ES2552515T3 - Derivados de piridopirazina y su uso - Google Patents

Derivados de piridopirazina y su uso Download PDF

Info

Publication number
ES2552515T3
ES2552515T3 ES12713705.7T ES12713705T ES2552515T3 ES 2552515 T3 ES2552515 T3 ES 2552515T3 ES 12713705 T ES12713705 T ES 12713705T ES 2552515 T3 ES2552515 T3 ES 2552515T3
Authority
ES
Spain
Prior art keywords
alkyl
aryl
heteroaryl
cycloalkyl
heterocyclyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
ES12713705.7T
Other languages
English (en)
Inventor
Matthias Gerlach
Irene Seipelt
Lars Blumenstein
Gilbert Mueller
Eckhard Günther
Tilmann Schuster
Michael Teifel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aeterna Zentaris GmbH
Original Assignee
Aeterna Zentaris GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Aeterna Zentaris GmbH filed Critical Aeterna Zentaris GmbH
Application granted granted Critical
Publication of ES2552515T3 publication Critical patent/ES2552515T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic 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
    • C07D471/02—Heterocyclic 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
    • C07D471/04—Ortho-condensed systems

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Cardiology (AREA)
  • Hematology (AREA)
  • Neurology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pulmonology (AREA)
  • Obesity (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Endocrinology (AREA)
  • Urology & Nephrology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Oncology (AREA)
  • Emergency Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Dermatology (AREA)
  • Rheumatology (AREA)
  • Virology (AREA)
  • Psychiatry (AREA)
  • Otolaryngology (AREA)
  • Child & Adolescent Psychology (AREA)

