ES2523720T3 - Benzoimidazoles como inhibidores de prolilhidroxilasa - Google Patents

Benzoimidazoles como inhibidores de prolilhidroxilasa Download PDF

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ES2523720T3
ES2523720T3 ES09739552.9T ES09739552T ES2523720T3 ES 2523720 T3 ES2523720 T3 ES 2523720T3 ES 09739552 T ES09739552 T ES 09739552T ES 2523720 T3 ES2523720 T3 ES 2523720T3
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carboxylic acid
chloro
benzimidazol
pyrazol
alkyl
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Frances Meredith Hocutt
Barry Eastman Leonard
Hillary M. Peltier
Victor K. Phuong
Michael H. Rabinowitz
Mark D. Rosen
Kyle T. Tarantino
Hariharan Venkatesan
Lucy Xiumin Zhao
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Janssen Pharmaceutica NV
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    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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    • C07D513/04—Ortho-condensed systems

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Abstract

Un compuesto que tiene actividad de inhibidor de PHD de fórmula (I):**Fórmula** en la que:~ n es 2-4 cada R1 está seleccionado independientemente de H, halógeno, -alquilo C1-4, -cicloalquilo C3-8, -perhaloalquilo C1-4, trifluoroalcoxi C1-4, -OH, -NO2, -CN, CO2H, -O-alquilo C1-4, -S-alquilo C1-4, -S(alquil C1-4)-Rc, -S(O)2(alquil C1-4)-Rc, - S(O)-alquilo C1-4, -SO2-alquilo C1-4, -S-Rc, -S(O)-Rc, -SO2-Rc, -SO2-NH-Rc, -O-Rc, -CH2-O-Rc, -C(O)NH-Rc, -NRaRb, benciloxi opcionalmente sustituido con Rd, fenilo o heteroarilo monocíclico opcionalmente sustituido con Rd, - cicloalquilo C3-8 que opcionalmente contiene uno o más O, S o N en el que dicho -cicloalquilo C3-8 está opcionalmente sustituido con Rd, benciloxi-fenilo opcionalmente sustituido con hasta tres halógeno, cianobifenil-4- ilmetilsulfanilo, ciano-bifenil-4-ilmetanosulfonilo, -S-(CH2)2-morfolina y -C(O)-NH-morfolina, y dos grupos R1 adyacentes pueden unirse para formar un anillo de 3-8 miembros opcionalmente sustituido que opcionalmente contiene uno o más O, S o N; Ra y Rb son cada uno independientemente H, alquilo C1-4, -C(O)alquilo C1-4, -C(O)-Rc, -C(O)CH2-Re, alquil C1-4-Re, - SO2-Rc, -SO2-alquilo C1-4, fenilo opcionalmente sustituido con Rd, bencilo opcionalmente sustituido con Rd o anillo de heteroarilo monocíclico opcionalmente sustituido con Rd; o Ra y Rb pueden tomarse conjuntamente con el nitrógeno al que están unidos para formar un anillo de heterocicloalquilo monocíclico opcionalmente sustituido que opcionalmente contiene uno o más heteroátomos; Rc es -cicloalquilo C3-8, fenilo opcionalmente sustituido con Rd, bencilo opcionalmente sustituido con Rd, o un anillo de heteroarilo monocíclico opcionalmente sustituido con Rd; Rd es independientemente -H, halógeno, -OH, -alquilo C1-4 o -perhaloalquilo C1-4, trifluoroalcoxi C1-4, -O-alquilo C1-4, - O-fenilo o -O-bencilo; Re es -heterocicloalquilo C3-8 que opcionalmente contiene uno o más O, S o N; R2 y R3 son ambos H, -CF3 o alquilo C1-3; cada Z es C; o cada Z es C o N, a condición de que exactamente dos Z sean simultáneamente N; y enantiómeros, diaestereómeros, racematos y sales farmacéuticamente aceptables de los mismos..

Description

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E09739552
12-11-2014
trifluorometilo, 6-cloro-5-(4-cloro-fenoxi), (4-cloro-fenoxi)-6-trifluorometoxi, 5-fenoxi-6-trifluorometoxi, 4-fluoro-fenoxi)6-trifluorometilo, (4-cloro-fenoxi)-6-trifluorometilo, 5-fenoxi-6-trifluorometilo, 6-cloro-5-fenoxi, 5-benciloxi-6-cloro, 6cloro-5-m-tolilsulfanilo, 6-cloro-5-(4-cloro-fenilsulfanilo, 6-cloro-5-fenilsulfanilo, 6-cloro-5-(3,4-dicloro-fenilsulfanilo, 6cloro-5-(3-metoxi-fenilsulfanilo, 6-cloro-5-(4-metoxi-fenilsulfanilo), 5-bencilsulfanil-6-cloro, 4-terc-butil-bencilsulfanil)5 6-cloro, 6-cloro-5-(4-fluoro-bencilsulfanilo, 6-cloro-5-(2-cloro-bencilsulfanilo, 6-cloro-5-fenetilsulfanilo, 6-cloro-5(tolueno-3-sulfonilo, 5-bencenosulfonil-6-cloro, 6-cloro-5-(4-metoxi-bencenosulfonilo, 6-cloro-5-(4-clorobencenosulfonilo, 6-cloro-5-(4-trifluorometoxi-bencenosulfonilo, 6-cloro-5-(3,4-dicloro-bencenosulfonilo, 6-cloro-5-(3metoxi-bencenosulfonilo, 6-cloro-5-fenilmetanosulfonilo, 6-cloro-5-(2,4,6-trimetil-fenilmetanosulfonilo, 6-cloro-5-(4metoxi-fenilmetanosulfonilo, cloro-5-(4-fluoro-fenilmetanosulfonilo, 6-cloro-5-(2-cloro-fenilmetanosulfonilo, 6-cloro-510 (2-fenil-etanosulfonilo, 5-bencenosulfinil-6-cloro, 5-fenilcarbamoílo, 5-bencilcarbamoílo, 5-(morfolin-4-ilcarbamoílo), 5benciloximetilo, 5-bencilamino, 6-cloro-5-fenilamino, 6-cloro-5-(2-morfolin-4-il-etilamino), 5-bencenosulfonilamino-6cloro, 5-benzoilamino-6-cloro, 6-cloro-5-(2-morfolin-4-il-acetilamino), 6-cloro-5-(2-piperidin-1-il-acetilamino), 6-cloro-5[2-(4-metil-piperazin-1-ilo, 6-cloro-5-(4-metoxi-fenoxi), 6-cloro-5-(4-cloro-2-fluoro-fenoxi), 6-cloro-5-(4-trifluorometoxifenoxi), 6-cloro-5-(3-cloro-4-fluoro-fenoxi), 5-fenilsulfanil-6-trifluorometilo, 5-(4-metoxi-fenilsulfanil)-6-trifluorometilo, 515 bencenosulfonil-6-trifluorometilo, 5-(4-metoxi-bencenosulfonil)-6-trifluorometilo, 6-cloro-5-(4-cloro-bencilsulfanilo, 6cloro-5-(3-cloro-bencilsulfanilo), 6-cloro-5-ciclohexilmetilsulfanilo, 6-cloro-5-(2-morfolin-4-il-etilsulfanilo), -cloro-5-(3,4dicloro-bencilsulfanilo, 6-cloro-5-(2,6-dicloro-bencilsulfanilo), 6-cloro-5-(4-metil-bencilsulfanilo), 6-cloro-5-(4trifluorometil-bencilsulfanilo), 5-(2,4-bis-trifluorometil-bencilsulfanil)-6-cloro, 6-cloro-5-(2'-ciano-bifenil-4ilmetilsulfanilo), 6-cloro-5-(4-cloro-fenilmetanosulfonilo), 6-cloro-5-(3-cloro-fenilmetanosulfonilo), cloro-5
