AR072201A1 - 2-arilaminoquinazolinas para el tratamiento de enfermedades proliferativas - Google Patents

2-arilaminoquinazolinas para el tratamiento de enfermedades proliferativas

Info

Publication number
AR072201A1
AR072201A1 ARP090102241A ARP090102241A AR072201A1 AR 072201 A1 AR072201 A1 AR 072201A1 AR P090102241 A ARP090102241 A AR P090102241A AR P090102241 A ARP090102241 A AR P090102241A AR 072201 A1 AR072201 A1 AR 072201A1
Authority
AR
Argentina
Prior art keywords
alkyl
amino
ring
phenyl
methyl
Prior art date
Application number
ARP090102241A
Other languages
English (en)
Original Assignee
Novartis Ag
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 Novartis Ag filed Critical Novartis Ag
Publication of AR072201A1 publication Critical patent/AR072201A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • 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
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
    • C07D239/84—Nitrogen atoms
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D403/10—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 carbon chain containing aromatic 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
    • C07D403/14—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
    • C07D413/10—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 carbon chain containing aromatic 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Dermatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Vascular Medicine (AREA)
  • Toxicology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pulmonology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Epidemiology (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Estos compuestos son inhibidores de PDK1. Tambien se proporcionan composiciones farmaceuticas que incluyen a los compuestos, y metodos para el tratamiento de enfermedades proliferativas, tales como c nceres, con los compuestos o composiciones. Reivindicacion 1: Un compuesto de la formula (1) o una sal farmaceuticamente aceptable del mismo, en donde R1a se selecciona a partir de H y halogeno; R3a se selecciona a partir de heterocicloalquiloxilo C2-6 y heteroarilo C1-6-alcoxilo C1-4; en donde este heterocicloalquiloxilo C2-6 y heteroarilo C1-6-alcoxilo C1-4 est n cada uno opcionalmente sustituidos por un grupo Rw; R4a se selecciona a partir de H, un anillo de tiazol, un anillo de pirazol, un anillo de triazol, un anillo de tetrazol, un anillo de piridina, cicloalquilo C3-6, ciano, halogeno, alquinilo C2-6, heteroarilo C1-6-alquilo C1-4, heteroarilo C1-6-alquinilo C1-4, -C(=O)Ra, y -C(=O)NRbRc; en donde el anillo de tiazol, el anillo de pirazol. el anillo de triazol, el anillo de tetrazol, el anillo de piridina, heteroarilo C1-6-alquilo C1-4 y heteroarilo C1-6-alquinilo C1-4 est n cada uno opcionalmente sustituidos por 1 o 2 grupos Rx'' independientemente seleccionados; Ar1a se selecciona a partir de fenilo opcionalmente sustituido en la posicion meta por un Ry' o, de una manera alternativa, en la posicion para por un grupo Ry''; cada Rw se selecciona independientemente a partir de halogeno, alquilo C1-6, amino, alquilo C1-6-amino, di-alquilo C1-4-amino, alcoxilo C1-6-carbonilo, y alquilo C1-6-carbamilo; en donde este alquilo C1-6, y alquilo C1-6-amino est n cada uno opcionalmente sustituidos por un grupo seleccionado a partir de hidroxilo, alcoxilo C1-6, amino, alquilo C1-6-amino, y di-alquilo C1-4-amino; cada Rx'' se selecciona independientemente a partir de halogeno, hidroxilo, alquilo C1-6, alcoxilo C1-6-carbonilo, y carbamilo; en donde este alquilo C1-6, y alcoxilo C1-6-carbonilo est n cada uno opcionalmente sustituidos por un grupo seleccionado a partir de hidroxilo, amino, alquilo C1-4-amino, y amino-sulfonilo; Ry' se selecciona a partir de halogeno. alcoxilo C1-6, alquilo C1-6, carbamilo, amino-sulfonilo, y alquilo C1-6-sulfonil-amino, en donde este alquilo C1-6, y alcoxilo C1-6 est n cada uno sustituidos por 1 o 2 grupos independientemente