AR045686A1 - Derivados de pirido[2,3-b]pirazinas, y su uso como moduladores de quinasas - Google Patents

Derivados de pirido[2,3-b]pirazinas, y su uso como moduladores de quinasas

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Publication number
AR045686A1
AR045686A1 ARP040101772A ARP040101772A AR045686A1 AR 045686 A1 AR045686 A1 AR 045686A1 AR P040101772 A ARP040101772 A AR P040101772A AR P040101772 A ARP040101772 A AR P040101772A AR 045686 A1 AR045686 A1 AR 045686A1
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Argentina
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alkyl
aryl
heteroaryl
cycloalkyl
heterocyclyl
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ARP040101772A
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Zentaris Gmbh
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Priority claimed from DE10323345A external-priority patent/DE10323345A1/de
Priority claimed from DE102004022383A external-priority patent/DE102004022383A1/de
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Publication of AR045686A1 publication Critical patent/AR045686A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50Pyridazines; Hydrogenated pyridazines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/08Drugs for disorders of the urinary system of the prostate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/14Drugs for dermatological disorders for baldness or alopecia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Epidemiology (AREA)
  • Vascular Medicine (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pulmonology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Derivados de pirido[2,3-b]pirazina, procedimientos para prepararlas y su uso como medicamentos, en especial para el tratamiento de enfermedades malignas y otras enfermedades basadas en proliferaciones celulares patológicas. Reivindicación 1: Derivados de pirido[2,3-b]pirazina de acuerdo con la fórmula (1) caracterizados porque los substituyentes R1-R4 tienen los siguientes significados: R1 y R2 pueden ser, de modo independiente entre sí: (i) hidrógeno (ii) hidroxilo (iii) halógeno (iv) alquilo, en donde el radical alquilo está saturado y puede estar compuesto por 1 a 8 átomos de carbono, (v) arilo insubstituido o substituido, en donde el radical arilo puede estar mono o polisubstituido, igual o diferente, con F, Cl, Br, I, CF3, CN, NH2, NH-alquilo, NH-cicloalquilo, NH-heterociclilo, NH-arilo, NH-heteroarilo, NH-alquil-cicloalquilo, NH-alquil-heterociclilo, NH-alquil-arilo, NH-alquil-heteroarilo, NH-alquil-NH2, NH-alquil-OH, N(alquilo)2, NHC(O)-alquilo, NHC(O)-cicloalquilo, NHC(O)-heterociclilo, NHC(O)-arilo, NHC(O)-heteroarilo, NHC(O)-alquil-arilo, NHC(O)-alquil-heteroarilo, NHSO2-alquilo, NHSO2-cicloalquilo, NHSO2-heterociclilo, NHSO2-arilo, NHSO2-heteroarilo, NHSO2-alquil-arilo, NHSO2-alquil-heteroarilo, NO2, SH, S-alquilo, S-arilo, S-heteroarilo, OH, OCF3, O-alquilo, O-cicloalquilo, O-heterociclilo, O-arilo, O-heteroarilo, O-alquil-cicloalquilo, O-alquil-heterociclilo, O-alquil-arilo, O-alquil-heteroarilo, O-alquil-OH, O-(CH2)n-O, OC(O)-alquilo, OC(O)-cicloalquilo, OC(O)-heterociclilo, OC(O)-arilo, OC(O)-heteroarilo, OC(O)-alquil-arilo, OC(O)-alquil-