Abstract

Un compuesto de acuerdo con la fórmula general (I)**Fórmula** en la que los sustituyentes R1, R2, X tienen el siguiente significado: X es O R1 (I) arilo sustituido, en donde el grupo arilo puede estar sustituido con uno o más 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, 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, O-(-CH2-CH2-O-)n-CH2-CH2-OH, OC(O)-alquilo, OC(O)-cicloalquilo, OC(O)-heterociclilo, OC(O)-arilo, OC(O)-heteroarilo, OC(O)-alquil-arilo, OC(O)-alquil-heteroarilo, OC(O)-NH-alquilo, 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, O- CO2-alquilo, 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)NHcicloalquilo, C(O)NH-heterociclilo, C(O)NH-arilo, C(O)NH-heteroarilo, C(O)NH-alquil-cicloalquilo, C(O)NH-alquilheterociclilo, 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-heterociclilo; 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 iguales o diferentes, n puede tener el valor 0, 1, 2 o 3 y los sustituyentes alquil-, cicloalquil-, heterociclil-, aril-, heteroaril-, alquil-cicloalquil-, alquil-heterociclil-, alquil-aril- y alquil-heteroarilo por su parte pueden estar a su vez sustituidos, (II) heteroarilo no sustituido o sustituido, en donde el grupo heteroarilo puede estar sustituido con uno o más 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, 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-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, SO2NH2, SO2NH-alquilo, SO2NH-arilo, SO2NH-heteroarilo, SO2NH-alquil-arilo, S03H, SO2O-alquilo, SO2O-arilo, SO2O-alquil-arilo, alquilo, cicloalquilo, heterociclilo, alquil-cicloalquilo, alquil-heterociclilo, alquil-arilo, alquil-heteroarilo, arilo o heteroarilo iguales o diferentes, y los sustituyentes alquil-, cicloalquil-, heterociclil-, alquil-heterociclilo, alquil-arilo, alquil-cicloalquilo, alquil-heteroarilo, aril- y heteroarilo por su parte pueden estar a su vez sustituidos, y R2: (I) alquil-arilo no sustituido o sustituido, en donde el grupo alquil-arilo puede estar sustituido con uno o más 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)-alquilarilo, NHC(O)-alquil-heteroarilo, NHSO2-alquilo, NHSO2-cicloalqui), NHSO2-heterociclilo, NHSO2-arilo, NHSO2-heteroarilo, NHSO2-alquil-arilo, NHSO2-alquil-heteroarilo, NO2, SH, S-alquilo, S-cicloalquilo, S-heterociclilo, S-arilo, S-heteroarilo, >=O, 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, alquilo, cicloalquilo, heterociclilo, arilo o heteroarilo iguales o diferentes, (II) alquil-heteroarilo no sustituido o sustituido, en donde el grupo alquil-heteroarilo puede estar sustituido con uno o más 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 iguales o diferentes; sus sales fisiológicamente tolerables, en forma de sus racematos, en forma de sus enantiómeros y/o diastereómeros puros o en forma de mezclas de estos enantiómeros y/o diastereómeros o en forma de sus tautómeros para su uso en el tratamiento o la prevención de estados fisiológicos y/o patofisiológicos en mamíferos mediados por la ruta de transducción de señal ras-Raf-Mek-Erk, en donde los estados fisiológicos y/o patofisiológicos se seleccionan entre el grupo que consiste en: "tumores malignos, tumores benignos, enfermedades inflamatorias, inflamaciones, dolor, enfermedades reumáticas, enfermedades artríticas, infecciones por VIH, enfermedades neurológicas o neurodegenerativas, reumatismo, artritis, SIDA, ARC (complejo relacionado con SIDA), sarcoma de Kaposi, tumores originados en el cerebro y/o en el sistema nervioso y/o en las meninges, demencia, enfermedad de Alzheimer, enfermedades hiperproliferativas, psoriasis, endometriosis, cicatrices, hiperplasia benigna de próstata (BPH), enfermedades del sistema inmune, enfermedades autoinmunes, enfermedades de inmunodeficiencia, tumor de colon, tumor gástrico, tumor intestinal, tumor pulmonar, tumor pancreático, tumor de ovario, tumor prostático, leucemia, melanoma, tumor hepático, tumor renal, tumor de cabeza, tumor de garganta, glioma, tumor de mama, cáncer uterino, cáncer endometrial, carcinoma cervico-uterino, tumor cerebral, adeno-acantoma, cáncer de la vejiga, tumor gástrico, tumor colorrectal, cáncer esofágico, tumor ginecológico, tumor de ovario, cáncer de la tiroides, linfoma, leucemia crónica, leucemia aguda, reestenosis, diabetes, nefropatía diabética, enfermedades fibróticas, fibrosis quística, nefroesclerosis maligna, síndrome de microangiopatía trombótica, rechazo de trasplante de órganos, glomerulopatía, enfermedades metabólicas, tumores sólidos/fijos, artritis

