ES2535166T3 - Pirimidinil-aminas sustituidas como inhibidores de proteína-quinasas - Google Patents

Pirimidinil-aminas sustituidas como inhibidores de proteína-quinasas Download PDF

Info

Publication number
ES2535166T3
ES2535166T3 ES08829943.3T ES08829943T ES2535166T3 ES 2535166 T3 ES2535166 T3 ES 2535166T3 ES 08829943 T ES08829943 T ES 08829943T ES 2535166 T3 ES2535166 T3 ES 2535166T3
Authority
ES
Spain
Prior art keywords
phenyl
substituted
pyrimidin
ring
acetamide
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
ES08829943.3T
Other languages
English (en)
Inventor
Theodore Mark Kamenecka
Rong Jiang
Xinyi Song
Philip Lograsso
Michael Darin Cameron
Derek R. Duckett
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.)
Scripps Research Institute
Original Assignee
Scripps Research Institute
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 Scripps Research Institute filed Critical Scripps Research Institute
Application granted granted Critical
Publication of ES2535166T3 publication Critical patent/ES2535166T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • 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
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • 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
    • A61P3/08—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
    • 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
    • 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
    • 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
    • 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
    • A61P9/10—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—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
    • C07D401/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Rheumatology (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Vascular Medicine (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Psychology (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Un compuesto o sal farmacéuticamente aceptable del mismo de fórmula Ib:**Fórmula** donde: Z1 y Z2 son cada uno CH; R1 es anillo heterocíclico de 4-10 miembros que tiene entre 1 y 4 miembros del anillo heteroatómicos seleccionados entre O, S(O)q, y N, donde el anillo heterocíclico está sustituido con 0-2 R5; R2, cuando está presente, es en forma independiente Cl, F, Br, I, CF3, OCF3, C1-4alquilo, C2-4alquenilo, C2-4-alquinilo, NO2, -CN, ORa, N(Ra)2, CORa, CO2Ra; R3 es H, CH3, CH2CH3, ciano, Cl, F, Br, o I; R4 es un anillo fenilo sustituido con 1-2 grupos R4a; cada R4a es en forma independiente >=O, Cl, F, Br, I, CF3, OCF3, C1-6alquilo sustituido con 0-3 R5, C2-6alquenilo sustituido con 0-3 R5, C2-6alquinilo sustituido con 0-3 R5, (CH2)pNO2, (CH2)pCN, (CH2)pOR, (CH2)pN(R)2, (CH2)pCOR, (CH2)pOCOR, (CH2)pCO2R, (CH2)pCON(R)2, (CH2)pOCON(R)2, (CH2)pNRCOR, (CH2)pNRCO2R, (CH2)pNRCON(R)2, (CH2)pC(>=NH)NH2, (CH2)pSO2R, (CH2)pSO2N(R)2, (CH2)pNRSO2R, (CH2)pNRSO2N(R)2, CH(CF3)NH2, o (CH2)p-(anillo heterocíclico de 5-6 miembros que tiene entre 1 y 4 miembros del anillo heteroatómicos seleccionados entre O, S(O)q, y N), donde el anillo heterocíclico está sustituido con 0-3 R5a, donde un primer grupo R4a es un anillo heteroaromático de 5-6 miembros; cada R es en forma independiente H, C1-6alquilo sustituido con 0-2 R5, C2-6alquenilo sustituido con 0-2 R5, C2- 6alquinilo sustituido con 0-2 R5, anillo carbocíclico de 3-10 miembros sustituido con 0-2 R5, o anillo heterocíclico de 5-10 miembros que tiene entre 