seleccionados a partir de hidroxilo, amino, alquilo C1-4-amino, y amino-sulfonilo; Ry'' se selecciona a partir de halo-alquilo C1-6; Ra se selecciona a partir de H, alcoxilo C1-6, y heterocicloalquilo C2-6; Rb se selecciona a partir de H y alquilo C1-6; y Rc se selecciona a partir de alquilo C1-6, cicloalquilo C3-6, heteroarilo C1-6, heterocicloalquilo C2-6, heterocicloalquilo C2-6-alquilo C1-4, y heteroarilo C1-6-alquilo C1-4; en donde este alquilo C1-6 est  opcionalmente sustituido por un grupo seleccionado a partir de hidroxilo y alcoxilo C1-4; en el entendido de que: (a) cuando R3a es piperidin-4-il-oxilo o N-metilpiperidin-4-iloxilo, entonces R4 no se selecciona a partir de tiazol-2-ilo, tiazol-4-ilo, tiazol-5-ilo, 5-metil-tiazol-2-ilo, 5-(hidroxi-metil)-tiazol-2-ilo, 5-(hidroxi-metil)-tiazol-4-ilo, piridin-2-ilo, piridin-4-ilo, piridin-3-ilo, 4-metil-piridin-3-ilo, 5-cloro-piridin-4-ilo, 3-metil-piridin-2-ilo, y 1-metil-pirazol-5-ilo; (b) cuando R4a es etinilo y Ar1a es 3-fluoro-fenilo, entonces R3 no se selecciona a partir de piridin-3-il-metoxilo, 6-cloro-piridin-3-il-metoxilo, piridin-2-il-metoxilo, piridin-4-il-metoxilo, 1-(piridin-4-il)-etoxilo, 6-metoxi-piridin-2-il-metoxilo, tiazol-5-il-metoxilo, pirazin-2-il-metoxilo, 5-metil-iso-oxazol-3-ilo, azetidin-3-iloxilo, N-metil-azetidin-3-iloxilo, N-isopropil-azetidin-3-iloxilo. pirrolidin-3-iloxilo, N-metilo, y pirrolidin-3-il-oxilo; (c) cuando R4a es etinilo, entonces Ar1a no se selecciona a partir de 3-(2-hidroxi-propan-2-il)-fenilo, 3-(1-hidroxietil)-fenilo, 3-amino-sulfonil-fenilo, fenilo, 3-(metil-sulfonil-amino)-fenilo, 3-(N,N-dimetil-amino-metil)-fenilo, 3-amino-sulfonil-fenilo, y 3-carbamil-fenilo; (d) cuando R4a es tiazol-2-ilo, entonces Ar1a no se selecciona a partir de 3-(metil-amino-sulfonil)-fenilo, 3-cloro-fenilo, 3-carbamil-fenilo, 3-fluoro-fenilo, 2-(hidroxi-propan-2-il)-fenilo, 1-hidroxi-etilo, 3-amino-sulfonil-fenilo, y fenilo; (e) cuando R4a es tiazol-2-ilo y Ar1a es 3-fluoro-fenilo, entonces R3 no se selecciona a partir de piridin-3-il-metoxilo, 6-cloro-piridin-3-il-metoxilo, 2-cloro-piridin-4-il-metoxilo, 5-metil-iso-oxazol-3-ilo, azetidin-3-iloxilo, N-metil-azetidin-3-iloxilo, N-isopropil-azetidin-3-iloxilo, pirrolidin-3-iloxilo, N-metilo, pirrolidin-3-iloxilo, piperidin-4-iloxilo, y N-metil-piperidin-4-il-oxilo; (f) cuando R4a es bromo, entonces Ar1a no se selecciona a partir de fenilo, 3-fluoro-fenilo, 2-(hidroxi-propan-2-il)-fenilo, 1-hidroxi-etilo, y 3-amino-sulfonil-fenilo; (g) cuando R4a es ciano, entonces R3a no se selecciona a partir de piridin-4-il-metoxilo, piridin-2-il-metoxilo, y 6-metoxi-piridin-2-il-metoxilo; (h) cuando R4a es ciclopropilo, entonces R3a no se selecciona a partir de azetidin-3-il-oxilo; y (i) cuando R4a es hidrogeno, entonces Ar1a es 3-(amino-sulfonil)-fenilo. Reivindicacion 10: Un compuesto de la formula (2) o una sal farmaceuticamente aceptable del mismo, en donde R1 se selecciona a partir de H y halogeno; R2 se selecciona a partir de H, halogeno, y alcoxilo C1-6; R3 se selecciona a partir de H, -OCH2-fenilo, -O-CH2-Het, -OCH2-CH2-Het, y -O-Hy; en donde Het es heteroarilo de 6 miembros que est  opcionalmente sustituido por 1 o 2 grupos independientemente seleccionados a partir de hidroxilo, alquilo C1-6, alcoxilo C1-4, amino, alquilo C1-4-amino, di-alquilo C1-4-amino, y alquilo C1-6-carbamilo; Hy es heterocicloalquilo de 6 miembros, el cual est  opcionalmente sustituido por 1 o 2 grupos independientemente seleccionados a partir de hidroxilo, alquilo C1-6, alcoxilo C1-4, amino, alquilo C1-4-amino, di-alquilo C1-4-amino, y alquilo C1-6-carbamilo; y fenilo est  opcionalmente sustituido por 1 o 2 grupos independientemente seleccionados a partir de hidroxilo, alquilo C1-6, alcoxilo C1-4, amino, alquilo C1-4-amino, di-alquilo C1-4-amino, y alquilo C1-6-carbamilo; R4 se selecciona a partir de ciano, halogeno, alquilo C1-6, alquinilo C2-6, cicloalquilo C3-6, un anillo de tiazol, un