20 ciclohexilmetanosulfonilo, 6-cloro-5-(3,4-dicloro-fenilmetanosulfonilo), 6-cloro-5-(2,6-dicloro-fenilmetanosulfonilo), cloro-5-p-tolilmetanosulfonilo, 6-cloro-5-(4-trifluorometil-fenilmetanosulfonilo), 5-(2,4-bis-trifluorometil-bencilsulfanilo), cloro-5-(2'-ciano-bifenil-4-ilmetanosulfonilo y 6-cloro-5-fenilsulfamoílo.
Compuestos a modo de ejemplo de la presente invención se exponen en la tabla a continuación. 25
30
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40
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50
55
Ex.
Nombre químico Encima pIC50 % Celular EPO Estimulación
1
1-(1H-benzimidazol-2-il) -1H-pirazol-4-ácidocarboxílico; 6.1 7.1
2
1-(5,6-dicloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.9 151.91
3
1-(5-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.6 109.74
4
1-(5-cloro-6-fluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.7 132.79
5
1-(5,6-dimetil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.1 2.1
6
1-(5-bromo-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.4 9.91
7
1-(5-metoxi-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.4 16.8
8
1-(4-cloro-6-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.8 20.97
9
1-(5,6-dimetoxi-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.4 4.26
10
1-(4,5-dimetil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 5.1 10.7
11
1-(5-trifluorometoxi -1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.5 123.68
13
E09739552
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(Continuación)
15
25
35
45
55
Ex.
Nombre químico Encima pIC50 % Celular EPO Estimulación
12
1-{5-[3-(3-cloro-benciloxi) fenil] -1H-benzimidazol-2-il} -1H-pirazol-4ácido carboxílico; 7.5 8.76
13
1-{5-[3-(2-cloro-benciloxi) fenil] -1H-benzimidazol-2-il} -1H-pirazol-4ácido carboxílico; 7.6 18
14
1-{5-[3-(4-cloro-benciloxi) fenil] -1H-benzimidazol-2-il} -1H-pirazol-4ácido carboxílico; 7.4 20.15
15
1-[5-(3-benciloxi-fenil) -1H-benzimidazol-2-il] -1H-pirazol-4-ácido carboxílico; 7.3 10.77
16
1-[5-(4-benciloxi-fenil) -1H-benzimidazol-2-il] -1H-pirazol-4-ácido carboxílico; 6.7 6.97
17
1-[5-(3-trifluorometil-fenil) -1H-bencimidazol-2-il] -1H-pirazol-4-ácido carboxílico; 7.1 5.8
18
1-[5-(3,4-dicloro-fenil) -1H-benzimidazol-2-il] -1H-pirazol-4-ácido carboxílico; 7.1 15.3
19
1-(5-bromo-1H-benzimidazol-2-il) -3-trifluorometil-1H-pirazol-4-ácido carboxílico; <4 20.52
20
1-(5,6-dicloro-1H-benzimidazol-2-il) -3-trifluorometil-1H-pirazol-4-ácido carboxílico; <4 18.81
21
1-(5-bromo-1H-benzimidazol-2-il) -3,5-dimetil-1-H-pirazol-4-ácido carboxílico; 4.2 7.24
22
1-(ácido 5,6-dicloro-1H-benzimidazol-2-il-3,5-dimetil-1H-pirazol-4-ácido carboxílico; <4 0.47
23
1-[5-(4-hidroxi-fenil) -1H-benzimidazol-2-il-1H-pirazol-4-ácido carboxílico; 6.6 6.49
24
1-[5-(3-hidroxi-fenil) -1H-benzimidazol-2-il] -1H-pirazol-4-ácido carboxílico; 6.5 11.15
25
1-(5-cloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.3 71.87
26
1-(5-Bromo-6,7-dimetil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.4 11.9
27
1-(4-cloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.1 19.12
28
1-(5-cloro-7-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.4 16.6
29
1-(7-Bromo-5-trifluorometoxi-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.8 57.55
30
1-(6-cloro-5-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico 7.14 128.94
31
1-(4,5,6-trifluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7 18.2
32
1-(4-Bromo-5,6-difluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.7 33
33
1-(6-cloro-4-metil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6 13.4
34
1-(4,6-dicloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.5 56.3
14
E09739552
12-11-2014
(Continuación)
15
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Nombre químico Encima pIC50 % Celular EPO Estimulación
35
1-(4-Bromo-6-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.8 29.7
36
1-(5,6-difluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.6 79.4
37
1-(4-Bromo-6-cloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.6 34.03
38
1-(6-metanosulfonil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.1 40.93
39
1-(6-cloro-5-ciano-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.4 29.93
40
1-(6-cloro-5-nitro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.5 93.44
41
1-(5-Amino-6-cloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.4 30
42
1-(5-fluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.3 33.76
43
1-(6-cloro-5-pirrolidin-1-il-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.7 177.5