1 y 4 miembros del anillo heteroatómicos seleccionados entre O, S(O)q, y N, donde el anillo heterocíclico está sustituido con 0-2 R5; o dos R unidos al mismo átomo de N se toman junto con el átomo de nitrógeno al cual están unidos para formar un heterocicloalquilo de 5-8 miembros sustituido con 0-2 R5; cada R5 es en forma independiente >=O, Cl, F, Br, I, CF3, OCF3, C1-4alquilo, C2-4alquenilo, C2-4alquinilo, NO2, -CN, ORa, N(Ra)2, CORa, CO2Ra, CON(Ra)2, NRaCORa, NRaCO2Ra, NRaCON(Ra)2, C(>=NH)NH2, SO2Ra, SO2N(Ra)2, NRaSO2Ra, NRaSO2N(Ra)2, (CH2)P-(anillo carbocíclico de 3-10 miembros sustituido con 0-2 Rb), o (CH2)p-(anillo heterocíclico de 5-10 miembros que tiene entre 1 y 4 miembros del anillo heteroatómicos seleccionados entre O, S(O)q, y N), donde el anillo heterocíclico está sustituido con 0-2 Rb; o dos R5 tomados junto con el átomo de carbono al cual ambos están conectados forman un anillo 1,3-dioxolano donde los dos átomos de oxígeno del anillo se unen al átomo de carbono que los conecta; R5a se selecciona entre >=O, Cl, F, Br, I, CF3, OCF3, C1-4alquilo, C2-4alquenilo, C2-4alquinilo, NO2, -CN, (CH2)pORa, N(Ra)2, CORa, CO2Ra, CON(Ra)2, NRaCORa, NRaCO2Ra, NRaCON(Ra)2, C(>=NH)NH2, SO2Ra, SO2N(Ra)2, NRaSO2Ra, NRaSO2N(Ra)2, (CH2)p-(anillo carbocíclico de 3-10 miembros sustituido con 0-2 Rb), o (CH2)p-(anillo heterocíclico de 5-10 miembros que tiene entre 1 y 4 miembros del anillo heteroatómicos seleccionados entre O, S(O)q, y N), donde el anillo heterocíclico está sustituido con 0-2 Rb; cada Ra es en forma independiente H, C1-4alquilo, C3-6 cicloalquilo, CH2-C3-6 cicloalquilo, fenilo, o bencilo; o dos Ra unidos al mismo átomo de N se toman junto con el átomo de nitrógeno al cual están unidos para formar un heterocicloalquilo de 5-8 miembros; Rb es H, Cl, F, Br, I, CF3, OCF3, C1-4alquilo opcionalmente sustituido con ORa, C2-4alquenilo, C2-4alquinilo, NO2, -CN, ORa, N(Ra)2, CORa, CO2Ra, o CON(Ra)2; p es 0, 1, 2, 3, o 4; q es 0, 1, o 2; y m es 1 y n es 0, o 1; con las siguientes condiciones: el primer grupo R4a tiene 3 o 4 miembros del anillo heteroatómicos; y el compuesto de fórmula I o sal farmacéuticamente aceptable del mismo no es: N-[3-({4-[4-(acetilamino)fenil]pirimidin-2-il}amino)ciclohexil] -2,6-diclorobenzamida; N-[4-(2-{[4-(1,4-dioxa-8-azaespiro[4.5]dec-8-il)fenil]amino}pirimidin-4-il)fenil]acetamida; N-{4-[2-(lH-indazol-6-ilamino)-5-metilpirimidin-4-il]fenil}acetamida; N-{4-[2-(lH-indol-5-ilamino)-5-metilpirimidin-4-il]fenil}acetamida; N-{4-[2-(lH-indazol-5-ilamino)-5-metilpirimidin-4-il]fenil}acetamida; 'N-[6-({4-[4-(acetilamino)fenil]pirimidin-2-il}amino)piridin-2-il]-2,6-diclorobenzamida 'N-[6-({4-[4-(acetilamino)fenil]pirimidin-2-il}amino)pirimidin-4-il]-2,6-diclorobenzamida; N-(4-{2-[(6-aminopiridin-2-il)amino]pirimidin-4-il}fenil)acetamida; N-(4-{2-[(6-aminopirimidm-4-il)amino]pirimidin-4-il}fenil)acetamida; (R)-N-(4-(2-(1,2,3,4-tetrahidroquinolin-6-ilamino)pirimidin-4-il)fenil)pirrolidin-2-carboxamida; (R)-N-(4-(2-(6-morfolinopiridin-3-ilamino)pirimidin-4-il)fenil)pirrolidin-2-carboxamida; N-{4-[2-(lH-bencimidazol-6-ilamino)-5-metilpirimidin-4-il]fenil}acetamida; 4-({4-[(acetilamino)fenil]pirimidin-2-il}aminopiperidin-1-carboxilato de etilo; 4-({4-[4-(acetilamino)fenil]pirimidin-2-il}amino)piperidin-1-carboxilato de 1,1-dimetiletilo; N-{4-[2-(piperidin-4-ilamino)pirimidin-4-il]fenil}acetamida; o N-{4-[2-({1-[(2,6-diclorofenil)carbonil]piperidin-4-il}amino)pirimidin-4-il]fenil}acetamida.

