[go: up one dir, main page]

AR074822A1 - Compuestos heterociclicos de pirazina utiles como inhibidores de proteinquinasas atr, composiciones farmaceuticas que los comprenden y uso de los mismos en el tratamiento del cancer - Google Patents

Compuestos heterociclicos de pirazina utiles como inhibidores de proteinquinasas atr, composiciones farmaceuticas que los comprenden y uso de los mismos en el tratamiento del cancer

Info

Publication number
AR074822A1
AR074822A1 ARP090105005A ARP090105005A AR074822A1 AR 074822 A1 AR074822 A1 AR 074822A1 AR P090105005 A ARP090105005 A AR P090105005A AR P090105005 A ARP090105005 A AR P090105005A AR 074822 A1 AR074822 A1 AR 074822A1
Authority
AR
Argentina
Prior art keywords
aliphatic
alkyl
halo
optionally substituted
nitrogen
Prior art date
Application number
ARP090105005A
Other languages
English (en)
Inventor
Philip Reaper
Alistair Rutherford
Jean-Damien Charrier
David Kay
Steven Durrant
Somhairle Maccormick
Ronald Knegtel
Michael Mortimore
Stephen Young
Donnell Michael O
Joanne Pinder
Anisa Nizarali Virani
Original Assignee
Vertex Pharma
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 Vertex Pharma filed Critical Vertex Pharma
Publication of AR074822A1 publication Critical patent/AR074822A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/20—Nitrogen atoms
    • 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
    • A61K31/4965—Non-condensed pyrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
    • C07D241/28—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or 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
    • C07D401/10—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 carbon chain containing aromatic rings
    • 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
    • C07D403/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D403/02—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
    • C07D405/02—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 two hetero rings
    • C07D405/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D405/02—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 two hetero rings
    • C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms 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
    • C07D413/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • 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
    • C07D417/02—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
    • 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
    • C07D417/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S507/00—Earth boring, well treating, and oil field chemistry
    • Y10S507/939—Corrosion inhibitor

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

Reivindicación 1: Un compuesto de la fórmula (1) o una sal farmacéuticamente aceptable del mismo; caracterizado porque Y es una cadena alifática de C1-10 donde hasta tres unidades de metileno de la cadena alifática opcionalmente son reemplazados por O, NR0, S, C(O), o S(O)2; el anillo A es un anillo heteroarilo de 5 miembros seleccionado entre el grupo de fórmulas (2); J3 es H o alquilo de C1-4 donde 1 unidad de metileno del grupo alquilo opcionalmente puede ser reemplazada por O, NR0, N(alquilo de C1-4), o S y opcionalmente sustituido con 1 - 3 halo; Q es un anillo aromático monocíclico de 5 - 6 miembros que contiene 0 - 4 heteroátomos seleccionados independientemente entre nitrógeno, oxigeno o azufre; o un anillo aromático bicíclico de 8 - 10 miembros que contiene 0 - 6 heteroátomos seleccionados independientemente entre nitrógeno, oxígeno o azufre; R5 es H; un anillo monocíclico de 3 - 7 miembros completamente saturado, parcialmente saturado o aromático que contiene 0 - 4 heteroátomos seleccionados independientemente entre nitrógeno, oxigeno o azufre; un anillo bicíclico de 8 - 10 miembros, completamente saturado, parcialmente saturado o aromático que contiene 0 - 6 heteroátomos seleccionados independientemente entre nitrógeno, oxigeno o azufre; R5 está opcionalmente sustituido con 1-5 grupos J5; L es una cadena alquilo de C1-4 donde hasta dos unidades de metileno de la cadena alquilo, opcionalmente, son reemplazadas por O, NR6, S, -C(O)-, -SO-, o -SO2-; R0 es H o alquilo de C1-6 donde una unidad de metileno de la cadena alquilo puede ser, opcionalmente. reemplazada por O, NH, N(alquilo C1-4), o S; R1 es H o alquilo de C1-6; R2 es H, alquilo de C1-6, -(alquilo de C2-6)-Z o un anillo cíclico de 4 - 8 miembros que contiene 0 - 2 átomos de nitrógeno; donde dicho anillo está ligado mediante un átomo de carbono y está opcionalmente sustituido con una presencia de JZ; o R1 y R2, tomados junto con el átomo al que están ligados, forman un anillo heterocíclico de 4 - 8 miembros que contiene 1 - 2 heteroátomos seleccionados entre oxigeno, nitrógeno o azufre; donde dicho anillo heterocíclico está opcionalmente sustituido con una presencia de JZ1; JZ1 es halo, CN, un grupo alifático de C1-8, -(X)t-CN, o -(X)r-Z; donde dichas hasta dos unidades de metileno de dicho grupo alifático C1-8 pueden ser, opcionalmente, reemplazadas por O, NR, S, P(O), C(O), S(O), o S(O)2; donde dicho grupo alifático de C1-8 está opcionalmente sustituido con halo, CN, o NO2; X es alquilo de C1-4; cada t, r y m es, independientemente, 0 ó 1; Z es-NR3R4; R3 es H o alquilo de C1-2; R4 es H o alquilo de C1-6; o R3 y R4, tomados junto con el átomo al que están ligados, forman un anillo heterocíclico de 4 - 8 miembros que contiene 1 - 2 heteroátomos seleccionados entre oxigeno, nitrógeno o azufre; donde dicho anillo está opcionalmente sustituido con una presencia de JZ; R6 es H, o alquilo de C1-6; JZ es, independientemente, NH2, NH(alifático de C1-4), N(alifático de C1-4)2, halógeno, alifático de C1-4, OH, O(alifático de C1-4), NO2, CN, CO2H, CO(alifático de C1-4), CO2(alifático de C1-4), O(haloalifático de C1-4), o haloalifático de C1-4; J5 es halo, oxo, CN, NO2, X'-R, o -(X1)p-Q4; X1 es un grupo alifático de C1-10 donde 1-3 unidades de metileno de dicho grupo alifático de C1-10 opcionalmente son reemplazadas por -NR'-, -O-, -S-, C(=NR'), C(O), S(O)2, o S(O); donde X1 está opcional e independientemente sustituido con 1 - 4 presencias de NH2, NH(alifático de C1-4), N(alifático de C1-4)2, halógeno, alifático de C1-4, OH, O(alifático de C1-4), NO2, CN, CO2H, CO2(alifático de C1-4), C(O)NH2, C(O)NH(alifático de C1-4), C(O)N(alifático de C1-4)2, SO(alifático de C1-4), SO2(alifático de C1-4), SO2NH(alifático de C1-4), SO2NH(alifático de C1-4), NHC(O)(alifático de C1-4), N(alifático de C1-4)C(O)(alifático de C1-4), donde dicho grupo alifático de C1-4 está opcionalmente sustituido con 1 - 3 presencias de halo; Q4 es un anillo monocíclico de 3 - 8 miembros saturado o insaturado que tiene 0 - 4 heteroátomos seleccionados independientemente entre nitrógeno, oxigeno o azufre, o un anillo bicíclico de 8 - 10 miembros saturado o insaturado que tiene 0 - 6 heteroátomos seleccionados independientemente entre nitrógeno, oxígeno o azufre; cada Q4 está opcionalmente sustituido con 1 - 5 JQ4; JQ4 es halo, CN, o alquilo de C1-4 donde hasta 2 unidades de metileno opcionalmente son reemplazadas por O, NR*, S, C(O). S(O), o S(O)2; R es H o alquilo de C1-4 donde dicho grupo alquilo de C1-4 está opcionalmente sustituido con 1-4 halo; J2 es halo; CN; un anillo monocíclico de 5 - 6 miembros aromático o no aromático que tiene 0 - 3 heteroátomos seleccionados entre oxígeno, nitrógeno o azufre; o un grupo alifático de C1-10 donde hasta 2 unidades de metileno opcionalmente son reemplazadas por O, NR'', C(O), S, S(O), o S(O)2 donde dicho grupo alifático de C1-10 está opcionalmente sustituido con 1 - 3 halo o CN; y dicho anillo monocíclico está opcionalmente sustituido con 1 - 3 presencias de halo; CN; un grupo cicloalquilo de C3-6; un heterociclilo de 3 - 7 miembros que contiene 0 - 2 heteroátomos seleccionados entre oxígeno, nitrógeno o azufre; o un grupo alquilo de C1-4 donde hasta una unidad de metileno de la cadera alquilo está opcionalmente reemplazada con O, NR'' o S; y donde dicho grupo alquilo de C1-4 está opcionalmente sustituido con 1 - 3 halo; q es 0, 1 ó 2; p es 0 ó 1; R', R'' y R* son, cada uno, independientemente H, alquilo de C1-4, o está ausente; donde dicho alquilo de C1-4 está opcionalmente sustituido con 1 - 4 halo.
ARP090105005A 2008-12-19 2009-12-21 Compuestos heterociclicos de pirazina utiles como inhibidores de proteinquinasas atr, composiciones farmaceuticas que los comprenden y uso de los mismos en el tratamiento del cancer AR074822A1 (es)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US13942008P 2008-12-19 2008-12-19
US13942408P 2008-12-19 2008-12-19
US13942608P 2008-12-19 2008-12-19
US13942908P 2008-12-19 2008-12-19
US18179409P 2009-05-28 2009-05-28
US21910009P 2009-06-22 2009-06-22