44
1-(6-cloro-5-piperidin-1-il-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.7 138.8
45
1-(6-cloro-5-morfolin-4-il-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.6 30.85
46
1-(6-cloro-5-metoxi-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.5 76
47
2-(4-carboxi-pirazol-1-il) ácido 1H-benzoimidazol-5-ácido carboxílico; 6.6 11
48
Ácido 1-(5-Bromo-7-fluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.3 44
49
1-(5-Bromo-7-metil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.1 24
50
1-[5-(3,4-dicloro-fenoxi) -6-trifluorometil-1H-benzimidazol-2-il] -1Hpirazol-4-ácido carboxílico; 7.4 17.98
51
1-[6-cloro-5-(4-cloro-fenoxi) -1H-benzimidazol-2-il] ácido 1H-pirazol-4ácido carboxílico; 7.4 150.4
52
1-[5-(4-cloro-fenoxi) -6-trifluorometoxi-1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 7.4 21.55
53
1-(5-fenoxi-6-trifluorometoxi-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.2 137.71
54
1-[5-(4-fluoro-fenoxi) -6-trifluorometil-1H-benzimidazol-2-il] -1H-pirazol-4ácido carboxílico; 7.3 75.52
55
1-[5-(4-cloro-fenoxi) -6-trifluorometil-1H-benzimidazol-2-il] -1H-pirazol-4ácido carboxílico; 7.5 44.23
56
1-(5-fenoxi-6-trifluorometil-1H-benzoim idazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.2 142.55
57
1-(6-cloro-5-fenoxi-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.9 55
15
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Nombre químico Encima pIC50 % celular EPO Estimulación
58
1-(5-Bromo-7-metil-1H-imidazo [4,5-f] quinolin-2-il) -1H-pirazol-4-ácido carboxílico; 7.2 50
59
1-(5-benciloxi-6-cloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.4 55.9
60
1-(6-cloro-5-m-tolylsulfanyl-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.9 42.30
61
1-[6-cloro-5-(4-cloro-fenilsulfanil) -1H-benzimidazol-2-il] -1H-pirazol-4ácido carboxílico; 7.07 101.2
62
1-(6-cloro-5-fenilsulfanil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.75 45.84
63
1-[6-cloro-5-(3,4-dicloro-fenilsulfanil) -1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 6.18 26.54
64
1-[6-cloro-5-(3-metoxi-fenilsulfanil) -1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 6.9 38.26
65
1-[6-cloro-5-(4-metoxi-fenilsulfanil) -1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 6.6 56.3
66
1-(5-bencilsulfanil-6-cloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.7 41.64
67
1-[5-(4-terc-Butil-bencilsulfanil) -6-cloro-1H-benzimidazol-2-il] -1Hpirazol-4-ácido carboxílico; 7.2 11.72
68
1-[6-cloro-5-(4-fluoro-bencilsulfanil) -1H-benzoim idazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 6.8 58.37
69
1-[6-Ch) oro-5-(2-cloro-bencilsulfanil) -1H-benzimidazol-2-il] -1H-pirazol4-ácido carboxílico; 6.8 85.3
70
1-(6-cloro-5-phenethylsulfanyl-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.7 74.24
71
1-(6-metilsulfanil-5-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4ácido carboxílico; 7.1 113.95
72
1-(6-propilsulfanil-5-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4ácido carboxílico; 7.1 NT
73
1-(6-isopropilsulfanil-5-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4ácido carboxílico; 7.2 NT
74
1-(5-fluoro-6-metilsulfanil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.9 77.795
75
1-(5-cloro-6-metilsulfanil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7 106.17
76
1-(5-cloro-6-etilsulfanil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.9 211.75
77
1-(5-cloro-6-isopropilsulfanil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.8 152.89
78
1-(5-cloro-6-propilsulfanil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7 125.21
79
1-(6-metilsulfanil-5-trifluorometoxi-1H-benzimidazol-2-il) -1H-pirazol-4ácido carboxílico; 7.1 83.83
16
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Nombre químico Encima pIC50 % Celular EPO Estimación
80
1-(6-isopropilsulfanil-5-trifluorometoxi-1H-benzimidazol-2-il) -1H-pirazol-4ácido carboxílico; 7 NT
81
1-(6-propilsulfanil-5-trifluorometoxi-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7 NT
82
1-[6-cloro-5-(tolueno-3-sulfonil) -1H-benzimidazol-2-il] -1H-pirazol-4-ácido carboxílico; 7.4 85.32
83
1-(5-bencenosulfonil-6-cloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.57 96.65
84
1-[6-cloro-5-(4-metoxi-bencenosulfonil) -1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 7.3 42.71
85
1-[6-cloro-5-(4-cloro-bencenosulfonil) -1H-benzimidazol-2-il] -1H-pirazol-4ácido carboxílico; 7.3 51.64
86
1-[6-cloro-5-(4-trifluorometoxi-bencenosulfonil) -1H-benzimidazol-2-il] ácido 1H-pirazol-4-ácido carboxílico; 7.3 48.9
87
1-[6-cloro-5-(3,4-dicloro-bencenosulfonil) -1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 6.68 32.39
88
1-[6-cloro-5-(3-metoxi-bencenosulfonil) -1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 7.4 69.43
89
1-(6-cloro-5-fenilmetanosulfonil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.5 28.45
90
1-[6-cloro-5-(metanosulfonil 2,4,6-trimetilfenil) -1H-bencimidazol-2-il] -1Hpirazol-4-ácido carboxílico; 7.3 8.25
91
1-[6-cloro-5-(4-metoxi-fenilmetanosulfonilo) -1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 7.7 22.01