heteroarilo, OSO3H, OSO2-alquilo, OSO2-cicloalquilo, OSO2-heterociclilo, OSO2-arilo, OSO2-heteroarilo, OSO2-alquil-arilo, OSO2-alquil-heteroarilo, OP(O)(OH)2, C(O)-alquilo, C(O)-arilo, C(O)-heteroarilo, CO2H, CO2-alquilo, CO2-cicloalquilo, CO2-heterociclilo, CO2-arilo, CO2-heteroarilo, CO2-alquil-cicloalquilo, CO2-alquil-heterociclilo, CO2-alquil-arilo, CO2-alquil-heteroarilo, C(O)-NH2, C(O)NH-alquilo, C(O)NH-cicloalquilo, C(O)NH-heterociclilo, C(O)NH-arilo, C(O)NH-heteroarilo, C(O)NH-alquil-cicloalquilo, C(O)NH-alquil-heterociclilo, C(O)NH-alquil-arilo, C(O)NH-alquil-heteroarilo, C(O)N(alquilo)2, C(O)N(cicloalquilo)2, C(O)N(arilo)2, C(O)N(heteroarilo)2, SO-alquilo, SO-arilo, SO2-alquilo, SO2-arilo, SO2NH2, SO2NH-alquilo, SO2NH-arilo, SO2NH-heteroarilo, SO2NH-alquil-arilo, SO3H, SO2O-alquilo, SO2O-arilo, SO2O-alquil-arilo, alquilo, cicloalquilo, heterociclilo, arilo o heteroarilo, n puede adoptar el valor 1,2 o 3 y los substituyentes de alquilo, cicloalquilo, heterociclilo, arilo, heteroarilo, alquil-cicloalquilo, alquil-heterociclilo, alquilarilo y alquil-heteroarilo pueden estar, a su vez, substituidos, (vi) heteroarilo insubstituido o substituido, en donde el radical heteroarilo puede estar mono o polisubstituido, igual o diferente, con F, Cl, Br, I, CF3, CN, NH2, NH-alquilo, NH-cicloalquilo, NH-heterociclilo, NH-arilo, NH-heteroarilo, NH-alquil-cicloalquilo, NH-alquil-heterociclilo, NH-alquil-arilo, NH-alquil-heteroarilo, NH-alquil-NH2, NH-alquil-OH, N(alquilo)2, NHC(O)-alquilo, NHC(O)-cicloalquilo, NHC(O)-heterociclilo, NHC(O)-arilo, NHC(O)-heteroarilo, NHC(O)-alquil-arilo, NHC(O)-alquil-heteroarilo, NHSO2-alquilo, NHSO2-cicloalquilo, NHSO2-heterociclilo, NHSO2-arilo, NHSO2-heteroarilo, NHSO2-alquil-arilo, NHSO2-alquil-heteroarilo, NO2, SH, S-alquilo, S-arilo, S-heteroarilo, OH, OCF3, O-alquilo, O-cicloalquilo, O-arilo, O-heteroarilo, O-alquil-cicloalquilo, O-alquil-arilo, O-alquil-heteroarilo, OC(O)-alquilo, OC(O)-cicloalquilo, OC(O)-heterociclilo, OC(O)-arilo, OC(O)-heteroarilo, OC(O)-alquil-arilo, OC(O)-alquil-heteroarilo, OSO3H, OSO2-alquilo, OSO2-cicloalquilo, OSO2-arilo, OSO2-heteroarilo, OSO2-alquil-arilo, OSO2-alquil-heteroarilo, OP(O)(OH)2, C(O)-alquilo, C(O)-arilo, C(O)-heteroarilo, CO2H, CO2-alquilo, CO2-cicloalquilo, CO2-heterociclilo, CO2-arilo, CO2-heteroarilo, CO2-alquil-cicloalquilo, CO2-alquil-heterociclilo, CO2-alquil-arilo, CO2-alquil-heteroarilo, C(O)-NH2, C(O)NH-alquilo, C(O)NH-cicloalquilo, C(O)NH-heterociclilo, C(O)NH-arilo, C(O)NH-heteroarilo, C(O)NH-alquil-cicloalquilo, C(O)NH-alquil-heterociclilo, C(O)NH-alquil-arilo, C(O)NH-alquil-heteroarilo, C(O)N(alquilo)2, C(O)N(cicloalquilo)2, C(O)N(arilo)2, C(O)N(heteroarilo)2, SO2NH2, SO2NH-alquilo, SO2NH-arilo, SO2NH-heteroarilo, SO2NH-alquil-arilo, SO3H, SO2O-alquilo, SO2O-arilo, SO2O-alquil-arilo, alquilo, cicloalquilo, heterociclilo, arilo o heteroarilo, y los substituyentes de alquilo, cicloalquilo, heterociclilo, arilo, heteroarilo, pueden estar, a su vez, substituidos, (vii) OR5, en donde R5 puede ser alquilo, cicloalquilo, heterociclilo, arilo, heteroarilo, alquilcicloalquilo, alquil-heterociclilo, alquil-arilo o alquil-heteroarilo, y los substituyentes de