophenyl)-7-methoxy-1H-1,3-benzodiazol-2-yl]-4-[(2-

oxopyrrolidin-1-yl)methyl]benzamide,

336

N-[4-(1H-indo1-6-yl)-7-methoxy-1H-1,3-benzodiazol-2-

yl]cyclopropanecarboxamide,

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

5. A process for the preparation of a compound of the formula I, of claim 1 , comprising

a) a compound of the formula II undergoes a nitration reaction, followed by a reduction to give a compound of formula IV, a compound of formula IVI is cyclized to give a compound of formula V, a compound of formula V is reacted in a Suzuki type reaction to formula VI employing the use of catalyst and base, a compound of formula VI is converted to a compound of the formula VII by standard amidation or carbamide formation conditions to give a compound of the formula I

b) a compound of the formula III is reacted with a boronic ester or acid under Suzuki-type reaction conditions to give a compound of the formula VII or reacted with an amine in a nucleophilic substitution reaction under increased temperature to form a compound of the formula VII, a compound of formula VII is reduced to a compound of the formula VII and cyclized to a compound of the formula VI and finally reacted with to compound of the formula I under standard amidation or carbamide formation conditions

c) the base of a compound of the formula I is converted into one of its salts by treatment with an acid, or

d) an acid of a compound of the formula I is converted into one of its salts by treatment with a base.

6. A method of inhibiting adenosine A 2A and/or A 2B receptors in a host in need thereof, comprising administering to said host a compound according to claim 1 or physiologically acceptable salts, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios an amount effective to inhibit adenosine A 2A and/or A 2B receptors.

7. A pharmaceutical preparation comprising at least one compound according to claim 1 and/or physiologically acceptable salts, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.

8. The pharmaceutical preparation according to claim 7 comprising further excipients and/or adjuvants.

9. The pharmaceutical preparation comprising at least one compound according to claim 1 and/or physiologically acceptable salts, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios, and at least one further medicament active compound.

10. A kit consisting of separate packs of

a) an effective amount of a compound according to claim 1 and/or physiologically acceptable salts, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios, and

b) an effective amount of a further medicament active compound.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 15, 2025
From: MERCK PATENT GMBH; MERCK HEALTHCARE KGAA
To: DOMAIN THERAPEUTICS
Reel/Frame 072033/0504 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 18, 2020
From: TANZER, EVA-MARIA; SCHIEMANN, KAI; KLEIN, MARKUS
To: MERCK PATENT GMBH
Reel/Frame 053524/0448 →
Priority Claims (1)
EP 17187101 · Aug 21, 2017 · regional
Continuity (1)
Related Publication 20200207720A1 · Jul 2, 2020