Publications (1)

Publication Number Publication Date
AR074822A1 true AR074822A1 (es) 2011-02-16

Family

ID=41683104

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP090105005A AR074822A1 (es) 2008-12-19 2009-12-21 Compuestos heterociclicos de pirazina utiles como inhibidores de proteinquinasas atr, composiciones farmaceuticas que los comprenden y uso de los mismos en el tratamiento del cancer

Country Status (29)

Country Link
US (7) US8841308B2 (es)
EP (3) EP4059932A1 (es)
JP (5) JP5753093B2 (es)
KR (3) KR101755216B1 (es)
CN (4) CN106518856B (es)
AR (1) AR074822A1 (es)
AU (3) AU2009327357C1 (es)
BR (1) BRPI0924084B1 (es)
CA (2) CA3013000C (es)
CY (1) CY1120002T1 (es)
DK (2) DK3354650T3 (es)
ES (2) ES2921576T3 (es)
HR (2) HRP20180385T1 (es)
HU (1) HUE036068T2 (es)
IL (3) IL213613A (es)
LT (2) LT3354650T (es)
MX (1) MX2011006503A (es)
NO (1) NO2376485T3 (es)
NZ (1) NZ593969A (es)
PL (2) PL3354650T3 (es)
PT (2) PT3354650T (es)
RS (1) RS56995B1 (es)
RU (2) RU2016141566A (es)
SG (2) SG172248A1 (es)
SI (2) SI3354650T1 (es)
SM (1) SMT201800181T1 (es)
TW (3) TWI543979B (es)
WO (1) WO2010071837A1 (es)
ZA (1) ZA201104498B (es)