alquilo, cicloalquilo, heterociclilo, arilo, heteroarilo, alquilcicloalquilo, alquil-heterociclilo, alquil-arilo o alquil-heteroarilo, pueden estar, a su vez, substituidos, (viii) SR6, en donde R6 puede ser alquilo, cicloalquilo, heterociclilo, arilo, heteroarilo, alquilcicloalquilo, alquil-heterociclilo, alquil-arilo o alquil-heteroarilo, y los substituyentes de alquilo, cicloalquilo, heterociclilo, arilo, heteroarilo, alquilcicloalquilo, alquil-heterociclilo, alquil-arilo o alquil-heteroarilo, pueden estar, a su vez, substituidos, (ix) NR7R8, en donde R7 y R8 pueden ser, de modo independiente entre sí, hidrógeno, alquilo, cicloalquilo, heterociclilo, arilo, heteroarilo, alquil-cicloalquilo, alquil-heterociclilo, alquil-arilo o alquil-heteroarilo, y los substituyentes de alquilo, cicloalquilo, heterociclilo, arilo, heteroarilo, alquilcicloalquilo, alquil-heterociclilo, alquil-arilo o alquil-heteroarilo, pueden estar, a su vez, substituidos, o R7 y R8 significan juntos cicloalquilo o heterociclilo, en donde cicloalquilo y heterociclilo pueden estar, a su vez, substituidos. R3 y R4 pueden significar, de modo independiente entre sí, hidrógeno o NR9R10, con la condición de que, cuando R3 = NR9R10, R4 = H, y cuando R4 = NR9R10, R3 = H, en donde R9 puede ser hidrógeno, alquilo, cicloalquilo, heterociclilo, arilo, heteroarilo, alquilcicloalquilo, alquil-heterociclilo, alquil-arilo o alquil-heteroarilo, y los substituyentes de alquilo, cicloalquilo, heterociclilo, arilo, heteroarilo, alquilcicloalquilo, alquil-heterociclilo, alquil-arilo o alquil-heteroarilo, pueden estar, a su vez, substituidos, y R10 puede significar -C(Y)NR11R12, en donde Y = O, S y R11 y R12 son de modo independiente entre sí, (i) hidrógeno, (ii) alquilo insubstituido o substituido, en donde el radical alquilo puede estar mono o polisubstituido, igual o diferente, con F, CI, Br, I, CF3, CN, NH2, NH-alquilo, NH-cicloalquilo, NH-heterociclilo, NH-arilo, NH-heteroarilo, NH-alquil-cicloalquilo, NH-alquil-heterociclilo, NH-alquil-arilo, NH-alquil-heteroarilo, N(alquilo)2, NHC(O)-alquilo, NHC(O)-cicloalquilo, NHC(O)-heterociclilo, NHC(O)-arilo, NHC(O)-heteroarilo, NHC(O)-alquil-arilo, NHC(O)-alquil-heteroarilo, NHSO2-alquilo, NHSO2-cicloalquilo, NHSO2-heterociclilo, NHSO2-arilo, NHSO2-heteroarilo, NHSO2-alquil-arilo, NHSO2-alquil-heteroarilo, NO2, SH, S-alquilo, S-cicloalquilo, S-heterociclilo, S-arilo, S-heteroarilo, OH, OCF3, O-alquilo, O-cicloalquilo, O-heterociclilo, O-arilo, O-heteroarilo, O-alquil-cicloalquilo, O-alquil-heterociclilo, O-alquil-arilo, O-alquil-heteroarilo, OC(O)-alquilo, OC(O)-cicloalquilo, OC(O)-heterociclilo, OC(O)-arilo, OC(O)-heteroarilo, OC(O)-alquil-arilo, OC(O)-alquil-heteroarilo, OSO3H, OSO2-alquilo, OSO2-cicloalquilo, OSO2-heterociclilo, OSO2-arilo, OSO2-heteroarilo, OSO2-alquil-arilo, OSO2-alquil-heteroarilo, OP(O)(OH)2, C(O)-alquilo, C(O)-arilo, C(O)-heteroarilo, CO2H, CO2-alquilo, CO2-cicloalquilo, CO2-heterociclilo, CO2-arilo, CO2-heteroarilo, CO2-alquil-cicloalquilo, CO2-alquil-heterociclilo, CO2-alquil-arilo, CO2-alquil-heteroarilo, C(O)-NH2, C(O)NH-alquilo, C(O)NH-cicloalquilo, C(O)NH-heterociclilo, C(O)NH-arilo, C(O)NH-heteroarilo, C(O)NH-alquil-cicloalquilo, C(O)NH-alquil-heterociclilo, C(O)NH-alquil-arilo, C(O)NH-alquil-heteroarilo, C(O)N(alquilo)2, C(O)N(cicloalquilo)2, C(O)N(arilo)2, C(O)N(heteroarilo)2, SO-alquilo, SO-arilo, SO2-alquilo, SO2-arilo, SO2NH2, SO2NH-alquilo, SO2NH-arilo, SO2NH-heteroarilo, SO2NH-alquil-arilo, SO3H, SO2O-alquilo, SO2O-arilo, SO2O-alquil-arilo, cicloalquilo, heterociclilo, arilo