Description

imagen1
imagen2
imagen3
imagen4
imagen5
imagen6
imagen7
imagen8
imagen9
imagen10
imagen11
imagen12
imagen13
imagen14
imagen15
imagen16
5
10
15
20
25
30
35
40
45
En la cápsula anterior, el ingrediente activo toma la forma de partículas que tienen un tamaño apropiado. La lactosa cristalina y la celulosa microcristalina se mezclan de manera homogénea y se tamizan, y luego se introduce el talco y el estearato de magnesio y se los mezcla. La mezcla final se introduce en cápsulas de gelatina dura que tienen un tamaño apropiado.
A continuación se detalla un ejemplo posible de una solución inyectable de la presente invención.
Ingrediente
cantidad
Sustancia activa
1,0 mg
HCl 1 N
20,0 µl
Ácido acético
0,5 mg
NaCl
8,0 mg
Fenol
10,0 mg
NaOH 1 N
una cantidad apropiada hasta alcanzar un pH de 5
H2O
una cantidad apropiada hasta alcanzar 1 ml
Síntesis
Los compuestos de la presente invención se pueden preparar de varias maneras conocidas por aquellos con experiencia en el arte de la síntesis orgánica (por ejemplo, véase la Patente de los EE.UU. N° 6.476.060 B2, J Med Chem 2004, 47, 627). Los compuestos de la presente invención se pueden sintetizar usando los métodos que se describen a continuación, junto con los métodos de síntesis conocidos en el arte de síntesis química orgánica, o por variaciones de la misma como podrán apreciar aquellos con experiencia en el arte. Los métodos preferidos incluyen, pero de manera no taxativa a, aquellos que se describen a continuación. Se contemplan que todos los procesos que se divulgan en asociación con la presente invención se pueden llevar a la práctica en cualquier escala, incluyendo de miligramos, gramos, de varios gramos, kilogramos, de varios kilogramos o a escala comercial o industrial. Las reacciones se llevan a cabo en un solvente apropiado para los reactivos y materiales que se emplean y que son apropiados para las transformaciones que se llevan a cabo. Aquellos con experiencia en el arte de la síntesis orgánica comprenderán que la funcionalidad presente en las moléculas debería ser consistente con las transformaciones propuestas. Esto a veces requerirá tomar una decisión sobre si se debe modificar el orden de los pasos de síntesis o seleccionar un esquema de proceso en particular con preferencia sobre otro para obtener un compuesto de la invención que se desea. Como se comprenderá fácilmente, los grupos funcionales presentes pueden contener grupos protectores durante el transcurso de la síntesis. Los grupos protectores son conocidos per se como grupos funcionales químicos que se pueden unir selectivamente a funcionalidades, como por ejemplo un grupos hidroxilo y grupos carboxilo y se pueden eliminar de las mismas. Dichos grupos están presentes en un compuesto químico para hacer que dicha funcionalidad sea inerte ante las condiciones de reacción de la reacción a las cuales se expone el compuesto. Con la presente invención se puede emplear cualquiera de una variedad de grupos protectores. Los grupos protectores preferidos incluyen el grupo benciloxicarbonilo y los grupos tertbutiloxicarbonilo. Los grupos protectores de hidroxilo preferidos incluyen a los grupos bencilo y el butildimetilsililo terciario. Otros grupos protectores preferidos que se pueden emplear de acuerdo con la presente invención han sido descritos en Greene, T.W. y Wuts, P.G.M., Protective Groups in Organic Synthesis 3a. Ed., Wiley & Sons, 1991, o Kocienski, P. J., Protecting Groups, 3a Ed., Georg Thieme Verlag, Stuttgart, 2005.
Los compuestos de la presente invención se pueden preparar de acuerdo con los siguientes métodos. Los sustituyentes son los mismos que en la Fórmula (I) excepto donde se los defina de otra manera, o según sea evidente para alguien con experiencia en el arte. Otros métodos representativos se pueden ver en la Sección de Ejemplos Experimentales que se da más adelante.
En el Esquema que se describe a continuación, R1, R2, R3, X y Z son según se definieron anteriormente. Alguien con experiencia en el arte comprenderá que pueden existir otras variables en base al contexto en el cual se las utiliza.
imagen17
Por lo tanto, en el Esquema 1, una pirimidina apropiadamente sustituida que contiene un átomo de halógeno Z (Cl, Br, o I) se puede acoplar con una anilina sustituida en la posición 3- o 4- funcionalizada apropiadamente en presencia de una cantidad estequiométrica o catalítica de un catalizador de paladio tal como Pd(Ph3P)4,
18
imagen18
imagen19
imagen20
imagen21
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
imagen69
imagen70
imagen71
imagen72
imagen73
imagen74
imagen75
imagen76
imagen77
imagen78
imagen79
imagen80
imagen81
imagen82
imagen83
imagen84
imagen85
imagen86
imagen87
imagen88
imagen89
imagen90
imagen91
imagen92
imagen93
imagen94
imagen95
imagen96
imagen97
imagen98
imagen99
imagen100
imagen101
imagen102
imagen103
Se obtuvo 3-(2-metoxietilamino)-5-(2-(4-(3-metil-1H-1,2,4-triazol-1-il)fenilamino)pirimidin-4-il)benzonitrilo siguiendo el
5 procedimiento G usando N-(4-(3-metil-1H-1,2,4-triazol-1-il)fenil)-4-(trimetilestannil)pirimidin-2-amina y 3-bromo-5-(2metoxietilamino)benzonitrilo que se preparó siguiendo el procedimiento general F usando 2-metoxietanamina y 3bromo-5-fluorobenzonitrilo. MS (ESI) 427 (M+H).
Ejemplo 192
10
3-(Ciclohexilamino)-5-(2-(4-(3-metil-1H-1,2,4-triazol-1-il)fenilamino)pirimidin-4-il)benzonitrilo
imagen104
15 [Se obtuvo 3-(ciclohexilamino)-5-(2-(4-(3-metil-1H-1,2,4-triazol-1-il)fenilamino)pirimidin-4-il)benzonitrilo siguiendo el procedimiento G usando N-(4-(3-metil-1H-1,2,4-triazol-1-il)fenil)-4-(trimetilestannil)pirimidin-2-amina y 3-bromo-5(ciclohexilamino)benzonitrilo que se preparó siguiendo el procedimiento general F usando ciclohexanamina y 3bromo-5-fluorobenzonitrilo. MS (ESI) 451 (M+H).
20 Ejemplo 193
3-(2-(4-(3-Metil-1H-1,2,4-triazol-1-il)fenilamino)pirimidin-4-il)-5-(tetrahidro-2H-piran-4-ilamino)benzonitrilo
imagen105
25 Se obtuvo 3-(2-(4-(3-metil-1H-1,2,4-triazol-1-il)fenilamino)pirimidin-4-il)-5-(tetrahidro-2H-piran-4-ilamino)benzonitrilo siguiendo el procedimiento G usando N-(4-(3-metil-1H-1,2,4-triazol-1-il)fenil)-4-(trimetilestannil)pirimidin-2-amina y 3bromo-5-(tetrahidro-2H-piran-4-ilamino)benzonitrilo que se preparó siguiendo el procedimiento general F usando tetrahidro-2H-piran-4-amina y 3-bromo-5-fluorobenzonitrilo. MS (ESI) 453 (M+H).
30
Ejemplo 194
3-(Isopropilamino)-5-(2-(4-(3-metil-1H-1,2,4-triazol-1-il)fenilamino)pirimidin-4-il)benzonitrilo
104
imagen106
imagen107
imagen108
imagen109
imagen110
imagen111
imagen112
imagen113
imagen114
imagen115
imagen116
imagen117
imagen118
imagen119
imagen120
imagen121
imagen122
imagen123
imagen124
imagen125
imagen126
imagen127
imagen128
imagen129
imagen130
imagen131
imagen132
imagen133
imagen134
imagen135
imagen136
imagen137
imagen138
imagen139
imagen140
imagen141
imagen142
imagen143
imagen144
imagen145
imagen146
imagen147
imagen148
imagen149
imagen150
imagen151
imagen152
imagen153
imagen154
imagen155
imagen156
imagen157
imagen158
imagen159
imagen160
imagen161
imagen162
imagen163
imagen164
imagen165
imagen166
imagen167
imagen168
imagen169
imagen170
imagen171
imagen172
imagen173
imagen174
imagen175
imagen176
imagen177

