[go: up one dir, main page]

AR086977A1 - Derivados heterociclicos nitrogenados utiles para el tratamiento del cancer y composiciones farmaceuticas que los contienen - Google Patents

Derivados heterociclicos nitrogenados utiles para el tratamiento del cancer y composiciones farmaceuticas que los contienen

Info

Publication number
AR086977A1
AR086977A1 ARP120102167A ARP120102167A AR086977A1 AR 086977 A1 AR086977 A1 AR 086977A1 AR P120102167 A ARP120102167 A AR P120102167A AR P120102167 A ARP120102167 A AR P120102167A AR 086977 A1 AR086977 A1 AR 086977A1
Authority
AR
Argentina
Prior art keywords
alkyl
alkylene
aryl
rent
heteroaryl
Prior art date
Application number
ARP120102167A
Other languages
English (en)
Inventor
Sheldon Cao
Janeta Popovici-Muller
Francesco G Salituro
Jeffrey Saunders
Xuefei Tan
Jeremy Travins
Shunqi Yan
Zhixiong Ye
Original Assignee
Agios Pharmaceuticals Inc
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 Agios Pharmaceuticals Inc filed Critical Agios Pharmaceuticals Inc
Publication of AR086977A1 publication Critical patent/AR086977A1/es

Links

Classifications

    • 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
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6509—Six-membered rings
    • C07F9/650952—Six-membered rings having the nitrogen atoms in the positions 1 and 4
    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
    • 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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/84—Nitriles
    • C07D213/85—Nitriles in position 3
    • 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
    • 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
    • C07D409/14—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
    • C07D413/14—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
    • 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Reivindicación 1: Un compuesto caracterizado porque tiene la fórmula estructural (1), o una sal aceptable farmacéuticamente de los mismos, donde: Y es -N(R5)-, -N(R5)-CH2-, -CH2-N(R5)- o -CH(R5)-; cada R1a y R1b es en forma independiente hidrógeno, -alquilo C1-4, -N(R7)(alquilen C1-4)-N(R7)(alquilo C1-4), arilo, heteroarilo, heterociclilo, -C(O)N(R7)-arilo, -N(R7)C(O)-arilo, -(alquilen C1-4)-arilo, -(alquilen C1-4)-heteroarilo, -O-(alquilen C0-4)-arilo, -O-(alquilen C0-4)-heteroarilo, -O-(alquilen C0-4)-heterociclilo, O-(alquilen C0-4)-carbociclilo, -N(R7)-arilo, o -N(R7)-heteroarilo, -N(R9)-arilo, -N(R9)-heteroarilo, -O-(alquenilen C1-4)-N(R7)C(O)O-(alquilen C1-4)-arilo, -N(R9)-C(O)-(alquenilo C2-4) donde: al menos uno de R1a y R1b no es hidrógeno ni metilo; cualquier unidad alquileno presente en R1a o R1b se sustituye opcionalmente con OH o F; cada R7 se selecciona en forma independiente entre hidrógeno y alquilo C1-4; y cualquier arilo, heteroarilo, o heterociclilo de R1a o R1b se sustituye opcionalmente con uno o más sustituyentes seleccionados entre -G-L-M, halo, alquilo C1-6, -CºN, =O, -CF3 y -OCF3; G es una unión o una cadena hidrocarbonada bivalente, saturada o insaturada, lineal o ramificada de C1-6 donde opcionalmente una, dos o tres unidades metileno de la cadena hidrocarbonada se reemplazan en forma independiente por -NR8-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -SO-, -SO2-, -C(=S)-, -C(=NR8)-, -N=N-, o -C(=N2)-; L es una unión covalente una cadena hidrocarbonada bivalente, saturada o insaturada, lineal o ramificada de C1-8, donde uno, dos o tres unidades metileno de L son opcionalmente y en forma independiente reemplazados por ciclopropileno, -NR8-, -N(R8)C(O)-, -C(O)N(R8)-, -N(R8)SO2-, SO2N(R8)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -SO-, -SO2-, -C(=S)-, -C(=NR8)-, -N=N-, o -C(=N2)-; M es E, o un anillo de 3 a 10 miembros monocíclico o bicíclico, saturado, parcialmente insaturado o aromático que tiene 0 - 3 heteroátomos seleccionados en forma independiente entre nitrógeno, oxígeno, o azufre, y donde dicho anillo se sustituye con 1 - 4 grupos seleccionados en forma independiente entre -D-E, oxo, NO2, halógeno, CN, alquilo C1-6, alquenilo C2-6, o alquinilo C2-6; D es una unión covalente o una cadena hidrocarbonada bivalente, saturada o insaturada, lineal