o heteroarilo, (iii) cicloalquilo insubstituido o substituido, en donde el radical cicloalquilo puede estar mono o polisubstituido, igual o diferente, con F, Cl, Br, I, NH2, NH-alquilo, NH-cicloalquilo, NH-heterociclilo, NH-arilo, NH-heteroarilo, NH-alquil-arilo, NH-alquil-heteroarilo, N(alquilo)2, NHC(O)-alquilo, NHC(O)-cicloalquilo, NHC(O)-heterociclilo, NHC(O)-arilo, NHC(O)-heteroarilo, NHC(O)-alquil-arilo, NHC(O)-alquil-heteroarilo, NHSO2-alquilo, NHSO2-cicloalquilo, NHSO2-heterociclilo, NHSO2-arilo, NHSO2-heteroarilo, NHSO2-alquil-arilo, NHSO2-alquil-heteroarilo, OH, O-alquilo, O-cicloalquilo, O-heterociclilo, O-arilo, O-heteroarilo, O-alquil-arilo, O-alquil-heteroarilo, OC(O)-alquilo, OC(O)-cicloalquilo, OC(O)-heterociclilo, OC(O)-arilo, OC(O)-heteroarilo, OC(O)-alquil-arilo, OC(O)-alquil-heteroarilo, OSO3H, OSO2-alquilo, OSO2-cicloalquilo, OSO2-heterociclilo, OSO2-arilo, OSO2-heteroarilo, OSO2-alquil-arilo, OSO2-alquil-heteroarilo, OP(O)(OH)2, CO2H, CO2-alquilo, CO2-cicloalquilo, CO2-heterociclilo, CO2-arilo, CO2-heteroarilo, CO2-alquil-cicloalquilo, CO2-alquil-heterociclilo, CO2-alquil-arilo, CO2-alquil-heteroarilo, C(O)-NH2, C(O)NH-alquilo, C(O)NH-cicloalquilo, C(O)NH-heterociclilo, C(O)NH-arilo, C(O)NH-heteroarilo, C(O)NH-alquil-cicloalquilo, C(O)NH-alquil-heterociclilo, C(O)NH-alquil-arilo, C(O)NH-alquil-heteroarilo, C(O)N(alquilo)2, C(O)N(cicloalquilo)2, C(O)N(arilo)2, C(O)N(heteroarilo)2, alquilo o arilo, (iv) heterociclilo insubstituido o substituido, en donde el radical heterociclilo puede estar mono o polisubstituido, igual o diferente, con OH, O-alquilo, O-arilo, NH2, NH-alquilo, NH-arilo, alquilo, alquil-aril
ARP040101772A 2003-05-23 2004-05-21 Derivados de pirido[2,3-b]pirazinas, y su uso como moduladores de quinasas AR045686A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10323345A DE10323345A1 (de) 2003-05-23 2003-05-23 Neue Pyridopyrazine und deren Verwendung als Kinase-Inhibitoren
DE102004022383A DE102004022383A1 (de) 2004-05-06 2004-05-06 Neue Pyridopyrazine und deren Verwendung als Modulatoren von Kinasen

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AR045686A1 true AR045686A1 (es) 2005-11-09

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KR (1) KR101111464B1 (es)
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AU2006216998B2 (en) * 2005-02-14 2010-12-23 Merck Sharp & Dohme Corp. Inhibitors of Akt activity
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US8217042B2 (en) 2005-11-11 2012-07-10 Zentaris Gmbh Pyridopyrazines and their use as modulators of kinases
EP1785423A1 (de) * 2005-11-11 2007-05-16 Zentaris GmbH Neue Pyridopyrazine und deren Verwendung als Modulatoren von Kinasen
EP1790342A1 (de) * 2005-11-11 2007-05-30 Zentaris GmbH Pyridopyrazin-Derivate und deren Verwendung als Modulatoren der Signaltransduktionswege
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