Families Citing this family (98)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102264721B (zh) 2008-11-10 2015-12-09 沃泰克斯药物股份有限公司 用作atr激酶抑制剂的化合物
CN106518856B (zh) 2008-12-19 2020-04-28 沃泰克斯药物股份有限公司 用作atr激酶抑制剂的化合物
US8415381B2 (en) * 2009-07-30 2013-04-09 Novartis Ag Heteroaryl compounds and their uses
JP2011057661A (ja) * 2009-08-14 2011-03-24 Bayer Cropscience Ag 殺虫性カルボキサミド類
JP2013526540A (ja) 2010-05-12 2013-06-24 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｔｒキナーゼ阻害剤として有用な化合物
US8969356B2 (en) 2010-05-12 2015-03-03 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8962631B2 (en) 2010-05-12 2015-02-24 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US9062008B2 (en) 2010-05-12 2015-06-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
SG185524A1 (en) * 2010-05-12 2012-12-28 Vertex Pharma Compounds useful as inhibitors of atr kinase
MX2012013082A (es) 2010-05-12 2013-05-09 Vertex Pharma Derivados de 2-aminopiridina utiles como iinhibidores de cinasa atr.
US8623869B2 (en) 2010-06-23 2014-01-07 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2012121939A2 (en) 2011-03-04 2012-09-13 Locus Pharmaceuticals, Inc. Aminopyrazine compounds
WO2012123522A1 (en) * 2011-03-16 2012-09-20 F. Hoffmann-La Roche Ag 6,5-heterocyclic propargylic alcohol compounds and uses therefor
CA2832100A1 (en) * 2011-04-05 2012-10-11 Vertex Pharmaceuticals Incorporated Aminopyrazine compounds useful as inhibitors of tra kinase
US9273029B2 (en) * 2011-05-23 2016-03-01 Merck Patent Gmbh Pyridine-and pyrazine derivatives
JP2014520161A (ja) 2011-06-22 2014-08-21 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｔｒキナーゼ阻害剤として有用な化合物
US9309250B2 (en) 2011-06-22 2016-04-12 Vertex Pharmaceuticals Incorporated Substituted pyrrolo[2,3-b]pyrazines as ATR kinase inhibitors
US9096602B2 (en) 2011-06-22 2015-08-04 Vertex Pharmaceuticals Incorporated Substituted pyrrolo[2,3-B]pyrazines as ATR kinase inhibitors
WO2013038386A1 (en) 2011-09-16 2013-03-21 Novartis Ag Heterocyclic compounds for the treatment of cystic fibrosis
WO2013038390A1 (en) 2011-09-16 2013-03-21 Novartis Ag N-substituted heterocyclyl carboxamides
CN103958507A (zh) 2011-09-30 2014-07-30 沃泰克斯药物股份有限公司 可用作atr激酶抑制剂的化合物
WO2013049719A1 (en) * 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
CA2850566C (en) 2011-09-30 2022-05-03 Vertex Pharmaceuticals Incorporated Process for making 4-[chloro-n-hydroxycarbonimidoyl]phenyl derivative
EP3733185B1 (en) * 2011-09-30 2022-12-07 Vertex Pharmaceuticals Incorporated Treating non-small cell lung cancer with atr inhibitors
WO2013049720A1 (en) * 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
US8846918B2 (en) 2011-11-09 2014-09-30 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2013071090A1 (en) 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
US8841449B2 (en) 2011-11-09 2014-09-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2013071088A1 (en) 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2013071093A1 (en) * 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Pyrazine compounds useful as inhibitors of atr kinase
EP2833973B1 (en) * 2012-04-05 2017-09-13 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase and combination therapies thereof
US9296701B2 (en) 2012-04-24 2016-03-29 Vertex Pharmaceuticals Incorporated DNA-PK inhibitors
US8999632B2 (en) 2012-10-04 2015-04-07 Vertex Pharmaceuticals Incorporated Method for measuring ATR inhibition mediated increases in DNA damage
US8912198B2 (en) 2012-10-16 2014-12-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
DK3418281T3 (da) * 2012-12-07 2020-12-07 Vertex Pharma Pyrazolo[1,5-a]pyrimidiner, der er anvendelige som inhibitorer af atr-kinase til behandling af cancersygdomme
ES2637170T3 (es) * 2013-01-02 2017-10-11 H. Lundbeck A/S Compuestos derivados de aminopiridina como inhibidores de LRRK2
AU2014208964B2 (en) * 2013-01-23 2016-09-01 Astrazeneca Ab Chemical compounds
CA2904641C (en) 2013-03-12 2021-07-20 Vertex Pharmaceuticals Incorporated Dna-pk inhibitors
US9242969B2 (en) 2013-03-14 2016-01-26 Novartis Ag Biaryl amide compounds as kinase inhibitors
JP2016512815A (ja) 2013-03-15 2016-05-09 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ Ａｔｒキナーゼの阻害剤として有用な縮合ピラゾロピリミジン誘導体
WO2015058067A1 (en) 2013-10-17 2015-04-23 Vertex Pharmaceuticals Incorporated Co-crystals of (s)-n-methyl-8-(1-((2'-methyl-[4,5'-bipyrimidin]-6-yl)amino)propan-2-yl)quinoline-4-carboxamide and deuterated derivatives thereof as dna-pk inhibitors
PT3077397T (pt) 2013-12-06 2020-01-22 Vertex Pharma Composto de 2-amino-6-fluoro-n-[5-fluoro-piridin-3-il]pirazolo[1,5-a]pirimidin-3-carboxamida útil como inibidor da atr quinase, a sua preparação, diferentes formas sólidas e derivados radiomarcados do mesmo
CN103804312B (zh) * 2014-02-17 2016-04-20 四川百利药业有限责任公司 一类氮杂环化合物及其制备方法和用途
BR112016024484A2 (pt) 2014-04-24 2017-08-15 Novartis Ag derivados de aminopiridina como inibidores de fosfatidilinositol 3-quinase
PL3134395T3 (pl) 2014-04-24 2018-07-31 Novartis Ag Pochodne pirazyny jako inhibitory 3-kinazy fosfatydyloinozytolu
JP6433509B2 (ja) * 2014-04-24 2018-12-05 ノバルティス アーゲー ホスファチジルイノシトール３−キナーゼ阻害薬としてのアミノピラジン誘導体
US10046156B2 (en) 2014-05-02 2018-08-14 Excelsior Medical Corporation Strip package for antiseptic cap
KR102575125B1 (ko) 2014-06-05 2023-09-07 버텍스 파마슈티칼스 인코포레이티드 Atr 키나제의 저해제로서 유용한 2-아미노-6-플루오로-n-[5-플루오로-피리딘-3-일]-피라졸로[1,5-a]피리미딘-3-카복스아미드 화합물의 방사성표지된 유도체, 상기 화합물의 제조 및 이의 다양한 고체 형태
DK3157566T3 (da) * 2014-06-17 2019-07-22 Vertex Pharma Fremgangsmåde til behandling af cancer under anvendelse af en kombination chk1- og atr-inhibitorer
TWI700283B (zh) 2014-08-04 2020-08-01 德商拜耳製藥公司 ２-(嗎啉-４-基)-１,７-萘啶
JO3589B1 (ar) 2014-08-06 2020-07-05 Novartis Ag مثبطات كيناز البروتين c وطرق استخداماتها
UY36294A (es) 2014-09-12 2016-04-29 Novartis Ag Compuestos y composiciones como inhibidores de quinasa
AU2015333738B2 (en) * 2014-10-13 2020-03-26 Atrin Pharmaceuticals LLC Ataxia telengiectasia and Rad3-related (ATR) protein kinase inhibitors
MX395066B (es) 2015-09-30 2025-03-24 Vertex Pharma Método para tratar cáncer usando una combinación de agentes que dañan el adn e inhibidores de proteína relacionada con ataxia telangiectasia y rad3 (atr).
IL313681A (en) 2016-01-11 2024-08-01 Celator Pharmaceuticals Inc Inhibiting ataxia telangiectasia and rad3-related protein (atr)
WO2018029117A1 (en) 2016-08-10 2018-02-15 Rheinisch-Westfälische Technische Hochschule Aachen (RWTH) New atr inhibitors for the use in cancer therapy
US11730734B2 (en) * 2016-09-12 2023-08-22 University Of Florida Research Foundation, Incorporated Use of ATR and Chk1 inhibitor compounds
JP7114575B2 (ja) 2016-09-19 2022-08-08 ノバルティス アーゲー Ｒａｆ阻害剤及びｅｒｋ阻害剤を含む治療用組合せ
EP3518931A4 (en) 2016-09-27 2020-05-13 Vertex Pharmaceuticals Incorporated METHOD FOR TREATING CANCER WITH A COMBINATION OF DNA-DAMAGING SUBSTANCES AND DNA-PK INHIBITORS
EA039513B1 (ru) * 2017-01-09 2022-02-04 Селатор Фармасьютикалз, Инк. Ингибитор атаксии-телеангиэкстазии и rad3-родственного белка (atr) и содержащие его липосомные композиции
WO2018153969A1 (en) 2017-02-24 2018-08-30 Bayer Aktiengesellschaft Combination of atr kinase inhibitors with radium-223 salt
JOP20190197A1 (ar) 2017-02-24 2019-08-22 Bayer Pharma AG مثبط كيناز ايه تي آر للاستخدام في طريقة لعلاج مرض فرط التكاثر
WO2018153972A1 (en) 2017-02-24 2018-08-30 Bayer Pharma Aktiengesellschaft Combination of atr kinase inhibitors and antiandrogens
WO2018187479A1 (en) 2017-04-04 2018-10-11 Case Western Reserve University Method of modulating ribonucleotide reductase
TWI771410B (zh) 2017-04-27 2022-07-21 日商石原產業股份有限公司 N-(4-吡啶基)菸鹼醯胺化合物或其鹽
IL311471A (en) 2017-05-02 2024-05-01 Novartis Ag Combination therapy
WO2018206547A1 (en) 2017-05-12 2018-11-15 Bayer Pharma Aktiengesellschaft Combination of bub1 and atr inhibitors
CA3071760A1 (en) 2017-08-04 2019-02-07 Bayer Pharma Aktiengesellschaft Combination of atr kinase inhibitors and pd-1/pd-l1 inhibitors
GB201715410D0 (en) 2017-09-22 2017-11-08 Syngenta Participations Ag Improvements in or relating to organic compounds
EP3461480A1 (en) 2017-09-27 2019-04-03 Onxeo Combination of a dna damage response cell cycle checkpoint inhibitors and belinostat for treating cancer
CA3084863A1 (en) 2017-12-08 2019-06-13 Bayer Aktiengesellschaft Predictive markers for atr kinase inhibitors
WO2019126505A1 (en) 2017-12-21 2019-06-27 Incyte Corporation 3-(5-amino-pyrazin-2-yl)-benzenesulfonamide derivatives and related compounds as pi3k-gamma kinase inhibitors for treating e.g. cancer
SG11202005156WA (en) * 2017-12-29 2020-07-29 Vertex Pharma Methods of cancer treatment using an atr inhibitor
CR20200464A (es) 2018-03-08 2021-04-14 Incyte Corp Compuestos diólicos de aminopirazina como inhibidores de pi3k-y
US11046658B2 (en) 2018-07-02 2021-06-29 Incyte Corporation Aminopyrazine derivatives as PI3K-γ inhibitors
JP2022502399A (ja) 2018-09-26 2022-01-11 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングMerck Patent Gesellschaft mit beschraenkter Haftung がんの治療のためのｐｄ−１アンタゴニスト、ａｔｒインヒビター、および白金製剤の組合せ
AU2019360608A1 (en) 2018-10-15 2021-06-03 Merck Patent Gmbh Combination therapy utilizing DNA alkylating agents and ATR inhibitors
EP3866805A1 (en) 2018-10-16 2021-08-25 Bayer Aktiengesellschaft Combination of atr kinase inhibitors with 2,3-dihydroimidazo[1,2-c]quinazoline compounds
CN113454080B (zh) 2018-10-30 2025-10-28 修复治疗公司 化合物、药物组合物和制备化合物的方法以及其使用方法
US11517732B2 (en) 2018-11-07 2022-12-06 Icu Medical, Inc. Syringe with antimicrobial properties
EP4563150A3 (en) 2019-05-13 2025-07-23 Novartis AG New crystalline forms of n-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methvlphenyl)-2(trifluoromethyl) isonicotinamide as raf inhibitors for the treatment of cancer
EP4027993A4 (en) * 2019-09-13 2023-09-20 The Broad Institute Inc. CYCLO-OXYGENASE 2 INHIBITORS AND THEIR USES
US12195490B2 (en) 2020-01-30 2025-01-14 The Regents Of The University Of California STRAD-binding agents and uses thereof
WO2022063869A2 (en) * 2020-09-24 2022-03-31 Merck Patent Gmbh Compounds for the treatment of viral infections
US20230301991A1 (en) 2020-10-26 2023-09-28 Merck Patent Gmbh Compounds for the treatment of viral infections
WO2023016525A1 (zh) * 2021-08-13 2023-02-16 苏州爱科百发生物医药技术有限公司 用作atr激酶抑制剂的化合物
CN115703768B (zh) * 2021-08-13 2024-12-17 苏州爱科百发生物医药技术有限公司 用作atr激酶抑制剂的化合物
CA3181279A1 (en) * 2022-03-24 2023-09-24 Bloom Energy Corporation Fuel cell stack assembly including heat sink inserts
WO2023242302A1 (en) 2022-06-15 2023-12-21 Astrazeneca Ab Combination therapy for treating cancer
CN118255760A (zh) * 2022-12-27 2024-06-28 江苏亚虹医药科技股份有限公司 一种嘧啶类化合物及其制备方法和医药用途
AR131690A1 (es) * 2023-01-30 2025-04-23 Eurofarma Laboratorios S A COMPUESTOS FENÓLICOS BLOQUEADORES DE Nav 1.7 Y/O Nav 1.8, SUS PROCESOS DE OBTENCIÓN, SUS COMPOSICIONES, SUS USOS, LOS MÉTODOS DE TRATAMIENTO DE LOS MISMOS Y LOS KITS
CN116655619A (zh) * 2023-06-05 2023-08-29 南京康立凯医药科技有限公司 一种2h-吲唑类化合物及其制备方法和应用
CN117024413B (zh) * 2023-10-07 2024-01-09 天津匠新致成科技有限公司 3-氨基吡嗪-2-甲酰胺类靶向蛋白水解嵌合体及其制备方法、药物组合物和应用
WO2025181153A1 (en) 2024-03-01 2025-09-04 F. Hoffmann-La Roche Ag Use of atr inhibitors in combination with pi3k alpha inhibitors
WO2025201332A1 (zh) * 2024-03-26 2025-10-02 勤浩医药（苏州）有限公司 噁二唑化合物、包含其的药物组合物及其用途
WO2025229051A1 (en) 2024-05-03 2025-11-06 F. Hoffmann-La Roche Ag Use of atr inhibitors in combination with antiandrogen agent
WO2025233224A1 (en) 2024-05-09 2025-11-13 F. Hoffmann-La Roche Ag Use of atr inhibitors in combination with anti-pd(l)1 therapy
CN120097926B (zh) * 2025-03-07 2026-01-30 杭州师范大学 一种选择性hpk1抑制剂及其制备方法和应用

