ES2644128T3 - Derivados de benzonitrilo como inhibidores de quinasa - Google Patents

Derivados de benzonitrilo como inhibidores de quinasa Download PDF

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Publication number
ES2644128T3
ES2644128T3 ES12747896.4T ES12747896T ES2644128T3 ES 2644128 T3 ES2644128 T3 ES 2644128T3 ES 12747896 T ES12747896 T ES 12747896T ES 2644128 T3 ES2644128 T3 ES 2644128T3
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Prior art keywords
tetrahydro
ylamino
yloxy
pyran
benzonitrile
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ES12747896.4T
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Guenter Hoelzemann
Dieter Dorsch
Hans-Michael Eggenweiler
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Merck Patent GmbH
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Merck Patent GmbH
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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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Abstract

Composición farmacéutica que contiene por lo menos un compuesto de acuerdo a la reivindicación 1 y/o sus sales, tautómeros y estereoisómeros farmacéuticamente aceptables, incluyendo las mezclas de los mismos en todas las proporciones, así como también opcionalmente transportadores y/o adyuvantes.

Description

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Busulfán Ifosfamida Melfalan Hexametilmelamina Tiotepa Clorambucil Dacarbazina Carmustina
Procarbazina Altretamina Estramustinfosfato Mecloroetamina Estreptozocina Temozolomid Semustina
Agentes de platino
Cisplatino Oxaliplatino Espiroplatino Carboxiftalatoplatino Tetraplatino Ormiplatino Iproplatino Carboplatino ZD-0473 (AnorMED) Lobaplatino (Aetema) Satraplatino (Johnson Matthey) BBR-3464 (Hoffrnann-La Roche) SM-11355 (Sumitomo) AP-5280 (Access)
Antimetabolitos
Azacitidina Gemcitabina Capecitabina 5-Fluorouracilo Floxuridina 2-clordesoxiadenosina 6-Mercaptopurina 6-Tioguanina Citarabina 2-Fluorodesoxicitidina Metotrexato Idatrexato Tomudex Trimetrexato Desoxicoformicina Fludarabina Pentostatina Raltitrexed Hidroxicarbamida Decitabina (SuperGen) Clofarabina (Bioenvision) Irofulven (MGI Pharrna) DMDC (Hoffmann-La Roche) Etinilcitidina (Taiho)
Inhibidores de Topoisomerasa
Amsacrina Epirubicina Etopósido Tenipósido o Mitoxantrón Irinotecán (CPT-11) 7-Etil-10-hidroxicamptotecina Topotecán Rubitecn (SuperGen) Exatecanmesyilato (Daiichi) Quinamed (ChemGenex) Gimatecán (Sigma-Tau) Diflomotecán (Beaufour-Ipsen) TAS-103 (Taiho)
Dexrazoxanet (TopoTarget) Pixantrón (Novuspharrna) análogo de Rebecamicina (Exelixis) BBR-3576 (Novuspharma)
Elsamitrucina (Spectrum) J-107088 (Merck & Co) BNP-1350 (BioNumerik) CKD-602 (Chong Kun Dang) KW-2170 (Kyowa Hakko)
18
Antibióticos Antitumorales
Dactinomicina (Actinomicina D) Doxorubicina (Adriamicina) Deoxirubicina Valrubicina Daunorubicina (Daunomicina) Epirubicina Terarubicina Idarubicina Rubidazona Plicamicinap Porfiromicina Cianomorfolinodoxorubicina Mitoxantrón (Novantron) Amonafid Azonafid Anthrapirazol Oxantrazol Losoxantron Bleomicina sulfato (Blenoxan) Bleomicina ácido Bleomicina A Bleomicina B Mitomicina C MEN-10755 (Menarini) GPX-100 (Gem Pharmaceuticals)
