US 9,284,301 B2 · Soluble guanylate cyclase activators

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.

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.

193 more elements

Soluble guanylate cyclase activators

Life of this patent

Soluble guanylate cyclase activators

Life of this patent

Abstract

Claims4