Family Cites Families (226)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4309430A (en) 1980-06-27 1982-01-05 Merck & Co., Inc. Pyrazinyl-1,2,4-oxadiazole-5-ones, for treatment of edema, and processes for preparing same
JPS62270623A (ja) 1985-12-07 1987-11-25 Daicel Chem Ind Ltd ビス（４−アミノフエニル）ピラジンおよびその製法、ならびにポリイミドおよびその製法
JPS63208520A (ja) 1987-02-26 1988-08-30 Terumo Corp ピラジン誘導体を含有する血小板凝集抑制剤
US5329012A (en) 1987-10-29 1994-07-12 The Research Foundation Of State University Of New York Bis(acyloxmethyl)imidazole compounds
JPH0272372A (ja) 1988-09-07 1990-03-12 Konica Corp 電子写真感光体
JPH0272370A (ja) 1988-09-07 1990-03-12 Konica Corp 電子写真感光体
JPH0374370A (ja) 1989-08-16 1991-03-28 Terumo Corp ピラジン誘導体およびこれを含有する血小板凝集抑制剤または抗炎症剤
JP2597917B2 (ja) 1990-04-26 1997-04-09 富士写真フイルム株式会社 新規な色素形成カプラー及びそれを用いたハロゲン化銀カラー写真感光材料
US5572248A (en) 1994-09-19 1996-11-05 Teleport Corporation Teleconferencing method and system for providing face-to-face, non-animated teleconference environment
CA2253910A1 (en) 1996-05-11 1997-11-20 King's College London Pyrazines
JP4026876B2 (ja) 1996-09-05 2007-12-26 日本食品化工株式会社 発光性シクロデキストリン誘導体及びその製造方法
JP2002241379A (ja) 1997-03-21 2002-08-28 Dainippon Pharmaceut Co Ltd ３−オキサジアゾリルキノキサリン誘導体
WO1999044609A1 (en) 1998-03-03 1999-09-10 Merck & Co., Inc. FUSED PIPERIDINE SUBSTITUTED ARYLSULFONAMIDES AS β3-AGONISTS
DE19826671A1 (de) 1998-06-16 1999-12-23 Hoechst Schering Agrevo Gmbh 1,3-Oxazolin- und 1,3-Thiazolin-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Schädlingsbekämpfungsmittel
KR20010071936A (ko) 1998-07-16 2001-07-31 시오노 요시히코 항종양 활성을 갖는 피리미딘 유도체
US7023913B1 (en) 2000-06-14 2006-04-04 Monroe David A Digital security multimedia sensor
ATE330968T1 (de) 1999-02-05 2006-07-15 Debiopharm Sa Cyclosporin-derivate und verfahren zu deren herstellung
US6738073B2 (en) 1999-05-12 2004-05-18 Imove, Inc. Camera system with both a wide angle view and a high resolution view
WO2000076982A1 (en) 1999-06-16 2000-12-21 University Of Iowa Research Foundation Antagonism of immunostimulatory cpg-oligonucleotides by 4-aminoquinolines and other weak bases
US7015954B1 (en) 1999-08-09 2006-03-21 Fuji Xerox Co., Ltd. Automatic video system using multiple cameras
US6660753B2 (en) 1999-08-19 2003-12-09 Nps Pharmaceuticals, Inc. Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists
US6608063B2 (en) 1999-12-17 2003-08-19 Chiron Corporation Pyrazine based inhibitors of glycogen synthase kinase 3
AR029489A1 (es) 2000-03-10 2003-07-02 Euro Celtique Sa Piridinas, pirimidinas, pirazinas, triazinas sustituidas por arilo, composiciones farmaceuticas y el uso de las mismas para la manufactura de un medicamento
US6849660B1 (en) 2000-08-01 2005-02-01 Isis Pharmaceuticals, Inc. Antimicrobial biaryl compounds
JP2002072370A (ja) 2000-08-29 2002-03-12 Fuji Photo Optical Co Ltd ペーパーマガジン及び写真焼付装置
JP2002072372A (ja) 2000-09-04 2002-03-12 Fuji Photo Film Co Ltd 画像形成用シート体の切断装置
US6829391B2 (en) 2000-09-08 2004-12-07 Siemens Corporate Research, Inc. Adaptive resolution system and method for providing efficient low bit rate transmission of image data for distributed applications
EP1217000A1 (en) 2000-12-23 2002-06-26 Aventis Pharma Deutschland GmbH Inhibitors of factor Xa and factor VIIa
MXPA03005838A (es) 2000-12-28 2003-09-10 Daichi Pharmaceutical Co Ltd Inhibidores de antigenos de aparicion muy tardia-4.
US8085293B2 (en) 2001-03-14 2011-12-27 Koninklijke Philips Electronics N.V. Self adjusting stereo camera system
US6759657B2 (en) 2001-03-27 2004-07-06 Kabushiki Kaisha Toshiba Infrared sensor
WO2002080899A1 (fr) 2001-03-30 2002-10-17 Eisai Co., Ltd. Agent de traitement de maladie digestive
US6469002B1 (en) 2001-04-19 2002-10-22 Millennium Pharmaceuticals, Inc. Imidazolidine compounds
AU2002305450A1 (en) 2001-05-08 2002-11-18 Yale University Proteomimetic compounds and methods
SE0102438D0 (sv) 2001-07-05 2001-07-05 Astrazeneca Ab New compounds
SE0102439D0 (sv) * 2001-07-05 2001-07-05 Astrazeneca Ab New compounds
JP2003074370A (ja) 2001-09-05 2003-03-12 Suzuki Motor Corp エンジンのベルト保護装置
CA2457642C (en) 2001-09-26 2009-01-06 Merck & Co., Inc. Crystalline forms of ertapenem sodium
GB0124939D0 (en) 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
US6992087B2 (en) 2001-11-21 2006-01-31 Pfizer Inc Substituted aryl 1,4-pyrazine derivatives
DK1446387T3 (da) 2001-11-21 2009-12-21 Pharmacia & Upjohn Co Llc Substituerede aryl, 1,4-pyrazinderivater
US6693097B2 (en) 2001-11-30 2004-02-17 Synta Pharmaceuticals Corp. Pyrimidine compounds
US20030187026A1 (en) 2001-12-13 2003-10-02 Qun Li Kinase inhibitors
WO2003066629A2 (en) 2002-02-06 2003-08-14 Vertex Pharmaceuticals Incorporated Heteroaryl compounds useful as inhibitors of gsk-3
MXPA04007775A (es) 2002-03-13 2004-10-15 Janssen Pharmaceutica Nv Derivados de sulfonilo como novedosos inhibidores de la histona desacetilasa.
GB0206860D0 (en) 2002-03-22 2002-05-01 Glaxo Group Ltd Compounds
TWI319387B (en) 2002-04-05 2010-01-11 Astrazeneca Ab Benzamide derivatives
US7043079B2 (en) 2002-04-25 2006-05-09 Microsoft Corporation “Don't care” pixel interpolation
GB0209715D0 (en) 2002-04-27 2002-06-05 Astrazeneca Ab Chemical compounds
US7704995B2 (en) * 2002-05-03 2010-04-27 Exelixis, Inc. Protein kinase modulators and methods of use
JP4901102B2 (ja) * 2002-05-03 2012-03-21 エクセリクシス， インク． プロテインキナーゼモジュレーターおよびその使用方法
KR20050004214A (ko) 2002-05-31 2005-01-12 에자이 가부시키가이샤 피라졸 화합물 및 이것을 포함하여 이루어지는 의약 조성물
US7015227B2 (en) 2002-06-21 2006-03-21 Cgi Pharmaceuticals, Inc. Certain amino-substituted monocycles as kinase modulators
AU2003245669A1 (en) 2002-06-21 2004-01-06 Cellular Genomics, Inc. Certain aromatic monocycles as kinase modulators
WO2004033431A2 (en) 2002-10-04 2004-04-22 Arena Pharmaceuticals, Inc. Hydroxypyrazoles for use against metabolic-related disorders
US20040075741A1 (en) 2002-10-17 2004-04-22 Berkey Thomas F. Multiple camera image multiplexer
US7385626B2 (en) 2002-10-21 2008-06-10 Sarnoff Corporation Method and system for performing surveillance
US20040100560A1 (en) 2002-11-22 2004-05-27 Stavely Donald J. Tracking digital zoom in a digital video camera
SE0203752D0 (sv) * 2002-12-17 2002-12-17 Astrazeneca Ab New compounds