Description

imagen1
imagen2
imagen3
imagen4
imagen5
Compuesto 97: 1-[3-(1-Metil-1H-pirazol-4-il)-pirido[2,3-b]pirazin-6-il]-3-(4-p-tolil-butil)-urea
imagen6
imagen7
imagen8
Compuesto 100: 1-(4-Metil-4-fenil-pentil)-3-[3-(1-propil-1H-pirazol-4-il)-pirido[2,3-b]pirazin-6-il]-urea
imagen9
Compuesto 101: 1-[3-(2,4-Dimetoxi-fenil)-pirido[2,3-b]pirazin-6-il]-3-(4-fenil-butil)-urea
imagen10
Compuesto 103: 1-[3-(3,5-Dicloro-4-hidroxi-fenil)-pirido[2,3-b]pirazin-6-il]-3-(4-fenil-butil)-urea
imagen11
Compuesto 104: 1-[3-(3-Hidroxi-fenil)-pirido[2,3-b]pirazin-6-il]-3-(4-fenil-butil)-urea
imagen12
Compuesto 105: 1-(4-fenil-butil)-3-[3-(2H-pirazol-3-il)-pirido[2,3-b]pirazin-6-il]-urea
imagen13
7
imagen14
Compuesto 114: 1-[3-(1-Butil-1H-pirazol-4-il)-pirido[2,3-b]pirazin-6-il]-3-(4-fenil-butil)-urea
imagen15
Compuesto 115: 1-[4-(4-Metoxi-fenil)-butil]-3-[3-(1-metil-1H-pirazol-4-il)-pirido[2,3-b]pirazin-6-il]-urea
imagen16
Compuesto 116: 1-(4-fenil-butil)-3-[3-(piperidin-4-ilamino)-pirido[2,3-b]pirazin-6-il]-urea
imagen17
Compuesto 117: 1-(4-fenil-butil)-3-{3-[(piridin-4-ilmetil)-amino]-pirido[2,3-b]pirazin-6-il}-urea
imagen18
Compuesto 118: 1-[3-(4-Metoxi-fenil)-pirido[2,3-b]pirazin-6-il]-3-(4-fenil-butil)-urea
imagen19
Compuesto 120: 1-(4-fenil-butil)-3-(3-o-tolil-pirido[2,3-b]pirazin-6-il)-urea
imagen20
Compuesto 121: Éster etílico del ácido 3-{6-[3-(4-fenil-butil)-ureido]-pirido[2,3-b]pirazin-3-il}-benzoico
imagen21
9
imagen22
imagen23
imagen24
imagen25
imagen26
imagen27
imagen28
imagen29
imagen30
imagen31
imagen32
imagen33
imagen34
imagen35
imagen36
imagen37
imagen38
imagen39
imagen40
imagen41
imagen42
imagen43
imagen44
imagen45
imagen46
imagen47
imagen48
imagen49
imagen50
imagen51
imagen52
imagen53
imagen54
imagen55
imagen56
imagen57
imagen58
imagen59
imagen60
imagen61
imagen62
imagen63
imagen64
imagen65
imagen66
imagen67
imagen68
Evaluación
Los valores de % de inhibición por concentración de sustancia se calcularon mediante la siguiente fórmula a partir de los datos sin procesar determinados en el lector de placa Envision:
imagen69
Se hicieron ocho determinaciones para cada control y dos para las muestras de sustancia. El 0 % de control contiene nada de ATP o nada de sustrato, el 100 % de control (quinasa completamente activa) contiene nada de sustancia de 10 ensayo. Los valores de CI50 se determinaron usando GraphPadPrism.
Los compuestos de la invención mostraron inhibición eficaz de Erk y/o PI3K con valores de CI50 de hasta 1 nM (véase la Tabla 1).
15 Tabla 1: resultados de ensayo para el ensayo de quinasa alfa de Erk2 (CI50 [µM] a ATP 10 µM)
Compuesto
Erk2
108
0,004
127
0,005
155
0,004
156
0,001
157
0,002
158
0,001
159
0,001
160
0,001
161
0,002
162
0,002
163
0,002
164
0,002
165
0,003
166
0,003
167
0,003
168
0,003
169
0,003
170
0,004
171
0,004
172
0,005
173
0,005
174
0,006
175
0,006
176
0,006
177
0,006
178
0,006
179
0,006
180
0,006
181
0,006
189
0,004
194
0,001
195
0,001
196
0,004
197
0,005
198
0,003
201
0,039
202
0,041
203
0,024
Ensayo celular: ensayo para el efecto antiproliferativo (ensayo XTT)
El principio de este ensayo se basa en la reducción intracelular del colorante tetrazolio XTT (ácido
20 3’-[1-(fenilaminocarbonil)-3,4-tetrazolio]-bis(4-metoxi-6-nitro)benzeno sulfónico sódico, Sigma) en un colorante formazán por deshidrogenasas mitocondriales. El colorante es el único formado por células metabólicamente activas y su intensidad fotométricamente medible es un indicador cuantitativo de la presencia de células vivas. La reducción de
57
imagen70

Claims (1)