92
1-[6-cloro-5-(4-fluoro-fenilmetanosulfonilo) -1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 7.5 61.2
93
1-[6-cloro-5-(2-cloro-fenilmetanosulfonilo) -1H-benzimidazol-2-il] -1H-pirazol4-ácido carboxílico; 7.5 78.5
94
1-[6-cloro-5-(2-fenil-etanosulfonil) -1H-benzimidazol-2-il] -1H-pirazol-4-ácido carboxílico; 7.4 65.1
95
1-(5-cloro-6-etanosulfinil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.2 46.3
96
1-(5-cloro-6-etanosulfonil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.4 67
97
1-(6-metanosulfonil-5-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.6 75.88
98
1-(5-fluoro-6-metanosulfonil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.3 41.37
99
1-(5-cloro-6-metanosulfonil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.4 34.85
100
1-(6-metanosulfonil-5-trifluorometoxi-1H-benzimidazol-2-il) -1H-pirazol-4ácido carboxílico; 7.5 50.16
101
1-[5-cloro-6-(propano-2-sulfonil) -1H-benzimidazol-2-il] -1H-pirazol-4-ácido carboxílico; 7.3 62.2
17
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Nombre químico Encima pIC50 % Celular EPO Estimulación
102
1-[5-cloro-6-(propano-1-sulfonil) -1H-benzimidazol-2-il] -1H-pirazol-4-ácido carboxílico; 7.5 54.94
103
1-[6-(propano-2-sulfonil) -5-trifluorometil-1H-benzimidazol-2-il] -1H-pirazol-4ácido carboxílico; 7.4 NT
104
1-[6-(propano-1-sulfonil) -5-trifluorometil-1H-benzimidazol-2-il] -1H-pirazol-4ácido carboxílico; 7.5 NT
105
1-[6-(propano-2-sulfonil) -5-trifluorometoxi-1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 7.4 NT
106
1-[6-(propano-1-sulfonil) -5-trifluorometoxi-1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 7.5 123.7
107
1-(5-bencenosulfinil-6-cloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.2 47.57
108
1-(6-Metanosulfinil-5-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxılico; 7.3 20.41
109
1-(6-Bromo-5-fluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.7 99
110
1-(4-fluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.2 45.87
111
1-(4,5-difluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.6 32.58
112
1-(4,6-difluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.8 31.96
113
1-(6-cloro-5-trifluorometoxi-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.98 109.33
114
1-(1H-nafto [2,3-d] imidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.3 144.2
115
1-(3H-nafto [1,2-d] imidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.1 50
116
1-(5-fluoro-4-metil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 5.8 18.3
117
1-(5-piperidin-1-il-6-trifluorometoxi-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico 6.5 80
118
1-(5-fluoro-6-piperidin-1-il-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.8 152
119
1-(6-etoxi-5-fluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.5 69
120
1-(5-fenilcarbamoil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.9 21.15
121
1-(5-bencilcarbamoil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.1 18.5
122
1-[5-(morfolin-4-ilcarbamoil) -1H-benzimidazol-2-il] -1H-pirazol-4-ácido carboxílico; 6.6 5.4
123
1-(5-benciloximetil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.3 61.15
124
1-(4-Bromo-6-fluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.3 2.4
125
1-(8H-imidazo (4 ', 5': 3,4] benzo [2,1-d] tiazol-7-il) -1H-pirazol-4-ácido carboxílico; 6 46.75
18
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Nombre químico Encima pIC50 % Celular EPO Estimulación
126
1-(5,6-bis-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.4 82.65
127
1-(4,5,6-tricloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.9 70.6
128
1-(4-Bromo-5,6-dicloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.1 24.1
129
1-(6-fluoro-5-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7 70.8
130
1-(6-cloro-5-etilamino-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.2 48
131
1-(6-cloro-5-propilamino-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.5 89
132
1-(5-bencilamino-6-cloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.2 52.6
133
1-(6-cloro-5-fenilamino-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.9 77
134
1-[6-cloro-5-(2-morfolin-4-il-etilamino) -1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 6.3 56.5
135
1-(6-cloro-5-cyclopropanesulfonylamino-1H-benzimidazol-2-il) -1H-pirazol-4ácido carboxílico; 6.8 17
136
1-(6-cloro-5-metanosulfonilamino-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.8 9
137
1-(6-cloro-5-etanosulfonilamino-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.6 11
138
1-(5-bencenosulfonilamino-6-cloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.8 19
139
1-(5-acetilamino-6-cloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.3 24
140
1-(6-cloro-5-propionilamino-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.4 10
141
1-(5-benzoilamino-6-cloro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.6 33
142
1-[6-cloro-5-(2-morfolin-4-il-acetilamino) -1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 6.4 17
143