SE0203754D0 (sv) 2002-12-17 2002-12-17 Astrazeneca Ab New compounds
US7230098B2 (en) 2003-02-26 2007-06-12 Sugen, Inc. Aminoheteroaryl compounds as protein kinase inhibitors
US7684624B2 (en) 2003-03-03 2010-03-23 Smart Technologies Ulc System and method for capturing images of a target area on which information is recorded
CA2517720A1 (en) 2003-03-11 2004-09-23 Pfizer Products Inc. Pyrazine compounds as transforming growth factor (tgf) inhibitors
WO2004084813A2 (en) 2003-03-21 2004-10-07 Smithkline Beecham Corporation Chemical compounds
US20060293339A1 (en) 2003-03-24 2006-12-28 Chakravarty Prasun K Biaryl substituted 6-membered heterocycles as sodium channel blockers
GB2400101A (en) 2003-03-28 2004-10-06 Biofocus Discovery Ltd Compounds capable of binding to the active site of protein kinases
GB2400514B (en) 2003-04-11 2006-07-26 Hewlett Packard Development Co Image capture method
AU2004240586A1 (en) 2003-05-15 2004-12-02 Merck & Co., Inc. 3-(2-amino-1-azacyclyl)-5-aryl-1,2,4-oxadiazoles as S1P receptor agonists
WO2004103991A1 (en) 2003-05-20 2004-12-02 'chemical Diversity Research Institute', Ltd. 2-substituted piperidines, focused library and a pharmaceutical compound
US20050123902A1 (en) 2003-05-21 2005-06-09 President And Fellows Of Harvard College Human papillomavirus inhibitors
PE20050206A1 (es) 2003-05-26 2005-03-26 Schering Ag Composicion farmaceutica que contiene un inhibidor de histona deacetilasa
US7986339B2 (en) 2003-06-12 2011-07-26 Redflex Traffic Systems Pty Ltd Automated traffic violation monitoring and reporting system with combined video and still-image data
JP2005020227A (ja) 2003-06-25 2005-01-20 Pfu Ltd 画像圧縮装置
TWI339206B (en) 2003-09-04 2011-03-21 Vertex Pharma Compositions useful as inhibitors of protein kinases
US7807696B2 (en) 2003-10-07 2010-10-05 The Feinstein Institute For Medical Research Isoxazole and isothiazole compounds useful in the treatment of inflammation
US20050116968A1 (en) 2003-12-02 2005-06-02 John Barrus Multi-capability display
EP1694670A1 (en) 2003-12-16 2006-08-30 GPC Biotech AG Pyrazine derivatives as effective compounds against infectious diseases
AU2005215379A1 (en) 2004-02-12 2005-09-01 Merck & Co., Inc. Bipyridyl amides as modulators of metabotropic glutamate receptor-5
US20050276765A1 (en) 2004-06-10 2005-12-15 Paul Nghiem Preventing skin damage
EP1773807A2 (en) 2004-06-14 2007-04-18 Takeda San Diego, Inc. Kinase inhibitors
CA2573573A1 (en) 2004-07-27 2006-02-09 Sgx Pharmaceuticals, Inc. Fused ring heterocycle kinase modulators
US7626021B2 (en) 2004-07-27 2009-12-01 Sgx Pharmaceuticals, Inc. Fused ring heterocycle kinase modulators
CA2578066C (en) 2004-08-26 2011-10-11 Pfizer Inc. Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
EP1786777A1 (en) 2004-08-26 2007-05-23 Pfizer, Inc. Aminoheteroaryl compounds as protein tyrosine kinase inhibitors
US7730406B2 (en) 2004-10-20 2010-06-01 Hewlett-Packard Development Company, L.P. Image processing system and method
EP1807407B1 (en) 2004-10-22 2009-07-29 Janssen Pharmaceutica N.V. Aromatic amides as inhibitors of c-fms kinase
US8003806B2 (en) 2004-11-12 2011-08-23 OSI Pharmaceuticals, LLC Integrin antagonists useful as anticancer agents
US7795259B2 (en) 2004-11-22 2010-09-14 Vertex Pharmaceuticals Incorporated Pyrrolopyrazines and pyrazolopyrazines useful as inhibitors of protein kinases
JP4810669B2 (ja) 2004-11-25 2011-11-09 コニカミノルタホールディングス株式会社 有機エレクトロルミネッセンス素子、表示装置及び照明装置
GB0428235D0 (en) 2004-12-23 2005-01-26 Glaxo Group Ltd Novel compounds
ATE519488T1 (de) 2004-12-27 2011-08-15 Novartis Ag Aminopyrazin-analoga zur behandlung von glaukomen und anderen durch rho-kinase verursachten krankheiten
GB0500492D0 (en) 2005-01-11 2005-02-16 Cyclacel Ltd Compound
US7622583B2 (en) 2005-01-14 2009-11-24 Chemocentryx, Inc. Heteroaryl sulfonamides and CCR2
GB0501999D0 (en) * 2005-02-01 2005-03-09 Sentinel Oncology Ltd Pharmaceutical compounds
US7868006B2 (en) 2005-02-16 2011-01-11 Schering Corporation Heterocyclic substituted piperazines with CXCR3 antagonist activity
US8859581B2 (en) 2005-04-25 2014-10-14 Merck Patent Gmbh Azaheterocyclic compounds as kinase inhibitors
WO2006124874A2 (en) 2005-05-12 2006-11-23 Kalypsys, Inc. Inhibitors of b-raf kinase
JP2008543754A (ja) 2005-06-09 2008-12-04 メルク エンド カムパニー インコーポレーテッド チェックポイントキナーゼの阻害剤
WO2007016674A2 (en) 2005-08-02 2007-02-08 Lexicon Genetics Incorporated 2-aminoaryl pyridines as protein kinases inhibitors
WO2007015632A1 (en) * 2005-08-04 2007-02-08 Cgk Co., Ltd. Atm and atr inhibitor
US7394926B2 (en) 2005-09-30 2008-07-01 Mitutoyo Corporation Magnified machine vision user interface
US7806604B2 (en) 2005-10-20 2010-10-05 Honeywell International Inc. Face detection and tracking in a wide field of view
TW200736260A (en) 2005-11-10 2007-10-01 Smithkline Beecham Corp Inhibitors of Akt activity
PT1959951E (pt) 2005-12-01 2010-03-02 Hoffmann La Roche Derivados de piperidina substituídos com heteroarilo, como inibidores de pct1-f
JP5064237B2 (ja) 2005-12-09 2012-10-31 Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 リンコマイシン誘導体およびこれを有効成分とする抗菌剤
EP1965645A2 (en) 2005-12-14 2008-09-10 E.I. Du Pont De Nemours And Company Isoxazolines for controlling invertebrate pests
BRPI0620463A2 (pt) 2005-12-22 2011-11-16 Alcon Res Ltd composição farmacêutica oftálmica, compostos, e seus usos
PE20070978A1 (es) 2006-02-14 2007-11-15 Novartis Ag COMPUESTOS HETEROCICLICOS COMO INHIBIDORES DE FOSFATIDILINOSITOL 3-QUINASAS (PI3Ks)
ITMI20060311A1 (it) 2006-02-21 2007-08-22 Btsr Int Spa Dispositivo perfezionato di alimentazione di filo o filatio ad una macchina tessile e metodo per attuare tale alimentazione
GB0603684D0 (en) 2006-02-23 2006-04-05 Novartis Ag Organic compounds
WO2007096764A2 (en) 2006-02-27 2007-08-30 Glenmark Pharmaceuticals S.A. Bicyclic heteroaryl derivatives as cannabinoid receptor modulators
TW200800203A (en) 2006-03-08 2008-01-01 Astrazeneca Ab New use
DE602007004092D1 (de) 2006-03-22 2010-02-11 Vertex Pharma C-met-proteinkinasehemmer zur behandlung proliferativer erkrankungen
US7574131B2 (en) 2006-03-29 2009-08-11 Sunvision Scientific Inc. Object detection system and method