  1. imagen1
    imagen2
    imagen3
    imagen4
    imagen5
    imagen6
    imagen7
    imagen8
    imagen9
    imagen10
    imagen11
    imagen12
    imagen13
    imagen14
    imagen15
    imagen16
    imagen17
    imagen18
    imagen19
    imagen20
    imagen21
    imagen22
    imagen23
    imagen24
    imagen25
ES12713705.7T 2011-04-06 2012-04-04 Derivados de piridopirazina y su uso Active ES2552515T3 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201161472245P 2011-04-06 2011-04-06
US201161472245P 2011-04-06
EP11161248A EP2508184A1 (en) 2011-04-06 2011-04-06 Pyridopyrazine derivatives and their use
EP11161248 2011-04-06
PCT/EP2012/056138 WO2012136691A1 (en) 2011-04-06 2012-04-04 Pyridopyrazine derivatives and their use

Publications (1)

Publication Number Publication Date
ES2552515T3 true ES2552515T3 (es) 2015-11-30

Family

ID=44350566

Family Applications (1)

Application Number Title Priority Date Filing Date
ES12713705.7T Active ES2552515T3 (es) 2011-04-06 2012-04-04 Derivados de piridopirazina y su uso

Country Status (20)

Country Link
US (2) US8791118B2 (es)
EP (3) EP2508184A1 (es)
JP (2) JP5963844B2 (es)
KR (2) KR20140025442A (es)
CN (2) CN103501788A (es)
AR (2) AR085843A1 (es)
AU (2) AU2012238681A1 (es)
BR (1) BR112013025630A2 (es)
CA (2) CA2832337A1 (es)
ES (1) ES2552515T3 (es)
IL (2) IL228436A0 (es)
MX (2) MX2013011444A (es)
NZ (1) NZ615578A (es)
PH (1) PH12013501904A1 (es)
PL (1) PL2694067T3 (es)
RU (2) RU2013146618A (es)
SG (2) SG193978A1 (es)
TW (2) TW201302742A (es)
WO (2) WO2012136691A1 (es)
ZA (2) ZA201306862B (es)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017033113A1 (en) 2015-08-21 2017-03-02 Acerta Pharma B.V. Therapeutic combinations of a mek inhibitor and a btk inhibitor
US20170168056A1 (en) * 2015-11-13 2017-06-15 Massachusetts Institute Of Technology Methods and compositions for detecting and modulating cancer cells
SG11201804901WA (en) 2015-12-22 2018-07-30 SHY Therapeutics LLC Compounds for the treatment of cancer and inflammatory disease
WO2017180817A1 (en) * 2016-04-15 2017-10-19 Musc Foundation For Research Development Treatment of septicemia and ards with erk inhibitors
EA201992780A1 (ru) 2017-06-21 2020-06-02 ШАЙ ТЕРАПЬЮТИКС ЭлЭлСи Соединения, которые взаимодействуют с суперсемейством ras, для лечения рака, воспалительных заболеваний, ras-опатий и фиброзного заболевания
US20200138921A1 (en) * 2017-06-23 2020-05-07 The Trustees Of Columbia University In The City Of New York Methods of preventing and treating diseases characterized by synaptic dysfunction and neurodegeneration including alzheimer's disease
EP3806833A1 (en) 2018-06-15 2021-04-21 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of pi3kc2b inhibitors for the preservation of vascular endothelial cell barrier integrity
US12391705B2 (en) 2018-12-19 2025-08-19 Shy Therapeutics, Llc Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease
CN112830897B (zh) * 2019-11-22 2022-09-09 石家庄以岭药业股份有限公司 含脲基苯并咪唑类衍生物及其制备方法和应用
US20240109883A1 (en) 2020-12-31 2024-04-04 Evrys Bio, Llc Anti-Tumor Compositions and Methods