anillo de pirazol, y un anillo de piridina; cada uno de los cuales est  opcionalmente sustituido por 1 o 2 grupos independientemente seleccionados a partir de hidroxilo, alquilo C1-6, alcoxilo C1-4, amino, alquilo C1-4-amino, y di-alquilo C1-4-amino; en donde este alquilo C1-6 est  adem s opcionalmente sustituido por 1 o 2 grupos hidroxilo; Ar1 es una fraccion del grupo de formulas (3), (4), o (5); A es un anillo de pirazol; que est  opcionalmente sustituido por 1 o 2 grupos independientemente seleccionados a partir de hidroxilo, alquilo C1-6, alcoxilo C1-4, amino, alquilo C1-4-amino, y di-alquilo C1-4-amino; A' se selecciona a partir de -L2-Ar2 y -L1-Cy1; A'' se selecciona a partir de -L2a-Ar2a y -Cy1a; L1 se selecciona partir de un enlace, -O-, -C(=O)-, -CH2C(=O)-, y -CH2-; en donde el extremo izquierdo del enlazador est  unido al anillo de fenilo, y el extremo derecho del enlazador est  unido a Cy1; Cy1 se selecciona a partir de un anillo de morfolina, un anillo de tetrahidro-2H-pirano, un anillo de pirrolidina, un anillo de 2-oxo-pirrolidina, y un anillo de piperidina, cada uno de los cuales est  opcionalmente sustituido por 1 o 2 grupos independientemente seleccionados a partir de halogeno, hidroxilo, alquilo C1-6, alcoxilo C1-4, amino, alquilo C1-4-amino, di-alquilo C1-4-amino, alquilo C1-6-carbonilo, y alcoxilo C1-6-carbonilo; Cy1a se selecciona a partir de un anillo de morfolina, un anillo de 2-oxo-pirrolidina y un anillo de piperidina; cada uno de los cuales est  opcionalmente sustituido por 1 o 2 grupos independientemente seleccionados a partir de halogeno, hidroxilo, alquilo C1-6, alcoxilo C1-4, amino, alquilo C1-4-amino, di-alquilo C1-4-amino, alquilo C1-6-carbonilo, y alcoxilo C1-6-carbonilo; L2 y L2a se seleccionan cada uno independientemente a partir de un enlace, -O-, y -OCH2-; y Ar2 se selecciona a partir de un anillo de pirazol, un anillo de oxazol, un anillo de imidazol, un anillo de triazol, un anillo de tiadiazol, un anillo de piridina, y un anillo de pirimidina; cada uno de los cuales est  opcionalmente sustituido con 1, 2 o 3 grupos independientemente seleccionados a partir de hidroxilo, alquilo C1-6, alcoxilo C1-4, amino, alquilo C1-4-amino, y di-alquilo C1-4-amino; Ar2a se selecciona a partir de un anillo de pirazol, un anillo de triazol, un anillo de piridina, y un anillo de pirimidina; cada uno de los cuales est  opcionalmente sustituido con 1 o 2 grupos independientemente seleccionados a partir de hidroxilo, alquilo C1-6, alcoxilo C1-4, amino, alquilo C1-4-amino, y di-alquilo C1-4-amino; en el entendido de que: (i) cuando R1 y R2 son cada uno H, R4 es tiazol-2-ilo, R3 es piperidin-4-iloxilo opcionalmente sustituido, y Ar1 es una fraccion del grupo de formula (3), entonces A' no se selecciona a partir de 1,2,4-triazol-1-H-metilo, 1-metil-pirazol-3-ilo, 2-oxo-pirrolidinilo, oxazol-5-ilo, pirazol-1-ilo, 1-metil-1,2,4-triazol-2-ilo, morfolin-4-il-carbonil-metilo, imidazol-2-ilo, 2-metil-tiazol-4-ilo, 1,3,5-trimetil-pirazol-4-ilo, pirimidin-5-ilo, 1,2,4-triazol-1-ilo, 4,5-dimetil-oxazol-2-ilo, pirimidin-5-ilo, 2-metoxi-pirimidin-5-ilo, 6-metoxi-piridin-3-ilo y piridin-3-ilo; (ii) cuando R1 y R2 son cada uno H, Ar1 es una fraccion del grupo de formula (3), A' se selecciona a partir de 1-metil-pirazol-3-ilo, y R3 se selecciona a partir de piridin-3-il-metoxilo y pirazin-2-il-metoxilo, entonces R4 no es tiazol-2-ilo; (iii) cuando R1 y R2 son cada uno H, R4 es tiazol-2-ilo, R3 es piperidin-4-iloxilo opcionalmente sustituido, y Ar1 es una fraccion del grupo de formula (4), entonces A'' no se selecciona a partir de morfolin-4-ilo, morfolin-4-il-carbonil-metilo, pirimidin-5-ilo, y pirazol-1-il-metilo; (iv) cuando R1 y R2 son cada uno H, R4 es bromo, R3 es piridin-3-il-met
ARP090102241A 2008-06-20 2009-06-19 2-arilaminoquinazolinas para el tratamiento de enfermedades proliferativas AR072201A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US7455608P 2008-06-20 2008-06-20

