IP Library › Granted Patent US 9,284,301

Granted Patent B2

US 9,284,301 · App. 13/636,760 · Granted Mar 15, 2016

Soluble guanylate cyclase activators

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Quick Facts

Patent No.: US 9,284,301
App. No.: 13/636,760
Granted: Mar 15, 2016
Kind: B2

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Abstract

The invention relates to compounds having the structure of Formula (I) and pharmaceutically acceptable salts thereof, which are soluble guanylate cyclase activators. The compounds are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver.

Claims (224)

1. A compound selected from the group consisting of:

1) 2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidin-4-amine,

2) 5-[1,5-dimethyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

3) 5-(2-methylpyridin-4-yl)-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

4) 5-quinolin-5-yl-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

5) 5-pyridin-4-yl-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

6) 5-pyridin-3-yl-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

7) 2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-[5-(trifluoromethyl)pyridin-3-yl]pyrimidin-4-amine,

8) 5-(5-fluoropyridin-3-yl)-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

9) 5-(2-methoxypyridin-3-yl)-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

10) 5-(4-methylpyridin-3-yl)-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

11) 5-(4-methoxypyridin-3-yl)-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

12) 5-(1-methyl-1H-pyrazol-4-yl)-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

13) 5-(1-methyl-1H-pyrazol-5-yl)-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

14) 5-(7-fluoroquinolin-4-yl)-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

15) 2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-[2-(trifluoromethyl)quinolin-4-yl]pyrimidin-4-amine,

16) 5-(3-fluoropyridin-4-yl)-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

17) 2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-[2-(trifluoromethyl)pyridin-4-yl]pyrimidin-4-amine,

18) 2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-[2-(trifluoromethyl)quinolin-4-yl]pyrimidin-4-amine,

19) 5-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

20) 5-pyridin-4-yl-2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

21) 5-pyridin-3-yl-2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

22) 5-(4-methoxypyridin-3-yl)-2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

23) 5-(4-methylpyridin-3-yl)-2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

24) 5-quinolin-5-yl-2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

25) 5-(2-methylpyridin-4-yl)-2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

26) 2-[7-(2-chloro-3,6-difluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-pyridin-4-ylpyrimidin-4-amine,

27) 2-[7-(2-chloro-3,6-difluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidin-4-amine,

28) 2-[7-(2-chloro-3,6-difluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-(2-methylpyridin-4-yl)pyrimidin-4-amine,

29) 2-[7-(2-chloro-3,6-difluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-quinolin-5-ylpyrimidin-4-amine,

30) 2-[7-(2-chloro-3,6-difluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-[2-(trifluoromethyl)pyridin-4-yl]pyrimidin-4-amine,

31) 2-[7-(2-chloro-3,6-difluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-pyridin-3-ylpyrimidin-4-amine,

32) 2-[7-(2-chloro-3,6-difluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-(4-methoxypyridin-3-yl)pyrimidin-4-amine,

33) 2-[7-(2-chloro-3,6-difluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-[5-(trifluoromethyl)pyridin-3-yl]pyrimidin-4-amine,

34) 2-[7-(2-chloro-3,6-difluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-(4-methylpyridin-3-yl)pyrimidin-4-amine,

35) 2-[7-(2-chloro-3,6-difluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-amine,

36) 2-[7-(2-chloro-3,6-difluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-[1,5-dimethyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrimidin-4-amine,

37) 2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidin-4-amine,

38) 5-[1,5-dimethyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

39) 2-[7-(3-chloro-2,6-difluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidin-4-amine,

40) 2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-[2-(trifluoromethyl)pyridin-4-yl]pyrimidin-4-amine,

41) 2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-[5-(trifluoromethyl)pyridin-3-yl]pyrimidin-4-amine,

42) 5-[3-(methylsulfonyl)phenyl]-2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

43) 2-[7-(2-chloro-3,5-difluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-[3-(methylsulfonyl)phenyl]pyrimidin-4-amine,

44) 5-[2-(methylsulfonyl)phenyl]-2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

45) 5-[4-(methylsulfonyl)phenyl]-2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

46) 5-(3-methoxyphenyl)-2-[7-(2,3,5-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine;

47) 5-(2-methoxypyridin-3-yl)-2-[7-(2,3,4-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

48) 5-(4-methoxypyridin-3-yl)-2-[7-(2,3,4-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