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3809695A (en) 1967-04-19 1974-05-07 Degussa 2,6-dichloro-3-nitro-pyridine
DE69600385T2 (de) 1995-03-28 1998-12-17 Sumitomo Chemical Co., Ltd., Osaka Verfahren zur Herstellung von Aminonitropyridinen
UA71555C2 (en) 1997-10-06 2004-12-15 Zentaris Gmbh Methods for modulating function of serine/threonine protein kinases by 5-azaquinoline derivatives
ATE529109T1 (de) 1997-12-22 2011-11-15 Bayer Healthcare Llc Hemmung der p38 kinase aktivität durch substituierte heterocyclische harnstoffe
CN101851173A (zh) 2001-09-14 2010-10-06 梅特希尔基因公司 组蛋白脱乙酰化酶抑制剂
US20040023961A1 (en) 2002-02-11 2004-02-05 Bayer Corporation Aryl ureas with raf kinase and angiogenisis inhibiting activity
US7223738B2 (en) 2002-04-08 2007-05-29 Merck & Co., Inc. Inhibitors of Akt activity
EP1496981A2 (en) 2002-04-08 2005-01-19 Merck & Co., Inc. Method of treating cancer
EP1496906A4 (en) 2002-04-08 2006-05-03 Merck & Co Inc HEMMER OF ACT ACTIVITY
US7718651B2 (en) 2002-07-02 2010-05-18 Southern Research Institute Inhibitors of FtsZ and uses thereof
DE10323345A1 (de) 2003-05-23 2004-12-16 Zentaris Gmbh Neue Pyridopyrazine und deren Verwendung als Kinase-Inhibitoren
PT1636228E (pt) * 2003-05-23 2009-02-02 Aeterna Zentaris Gmbh Novas piridopirazinas e sua utilização como moduladores de cinases
WO2005007099A2 (en) 2003-07-10 2005-01-27 Imclone Systems Incorporated Pkb inhibitors as anti-tumor agents
US7592340B2 (en) 2003-12-04 2009-09-22 Vertex Pharmaceuticals Incorporated Quinoxalines useful as inhibitors of protein kinases
GB0413953D0 (en) 2004-06-22 2004-07-28 Syngenta Participations Ag Chemical compounds
EP1790342A1 (de) 2005-11-11 2007-05-30 Zentaris GmbH Pyridopyrazin-Derivate und deren Verwendung als Modulatoren der Signaltransduktionswege
WO2007054556A1 (de) 2005-11-11 2007-05-18 Æterna Zentaris Gmbh Neue pyridopyrazine und deren verwendung als modulatoren von kinasen
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
US7733554B2 (en) * 2006-03-08 2010-06-08 E Ink Corporation Electro-optic displays, and materials and methods for production thereof
KR101097177B1 (ko) 2006-07-06 2011-12-22 한국화학연구원 2-알킬레닐옥시-3-에티닐피리도［2,3-ｂ］피라진 유도체
GB0614471D0 (en) 2006-07-20 2006-08-30 Syngenta Ltd Herbicidal Compounds
US20100093738A1 (en) 2006-10-06 2010-04-15 Basf Se Fungicidal Compounds and Fungicidal Compositions
EP1990342A1 (en) 2007-05-10 2008-11-12 AEterna Zentaris GmbH Pyridopyrazine Derivatives, Process of Manufacturing and Uses thereof
MX2010005960A (es) * 2007-11-30 2010-06-11 Schering Corp Biomarcadores de braf.
NZ586418A (en) 2007-12-19 2012-09-28 Cancer Rec Tech Ltd Pyrido[2,3-b]pyrazine-8-substituted compounds and their use