Claims (1)

  1. imagen1
    imagen2
    imagen3
    imagen4
    imagen5
    imagen6
ES08829943.3T 2007-09-04 2008-09-03 Pirimidinil-aminas sustituidas como inhibidores de proteína-quinasas Active ES2535166T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US96984907P 2007-09-04 2007-09-04
US969849P 2007-09-04
PCT/US2008/075151 WO2009032861A1 (en) 2007-09-04 2008-09-03 Substituted pyrimidinyl-amines as protein kinase inhibitors

Publications (1)

Publication Number Publication Date
ES2535166T3 true ES2535166T3 (es) 2015-05-06

Family

ID=40429327

Family Applications (1)

Application Number Title Priority Date Filing Date
ES08829943.3T Active ES2535166T3 (es) 2007-09-04 2008-09-03 Pirimidinil-aminas sustituidas como inhibidores de proteína-quinasas

Country Status (7)

Country Link
US (3) US8530480B2 (es)
EP (1) EP2200436B1 (es)
JP (2) JP5611826B2 (es)
CA (1) CA2698511C (es)
ES (1) ES2535166T3 (es)
PT (1) PT2200436E (es)
WO (1) WO2009032861A1 (es)

Families Citing this family (93)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008077810A2 (en) 2006-12-22 2008-07-03 F. Hoffmann-La Roche Ag Spiro-piperidine derivatives
KR20150043565A (ko) * 2007-03-12 2015-04-22 와이엠 바이오사이언시즈 오스트레일리아 피티와이 엘티디 페닐 아미노 피리미딘 화합물 및 이의 용도
AU2013201306B2 (en) * 2007-03-12 2015-11-12 Glaxosmithkline Llc Phenyl Amino Pyrimidine Compounds and Uses Thereof
AU2016200866B2 (en) * 2007-03-12 2017-06-22 Glaxosmithkline Llc Phenyl amino pyrimidine compounds and uses thereof
US8507511B2 (en) * 2007-04-24 2013-08-13 Ingenium Pharmaceuticals Gmbh Inhibitors of protein kinases
EP2200436B1 (en) 2007-09-04 2015-01-21 The Scripps Research Institute Substituted pyrimidinyl-amines as protein kinase inhibitors
US7923450B2 (en) 2008-01-11 2011-04-12 Hoffmann-La Roche Inc. Modulators for amyloid beta
CN101952275B (zh) * 2008-02-22 2014-06-18 弗·哈夫曼-拉罗切有限公司 β-淀粉样蛋白的调节剂
CA2736924C (en) 2008-10-09 2016-06-28 F. Hoffmann-La Roche Ag Modulators for amyloid beta
KR101293421B1 (ko) 2008-11-10 2013-08-05 에프. 호프만-라 로슈 아게 헤테로사이클릭 감마 분비효소 조절제
BR112012008677A2 (pt) * 2009-10-12 2018-03-20 Myrexis Inc compostos amino-pirimidina como inibidores de tbkl e/ou ikk epsilon
WO2011075560A1 (en) 2009-12-17 2011-06-23 Merck Sharp & Dohme Corp. Aminopyrimidines as syk inhibitors
CA2782889C (en) 2009-12-17 2014-08-05 Merck Canada Inc. Aminopyrimidines as syk inhibitors
US8486967B2 (en) 2010-02-17 2013-07-16 Hoffmann-La Roche Inc. Heteroaryl substituted piperidines
CN103140483B (zh) 2010-07-15 2015-06-24 拜耳知识产权有限责任公司 作为杀虫剂的新杂环化合物
GB201012105D0 (en) 2010-07-19 2010-09-01 Domainex Ltd Novel pyrimidine compounds
WO2012018639A2 (en) 2010-07-26 2012-02-09 Biomatrica, Inc. Compositions for stabilizing dna, rna and proteins in saliva and other biological samples during shipping and storage at ambient temperatures
WO2012018638A2 (en) 2010-07-26 2012-02-09 Biomatrica, Inc. Compositions for stabilizing dna, rna and proteins in blood and other biological samples during shipping and storage at ambient temperatures
WO2012052412A1 (de) * 2010-10-22 2012-04-26 Bayer Cropscience Ag Neue heterocylische verbindungen als schädlingsbekämpfungsmittel
US8754114B2 (en) 2010-12-22 2014-06-17 Incyte Corporation Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3
BR112013021896A2 (pt) 2011-02-28 2016-11-08 Array Biopharma Inc inibidores de serina/treonina cinase
EP2694486B1 (en) 2011-04-01 2018-01-10 University of Utah Research Foundation Substituted n-(3-(pyrimidin-4-yl)phenyl)acrylamide analogs as tyrosine receptor kinase btk inhibitors
CA2832919A1 (en) * 2011-04-12 2012-10-18 Ryan C. Holcomb Compounds, compositions, and therapeutic uses thereof
MX2013012233A (es) 2011-04-19 2014-01-23 Bayer Pharma AG 4-aril-n-fenil-1,3,5-triazin-2-aminas sustituidas.
CA2834062A1 (en) 2011-05-10 2012-11-15 Merck Sharp & Dohme Corp. Pyridyl aminopyridines as syk inhibitors