Publications (1)

Publication Number Publication Date
AR072201A1 true AR072201A1 (es) 2010-08-11

Family

ID=40983363

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP090102241A AR072201A1 (es) 2008-06-20 2009-06-19 2-arilaminoquinazolinas para el tratamiento de enfermedades proliferativas

Country Status (10)

Country Link
US (1) US20100121052A1 (es)
EP (1) EP2307385A1 (es)
JP (1) JP2011524881A (es)
KR (1) KR20110026485A (es)
CN (1) CN102123991A (es)
AR (1) AR072201A1 (es)
AU (1) AU2009259358A1 (es)
BR (1) BRPI0914614A2 (es)
CA (1) CA2727251A1 (es)
WO (1) WO2009153313A1 (es)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT2762466T (pt) 2011-09-29 2017-07-31 Ono Pharmaceutical Co Derivado de fenilo
KR102219695B1 (ko) 2013-03-15 2021-02-25 셀젠 카르 엘엘씨 헤테로아릴 화합물 및 이의 용도
UA120248C2 (uk) 2013-03-15 2019-11-11 Селджен Кар Ллс Гетероарильні сполуки та їх застосування
EP2980072B1 (en) 2013-03-26 2018-04-25 ONO Pharmaceutical Co., Ltd. Phenyl derivative
WO2017015152A1 (en) 2015-07-17 2017-01-26 Memorial Sloan-Kettering Cancer Center Combination therapy using pdk1 and pi3k inhibitors
US10344033B2 (en) 2015-10-02 2019-07-09 Sentinel Oncology Limited 2-aminoquinazoline derivatives as P70S6 kinase inhibitors
CN108329330B (zh) * 2017-01-20 2021-05-04 复旦大学 2-苄氧苯基噁唑并吡啶类化合物及其药物用途
KR20200094734A (ko) 2017-09-22 2020-08-07 주빌런트 에피파드 엘엘씨 Pad 억제제로서의 헤테로사이클릭 화합물
MX2020003341A (es) 2017-10-18 2020-09-17 Jubilant Epipad LLC Compuestos de imidazo-piridina como inhibidores de pad.
JP7279057B6 (ja) 2017-11-06 2024-02-15 ジュビラント プローデル エルエルシー Ｐｄ１／ｐｄ－ｌ１活性化の阻害剤としてのピリミジン誘導体
EP3704120B1 (en) 2017-11-24 2024-03-06 Jubilant Episcribe LLC Heterocyclic compounds as prmt5 inhibitors
MX2020009517A (es) 2018-03-13 2021-01-20 Jubilant Prodel LLC Compuestos biciclicos como inhibidores de la interaccion/activacio n de pdl/pd-l1.
CN111170986A (zh) * 2018-11-13 2020-05-19 北京睿熙生物科技有限公司 布鲁顿酪氨酸激酶的抑制剂
CN116731046A (zh) * 2020-10-28 2023-09-12 杭州阿诺生物医药科技有限公司 一种高活性的hpk1激酶抑制剂
WO2023138412A1 (en) * 2022-01-20 2023-07-27 Insilico Medicine Ip Limited Fused pyrimidin-2-amine compounds as cdk20 inhibitors
KR20230153951A (ko) * 2022-04-29 2023-11-07 보로노이 주식회사 헤테로아릴 유도체 화합물 및 이의 용도
WO2023218241A1 (en) * 2022-05-13 2023-11-16 Voronoi Inc. Heteroaryl derivative compounds, and pharmaceutical composition comprising thereof