49) 2-[7-(2,3,4-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]-5-[5-(trifluoromethyl)pyridin-3-yl]pyrimidin-4-amine,

50) 5-pyridin-4-yl-2-[7-(2,3,4-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

51) 5-(1-methyl-1H-pyrazol-5-yl)-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

52) 5-[3-(methylsulfonyl)phenyl]-2-[7-(2,3,4-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

53) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-pyridin-3-ylpyrimidin-4-amine,

54) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-quinolin-5-ylpyrimidin-4-amine,

55) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-pyridin-4-ylpyrimidin-4-amine,

56) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidin-4-amine,

57) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-[5-(trifluoromethyl)pyridin-3-yl]pyrimidin-4-amine,

58) 5-(5-fluoropyridin-3-yl)-2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]pyrimidin-4-amine,

59) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-(2-methoxypyridin-3-yl)pyrimidin-4-amine,

60) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-(4-methylpyridin-3-yl)pyrimidin-4-amine,

61) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-(2-methylpyridin-4-yl)pyrimidin-4-amine,

62) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-(4-methoxypyridin-3-yl)pyrimidin-4-amine,

63) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5,5′-bipyrimidin-4-amine,

64) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-amine,

65) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-(1-methyl-1H-pyrazol-5-yl)pyrimidin-4-amine,

66) 5-[1,5-dimethyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]pyrimidin-4-amine,

67) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-[2-(trifluoromethyl)pyridin-4-yl]pyrimidin-4-amine,

68) 5-(3-fluoropyridin-4-yl)-2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]pyrimidin-4-amine,

69) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-[2-(trifluoromethyl)quinolin-4-yl]pyrimidin-4-amine,

70) 5-(6-fluoroquinolin-4-yl)-2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]pyrimidin-4-amine,

71) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-quinolin-4-ylpyrimidin-4-amine,

72) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrimidin-4-amine,

73) 5-[5-(methoxymethyl)-1,3-dimethyl-1H-pyrazol-4-yl]-2-[7-(2,3,6-trifluorobenzyl)imidazo[1,5-b]pyridazin-5-yl]pyrimidin-4-amine,

74) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-amine,

75) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-(3-methylpyridin-4-yl)pyrimidin-4-amine,

76) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-(2-methoxypyridin-4-yl)pyrimidin-4-amine,

77) 5-(3,5-dimethylisoxazol-4-yl)-2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]pyrimidin-4-amine,

78) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-(1-methyl-1H-imidazol-5-yl)pyrimidin-4-amine,

79) 2-[6-fluoro-3-(2,3,6-trifluorobenzyl)imidazo[1,5-a]pyridin-1-yl]-5-[3-(methylsulfonyl)phenyl]pyrimidin-4-amine,

80) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(1-methyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

81) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-2′-methyl-5,5′-bipyrimidine-4,6-diamine,

82) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-pyridin-4-ylpyrimidine-4,6-diamine,

83) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(1-isobutyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

84) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-[1-(3-methylbutyl)-1H-pyrazol-4-yl]pyrimidine-4,6-diamine,

85) 5-(1-tert-butyl-3-methyl-1H-pyrazol-4-yl)-2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

86) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-[1-(cyclopropylmethyl)-3-methyl-1H-pyrazol-4-yl]pyrimidine-4,6-diamine,

87) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-[5-(methoxymethyl)-1,3-dimethyl-1H-pyrazol-4-yl]pyrimidine-4,6-diamine,

88) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

89) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-pyridin-3-ylpyrimidine-4,6-diamine,

90) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(6-fluoropyridin-3-yl)pyrimidine-4,6-diamine,

91) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-[3-(methylsulfonyl)phenyl]pyrimidine-4,6-diamine,

92) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(2-methylpyridin-4-yl)pyrimidine-4,6-diamine,

93) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(5-fluoropyridin-3-yl)pyrimidine-4,6-diamine,

94) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-4-yl]pyrimidine-4,6-diamine,

95) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(5-methoxypyridin-3-yl)pyrimidine-4,6-diamine,

96) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(3,5-dimethylisoxazol-4-yl)pyrimidine-4,6-diamine;

97) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(2-methylpyridin-3-yl)pyrimidine-4,6-diamine,

98) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(6-methylpyridin-3-yl)pyrimidine-4,6-diamine,

99) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(5-methylpyridin-3-yl)pyrimidine-4,6-diamine,

100) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(1-methyl-1H-pyrazol-5-yl)pyrimidine-4,6-diamine,

101) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(6-methoxypyridin-3-yl)pyrimidine-4,6-diamine,

102) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(2-methoxypyridin-4-yl)pyrimidine-4,6-diamine,

103) 5-(2-aminopyridin-4-yl)-2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

104) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(3,5-dimethyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

105) methyl (4-{4,6-diamino-2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidin-5-yl}pyridin-2-yl)carbamate,

106) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(6-methoxypyridin-2-yl)pyrimidine-4,6-diamine,

107) methyl (5-{4,6-diamino-2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidin-5-yl}pyridin-2-yl)carbamate,

108) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(2-methoxypyridin-3-yl)pyrimidine-4,6-diamine,

109) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(3-fluoro-2-morpholin-4-ylpyridin-4-yl)pyrimidine-4,6-diamine,

110) 2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-pyrazin-2-ylpyrimidine-4,6-diamine,

111) N-(5-{4,6-diamino-2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidin-5-yl}pyridin-2-yl)acetamide,

112) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(2-methoxypyridin-4-yl)pyrimidine-4,6-diamine,

113) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-[5-(trifluoromethyl)pyridin-3-yl]pyrimidine-4,6-diamine,

114) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-pyridin-3-ylpyrimidine-4,6-diamine,

115) 5-(6-fluoropyridin-3-yl)-2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

116) 5-(6-aminopyridin-3-yl)-2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

117) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-[3-(methylsulfonyl)phenyl]pyrimidine-4,6-diamine,

118) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-quinolin-5-ylpyrimidine-4,6-diamine,

119) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(2-methylpyridin-4-yl)pyrimidine-4,6-diamine,

120) 3-{4,6-diamino-2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidin-5-yl}quinolin-2-ol,

121) 5-(5-fluoropyridin-3-yl)-2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

122) 5-(2-fluoroquinolin-3-yl)-2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

123) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-pyridin-4-ylpyrimidine-4,6-diamine,

124) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

125) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-4-yl]pyrimidine-4,6-diamine,

126) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]pyrimidine-4,6-diamine,

127) 5-(3,5-dimethylisoxazol-4-yl)-2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

128) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(2-methoxypyridin-4-yl)pyrimidine-4,6-diamine,

129) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-2′,4′-dimethoxy-5,5′-bipyrimidine-4,6-diamine,

130) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(2-methoxypyridin-3-yl)pyrimidine-4,6-diamine,

131) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(5-methoxypyridin-3-yl)pyrimidine-4,6-diamine,

132) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-2′-methyl-5,5′-bipyrimidine-4,6-diamine,

133) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-2′-methoxy-5,5′-bipyrimidine-4,6-diamine,

134) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(6-methoxypyridin-2-yl)pyrimidine-4,6-diamine,

135) 5-(2,6-dimethoxypyridin-3-yl)-2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

136) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(4-methoxypyridin-3-yl)pyrimidine-4,6-diamine,

137) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5,5′-bipyrimidine-4,6-diamine,

138) 5-(4-fluoropyridin-3-yl)-2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

139) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(1,3-thiazol-2-yl)pyrimidine-4,6-diamine,

140) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(4-methyl-2-phenyl-1,3-thiazol-5-yl)pyrimidine-4,6-diamine,

141) N-{4,6-diamino-2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidin-5-yl}-2-methylpropanamide,

142) 2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(1,3-oxazol-2-yl)pyrimidine-4,6-diamine,

143) 5-(2-methylpyridin-4-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

144) 5-(6-fluoropyridin-3-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

145) 2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

146) 5-(5-fluoropyridin-3-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

147) 5-(1-methyl-1H-pyrazol-4-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

148) 5-(2-methylpyridin-4-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

149) 5-pyridin-4-yl-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

150) 5-pyridin-3-yl-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

151) 5-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-4-yl]-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

152) 5-(2-methoxypyridin-4-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

153) 5-(3,5-dimethylisoxazol-4-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

154) 5-(2-methylpyridin-3-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

155) 5-(6-methylpyridin-3-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

156) 2′-methyl-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5,5′-bipyrimidine-4,6-diamine,