WO2012154518A1 (en) 2011-05-10 2012-11-15 Merck Sharp & Dohme Corp. Bipyridylaminopyridines as syk inhibitors
CA2834604A1 (en) 2011-05-10 2012-11-15 Merck Sharp & Dohme Corp. Aminopyrimidines as syk inhibitors
TW201636330A (zh) 2011-05-24 2016-10-16 拜耳知識產權公司 含有硫醯亞胺基團之４－芳基－ｎ－苯基－１，３，５－三氮雜苯－２－胺
AU2012282693B2 (en) * 2011-07-12 2015-11-05 Corteva Agriscience Llc Pesticidal compositions and processes related thereto
ES2552989T3 (es) 2011-08-04 2015-12-03 Array Biopharma, Inc. Compuestos de quinazolina como inhibidores de la cinasa de serina / treonina
DE102011112978A1 (de) * 2011-09-09 2013-03-14 Merck Patent Gmbh Benzonitrilderivate
EP2755948B1 (en) 2011-09-16 2016-05-25 Bayer Intellectual Property GmbH Disubstituted 5-fluoro pyrimidine derivatives containing a sulfoximine group
CA2848616A1 (en) 2011-09-16 2013-03-21 Bayer Intellectual Property Gmbh Disubstituted 5-fluoro-pyrimidines
PL3321262T3 (pl) 2012-03-01 2021-06-28 Array Biopharma, Inc. Inhibitory kinaz serynowo/treoninowych
ES2704744T3 (es) 2012-06-13 2019-03-19 Incyte Holdings Corp Compuestos tricíclicos sustituidos como inhibidores de FGFR
US8809359B2 (en) 2012-06-29 2014-08-19 Ym Biosciences Australia Pty Ltd Phenyl amino pyrimidine bicyclic compounds and uses thereof
WO2014026125A1 (en) 2012-08-10 2014-02-13 Incyte Corporation Pyrazine derivatives as fgfr inhibitors
AR092253A1 (es) 2012-08-27 2015-04-08 Array Biopharma Inc Inhibidores de serina/treonina cinasa
CA2887435A1 (en) * 2012-10-04 2014-04-10 University Of Utah Research Foundation Substituted n-(3-(pyrimidin-4-yl)phenyl)acrylamide analogs as tyrosine receptor kinase btk inhibitors
WO2014055934A2 (en) * 2012-10-04 2014-04-10 University Of Utah Research Foundation Substituted n-(3-(pyrimidin-4-yl)phenyl)acrylamide analogs as tyrosine receptor kinase btk inhibitors
CA2888381A1 (en) 2012-10-18 2014-04-24 Bayer Pharma Aktiengesellschaft 4-(ortho)-fluorophenyl-5-fluoropyrimidin-2-yl amines containing a sulfone group
CN104854091B (zh) 2012-10-18 2018-04-03 拜耳药业股份公司 含砜基团的5‑氟‑n‑(吡啶‑2‑基)吡啶‑2‑胺衍生物
TW201418243A (zh) 2012-11-15 2014-05-16 Bayer Pharma AG 含有磺醯亞胺基團之ｎ－（吡啶－２－基）嘧啶－４－胺衍生物
US9266892B2 (en) 2012-12-19 2016-02-23 Incyte Holdings Corporation Fused pyrazoles as FGFR inhibitors
EP3249054A1 (en) 2012-12-20 2017-11-29 Biomatrica, INC. Formulations and methods for stabilizing pcr reagents
GB201303109D0 (en) * 2013-02-21 2013-04-10 Domainex Ltd Novel pyrimidine compounds
CN109776525B (zh) 2013-04-19 2022-01-21 因赛特控股公司 作为fgfr抑制剂的双环杂环
EP3007556B1 (en) 2013-06-13 2020-05-20 Biomatrica, INC. Cell stabilization
ES2891555T3 (es) 2014-06-10 2022-01-28 Biomatrica Inc Estabilización de trombocitos a temperaturas ambiente
TWI729644B (zh) 2014-06-12 2021-06-01 美商西爾拉癌症醫學公司 N-(氰基甲基)-4-(2-(4-𠰌啉基苯基胺基)嘧啶-4-基)苯甲醯胺
CN107207475A (zh) 2014-10-16 2017-09-26 拜耳医药股份有限公司 含有砜基团的氟化苯并呋喃基‑嘧啶衍生物
US10851105B2 (en) 2014-10-22 2020-12-01 Incyte Corporation Bicyclic heterocycles as FGFR4 inhibitors
US9580423B2 (en) 2015-02-20 2017-02-28 Incyte Corporation Bicyclic heterocycles as FGFR4 inhibitors
MA41551A (fr) 2015-02-20 2017-12-26 Incyte Corp Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4
AU2016219822B2 (en) 2015-02-20 2020-07-09 Incyte Holdings Corporation Bicyclic heterocycles as FGFR inhibitors
CA2980493A1 (en) 2015-03-24 2016-09-29 Bayer Pharma Aktiengesellschaft Use of 4-(4-fluoro-2-methoxyphenyl)-n-{3-[(s-methylsulfonimidoyl)methyl]phenyl}-1,3,5-triazin-2-amine for treating multiple myeloma
WO2016150902A1 (en) 2015-03-24 2016-09-29 Bayer Pharma Aktiengesellschaft Use of 4-(4-fluoro-2-methoxyphenyl)-n-{3-[(s-methylsulfonimidoyl)methyl]phenyl}-1,3,5-triazin-2-amine for treating gastric cancers
CN107427520A (zh) 2015-03-24 2017-12-01 拜耳医药股份有限公司 4‑(4‑氟‑2‑甲氧基苯基)‑n‑{3‑[(s‑甲基磺酰亚氨基)甲基]苯基}‑1，3，5‑三嗪‑2‑胺用于治疗淋巴瘤的用途
EP3319968A1 (en) 2015-07-06 2018-05-16 Rodin Therapeutics, Inc. Heterobicyclic n-aminophenyl-amides as inhibitors of histone deacetylase