MX2008012658A (es) 2006-03-31 2008-12-16 Schering Corp Inhibidores de cinasa.
US7629346B2 (en) 2006-06-19 2009-12-08 Hoffmann-La Roche Inc. Pyrazinecarboxamide derivatives as CB1 antagonists
WO2007149478A2 (en) 2006-06-22 2007-12-27 Mallinckrodt Inc. Pyrazine derivatives with extended conjugation and uses thereof
ES2340093T3 (es) 2006-06-22 2010-05-28 Biovitrum Ab (Publ) Derivados pirazina y piridina como inhibidores de cinasa mnk.
EP1900727A1 (en) 2006-08-30 2008-03-19 Cellzome Ag Aminopyridine derivatives as kinase inhibitors
JP2010504933A (ja) 2006-09-29 2010-02-18 ノバルティス アーゲー Ｐｉ３ｋ脂質キナーゼ阻害剤としてのピラゾロピリミジン
GB0619342D0 (en) 2006-09-30 2006-11-08 Vernalis R&D Ltd New chemical compounds
AU2007304365A1 (en) 2006-10-04 2008-04-10 F. Hoffmann-La Roche Ag 3-pyridinecarboxamide and 2-pyrazinecarboxamide derivatives as HDL-cholesterol raising agents
ES2631003T3 (es) 2006-10-19 2017-08-25 Signal Pharmaceuticals, Llc Compuestos heteroarilo, sus composiciones y métodos de tratamiento con ellos
EP2081928B1 (en) 2006-11-10 2014-02-26 Bristol-Myers Squibb Company Pyrrolo-pyridine kinase inhibitors
US20080132698A1 (en) 2006-11-30 2008-06-05 University Of Ottawa Use of N-oxide compounds in coupling reactions
JP2010513232A (ja) 2006-12-15 2010-04-30 バイエル・シエーリング・ファーマ アクチエンゲゼルシャフト ３−ｈ−ピラゾロピリジン類及びそれらの塩類、それらを含んで成る医薬組成物類、それらの調製方法及びそれらの使用
CA2672438A1 (en) 2006-12-20 2008-07-03 Amgen Inc. Substituted heterocycles and methods of use
PE20121126A1 (es) 2006-12-21 2012-08-24 Plexxikon Inc Compuestos pirrolo [2,3-b] piridinas como moduladores de quinasa
GB0625659D0 (en) 2006-12-21 2007-01-31 Cancer Rec Tech Ltd Therapeutic compounds and their use
MX2009008531A (es) 2007-02-16 2009-08-26 Amgen Inc Cetonas de heterociclilo que contienen nitrogeno y su uso como inhibidores de c-met.
AU2008221263B2 (en) 2007-03-01 2012-02-23 Novartis Ag Pim kinase inhibitors and methods of their use
CA2683180A1 (en) 2007-04-10 2008-10-16 Bayer Cropscience Ag Insecticidal aryl isoxazoline derivatives
JP2008260691A (ja) 2007-04-10 2008-10-30 Bayer Cropscience Ag 殺虫性アリールイソオキサゾリン誘導体
EP2150255A4 (en) 2007-05-10 2011-10-05 Glaxosmithkline Llc CHINOXALINE DERIVATIVES AS P13 KINASE INHIBITORS
PE20090717A1 (es) 2007-05-18 2009-07-18 Smithkline Beecham Corp Derivados de quinolina como inhibidores de la pi3 quinasa
UY31137A1 (es) 2007-06-14 2009-01-05 Smithkline Beecham Corp Derivados de quinazolina como inhibidores de la pi3 quinasa
EP2012409A2 (en) 2007-06-19 2009-01-07 Hitachi, Ltd. Rotating electrical machine
JP2009027904A (ja) 2007-06-19 2009-02-05 Hitachi Ltd 回転電機
EP2157090A4 (en) 2007-06-21 2011-09-07 Taisho Pharmaceutical Co Ltd PYRAZINAMIDE COMPOUND
WO2009002964A1 (en) 2007-06-26 2008-12-31 Lexicon Pharmaceuticals, Inc. Methods of treating serotonin-mediated diseases and disorders
JP2010531358A (ja) 2007-06-27 2010-09-24 メルク・シャープ・エンド・ドーム・コーポレイション ヒストン脱アセチル化酵素阻害剤としてのピリジル及びピリミジニル誘導体
GB0713259D0 (en) * 2007-07-09 2007-08-15 Astrazeneca Ab Pyrazine derivatives 954
SI2178865T1 (sl) 2007-07-19 2015-11-30 Lundbeck, H., A/S 5-členski heterociklični amidi in sorodne spojine
AU2008279776B2 (en) 2007-07-19 2013-05-23 Merck Sharp & Dohme Corp. Heterocyclic amide compounds as protein kinase inhibitors
EA201000113A1 (ru) 2007-08-01 2010-08-30 Пфайзер Инк. Пиразольные соединения
WO2009024825A1 (en) 2007-08-21 2009-02-26 Astrazeneca Ab 2-pyrazinylbenzimidazole derivatives as receptor tyrosine kinase inhibitors
EP2203436A1 (en) 2007-09-17 2010-07-07 Neurosearch A/S Pyrazine derivatives and their use as potassium channel modulators
WO2009053737A2 (en) 2007-10-25 2009-04-30 Astrazeneca Ab Pyridine and pyrazine derivatives useful in the treatment of cell proliferative disorders
EP2265270A1 (en) 2008-02-04 2010-12-29 OSI Pharmaceuticals, Inc. 2-aminopyridine kinase inhibitors
WO2009106445A1 (en) 2008-02-25 2009-09-03 F. Hoffmann-La Roche Ag Pyrrolopyrazine kinase inhibitors
CA2713710A1 (en) 2008-02-25 2009-09-03 F. Hoffmann-La Roche Ag Pyrrolopyrazine kinase inhibitors
CN101952294B (zh) 2008-02-25 2014-11-26 霍夫曼-拉罗奇有限公司 吡咯并吡嗪激酶抑制剂
EP2247593B1 (en) 2008-02-25 2011-08-10 F. Hoffmann-La Roche AG Pyrrolopyrazine kinase inhibitors
TW200940537A (en) 2008-02-26 2009-10-01 Astrazeneca Ab Heterocyclic urea derivatives and methods of use thereof
WO2009111280A1 (en) 2008-02-29 2009-09-11 Array Biopharma Inc. N- (6-aminopyridin-3-yl) -3- (sulfonamido) benzamide derivatives as b-raf inhibitors for the treatment of cancer
US8268834B2 (en) 2008-03-19 2012-09-18 Novartis Ag Pyrazine derivatives that inhibit phosphatidylinositol 3-kinase enzyme
US8110576B2 (en) 2008-06-10 2012-02-07 Plexxikon Inc. Substituted pyrrolo[2,3b]pyrazines and methods for treatment of raf protein kinase-mediated indications
GB0814364D0 (en) 2008-08-05 2008-09-10 Eisai London Res Lab Ltd Diazaindole derivatives and their use in the inhibition of c-Jun N-terminal kinase
CN102171214B (zh) 2008-08-06 2015-06-24 生物马林药物股份有限公司 聚(adp-核糖)聚合酶(parp)的二氢吡啶并酞嗪酮抑制剂
EP2328890B1 (en) 2008-08-06 2012-01-25 Pfizer Inc. 6 substituted 2-heterocyclylamino pyrazine compounds as chk-1 inhibitors
JP2010077286A (ja) 2008-09-26 2010-04-08 Aica Kogyo Co Ltd シリコーン樹脂組成物および粘着フィルム
NZ592569A (en) 2008-10-21 2012-05-25 Vertex Pharma C-met protein kinase inhibitors
CN102264721B (zh) 2008-11-10 2015-12-09 沃泰克斯药物股份有限公司 用作atr激酶抑制剂的化合物
AU2009324894B2 (en) 2008-11-25 2015-04-09 University Of Rochester MLK inhibitors and methods of use
ES2464458T3 (es) 2008-12-05 2014-06-02 F. Hoffmann-La Roche Ag Pirrolopirazinil-ureas como inhibidores de quinasas
CN106518856B (zh) 2008-12-19 2020-04-28 沃泰克斯药物股份有限公司 用作atr激酶抑制剂的化合物
UY32351A (es) 2008-12-22 2010-07-30 Astrazeneca Ab Compuestos de pirimidinil indol para uso como inhibidores de atr
US8785445B2 (en) 2008-12-22 2014-07-22 Array Biopharma Inc. 7-phenoxychroman carboxylic acid derivatives
CA2740193A1 (en) 2008-12-23 2010-07-01 Abbott Laboratories Anti-viral compounds
SG173027A1 (en) 2009-01-30 2011-08-29 Toyama Chemical Co Ltd N-acyl anthranilic acid derivative or salt thereof
JP5353279B2 (ja) 2009-02-06 2013-11-27 Ｊｎｃ株式会社 セレンテラミド又はその類縁体の製造方法