1-[6-cloro-5-(2-piperidin-1-il-acetilamino) -1H-benzimidazol-2-il] ácido 1Hpirazol-4-ácido carboxílico; 6.2 20
144
1-{6-cloro-5-[2-(4-metil-piperazin-1-il) acetil amino] -1H-bencimidazol-2-il} 1H-pirazol-4-ácido carboxílico; 6.4 16
145
1-[6-cloro-5-(4-metoxi-fenoxi) -1H-benzimidazol-2-il] ácido 1H-pirazol-4carboxílico; 7.1 13.92
146
1-[6-cloro-5-(4-cloro-2-fluoro-fenoxi) -1H-benzimidazol-2-il] ácido 1H-pirazol4-carboxílico; 7.2 49.85
147
1-[6-cloro-5-(4-trifluorometoxi-fenoxi) -1H-benzimidazol-2-il] ácido 1Hpirazol-4-carboxílico; 7.4 45.85
19
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Nombre químico Encima pIC50 % Celular EPO Estimulación
148
1-[6-cloro-5-(3-cloro-4-fluoro-fenoxi) -1H-benzimidazol-2-il] ácido 1H-pirazol4-ácido carboxílico; 7.1 38.12
149
1-(5-etilsulfanil-6-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.3 57.8
150
1-(5-etilsulfanil-6-trifluorometoxi-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.2 47.2
151
1-(5-etilsulfanil-6-fluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.9 106.61
152
1-(6-fluoro-5-propilsulfanil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.9 91.38
153
1-(6-fluoro-5-isopropilsulfanil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 6.9 NT
154
1-(5-etilsulfonil-6-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4-acído carboxílico; 7.6 53.82
155
1-(5-etilsulfonil-6-trifluorometoxi-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.6 47.21
156
1-(5-etilsulfonil-6-fluoro-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.4 51.9
157
1-(6-fluoro-5-propilsulfonilo-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.4 NT
158
1-(6-fluoro-5-isopropil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.3 NT
159
1-(5-fenilsulfanil-6-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.4 11.01
160
1-[5-(4-metoxi-fenilsulfanil) -6-trifluorometil-1H-benzimidazol-2-il] -1H-pirazol4-ácido carboxílico; 7.5 36.1
161
1-(5-bencenosulfonil-6-trifluorometil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.6 98.15
162
1-[5-(4-metoxi-bencenosulfonil) -6-trifluorometil-1H-benzimidazol-2-il] -1Hpirazol-4-ácido carboxílico; 7.6 45.8
163
1-[6-cloro-5-(4-cloro-bencilsulfanil) -1H-benzimidazol-2-il] -1H-pirazol-4-ácido carboxílico; 6.5 36.98
164
1-[6-cloro-5-(3-cloro-bencilsulfanil) -1H-benzimidazol-2-il] -1H-pirazol-4-ácido carboxílico; 6.6 27.4
165
1-(6-cloro-5-cyclohexylmethylsulfanyl-1H-benzimidazol-2-il) -1H-pirazol-4ácido carboxílico; 6.9 27.3
166
1-[6-cloro-5-(2-morfolin-4-il-etilsulfanil) -1H-benzimidazol-2-il] 1H-pirazol-4ácido carboxílico; 7 15.1
167
1-[6-cloro-5-(3,4-dicloro-bencilsulfanil) -1H-benzimidazol-2-il] 1H-pirazol-4ácido carboxílico; 6.4 25.8
168
1-[6-cloro-5-(2,6-dicloro-bencilsulfanil) -1H-benzimidazol-2-il] 1H-pirazol-4ácido carboxílico; 7.3 50.14
169
1-[6-cloro-5-(4-metil-bencilsulfanil) -1H-benzoim idazol-2-il] -1H-pirazol-4ácido carboxílico; 6.7 NT
20
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Nombre químico Encima pIC50 % Celular EPO Estimulación
170
1-[6-cloro-5-(4-trifluorometil-bencilsulfanil) -1H-benzimidazol-2-il] -1H-pirazol4-ácido carboxílico; 6.7 NT
171
1-[5-(2,4-Bis-trifluorometil-benzilsulfanil)-6-cloro-1H-benzoimidazol-2-il]-1Hpirazol-4-carboxílico ácido; 6.7 NT
172
1-[6-Cloro-5-(2’-ciano-bifenil-4-ilmetillsulfanil)-1H-benzoimidazol-2-yl]-1Hpirazol-4-carboxílico ácido; 7.5 NT
173
1-[6-cloro-5-(4-cloro-fenilmetanosulfonilo) -1H-benzimidazol-2-il] -1H-pirazol4-ácido carboxílico; 7.8 60.41
174
1-[6-cloro-5-(3-cloro-fenilmetanosulfonilo) -1H-benzimidazol-2-il] -1H-pirazol4-ácido carboxílico; 7.6 40.9
175
1-(6-cloro-5-ciclohexil metanosulfonil-1H-bencimidazol-2-il) -1H-pirazol-4ácido carboxílico; 7.7 48.7
176
1-[6-cloro-5-(3,4-dicloro-fenilmetanosulfonilo) -1H-benzimidazol-2-il] ácido 1H-pirazol-4-ácido carboxílico; 7.6 44.23
177
1-[6-cloro-5-(2,6-dicloro-fenilmetanosulfonilo) -1H-benzimidazol-2-il] ácido 1H-pirazol-4-ácido carboxílico; 7.5 66.6
178
1-(6-cloro-5-p-tolylmethanesulfonyl-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico; 7.7 NT
179
1-[6-cloro-5-(metanosulfonil 4-trifluorometil-fenil) -1H-bencimidazol-2-il] -1Hpirazol-4-ácido carboxílico; 7.7 NT
180
1-[5-(metanosulfonil 2,4-Bis-trifluorometil-fenil) -6-cloro-1H-bencimidazol-2-il] -1H-pirazol-4-ácido carboxílico; 7.6 NT
181
1-[1H-bencimidazol-2-il 6-cloro-5-(2 '-cianobifenil-4-il metanosulfonilo)] -1Hpirazol-4-ácido carboxílico; 7.7 NT
182
1-(1H-imidazo [4,5-b] quinoxalin-2-il) -1H-pirazol-4-ácido carboxílico; 5.5 13.4
183
1-(6,7-dicloro-1H-imidazo [4,5-b] quinoxalin-2-il) -1H-pirazol-4-ácido carboxílico; 6.4 3.3
184
1-(1H-imidazo [4,5-b] pirazin-2-il) -1H-pirazol-4-ácido carboxílico; 5.9 8.3
185
1-(6-cloro-9H-purin-8-il) -1H-pirazol-4-ácido carboxílico 5.3 11.7
186
1-(6-cloro-5-fenilsulfamoil-1H-benzimidazol-2-il) -1H-pirazol-4-ácido carboxílico. 7.4 39.1
La invención también incluye sales farmacéuticamente aceptables de los compuestos de fórmula (I), preferentemente de aquellos descritos anteriormente y de los compuestos específicos ejemplificados en el presente documento, y su uso en procedimientos de tratamiento.