RS62639B1 (sr) 2015-07-06 2021-12-31 Alkermes Inc Hetero-halo inhibitori histonskih deacetilaza
CN108290903B (zh) 2015-09-29 2021-09-03 拜耳医药股份有限公司 新的大环磺酰二亚胺化合物
EP3359544B1 (en) 2015-10-08 2020-08-12 Bayer Pharma Aktiengesellschaft Novel modified macrocyclic compounds
WO2017060322A2 (en) 2015-10-10 2017-04-13 Bayer Pharma Aktiengesellschaft Ptefb-inhibitor-adc
PL3362445T3 (pl) 2015-10-12 2023-08-07 Chong Kun Dang Pharmaceutical Corp. Związki będące pochodnymi oksadiazoloamin jako inhibitor deacetylazy histonowej 6 oraz kompozycja farmaceutyczna obejmujące takie związki
EP4242628A3 (en) 2015-12-08 2023-11-08 Biomatrica, INC. Reduction of erythrocyte sedimentation rate
JP6740452B2 (ja) 2016-07-26 2020-08-12 深▲セン▼市塔吉瑞生物医▲薬▼有限公司Ｓｈｅｎｚｈｅｎ ＴａｒｇｅｔＲｘ，Ｉｎｃ． プロテインチロシンキナーゼの活性を阻害するためのアミノピリミジン系化合物
WO2018049353A1 (en) * 2016-09-12 2018-03-15 Imago Pharmaceuticals, Inc. Treatment of fibrotic disorders with jun n-terminal kinase inhibitors
RS62959B1 (sr) 2017-01-11 2022-03-31 Alkermes Inc Biciklični inhibitori histon-deacetilaze
US20190381125A1 (en) * 2017-02-15 2019-12-19 University Of Massachusetts Methods of Treating Angiogenesis-Related Disorders Using JNK3 Inhibitors
GB201702947D0 (en) 2017-02-23 2017-04-12 Domainex Ltd Novel compounds
EP3601253B1 (en) 2017-03-28 2021-09-15 Bayer Aktiengesellschaft Novel ptefb inhibiting macrocyclic compounds
WO2018177889A1 (en) 2017-03-28 2018-10-04 Bayer Aktiengesellschaft Novel ptefb inhibiting macrocyclic compounds
GB201705263D0 (en) * 2017-03-31 2017-05-17 Probiodrug Ag Novel inhibitors
AR111960A1 (es) 2017-05-26 2019-09-04 Incyte Corp Formas cristalinas de un inhibidor de fgfr y procesos para su preparación
MD3664802T2 (ro) 2017-08-07 2022-07-31 Alkermes Inc Inhibitori biciclici ai deacetilazei histonei
SG11202003441VA (en) * 2017-10-17 2020-05-28 Merck Patent Gmbh PYRIMIDINE ΤΒΚ/ΙΚΚε INHIBITOR COMPOUNDS AND USES THEREOF
BR112020007466A2 (pt) * 2017-10-17 2020-09-24 Merck Patent Gmbh compostos inibidores de tbk/ikképsilon de pirimidina e usos dos mesmos
EP3732285A1 (en) 2017-12-28 2020-11-04 Tract Pharmaceuticals, Inc. Stem cell culture systems for columnar epithelial stem cells, and uses related thereto
BR112020016389A2 (pt) 2018-02-13 2020-12-15 Bayer Aktiengesellschaft Uso de 5-fluor-4-(4-fluor-2-metoxifenil)-n-{4-[(s-metilsulfonimidoil)metil]piridin-2-il}piridin-2-amina para tratamento de linfoma difuso de células b grandes
MX2020011639A (es) 2018-05-04 2021-02-15 Incyte Corp Sales de un inhibidor de receptores de factor de crecimiento de fibroblastos (fgfr).
BR112020022392A2 (pt) 2018-05-04 2021-02-02 Incyte Corporation formas sólidas de um inibidor de fgfr e processos para preparação das mesmas
WO2020068854A1 (en) * 2018-09-25 2020-04-02 Cardurion Pharmaceuticals, Llc Aminopyrimidine compound
WO2020068846A1 (en) * 2018-09-25 2020-04-02 Heterocyclic Compound Heterocyclic compound
WO2020185532A1 (en) 2019-03-08 2020-09-17 Incyte Corporation Methods of treating cancer with an fgfr inhibitor
US11591329B2 (en) 2019-07-09 2023-02-28 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
IL291901A (en) 2019-10-14 2022-06-01 Incyte Corp Bicyclyl heterocycles as fgr suppressors
WO2021076728A1 (en) 2019-10-16 2021-04-22 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
WO2021113479A1 (en) 2019-12-04 2021-06-10 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
KR20220131900A (ko) 2019-12-04 2022-09-29 인사이트 코포레이션 Fgfr 억제제의 유도체
WO2021146424A1 (en) 2020-01-15 2021-07-22 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
CA3215903A1 (en) 2021-04-12 2022-10-20 Incyte Corporation Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent
EP4352059A1 (en) 2021-06-09 2024-04-17 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
US12084453B2 (en) 2021-12-10 2024-09-10 Incyte Corporation Bicyclic amines as CDK12 inhibitors