Agentes Antimitóticos
Paclitaxel Docetaxel Colchicina Vinblastina Vincristina Vinorelbina Vindesina Dolastatina 10 (NCI) Rizoxina (Fujisawa) Mivobulina (Warner-Lambert) Cemadotina (BASF) RPR 109881A (Aventis) TXD 258 (Aventis) Epotilón B (Novartis) T 900607 (Tularik) T 138067 (Tularik) Criptoficina 52 (Eli Lilly) Vinflunina (Fabre) Auristatina PE (Teikoku Hormone) BMS 247550 (BMS) BMS 184476 (BMS) BMS 188797 (BMS) Taxoprexina (Protarga) SB 408075 (GlaxoSmithKline) E7010 (Abbott) PG-TXL (Cell Therapeutics) IDN 5109 (Bayer) A 105972 (Abbott) A 204197 (Abbott) LU 223651 (BASF) D 24851 (ASTA Medica) ER-86526 (Eisai) Combretastatins A4 (BMS) Isohomohalicondrin-B (PharmaMar) ZD 6126 (AstraZeneca) PEG-Paclitaxel (Enzon) AZ10992 (Asahi) IDN-5109 (Indena) AVLB (Prescient NeuroPharma) Azaepotilón B (BMS) BNP7787 (BioNumerik) CA-4-Profármaco Dolastatina-10 (NrH) CA-4 (OXiGENE)
Inhibidores de Aromatasa
Aminoglutetimida Exemestano Letrozol Atamestano (BioMedicines) Anastrazol YM-511 (Yamanouchi) Formestano
Inhibidores de timidilato sintasa
Pemetrexed (Eli Lilly) Nolatrexed (Eximias) ZD-9331 (BTG) CoFactorTM (BioKeys)
19
Antagonistas de ADN
Trabectedina (PharmaMar) Glufosfamida (Baxter Mafosfamida (Baxter International) Albúmina + 32P (Isotope Solutions) International) Apaziquon Timectacina (NewBiotics) Edotreotide (Novartis) (Spectrum Pharmaceuticals) O6-Bencilguanina (Paligent)
Inhibidores de farnesiltransferasa
Arglabina (NuOncology Labs) lonafarnib (Schering-Plough) Tipifarnib (Johnson & BAY43-9006 (Bayer) Johnson) Perililalcohol (DOR BioPharma)
Inhibidores de bombas
CBT-1 (CBA Pharma) Tariquidar (Xenova) MS-209 (Schering AG) Zosuquidartrihidrocloruro (Eli Lilly) Biricodar-dicitrato (Vertex)
Inhibidores de histona acetiltransferasa
Tacedinalina (Pfizer) SAHA (Aton Pharma) MS-275 Pivaloiloximetilbutirato (Schering AG) (Titan) Depsipéptido (Fujisawa)
Inhibidores de
Neovastat (Aeterna Laboratories) Marimastat (British CMT -3 (CollaGenex)
metaloproteinasa
Biotech) Maltolato de galio (Titan) Triapina (Vion) BMS-275291 (Celltech)
Inhibidores de
Tezacitabina (Aventis) Didox (Molecules for Health)
ribonucleósido reductasa
Agonistas7antagonistas de TNF-alfa
Virulizina (Lorus Therapeutics) CDC-394 (Celgene) Revimid (Celgene)
Antagonistas de receptor de endotelina A
Atrasentano (Abbot) ZD-4054 (AstraZeneca) YM-598 (Yamanouchi)
Agonistas de receptor de ácido retinoico
Fenretinid (Johnson & Johnson) LGD-1550 (Ligand) Alitretinoína (Ligand)
Inmunomoduladores
Interferón Oncophage (Antigenics) GMK (Progenics) Adenokarzinom-Impfstoff (Biomira) CTP-37 (AVI BioPharma) Terapia con Dexosom (Anosys) Pentrix (Australian Cancer Technology) JSF-154 (Tragen) Vacuna para cáncer (Intercell)
20
JRX-2 (Immuno-Rx) PEP-005 (Peplin Biotech) Synchrovax-Vacunas (CTL Immuno) Vacunas para Melanoma (CTL Immuno) Vacunas para p21-RAS (GemVax) Norelin (Biostar) BLP-25 (Biomira) MGV (Progenics) !3-Aletina (Dovetail) CLL-Thera (Vasogen)