55 Una “sal farmacéuticamente aceptable” pretende significar una sal de un ácido o base libre de un compuesto representado por la fórmula (I) que es no tóxico, biológicamente tolerable, o de otro modo biológicamente adecuado para administración al sujeto. Véanse, generalmente, G.S. Paulekuhn y col., “Trends in Active Pharmaceutical Ingredient Salt Selection based on Analysis of the Orange Book Database”, J. Med. Chem., 2007, 50:6665-72, S.M. Berge y col., “Pharmaceutical Salts”, J Pharm Sci., 1977, 66:1-19, y Handbook of Pharmaceutical Salts, Properties, Selection, and Use, Stahl and Wermuth, Eds., Wiley-VCH and VHCA, Zurich, 2002. Ejemplos de sales farmacéuticamente aceptables son aquellas que son farmacológicamente eficaces y adecuadas para el contacto con los tejidos de pacientes sin excesiva toxicidad, irritación o respuesta alérgica. Un compuesto de fórmula (I) puede poseer un grupo suficientemente ácido, un grupo suficientemente básico, o ambos tipos de grupos funcionales, y por
65 consiguiente reaccionar con varias bases inorgánicas u orgánicas, y ácidos inorgánicos y orgánicos, para formar una sal farmacéuticamente aceptable. Ejemplos de sales farmacéuticamente aceptables incluyen sulfatos, pirosulfatos,
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Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2294066B9 (en) * 2008-04-28 2015-03-11 Janssen Pharmaceutica, N.V. Benzoimidazoles as prolyl hydroxylase inhibitors
ES2360316B1 (es) 2008-12-10 2012-05-08 Antonio Avila Chulia Procedimiento para la encriptación y autentificación de una señal de datos.
EP2396316B1 (en) 2009-02-10 2015-07-01 Janssen Pharmaceutica, N.V. Quinazolinones as prolyl hydroxylase inhibitors
JP2013500267A (ja) * 2009-07-23 2013-01-07 ヴァンダービルト ユニバーシティー ｍＧＬｕＲ４増強剤としての置換されたベンゾイミダゾールスルホンアミド類および置換されたインドールスルホンアミド類
JP5934645B2 (ja) 2009-09-11 2016-06-15 プロビオドルグ エージー グルタミニルシクラーゼ阻害剤としてのヘテロ環式誘導体
US8242284B1 (en) * 2009-09-21 2012-08-14 The United States Of America As Represented By The United States Department Of Energy Anti-cancer agents based on 6-trifluoromethoxybenzimidazole derivatives and method of making
BR112012010738A2 (pt) * 2009-11-06 2019-09-24 Univ Vanderbilt ''aril e heteroaril sulfonas como potenciadores alostéricos de mglur4,composições e métodos de tratamento de disfunção neurológica''
US8680098B2 (en) 2010-03-05 2014-03-25 Janssen Pharmaceutica, Nv Substituted aza-bicyclic imidazole derivatives useful as TRPM8 receptor modulators
WO2012033149A1 (ja) 2010-09-10 2012-03-15 塩野義製薬株式会社 Ａｍｐｋ活性化作用を有するヘテロ環縮合イミダゾール誘導体
GB201102659D0 (en) 2011-02-15 2011-03-30 Isis Innovation Assay
CN102219745B (zh) * 2011-04-15 2013-10-30 清华大学深圳研究生院 2-芳基取代苯并咪唑类衍生物及其制备方法与应用
GB201113101D0 (en) 2011-07-28 2011-09-14 Isis Innovation Assay
WO2013043624A1 (en) * 2011-09-23 2013-03-28 Merck Sharp & Dohme Corp. Substituted pyrimidines
WO2013043621A1 (en) 2011-09-23 2013-03-28 Merck Sharp & Dohme Corp. Substituted pyrimidines
US9273034B2 (en) * 2011-10-25 2016-03-01 Janssen Pharmaceutica Nv Meglumine salt formulations of 1-(5,6-dichloro-1H-benzo[D]imidazol-2-yl)-1H-pyrazole-4-carboxylic acid
CA2881806A1 (en) * 2012-08-23 2014-02-27 Mitsubishi Tanabe Pharma Corporation Pyrazolopyrimidine compound
TW201534597A (zh) 2013-06-20 2015-09-16 Ab Science 作為選擇性蛋白質激酶抑制劑之苯并咪唑衍生物
JP6506390B2 (ja) 2014-09-02 2019-04-24 サンシャイン・レイク・ファーマ・カンパニー・リミテッドＳｕｎｓｈｉｎｅ Ｌａｋｅ Ｐｈａｒｍａ Ｃｏ．，Ｌｔｄ． キノリノン系化合物及びその薬物への使用
BR112019010511A2 (pt) 2016-11-23 2019-09-17 Bayer Ag derivados de heterociclo bicíclico fundido como pesticidas
CR20200059A (es) 2017-07-07 2020-06-01 Immatics Biotechnologies Gmbh Nuevos péptidos y nuevas combinaciones de péptidos para el uso en la inmunoterapia contra el cáncer de pulmón, incluyendo el nsclc, el sclc y otros cánceres
JP7458987B2 (ja) * 2018-09-13 2024-04-01 キッセイ薬品工業株式会社 イミダゾピリジノン化合物
TWI803696B (zh) * 2018-09-14 2023-06-01 日商橘生藥品工業股份有限公司 次黃嘌呤化合物
US20210369678A1 (en) * 2018-10-03 2021-12-02 Akebia Therapeutics, Inc. Benzimidazole derivative for use in the treatment of inflammatory disorders