Also Published As

Publication number Publication date
RU2013146619A (ru) 2015-05-20
CA2832337A1 (en) 2012-10-11
WO2012136694A1 (en) 2012-10-11
AU2012238681A1 (en) 2013-10-03
JP5963844B2 (ja) 2016-08-03
CA2832321A1 (en) 2012-10-11
IL228433A0 (en) 2013-12-31
JP2014510125A (ja) 2014-04-24
EP2694067A1 (en) 2014-02-12
SG193978A1 (en) 2013-11-29
TWI564299B (zh) 2017-01-01
KR20140025443A (ko) 2014-03-04
ZA201306864B (en) 2014-11-26
EP2694068A1 (en) 2014-02-12
AR085843A1 (es) 2013-10-30
US8791118B2 (en) 2014-07-29
PH12013501904A1 (en) 2015-04-22
PL2694067T3 (pl) 2016-01-29
AU2012238678A1 (en) 2013-10-03
RU2013146618A (ru) 2015-05-20
AR085844A1 (es) 2013-10-30
TW201302743A (zh) 2013-01-16
BR112013025630A2 (pt) 2016-12-27
WO2012136691A1 (en) 2012-10-11
JP2014510124A (ja) 2014-04-24
CN103501788A (zh) 2014-01-08
US8912189B2 (en) 2014-12-16
IL228436A0 (en) 2013-12-31
EP2508184A1 (en) 2012-10-10
US20120259151A1 (en) 2012-10-11
SG194097A1 (en) 2013-11-29
NZ615578A (en) 2015-08-28
EP2694067B1 (en) 2015-08-26
ZA201306862B (en) 2014-06-25
AU2012238678B2 (en) 2016-11-17
MX2013011444A (es) 2013-10-17
KR20140025442A (ko) 2014-03-04
TW201302742A (zh) 2013-01-16
US20120258080A1 (en) 2012-10-11
MX2013011490A (es) 2013-11-04
CN103826636A (zh) 2014-05-28

Similar Documents

Publication Publication Date Title
ES2552515T3 (es) Derivados de piridopirazina y su uso
KR102288281B1 (ko) Fgfr4 억제제, 이의 제조 방법 및 약학적 응용
ES2763527T3 (es) Inhibidores de molécula pequeña de mcl-1 y usos de los mismos
JP6559785B2 (ja) Ｅｇｆｒ及びｐｉ３ｋの小分子阻害剤
JP5337313B2 (ja) 特定のトリアゾロピリジンおよびトリアゾロピラジン、それらの組成物並びにそれらの使用方法
ES2543962T3 (es) Derivados de piridopirazina y su uso como moduladores de las vías de transducción de señales
AU2016272057B2 (en) Use of pteridinone derivative serving as EGFR inhibitor
CA2789655A1 (en) Bicyclic compounds and their uses as dual c-src / jak inhibitors
WO2008067119A2 (en) Novel compounds
CA2646166A1 (en) 3-substituted n-(aryl- or heteroaryl)-pyrazo[1,5-a]pyrimidines as kinase inhibitors
Abbas et al. Synthesis and antitumor activity of certain 2, 3, 6-trisubstituted quinazolin-4 (3H)-one derivatives
JP2026053706A (ja) Ｃｄ２０６モジュレーター、その使用、および調製方法
JP2020537669A (ja) ピラゾリル基を含む三環式誘導体、その製造方法及び用途
CN106380465B (zh) 含1，2，3-三氮唑结构单元的2，4-二取代喹唑啉类化合物及其制备方法和用途
Ghorab et al. Synthesis of some tricyclic indeno [1, 2-d] pyrimidine derivatives as a new class of anti-breast cancer agents
CA2646515A1 (en) 3-unsubstituted n-(aryl- or heteroarvl)-pyrazolori [1,5-a]pyrimidines as kinase inhibitors
Ghorab et al. Synthesis of some sulfonamide incorporating enaminone, quinolone moieties and thiazoloquinazoline derivative induce the cytoprotective enzyme NAD (P) H: quinone oxidoreductase 1
El-Essawy et al. Synthesis, characterization and anticancer evaluation of different fused pyridopyrimidopyrimidines as dual EGFR/ACK1 inhibitors with c-Met activity in solid tumor cancer cell lines
CN117886821A (zh) 含氮稠环类衍生物抑制剂、其制备方法和应用
HK40049874B (en) Certain triazolopyrazines, compositions thereof and methods of use therefor
HK40049874A (en) Certain triazolopyrazines, compositions thereof and methods of use therefor
HK40011539B (en) Synthetic intermediate useful in the preparation of triazolopyridine c-met inhibitors
HK1194071B (en) Certain triazolopyrazines, compositions thereof and methods of use therefor