Agentes hormonales y
Estrógenos, Prednisona
antihormonales
Estrógenos conjugados, Etinilestradiol Clortrianiseno Idenestrol Hidroxiprogesterona caproato Medroxiprogesterona Testosterona Testosterona propionato Fluoximesterona Metiltestosterona Dietilestilbestrol Megestrol Tamoxifeno Toremofina Dexametasona Metilprednisolona Prednisolona Aminoglutetimida Leuprolida Goserelina Leuporelina Bicalutamida Flutamida Octreotido Nilutamid Mitotano P-04 (Novogen) 2-metoxiestradiol (EntreMed) Arzoxifeno (Eli Lilly)
Agentes fotodinámicos
Talaporfin (Light Sciences) Theralux (Theratechnologies) Motexafin-Gadolinium (Pharmacyclics) Pd-Bacteriopheophorbid (Yeda) Lutecio-Texafirina (Pharmacyclics) Hipericina
Inhibidores de tirosina quinasa
Imatinib (Novartis) Leflunomida (Sugen/Pharmacia) ZDI839 (AstraZeneca) Erlotinib (Oncogene Science) Canertjnib (Pfizer) Squalamina (Genaera) Kahalid F (PharmaMar) CEP701 (Cephalon) CEP-751 (Cephalon) MLN518 (Millenium) PKC412 (Novartis) Phenoxodiol O
SU5416 (Pharmacia) SU6668 (Pharmacia) ZD4190 (AstraZeneca) ZD6474 (AstraZeneca) Vatalanib (Novartis) PKI166 (Novartis) GW2016 (GlaxoSmithKline) EKB-509 (Wyeth) EKB-569 (Wyeth) Trastuzumab (Genentech) C225 (ImClone) rhu-Mab (Genentech) MDX-H210 (Medarex) 2C4 (Genentech) MDX-447 (Medarex) ABX-EGF (Abgenix) IMC-1C11 (ImClone)
Agentes varios
SR-27897 (inhibidor de CCK-A, BCX-1777 (inhibidor de PNP,
21
imagen17
imagen18
imagen19
imagen20
imagen21
imagen22
imagen23
imagen24
imagen25
imagen26
imagen27
imagen28
imagen29
imagen30
imagen31
imagen32
imagen33
imagen34
imagen35
Los siguientes compuestos se preparan de forma análoga
Compuesto No.
Estructura y/o Nombre
"A53"
"A58"
"A59"
"A60"
41
"A61"
"A62"
"A63"
Valores de IC50 de los compuestos inhibidores de TBK1 y IKKε de acuerdo a la invención
Compuesto No.
Ensayo enzimático de TBK1-IC50 [nM] Ensayo enzimático de IKKε-IC50 [nM] Ensayo celular de TBK1 + IKKε-IC50 [nM]
"A1"
"A2"
83 20 960
"A3"
260 370 3300
"A4"
34 38 6600
"A5"
97 110 2900
"A6"
"A7"
8 15 350
"A8"
"A9"
120 100 3000
"A10"
21 43 1200
"A11"
250 240 5200
42
"A12"
30 25 1300
"A13"
310 530
"A14"
670 1200
"A15"
14 21 1100
"A16"
71 7 5000
"A17"
"A18"
8 13
"A19"
1900 390
"A20"
55 51 4800
"A21"
70 37 5300
"A22"
100 150 9600
"A23"
120 160 7800
"A24"
110 89 4800
"A25"
290 67
"A26"
18 27 3300
"A27"
85 77 5000
"A28"
280 74 23000
"A29"
120 88 6700
"A30"
42 45
"A31"
860 850 19000
"A32"
"A33"
130 58 5000
"A34"
6 6 370
"A35"
6 18 670
"A36"
140
"A37"
32 21
"A38"
460 320
"A39"
16 25
"A40"
7 5
"A41"
12 25
"A42"
10 15
"A43"
70 65
"A44"
5 10
"A45"
2 2

Ejemplo A: viales para inyección
Los siguientes ejemplos se relacionan con composiciones farmacéuticas:
Una solución de 100 g de un ingrediente activo de acuerdo a la invención y 5 g de fosfato ácido de disodio se lleva a pH 6,5 en 3 L de agua bidestilada con ácido clorhídrico 2 N, se esteriliza por filtración, se coloca dentro de viales 5 para inyección, se liofiliza bajo condiciones estériles y se cierra en forma estéril. Cada vial para inyección contiene 5 mg de ingrediente activo.