CN110305072B (zh) * 2019-06-25 2023-09-19 中国药科大学 具有磷酸二酯酶4d和酸性鞘磷脂酶抑制活性的化合物及其应用
CN115135384B (zh) 2019-11-28 2024-03-22 日本农药株式会社 苯并咪唑化合物或其盐类、和含有该化合物的农艺和园艺用杀虫杀螨剂以及其使用方法
JP7385467B2 (ja) * 2019-12-26 2023-11-22 キッセイ薬品工業株式会社 ヒポキサンチン化合物
CN113248475B (zh) * 2020-02-11 2023-03-17 中国科学院上海药物研究所 一类杂环取代的苯并咪唑二聚体或其药学上可接受的盐、组合物及其用途
CN115244054B (zh) * 2020-03-11 2024-07-16 橘生药品工业株式会社 次黄嘌呤化合物的晶体
JP7504822B2 (ja) * 2020-03-12 2024-06-24 キッセイ薬品工業株式会社 イミダゾピリジノン化合物を含む医薬組成物
WO2021216530A1 (en) 2020-04-20 2021-10-28 Akebia Therapeutics, Inc. Treatment of viral infections, of organ injury, and of related conditions using a hif prolyl hydroxylase inhibitor or a hif-alpha stabilizer
CN112209885A (zh) * 2020-09-07 2021-01-12 宁夏大漠药业有限公司 芬苯达唑生产工艺及生产装置
WO2022150623A1 (en) 2021-01-08 2022-07-14 Akebia Therapeutics, Inc. Compounds and composition for the treatment of anemia
CN117999069A (zh) 2021-05-27 2024-05-07 凯克斯生物制药公司 柠檬酸铁的儿科调配物
USD1029155S1 (en) 2021-06-25 2024-05-28 Spin Master Ltd. Toy
US11376515B1 (en) * 2021-06-29 2022-07-05 Spin Master Ltd. Transformable toy
EP4479403A4 (en) * 2022-02-18 2026-02-11 Insilico Medicine Ip Ltd MEMBRANE-ASSOCIATED TYROSINE AND THREONIN-SPECIFIC CDC2 KINASE INHIBITORS (PKMYT1) AND THEIR USES
US12576341B2 (en) 2022-08-12 2026-03-17 Spin Master Ltd. Transformable toy
US11712636B1 (en) 2022-08-12 2023-08-01 Spin Master Ltd. Transformable toy
WO2025049599A1 (en) 2023-08-29 2025-03-06 President And Fellows Of Harvard College Methods for treating muscle-related disorders by modulating prolyl hydroxylase 3

Family Cites Families (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS60227260A (ja) 1983-11-14 1985-11-12 Toppan Printing Co Ltd セツトアツプ方法
EP0266940B1 (en) 1986-10-22 1992-12-16 Schering Corporation Use of recombinant human alpha interferon for the manufacture of a medicament for the treatment of aids virus
DE3824658A1 (de) 1988-07-15 1990-01-18 Schering Ag N-hetaryl-imidazolderivate
US5258362A (en) 1991-06-11 1993-11-02 Abbott Laboratories Renin inhibiting compounds
CA2224062C (en) 1995-06-06 2001-09-04 Pfizer Limited Substituted n-(indole-2-carbonyl)-glycinamides and derivatives as glycogen phosphorylase inhibitors
DE19649460A1 (de) 1996-11-26 1998-05-28 Bayer Ag Neue substituierte Pyrazolderivate
DE69819311T2 (de) 1997-03-07 2004-07-29 Metabasis Therapeutics Inc., San Diego Neue benzimidazol inhibitoren der fructose-1,6-bisphosphatase
DE19746287A1 (de) 1997-10-20 1999-04-22 Hoechst Marion Roussel De Gmbh Substituierte Isochinolin-2-Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel
PT1056729E (pt) * 1998-02-27 2005-04-29 Pfizer Prod Inc Derivados de n-[ciclo di- ou tri-aza di-insaturado de cinco membros substituido) carbonil] guanidina para o tratamento de isquemia
US8124582B2 (en) 2002-12-06 2012-02-28 Fibrogen, Inc. Treatment of diabetes
US7618940B2 (en) 2002-12-06 2009-11-17 Fibrogen, Inc. Fat regulation
CA2528232C (en) 2003-06-06 2010-05-25 Fibrogen, Inc. Novel nitrogen-containing heteroaryl compounds and their use in increasing endogenous erythropoietin
CN1856490A (zh) 2003-07-28 2006-11-01 詹森药业有限公司 苯并咪唑、苯并噻唑和苯并噁唑衍生物及其作为lta4h调节剂的应用
CA2553160C (en) 2003-12-29 2010-09-28 Banyu Pharmaceutical Co., Ltd. 2-heteroaryl-substituted benzimidazole derivative
JP2006022769A (ja) * 2004-07-09 2006-01-26 Toyota Motor Corp 内燃機関の排気浄化装置
WO2006094292A2 (en) 2005-03-02 2006-09-08 Fibrogen, Inc. Thienopyridine compounds, and methods of use thereof
JP2006254624A (ja) * 2005-03-11 2006-09-21 Fuji Electric Holdings Co Ltd 交流交流変換器の制御装置
DE102005019712A1 (de) * 2005-04-28 2006-11-09 Bayer Healthcare Ag Dipyridyl-dihydropyrazolone und ihre Verwendung
US20060276477A1 (en) 2005-06-06 2006-12-07 Fibrogen, Inc. Treatment method for anemia
WO2007038571A2 (en) 2005-09-26 2007-04-05 Smithkline Beecham Corporation Prolyl hydroxylase antagonists
ES2274712B1 (es) 2005-10-06 2008-03-01 Laboratorios Almirall S.A. Nuevos derivados imidazopiridina.