o ramificada de C1-6, donde una o dos unidades metileno de D son opcionalmente y en forma independiente reemplazadas por NR8-, -S-, -O-, -C(O)-,-SO-, o -SO2-; E es hidrógeno, alquilo C1-6, alquenilo C2-6, o alquinilo C2-6, donde dicho alquilo, alquenilo o alquinilo se sustituye opcionalmente con oxo, halógeno, o CN; y cada R8 es en forma independiente hidrógeno, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, alcoxi C1-6, -S(O)2-alquenilo C2-4, o un grupo opcionalmente sustituido seleccionado entre fenilo, un heterociclilo de 4 a 7 miembros que tiene 1 - 2 heteroátomos seleccionados en forma independiente entre nitrógeno, oxígeno, o azufre, o un heterociclilo de 5 - 6 miembros que tiene 1 - 4 heteroátomos seleccionados en forma independiente entre nitrógeno, oxígeno, o azufre; R2 se selecciona entre fenilo, un cicloalquilo de 3 - 7 miembros, alquilo C2-4, o CF3, donde el fenilo o cicloalquilo se sustituye opcionalmente con un sustituyente seleccionado entre metilo o fluoro; cada R3 se selecciona en forma independiente entre halo, -(alquilen C1-4)-O-(alquilo C1-4), -fluoroalquilo C1-4, -C(O)-O-(alquilo C1-4), -fenilo, -heteroarilo, cicloalquilo C3-7, -CH2-N(alquil C1-4)2, C(O)-N-(alquil C1-4)2, -C(O)-NH-(alquilo C1-4), -alquilo C1-4 opcionalmente sustituido con uno o más halo o -OH, o dos R3s son tomados juntos para formar un anillo saturado de 3 - 8 miembros o un fenilo fusionado donde dicho anillo saturado o fenilo fusionado se sustituye opcionalmente con 1 a 2 metilo; R4 se selecciona entre hidrógeno, -CN, halo, alcoxi C1-4, -CH2NH(alquilo C1-4), alquenilo C2-4, alquinilo C2-4, -(alquil C1-4)-O-(alquilo C1-4), fluoroalquilo C1-4, C(O)-N-(alquil C1-4)2, -C(O)-NH-(alquilo C1-4), -C(O)-O-(alquilo C1-4), -C(O)-OH, -S(O)2-(alquilo C1-4), y un heteroarilo de 5 miembros; R5 se selecciona entre: -C(O)-(alquilo C1-5), -C(O)-(alquenilo C2-6), -C(O)-(alquilen C0-2)-Q, -C(O)-(alquenilen C1-4)-Q, -C(O)-(alquilen C0-2)-N(R6)-(alquilen C0-2)-Q, -C(O)-O-(alquilen C0-2)-Q, -C(O)-(alquilen C1-2)-O-(alquilen C0-2)-Q, -C(O)-C(O)-Q, -S(O)2-Q, -C(O)-(alquilen C1-4)-O-C(O)-(alquilo C1-4), -C(O)-(alquilen C1-4)-C(O)-O-(alquilo C1-4), -C(O)-N(R6)-(alquilen C1-4)-O-C(O)-(alquilo C1-4), -C(O)-N(R6)-(alquilen C1-4)-C(O)-O-(alquilo C1-4), -C(O)-(alquilen C0-2)-N(R6)-(alquilo C1-6), -C(O)-(alquilen C0-2)N(R6)-(alquinilo C2-6), -C(O)-(alquilen C0-2)-N(R6)-(alquenilo C2-6), -C(O)-(alquilen C0-2)-N(R6)-(alquilen C0-2)-O-(alquilo C1-4), -C(O)-(alquilen C1-2)-O-(alquilo C1-4), -C(O)-(alquilen C1-2)-C(O)C(O)N(R)(alquilo C1-4), -C(O)-O-(alquilen C1-4)-O-(alquilo C1-4), -(alquilen C0-4)-O-C(O)-(alquilo C1-4), -(alquilen C0-4)-C(O)-O-(alquilo C1-4), -(alquilen C0-4)-O-(alquilo C1-4), -C(O)-(alquilen C1-2)S(O)0-2-(alquilo C1-4), -S(O)2-(alquilo C1-4), -C(O)-(alquilen C1-4)-C(O)C(O)N(R6)(alquilo C1-6), -C(O)-(alquilen C1-4)-N(R6)S(O)2-(alquilo C1-6), o -C(O)-(alquilen C1-4)N(R6)S(O)2Q, donde: cualquier unidad alquileno presente en R5 se sustituye opcionalmente con OCH3, OH o F; cualquier unidad metilo terminal presente en R5 se reemplaza opcionalmente con -CH2OH, CF3, -CH2F, -CH2CI, C(O)CH3, C(O)CF3, CN, -OCH3, -C(O)H, -OP(O)(OH)2, -OP(O)(alcoxi C1-4)2 o CO2H; cada R6 se selecciona en forma independiente entre hidrógeno y metilo; Q se selecciona entre arilo, heteroarilo, carbociclilo y heterociclilo, donde Q se sustituye opcionalmente con hasta 3 sustituyentes seleccionados en forma independiente entre alquilo C1-4, opcionalmente sustituido con OH, alcoxi C1-4, -C(O)O-(alquilo C1-4), -(alquilen C1-4)-(alcoxi C1-4), -CN, -OH, fluoro, cloro, y bromo; R9 se selecciona entre arilo y heteroarilo, donde cada arilo o heteroarilo se sustituye opcionalmente con uno o más sustituyentes seleccionados entre -G-L-M, halo, alquilo C1-6, -CºN, =O, -CF3 y -OCF3; o C(O)(alquenilo C2-4); y m es 0, 1, 2 ó 3.
ARP120102167A 2011-06-17 2012-06-18 Derivados heterociclicos nitrogenados utiles para el tratamiento del cancer y composiciones farmaceuticas que los contienen AR086977A1 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN2011101721691A CN102827073A (zh) 2011-06-17 2011-06-17 治疗活性组合物和它们的使用方法
US201161509071P 2011-07-18 2011-07-18
US201261584210P 2012-01-06 2012-01-06