Ejemplo B: supositorios
Se funde una mezcla de 20 g de un ingrediente activo de acuerdo a la invención con 100 g de lecitina de soja y 1400 g de manteca de cacao, se coloca en moldes y se deja enfriar. Cada supositorio contiene 20 mg de ingrediente 10 activo.
Ejemplo C: solución
Se prepara una solución de 1 g de un ingrediente activo de acuerdo a la invención, 9,38 g de NaH2P04 · 2 H20, 28,48 g de Na2HP04 · 12 H20 y 0,1 g de cloruro de benzalconio en 940 ml de agua bidestilada. Se ajusta el pH a
43

Claims (4)

  1. REIVINDICACIONES
    1. Compuestos que se seleccionan a partir del grupo
    Compuesto No.
    Nombre y/o Estructura
    "A1"
    2-(tetrahidro-piran-4-iloxi)-5-{2-[1-(3-trifluorometil-fenil)-1H-pirazol-4-ilamino]-piridin-4-il}benzonitrilo
    "A2"
    5-{2-[1-(1-metil-piperidin-4-il)-1H-pirazol-4-ilamino]-piridin-4-il}-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A3"
    5-[2-([3,3']Bipiridinil-6-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A4"
    5-[2-(5-metil-isoxazol-3-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitriloo
    "A5"
    5-[2-(1-metil-1H-pirazol-3-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A6"
    5-[2-(2-furan-2-ilmetil-2H-pirazol-3-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A7"
    5-[2-(5-morfolin-4-il-piridin-2-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A8"
    5-[2-(1-fenil-1H-pirazol-4-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A9"
    5-{2-[5-(1-H-pirazol-4-il)-piridin-2-ilamino]-piridin-4-il}-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A10"
    5-[2-(5-tert.-butil-1-H-pirazol-3-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A11"
    6-{4-[3-ciano-4-(tetrahidro-piran-4-iloxi)-fenil]-piridin-2-ilamino}-nicotinonitrilo
    "A12"
    5-[2-(5-Ciclopropil-2H-pirazol-3-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A13"
    2-(tetrahidro-piran-4-iloxi)-5-[2-(5-trifluorometil-piridin-2-ilamino)-piridin-4-il]-benzonitrilo
    "A14"
    5-[2-(pirimidin-2-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A15"
    5-[2-(5-hidroximetil-piridin-2-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A16"
    5-[2-( 1-piperidin-4-il-1H-pirazol-4-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A17"
    2-{4-[3-ciano-4-(tetrahidro-piran-4-iloxi)-fenil]-piridin-2-ilamino}-isonicotinonitrilo
    "A18"
    5-[2-(4-hidroximetil-piridin-2-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A19"
    5-{4-[3-ciano-4-(tetrahidro-piran-4-iloxi)-fenil]-piridin-2-ilamino}-benzofuran-2carboxamida
    "A20"
    5-{2-[1-(2,2-difluoro-etil)-1H-pirazol-4-ilamino]-piridin-4-il)-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A21"
    5-{2-[1-(2-piperidin-4-il-etil)-1H-pirazol-4-ilamino]-piridin-4-il}-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A22"
    5-{2-[1-(2-morfolin-4-il-etil)-1H-pirazol-4-ilamino]-piridin-4-il}-2-(tetra hidro-piran-4-iloxi)benzonitrilo
    "A23"
    5-{2-[1-(3-metoxi-propil)-1H-pirazol-4-ilamino]-piridin-4-il}-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A24"
    5-{2-[1-(2-ciano-ciclopropilmetil)-1H-pirazol-4-ilamino]-piridin-4-il}-2-(tetrahidro-piran-4iloxi)-benzonitrilo
    "A25"