JP5202327B2 (ja) 2005-12-09 2013-06-05 アムジエン・インコーポレーテツド プロリルヒドロキシラーゼ阻害活性を示すキノロンベースの化合物、およびこの組成物、およびこの使用
EP2476669A1 (en) 2006-01-27 2012-07-18 Fibrogen, Inc. Cyanoisoquinoline compounds and methods of use thereof
AR059733A1 (es) 2006-03-07 2008-04-23 Smithkline Beecham Corp Compuesto derivado de glicina n- sustituida con heteroaromaticos bicicicos, composicion farmaceutica que lo comprende, uso para preparar un medicamento para tratar la anemia y proceso para su preparacion
WO2007136990A2 (en) * 2006-05-16 2007-11-29 Smithkline Beecham Corporation Prolyl hydroxylase inhibitors
JO2934B1 (en) 2006-06-23 2015-09-15 سميث كلاين بيتشام كوربوريشن Prolyl hydroxylase inhibitors
BRPI0713350B1 (pt) 2006-06-26 2022-04-12 Akebia Therapeutics Inc Composto, e, composição
WO2008033739A2 (en) 2006-09-12 2008-03-20 Neurogen Corporation Benzimidazole carboxamide derivatives
DE102006050516A1 (de) 2006-10-26 2008-04-30 Bayer Healthcare Ag Substituierte Dihydropyrazolone und ihre Verwendung
CN101611007A (zh) 2006-12-20 2009-12-23 先灵公司 新颖的jnk抑制剂
CL2008000065A1 (es) 2007-01-12 2008-09-22 Smithkline Beecham Corp Compuestos derivados de glicina n-sustituida, inhibidores de hif prolil hidroxilasas; su proceso de preparacion; composicion farmaceutica que comprende a dichos compuestos; y su uso en el tratamiento de la anemia.
TW200845991A (en) 2007-01-12 2008-12-01 Smithkline Beecham Corp N-substituted glycine derivatives: hydroxylase inhibitors
CA2683758A1 (en) 2007-04-18 2008-10-30 Merck & Co., Inc. Novel 1,8-naphthyridine compounds
EP2142509B1 (en) 2007-04-18 2013-12-04 Amgen, Inc Quinolones and azaquinolones that inhibit prolyl hydroxylase
US8097620B2 (en) 2007-05-04 2012-01-17 Amgen Inc. Diazaquinolones that inhibit prolyl hydroxylase activity
ES2389063T3 (es) 2007-05-04 2012-10-22 Amgen, Inc Derivados de tienopiridina y tiazolopiridina que inhiben la actividad prolil hidroxilasa
DE102007048447A1 (de) 2007-10-10 2009-04-16 Bayer Healthcare Ag Substituierte Dihydropyrazolthione und ihre Verwendung
DE102007049157A1 (de) 2007-10-13 2009-04-16 Bayer Healthcare Ag Substituierte Dihydrotriazolone und ihre Verwendung
US8269008B2 (en) 2007-12-03 2012-09-18 Fibrogen, Inc. Oxazolopyridine and isoxazolopyridine derivatives for use in the treatment of HIF-mediated conditions
WO2009086044A1 (en) 2007-12-19 2009-07-09 Smith Kline Beecham Corporation Prolyl hydroxylase inhibitors
WO2009086592A1 (en) 2008-01-04 2009-07-16 Garvan Institute Of Medical Research Method of increasing metabolism
EP2252619B1 (en) 2008-01-11 2013-10-09 Fibrogen, Inc. Isothiazole-pyridine derivatives as modulators of hif (hypoxia inducible factor) activity
CA2714111A1 (en) 2008-02-25 2009-09-03 Merck Sharp & Dohme Corp. Tetrahydro-1h-pyrrolo fused pyridones
CN101951777A (zh) 2008-02-25 2011-01-19 默沙东公司 四氢呋喃并吡啶酮
JP2011513222A (ja) 2008-02-25 2011-04-28 メルク・シャープ・エンド・ドーム・コーポレイション テトラヒドロチエノピリジン
JP5557832B2 (ja) 2008-03-18 2014-07-23 メルク・シャープ・アンド・ドーム・コーポレーション 置換４−ヒドロキシピリジン−５−カルボキサミド
EP2294066B9 (en) * 2008-04-28 2015-03-11 Janssen Pharmaceutica, N.V. Benzoimidazoles as prolyl hydroxylase inhibitors
US9273034B2 (en) * 2011-10-25 2016-03-01 Janssen Pharmaceutica Nv Meglumine salt formulations of 1-(5,6-dichloro-1H-benzo[D]imidazol-2-yl)-1H-pyrazole-4-carboxylic acid

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