SG173639A1 (en) 2009-02-11 2011-09-29 Sunovion Pharmaceuticals Inc Histamine h3 inverse agonists and antagonists and methods of use thereof
CN101537007A (zh) 2009-03-18 2009-09-23 中国医学科学院血液病医院（血液学研究所） N-(噻吩-2)吡唑并[1,5-a]嘧啶-3-甲酰胺类化合物在制备抗恶性肿瘤药物方面的应用
US20120065247A1 (en) 2009-03-27 2012-03-15 Discoverybiomed, Inc. Modulating ires-mediated translation
AR077468A1 (es) 2009-07-09 2011-08-31 Array Biopharma Inc Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa
SG177606A1 (en) 2009-07-13 2012-03-29 Widex As A hearing aid adapted fordetecting brain waves and a method for adapting such a hearing aid
MX2012000711A (es) 2009-07-15 2012-03-16 Abbott Lab Inhibidores de pirrolopirazina de cinasas.
CN102548411B (zh) 2009-08-07 2014-07-02 陶氏益农公司 杀虫组合物
JP2011042639A (ja) 2009-08-24 2011-03-03 Kowa Co ビフェニルピラジン化合物及びこれを有効成分として含有するエリスロポエチン産生促進剤
CN101671336B (zh) 2009-09-23 2013-11-13 辽宁利锋科技开发有限公司 芳杂环并嘧啶衍生物和类似物及其制备方法和用途
DE102009043260A1 (de) 2009-09-28 2011-04-28 Merck Patent Gmbh Pyridinyl-imidazolonderivate
RU2615130C2 (ru) 2009-10-06 2017-04-04 Милленниум Фармасьютикалз, Инк Гетероциклические соединения, используемые в качестве ингибиторов pdk1
US9205091B2 (en) 2009-11-13 2015-12-08 The United States Of America, As Represented By The Secretary Department Of Health And Human Services Diazeniumdiolated compounds, pharmaceutical compositions, and method of treating cancer
PT2526090E (pt) 2010-01-18 2015-11-30 Medicines For Malaria Venture Mmv Novos agentes antimaláricos
US8518945B2 (en) 2010-03-22 2013-08-27 Hoffmann-La Roche Inc. Pyrrolopyrazine kinase inhibitors
MX2012011549A (es) 2010-04-08 2013-01-29 Ah Usa 42 Llc Derivados de 3,5-difenil-isoxazolina sustituida como insecticidas y acaricidas.
US20130030237A1 (en) 2010-04-15 2013-01-31 Charles Theuer Potentiation of anti-cancer activity through combination therapy with ber pathway inhibitors
JP2013525476A (ja) 2010-05-04 2013-06-20 ファイザー・インク Ａｌｋ阻害剤としての複素環式誘導体
US9062008B2 (en) 2010-05-12 2015-06-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
SG185524A1 (en) 2010-05-12 2012-12-28 Vertex Pharma Compounds useful as inhibitors of atr kinase
JP2013526540A (ja) 2010-05-12 2013-06-24 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｔｒキナーゼ阻害剤として有用な化合物
US8962631B2 (en) 2010-05-12 2015-02-24 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
MX2012013082A (es) 2010-05-12 2013-05-09 Vertex Pharma Derivados de 2-aminopiridina utiles como iinhibidores de cinasa atr.
US8969356B2 (en) 2010-05-12 2015-03-03 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
CA2798970A1 (en) 2010-05-20 2011-11-24 F. Hoffmann-La Roche Ag Pyrrolopyrazine derivatives as syk and jak inhibitors
KR20130083386A (ko) 2010-05-20 2013-07-22 에프. 호프만-라 로슈 아게 피롤로[2,3-ｂ]피라진-7-카복스아마이드 유도체 및 ＪＡＫ 및 ＳＹＫ 억제제로서의 그의 용도
US8623869B2 (en) 2010-06-23 2014-01-07 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
CN102311396B (zh) 2010-07-05 2015-01-07 暨南大学 一种吡嗪类衍生物和其制备方法及在制药中的应用
EP2407478A1 (en) 2010-07-14 2012-01-18 GENETADI Biotech, S.L. New cyclotetrapeptides with pro-angiogenic properties
JP5782238B2 (ja) 2010-07-30 2015-09-24 ルネサスエレクトロニクス株式会社 電圧検出回路及びその制御方法
US8440652B2 (en) 2011-03-04 2013-05-14 Lexicon Pharmaceuticals, Inc. MST1 kinase inhibitors and methods of their use
WO2012121939A2 (en) 2011-03-04 2012-09-13 Locus Pharmaceuticals, Inc. Aminopyrazine compounds
CA2832100A1 (en) 2011-04-05 2012-10-11 Vertex Pharmaceuticals Incorporated Aminopyrazine compounds useful as inhibitors of tra kinase
WO2012158785A1 (en) 2011-05-17 2012-11-22 Principia Biopharma Inc. Azaindole derivatives as tyrosine kinase inhibitors
US9309250B2 (en) 2011-06-22 2016-04-12 Vertex Pharmaceuticals Incorporated Substituted pyrrolo[2,3-b]pyrazines as ATR kinase inhibitors
JP2014520161A (ja) 2011-06-22 2014-08-21 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｔｒキナーゼ阻害剤として有用な化合物
US9096602B2 (en) 2011-06-22 2015-08-04 Vertex Pharmaceuticals Incorporated Substituted pyrrolo[2,3-B]pyrazines as ATR kinase inhibitors
WO2013049720A1 (en) 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
CA2850566C (en) 2011-09-30 2022-05-03 Vertex Pharmaceuticals Incorporated Process for making 4-[chloro-n-hydroxycarbonimidoyl]phenyl derivative
EP3733185B1 (en) 2011-09-30 2022-12-07 Vertex Pharmaceuticals Incorporated Treating non-small cell lung cancer with atr inhibitors
WO2013049719A1 (en) 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
CN103958507A (zh) 2011-09-30 2014-07-30 沃泰克斯药物股份有限公司 可用作atr激酶抑制剂的化合物
WO2013071088A1 (en) 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
WO2013071093A1 (en) 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Pyrazine compounds useful as inhibitors of atr kinase
US8841449B2 (en) 2011-11-09 2014-09-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US8846918B2 (en) 2011-11-09 2014-09-30 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2013071090A1 (en) 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
EP2833973B1 (en) 2012-04-05 2017-09-13 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase and combination therapies thereof
CN103373996A (zh) 2012-04-20 2013-10-30 山东亨利医药科技有限责任公司 作为crth2受体拮抗剂的二并环衍生物
US8999632B2 (en) 2012-10-04 2015-04-07 Vertex Pharmaceuticals Incorporated Method for measuring ATR inhibition mediated increases in DNA damage
US8912198B2 (en) 2012-10-16 2014-12-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
DK3418281T3 (da) 2012-12-07 2020-12-07 Vertex Pharma Pyrazolo[1,5-a]pyrimidiner, der er anvendelige som inhibitorer af atr-kinase til behandling af cancersygdomme
JP6096005B2 (ja) 2013-02-26 2017-03-15 リンテック株式会社 シート剥離装置および剥離方法
PT3077397T (pt) 2013-12-06 2020-01-22 Vertex Pharma Composto de 2-amino-6-fluoro-n-[5-fluoro-piridin-3-il]pirazolo[1,5-a]pirimidin-3-carboxamida útil como inibidor da atr quinase, a sua preparação, diferentes formas sólidas e derivados radiomarcados do mesmo
KR102575125B1 (ko) 2014-06-05 2023-09-07 버텍스 파마슈티칼스 인코포레이티드 Atr 키나제의 저해제로서 유용한 2-아미노-6-플루오로-n-[5-플루오로-피리딘-3-일]-피라졸로[1,5-a]피리미딘-3-카복스아미드 화합물의 방사성표지된 유도체, 상기 화합물의 제조 및 이의 다양한 고체 형태
DK3157566T3 (da) 2014-06-17 2019-07-22 Vertex Pharma Fremgangsmåde til behandling af cancer under anvendelse af en kombination chk1- og atr-inhibitorer