157) 5-(3-fluoropyridin-4-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

158) 5-[6-(dimethylamino)pyridin-3-yl]-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

159) 5-(2-methoxypyridin-3-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

160) 5-(6-methoxypyridin-3-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

161) 5-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

162) 5-pyrazin-2-yl-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

163) 5-(4-methoxypyridin-3-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

164) 5-(2,6-dimethoxypyridin-3-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

165) 5-(6-methoxypyridin-2-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

166) 5-pyridin-2-yl-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidine-4,6-diamine,

167) 2-[5-methoxy-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(1-methyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

168) 2-[5-methoxy-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-pyridin-3-ylpyrimidine-4,6-diamine,

169) 2-[5-methoxy-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-[5-(trifluoromethyl)pyridin-3-yl]pyrimidine-4,6-diamine,

170) 2-[5-methoxy-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

171) 5-pyridin-4-yl-2-[3-(2,3,6-trifluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidine-4,6-diamine,

172) 5-(1-methyl-1H-pyrazol-4-yl)-2-[3-(2,3,6-trifluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidine-4,6-diamine,

173) N-{4,6-diamino-2-[5-chloro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidin-5-yl}cyclopropanecarboxamide

174) N-{4,6-diamino-2-[5-fluoro-3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidin-5-yl}cyclopropanecarboxamide,

175) N-{4,6-diamino-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]pyrimidin-5-yl}cyclopropanecarboxamide,

176) 2-[3-(2-cyclopentylethyl)-1H-indazol-1-yl]-5-pyridin-3-ylpyrimidine-4,6-diamine,

177) 2-[3-(2-cyclopentylethyl)-1H-indazol-1-yl]-5-(1-methyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

178) 2-[3-(2-cyclopentylethyl)-1H-indazol-1-yl]-5-(2-methylpyridin-4-yl)pyrimidine-4,6-diamine,

179) 2-[3-(2-cyclopentylethyl)-1H-indazol-1-yl]-5-pyridin-4-ylpyrimidine-4,6-diamine,

180) 2-[3-(2-cyclopentylethyl)-1H-indazol-1-yl]-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

181) 2-[3-(2-cyclopentylethyl)-1H-indazol-1-yl]-5-[5-(trifluoromethyl)pyridin-3-yl]pyrimidine-4,6-diamine,

182) 2-[3-(2-cyclopentylethyl)-1H-indazol-1-yl]-5-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrimidine-4,6-diamine,

183) 2-[5-chloro-3-(2-cyclopentylethyl)-1H-indazol-1-yl]-5-pyridin-3-ylpyrimidine-4,6-diamine,

184) 2-[5-chloro-3-(2-cyclopentylethyl)-1H-indazol-1-yl]-5-(2-methylpyridin-4-yl)pyrimidine-4,6-diamine,

185) 2-[5-chloro-3-(2-cyclopentylethyl)-1H-indazol-1-yl]-5-(1-methyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

186) 2-[5-chloro-3-(2-cyclopentylethyl)-1H-indazol-1-yl]-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

187) 2-{3-(2-cyclopentylethyl)-5-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-1-yl}-5-[5-(trifluoromethyl)pyridin-3-yl]pyrimidine-4,6-diamine,

188) 2-[3-(2-cyclopentylethyl)-5-fluoro-1H-indazol-1-yl]-5-pyridin-3-ylpyrimidine-4,6-diamine,

189) 2-[3-(2-cyclopentylethyl)-5-fluoro-1H-indazol-1-yl]-5-(2-methylpyridin-4-yl)pyrimidine-4,6-diamine,

190) 2-[3-(2-cyclopentylethyl)-5-fluoro-1H-indazol-1-yl]-5-(1-methyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

191) 2-[3-(2-cyclopentylethyl)-5-fluoro-1H-indazol-1-yl]-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

192) 2-(5-chloro-3-pentyl-1H-indazol-1-yl)-5-(1-methyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

193) 2-(5-chloro-3-pentyl-1H-indazol-1-yl)-5-(2-methylpyridin-4-yl)pyrimidine-4,6-diamine,

194) 2-(5-chloro-3-pentyl-1H-indazol-1-yl)-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine, and

195) 2-(3-pentyl-1H-indazol-1-yl)-5-(1,3,5-trimethyl-1H-pyrazol-4-yl)pyrimidine-4,6-diamine,

or a pharmaceutically acceptable salt thereof.