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR060358A1 (es) * 2006-04-06 2008-06-11 Novartis Vaccines & Diagnostic Quinazolinas para la inhibicion de pdk 1
EA200900819A1 (ru) * 2006-12-22 2010-02-26 Новартис Аг Хиназолины для ингибирования pdk1

Also Published As

Publication number Publication date
CA2727251A1 (en) 2009-12-23
EP2307385A1 (en) 2011-04-13
CN102123991A (zh) 2011-07-13
BRPI0914614A2 (pt) 2019-09-24
JP2011524881A (ja) 2011-09-08
AU2009259358A1 (en) 2009-12-23
WO2009153313A1 (en) 2009-12-23
US20100121052A1 (en) 2010-05-13
KR20110026485A (ko) 2011-03-15

Similar Documents

Publication Publication Date Title
AR072201A1 (es) 2-arilaminoquinazolinas para el tratamiento de enfermedades proliferativas
ES2250186T3 (es) Inhibidores de tirosina quinasa.
AU2006290814B2 (en) 2-aniline-4-aryl substituted thiazole derivatives
ES2255621T3 (es) Inhibidores de tirosina quinasa.
JP2019504821A (ja) ユビキチン特異的プロテアーゼ１阻害剤としてのプリノン
RU2481333C2 (ru) Производные 1,1,1-трифтор-2-гидрокси-3-фенилпропана
JP2014525444A5 (es)
EA028626B1 (ru) БЕНЗИМИДАЗОЛЫ, МОДУЛИРУЮЩИЕ TNF-α
HRP20180382T1 (hr) Inhibitori protein kinaze
JP2018535999A5 (es)
IL187690A (en) Derivatives 1, 2, 4 - Triazolo - 1, 6 - Naphthiridines as inhibitors of AKT activity for use in the preparation of drugs for the treatment of cancer
RU2019118623A (ru) Пирролопиримидины в качестве потенциаторов мвтр
JP2009536196A5 (es)
JP2018524331A5 (es)
JP2010513272A5 (es)
JP2005511608A5 (es)
JP2015533157A5 (es)
HRP20131210T1 (hr) Heteroaromatski aril triazol derivati kao inhibitori pde10a enzima
JP2012502099A5 (es)
IL148891A (en) History of indole, pharmaceutical preparations containing them and their use in the preparation of medicines
RU2014152625A (ru) Конденсированные с гетероарилкетонами азадекалины - модуляторы глюкокортикоидных рецепторов
HRP20160539T1 (hr) Antagonisti trpv4
IL263511A (en) H1-pyrazolo[4, 3-b]pyridines as pde1 inhibitors
EA029718B1 (ru) Бифтордиоксалан-аминобензимидазольные ингибиторы киназы для лечения рака, аутоиммунного воспаления и нарушений цнс
JP2006507302A (ja) キナーゼ阻害剤

Legal Events

Date Code Title Description
FB Suspension of granting procedure