Also Published As

Publication number Publication date
BRPI0924084B1 (pt) 2021-12-21
TWI643854B (zh) 2018-12-11
US20180170922A1 (en) 2018-06-21
CN106518856B (zh) 2020-04-28
KR20170081739A (ko) 2017-07-12
TW201028404A (en) 2010-08-01
AU2016222396A1 (en) 2016-10-13
US10479784B2 (en) 2019-11-19
CN102300862B (zh) 2016-11-23
WO2010071837A1 (en) 2010-06-24
TWI543979B (zh) 2016-08-01
US20150031661A1 (en) 2015-01-29
EP2376485B1 (en) 2017-12-06
RU2011129761A (ru) 2013-05-20
US9365557B2 (en) 2016-06-14
TW201520210A (zh) 2015-06-01
BRPI0924084A2 (pt) 2020-11-10
JP2018009010A (ja) 2018-01-18
ES2921576T3 (es) 2022-08-29
US20160311809A1 (en) 2016-10-27
JP2019194250A (ja) 2019-11-07
ZA201104498B (en) 2012-10-31
US9701674B2 (en) 2017-07-11
AU2018201363A1 (en) 2018-03-15
PL2376485T3 (pl) 2018-05-30
CA2747252C (en) 2018-09-18
LT2376485T (lt) 2018-03-26
IL236602A0 (en) 2015-02-26
CY1120002T1 (el) 2018-12-12
PL3354650T3 (pl) 2022-06-13
CN106518856A (zh) 2017-03-22
HRP20220581T1 (hr) 2022-06-10
JP6577537B2 (ja) 2019-09-18
IL213613A0 (en) 2011-07-31
TWI478918B (zh) 2015-04-01
SG10201607592PA (en) 2016-11-29
PT3354650T (pt) 2022-06-20
AU2018201363B2 (en) 2020-02-20
KR101755216B1 (ko) 2017-07-07
AU2016222396B2 (en) 2018-04-05
HK1259148A1 (en) 2019-11-29
IL260158B (en) 2020-10-29
HUE036068T2 (hu) 2018-06-28
DK2376485T3 (en) 2018-03-12
CN102300862A (zh) 2011-12-28
EP3354650A1 (en) 2018-08-01
AU2009327357B2 (en) 2016-06-16
SI3354650T1 (sl) 2022-06-30
AU2009327357A1 (en) 2011-07-28
AU2009327357C1 (en) 2017-02-02
KR20150003924A (ko) 2015-01-09
CN106496210A (zh) 2017-03-15
JP6212527B2 (ja) 2017-10-11
JP5753093B2 (ja) 2015-07-22
KR101958632B1 (ko) 2019-03-15
SI2376485T1 (en) 2018-04-30
RU2604066C2 (ru) 2016-12-10
TW201708213A (zh) 2017-03-01
NZ593969A (en) 2013-11-29
IL236602B (en) 2018-07-31
CN106496209A (zh) 2017-03-15
MX2011006503A (es) 2011-09-06
US8841308B2 (en) 2014-09-23
IL213613A (en) 2015-01-29
KR101745331B1 (ko) 2017-06-09
NO2376485T3 (es) 2018-05-05
US10961232B2 (en) 2021-03-30
US20230030414A1 (en) 2023-02-02
EP4059932A1 (en) 2022-09-21
SMT201800181T1 (it) 2018-05-02
JP2015024996A (ja) 2015-02-05
JP2012512906A (ja) 2012-06-07
HRP20180385T1 (hr) 2018-04-06
SG172248A1 (en) 2011-07-28
US20100222318A1 (en) 2010-09-02
IL260158A (en) 2018-07-31
ES2663222T3 (es) 2018-04-11
CN106496210B (zh) 2020-06-09
KR20110096158A (ko) 2011-08-29
EP2376485A1 (en) 2011-10-19
US20190047995A1 (en) 2019-02-14
JP5894643B2 (ja) 2016-03-30
AU2018201363C1 (en) 2020-06-18
JP2016030756A (ja) 2016-03-07
LT3354650T (lt) 2022-06-27
DK3354650T3 (da) 2022-05-30
US20150051187A1 (en) 2015-02-19
RU2016141566A (ru) 2018-12-20
PT2376485T (pt) 2018-03-12
CN106496209B (zh) 2020-06-30
RU2016141566A3 (es) 2020-02-17
CA3013000C (en) 2022-12-13
EP3354650B1 (en) 2022-02-16
CA3013000A1 (en) 2010-06-24
CA2747252A1 (en) 2010-06-24
RS56995B1 (sr) 2018-05-31

Similar Documents

Publication Publication Date Title
AR074822A1 (es) Compuestos heterociclicos de pirazina utiles como inhibidores de proteinquinasas atr, composiciones farmaceuticas que los comprenden y uso de los mismos en el tratamiento del cancer
CY1117113T1 (el) Αναστολεις πρωτεασης σερινης hcv λαμβανομενοι απο μακροκυκλικη προλινη
AR043180A1 (es) Derivados de heterociclil-3-sulfonilazaindol o -azaindazol como ligandos de 5-hidroxitriptamina-6
AR063684A1 (es) Derivados de 4, 4´-bifenildiilbis(1h-imidazol-5, 2-diil) como inhibidores del virus de la hepatitis c, composicion que los comprende y su uso para tratar una infeccion con vhc.
AR049443A1 (es) Derivados de pirrolpiridinas
AR080863A1 (es) Derivados del acido1-amino-2-ciclopropiletilboronico, composiciones farmaceuticas que los contienen y uso de los mismos en el tratamiento del cancer.
AR083070A1 (es) Analogos de nucleotidos sustituidos con heterociclos nitrogenados, composiciones farmaceuticas que los contienen y uso de los mismos para tratar enfermedades virales, en particular infecciones por vhc
CO6170361A2 (es) Composiciones y metodos para modular receptores de c-kit y pdgfr
CO6220972A2 (es) Derivados de 6-amino dihidropurin -8-ona utiles como agentes terapeuticos y/o preventivos para el tratamiento de enfermedades alergicas, virales o cancer
CO5031253A1 (es) Antagonistas receptores y5 de neuropeptidos composiciones farmaceuticas que las contienen
AR086096A1 (es) Derivados de nucleosidos 2’-ciano sustituidos y metodos de uso de los mismos para el tratamiento de enfermedades virales
PE20071020A1 (es) Compuestos derivados de glicina n-sustituidos como inhibidores de prolil hidroxilasa
ECSP099371A (es) INHIBIDORES ESPIRO CETONA DE ACETIL-CoA CARBOXILASA
AR068503A1 (es) Derivados de amidas sustituidas, composicion farmaceutica y usos.
AR038202A1 (es) Compuestos de indazol utiles como inhibidores de la proteina quinasa
AR086546A1 (es) Derivados de 7h-purin-8(9h)-ona como inhibidores de jak
AR093038A1 (es) Conjugados de suministro de farmacos que contienen aminoacidos no naturales y metodos para usarlos, composicion y uso
AR088180A1 (es) Derivados de estra-1,3,5(10),16-tetraen-3-carboxamida, procedimientos para su preparacion, preparados farmaceuticos que los contienen, asi como su uso para la preparacion de medicamentos
AR086357A1 (es) Derivados de indazol sustituidos activos como inhibidores de quinasas
AR055395A1 (es) Compuestos inhibidores de la actividad de la serina proteasa ns3-ns4a del virus de la hepatitis c
AR081058A1 (es) Derivados de arilmetoxi isoindolina, composiciones que los comprenden y su uso en el tratamiento del cancer.
AR078522A1 (es) Compuesto de espiropiperidina, composicion farmaceutica que lo comprende, su uso para preparar un medicamento util para tratar diabetes y compuesto intermediario para su sintesis
AR065806A1 (es) Derivados de quinolina, procesos para su preparacion, composiciones farmaceuticas que los contienen y usos para el tratamiento de la artritis reumatoidea.
AR035858A1 (es) Derivados de cromano 2,6-sustituidos,composiciones farmaceuticas,uso de dichos derivados para la manufactura de medicamentos utiles como agonistas adrenorreceptores beta-3
PE20250759A1 (es) Conjugado de anticuerpo bispecifico-farmaco de camptotecina y uso farmaceutico de este

Legal Events

Date Code Title Description
FG Grant, registration