Family Cites Families (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4876252A (en) 1986-01-13 1989-10-24 American Cyanamid Company 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines
ATE135699T1 (de) * 1986-01-13 1996-04-15 American Cyanamid Co 4,5,6-substituierte 2-pyrimidinamine
US4788195A (en) * 1986-01-13 1988-11-29 American Cyanamid Company 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines
TW225528B (es) 1992-04-03 1994-06-21 Ciba Geigy Ag
US5521184A (en) 1992-04-03 1996-05-28 Ciba-Geigy Corporation Pyrimidine derivatives and processes for the preparation thereof
AU693114B2 (en) 1993-10-01 1998-06-25 Novartis Ag Pharmacologically active pyrimidineamine derivatives and processes for the preparation thereof
GB9523675D0 (en) * 1995-11-20 1996-01-24 Celltech Therapeutics Ltd Chemical compounds
GB9619284D0 (en) 1996-09-16 1996-10-30 Celltech Therapeutics Ltd Chemical compounds
GB9914258D0 (en) * 1999-06-18 1999-08-18 Celltech Therapeutics Ltd Chemical compounds
GB9924862D0 (en) * 1999-10-20 1999-12-22 Celltech Therapeutics Ltd Chemical compounds
GB0004887D0 (en) * 2000-03-01 2000-04-19 Astrazeneca Uk Ltd Chemical compounds
US7129242B2 (en) 2000-12-06 2006-10-31 Signal Pharmaceuticals, Llc Anilinopyrimidine derivatives as JNK pathway inhibitors and compositions and methods related thereto
ES2292753T4 (es) * 2001-03-29 2009-02-16 Vertex Pharmaceuticals Incorporated Inhibidores de quinasas n-terminales c-jun (jnk) y otras proteina quinasas.
ATE331519T1 (de) 2001-05-16 2006-07-15 Gpc Biotech Ag Pyridylpyrimidin-derivate als wirksame verbindungen gegen prionen-krankheiten
GB0215676D0 (en) 2002-07-05 2002-08-14 Novartis Ag Organic compounds
CA2506772A1 (en) 2002-11-01 2004-05-21 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of jak and other protein kinases
WO2004041814A1 (en) * 2002-11-04 2004-05-21 Vertex Pharmaceuticals Incorporated Heteroaryl-pyramidine derivatives as jak inhibitors
WO2004041810A1 (en) 2002-11-05 2004-05-21 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of jak and other protein kinases
GB0308466D0 (en) * 2003-04-11 2003-05-21 Novartis Ag Organic compounds
CA2533474A1 (en) * 2003-07-30 2005-02-10 Shudong Wang 2-aminophenyl-4-phenylpyrimidines as kinase inhibitors
WO2006021458A2 (en) 2004-08-27 2006-03-02 Gpc Biotech Ag Pyrimidine derivatives
BRPI0516597A (pt) * 2004-10-13 2008-09-16 Wyeth Corp composto da fórmula
WO2007081690A2 (en) * 2006-01-04 2007-07-19 Locus Pharmaceuticals, Inc. Inhibitors of protein kinases
BRPI0706747A2 (pt) * 2006-01-30 2011-04-05 Exelixis Inc 4-aril-2-amino-pirimidinas ou 4-aril-2-aminoalquil-pirimidinas como moduladores jak-2 e composições farmacêuticas que os contenham
US20100145851A1 (en) 2006-12-18 2010-06-10 Fundamo (Proprietary) Limited Transaction system with enhanced instruction recognition
US20100048597A1 (en) 2006-12-22 2010-02-25 Novartis Ag Organic Compounds and Their Uses
AT504205B1 (de) * 2007-01-02 2008-04-15 Hoermann Richard Dr Einrichtung zur entkeimung eines fluids
PE20090054A1 (es) * 2007-01-23 2009-01-26 Palau Pharma Sa Derivados de purina
KR20150043565A (ko) * 2007-03-12 2015-04-22 와이엠 바이오사이언시즈 오스트레일리아 피티와이 엘티디 페닐 아미노 피리미딘 화합물 및 이의 용도
WO2008124085A2 (en) * 2007-04-03 2008-10-16 Exelixis, Inc. Methods of using combinations of mek and jak-2 inhibitors
WO2009017838A2 (en) * 2007-08-01 2009-02-05 Exelixis, Inc. Combinations of jak-2 inhibitors and other agents
EP2200436B1 (en) 2007-09-04 2015-01-21 The Scripps Research Institute Substituted pyrimidinyl-amines as protein kinase inhibitors
WO2009103032A1 (en) * 2008-02-15 2009-08-20 Rigel Pharmaceuticals, Inc. Pyrimidine-2-amine compounds and their use as inhibitors of jak kinases
CN101952275B (zh) * 2008-02-22 2014-06-18 弗·哈夫曼-拉罗切有限公司 β-淀粉样蛋白的调节剂