    5-[2-(1-azetidin-3-il-1H-pirazol-4-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A26"
    5-{2-[1-((1S,2S)-2-hidroximetil-ciclopropilmetil)-1H-pirazol-4-ilamino]-piridin-4-il}-2(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A27"
    5-{2-[1-(tetrahidro-furan-3-ilmetil)-1H-pirazol-4-ilamino]-piridin-4-il}-2-(tetrahidro-piran-4iloxi)-benzonitrilo
    "A28"
    5-[2-(1-pirrolidin-3-il-1H-pirazol-4-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A29"
    5-[2-(1-{2-[1-(2-hidroxi-acetil)-piperidin-4-il]-etil}-1H-pirazol-4-ilamino)-piridin-4-il]-2(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A30"
    5-[2-(1-{2-[1-(2-amino-acetil)-piperidin-4-il]-etil}-1H-pirazol-4-ilamino)-piridin-4-il]-2(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A31"
    5-[2-(3-tert.-butil-isoxazol-5-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A32"
    2-(tetrahidro-piran-4-iloxi)-5-{2-[1-(3-trifluormetil-fenil)-1H-pirazol-4-ilamino]-pirimidin-4-il}benzonitrilo
    "A33"
    5-[2-(1-metil-1H-pirazol-3-ilamino)-pirimidin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A34"
    5-[2-(1H-pirazol-4-ilamino)-pirimidin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A35"
    5-{2-[1-(2-metoxi-etil)-1H-pirazol-4-ilamino]-pirimidin-4-il}-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A36"
    2-(tetrahidro-piran-4-iloxi)-5-[2-(5,6,7,8-tetrahidro-pirido[4,3-d]pirimidin-2-ilamino)-piridin-4il]-benzonitrilo
    "A37"
    6-{4-[3-ciano-4-(tetrahidro-piran-4-iloxi)-fenil]-piridin-2-ilamino}-nicotinamida
    "A38"
    5-{2-[1-(2-pirazol-1-il-etil)-1H-pirazol-4-ilamino]-piridin-4-il}-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A39"
    5-{2-[1-(2-morfolin-4-il-etil)-1H-pirazol-4-ilamino]-pirimidin-4-il}-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A40"
    5-[2-(1-pirrolidin-3-il-1H-pirazol-4-ilamino)-pirimidin-4-il]-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A41"
    5-{2-[1-(tetrahidro-furan-3-ilmetil)-1H-pirazol-4-ilamino]-pirimidin-4-il}-2-(tetrahidro-piran-4iloxi)-benzonitrilo
    "A42"
    5-{4-[3-ciano-4-(tetrahidro-piran-4-iloxi)-fenil]-pirimidin-2-ilamino}-benzofuran-2carboxamida
    "A43"
    5-{2-[1-(2-pirazol-1-il-etil)-1H-pirazol-4-ilamino]-pirimidin-4-il}-2-(tetra hidro-piran-4-iloxi)benzonitrilo
    "A44"
    5-{2-[1-(2,2-difluoro-etil)-1H-pirazol-4-ilamino]-pirimidin-4-il}-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A45"
    5-{2-[1-(2-piperidin-4-il-etil)-1H-pirazol-4-ilamino]-pirimidin-4-il}-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A46"
    5-{2-[1-(3-metoxi-propil)-1H-pirazol-4-ilamino]-pirimidin-4-il}-2-(tetra hidro-piran-4-iloxi)benzonitrilo
    "A47"
    5-{2-[5-(3,6-dihidro-2H-piran-4-il)-piridin-2-ilamino]-piriin-4-il}-2-(tetrahidro-piran-4-iloxi)-benzonitrilo
    "A48"
    5-[2-(1',2',3',6'-tetrahidro-[3,4']bipiridinil-6-ilamino)-piridin-4-il]-2-(tetrahidro-piran-4-iloxi)benzonitrilo
    "A53"
    imagen1
    "A58"
    imagen2
    "A59"
    imagen3
    "A60"
    imagen4
    "A61"
    imagen5
    "A62"
    imagen6
    "A63"
    imagen7
    así como también sus sales, tautómeros y estereoisómeros farmacéuticamente aceptables, incluyendo las mezclas de los mismos en todas las proporciones.
  2. 2. Composición farmacéutica que contiene por lo menos un compuesto de acuerdo a la reivindicación 1
    y/o sus sales, tautómeros y estereoisómeros farmacéuticamente aceptables, incluyendo las mezclas de los 5 mismos en todas las proporciones, así como también opcionalmente transportadores y/o adyuvantes.
  3. 3. Compuestos de acuerdo a la reivindicación 1 así como también sus sales, tautómeros y estereoisómeros farmacéuticamente aceptables, incluyendo las mezclas de los mismos en todas las proporciones, para usar en el tratamiento de cáncer, choque séptico, glaucoma de ángulo abierto primario (POAG), hiperplasia, aterosclerosis, retinopatía, osteoartritis, endometriosis, inflamación crónica,
    10 enfermedades neurodegenerativas, artritis reumatoide (RA), lupus eritematoso sistémico (SLE), síndrome de Sjögren, síndrome de Aicardi-Goutiéres, lupus pernio, vasculopatía retinal, leucodistrofia cerebral (RVCL), esclerosis sistémica, miositis, psoriasis, enfermedad pulmonar obstructiva crónica (EPOC), enfermedad inflamatoria intestinal (IBD), obesidad, resistencia a la insulina, diabetes de tipo 2 (NIDDM) y/o síndrome metabólico.
    15 4. Compuestos de acuerdo a la reivindicación 1 y/o sales, tautómeros y estereoisómeros de los mismos
    fisiológicamente aceptables para usar en el tratamiento de tumores, en donde se administra una cantidad terapéuticamente eficaz de un compuesto de acuerdo a la reivindicación 1 en combinación con un compuesto que se selecciona del grupo de 1) modulador de receptor de estrógenos, 2) modulador de receptor de andrógenos, 3) modulador de receptor retinoide, 4) agente citotóxico, 5) agente antiproliferativo,
    5 6) inhibidor de prenil proteína transferasa, 7) inhibidor de HMG-CoA reductasa, 8) inhibidor de proteasa de HIV, 9) inhibidor de transcriptasa reversa así como también 10) otros inhibidores de angiogénesis.
  4. 5. Compuestos de acuerdo a la reivindicación 1 y/o sales, tautómeros y estereoisómeros de los mismos fisiológicamente aceptables para usar en el tratamiento de tumores, en donde se administra una cantidad terapéuticamente eficaz de un compuesto de acuerdo a la reivindicación 1 en combinación con radioterapia
    10 y un compuesto que se selecciona del grupo de 1) modulador de receptor de estrógenos, 2) modulador de receptor de andrógenos, 3) modulador de receptor retinoide, 4) agente citotóxico, 5) agente antiproliferativo, 6) inhibidor de prenil proteína transferasa, 7) inhibidor de HMG-CoA reductasa, 8) inhibidor de proteasa de HIV, 9) inhibidor de transcriptasa reversa así como también 10) otros inhibidores de angiogénesis.
ES12747896.4T 2011-09-09 2012-08-13 Derivados de benzonitrilo como inhibidores de quinasa Active ES2644128T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE102011112978 2011-09-09
DE102011112978A DE102011112978A1 (de) 2011-09-09 2011-09-09 Benzonitrilderivate
PCT/EP2012/003449 WO2013034238A1 (de) 2011-09-09 2012-08-13 Benzonitrilderivate als kinasehemmer

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