Also Published As

Publication number Publication date
JP2015007102A (ja) 2015-01-15
US8530480B2 (en) 2013-09-10
JP5611826B2 (ja) 2014-10-22
US20100298312A1 (en) 2010-11-25
US20150232429A1 (en) 2015-08-20
WO2009032861A1 (en) 2009-03-12
JP2010538076A (ja) 2010-12-09
EP2200436A4 (en) 2011-12-28
PT2200436E (pt) 2015-04-29
EP2200436A1 (en) 2010-06-30
EP2200436B1 (en) 2015-01-21
CA2698511A1 (en) 2009-03-12
US20130231336A1 (en) 2013-09-05
CA2698511C (en) 2016-10-11
US9018205B2 (en) 2015-04-28
JP5937648B2 (ja) 2016-06-22

Similar Documents

Publication Publication Date Title
ES2535166T3 (es) Pirimidinil-aminas sustituidas como inhibidores de proteína-quinasas
KR101671341B1 (ko) 다이아미노피리미딘 유도체 및 그의 제조방법
JP2010538076A5 (es)
ES2333824T3 (es) Derivados de piridinilo y pirimidinilo sustituidos como moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo.
RU2373209C2 (ru) Пирролотриазиновые соединения как ингибиторы киназ
ES2344484T3 (es) Derivados de piperazinilo utiles en el tratamiento de enfermedades mediadas por el receptor gpr38.
CA2690953A1 (en) Benzimidazole derivatives
CN101735197B (zh) 一种伊马替尼的合成方法
IL276946B (en) Antiproliferative compounds and methods of use
JP2017530199A5 (es)
JP2007527909A5 (es)
AR073920A1 (es) Derivados urea de nortropanos sustituidos, medicamentos que contienen dichos compuestos , su uso en el tratamiento de enfermedades mediadas por la inhibicion de la enzima 11beta-hidroxiesteroide deshidrogenasa y proceso para su preparacion.
BG64848B1 (bg) Циклични аминопроизводни и използването им като лекарства
RU2010101633A (ru) Новое сульфонамидное производное малоновой кислоты и его фармацевтическое применение
CN1820001A (zh) 经取代的杂环二芳基胺类似物
JP2007532596A5 (es)
Vasbinder et al. Discovery and optimization of a novel series of potent mutant B-RafV600E selective kinase inhibitors
JP2011526913A5 (ja) キナゾリン化合物及び同化合物を含む治療薬
KR20140083058A (ko) G 단백질-커플링된 Mas 수용체의 조절제 및 그와 관련된 장애의 치료
KR20120114355A (ko) 화합물 및 방법
RU2013130925A (ru) Оксимовые соединения в качестве средств для повышения уровня холестерина высокой плотности
RU2008140020A (ru) Гетеробициклические карбоксамиды в качестве ингибиторов киназ
CN1777591A (zh) 具有喹唑二酮骨架的苯丙氨酸衍生物的制造方法及制造中间体
JP2008503573A5 (es)
JP2013505262A (ja) ｍＧｌｕＲ５ネガティブアロステリックモジュレータとしての置換ヘテロアリールアミンカルボキサミド類似体、ならびに、その形成方法および使用方法