Publications (1)

Publication Number Publication Date
AR086977A1 true AR086977A1 (es) 2014-02-05

Family

ID=47330415

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP120102167A AR086977A1 (es) 2011-06-17 2012-06-18 Derivados heterociclicos nitrogenados utiles para el tratamiento del cancer y composiciones farmaceuticas que los contienen

Country Status (11)

Country Link
US (2) US20140213580A1 (es)
EP (1) EP2721019B1 (es)
JP (1) JP6152098B2 (es)
CN (1) CN102827073A (es)
AR (1) AR086977A1 (es)
AU (1) AU2012269648B2 (es)
CA (1) CA2839675C (es)
ES (1) ES2694160T3 (es)
MX (1) MX345928B (es)
TW (1) TWI628165B (es)
WO (1) WO2012171337A1 (es)

Families Citing this family (77)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG177434A1 (en) 2009-06-29 2012-02-28 Agios Pharmaceuticals Inc Therapeutic compounds and compositions
US20130225548A1 (en) * 2010-10-28 2013-08-29 Nippon Shinyaku Co., Ltd. Pyridine Derivative and Medicinal Agent
CN102827073A (zh) 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
CN102827170A (zh) 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
TWI547493B (zh) 2011-09-27 2016-09-01 諾華公司 作為突變ｉｄｈ之抑制劑之３－嘧啶－４－基－唑啶－２－酮
UA117451C2 (uk) 2012-01-06 2018-08-10 Аджиос Фармасьютікалз, Інк. Терапевтично активні сполуки і способи їх застосування
US9474779B2 (en) 2012-01-19 2016-10-25 Agios Pharmaceuticals, Inc. Therapeutically active compositions and their methods of use
AU2013216354B2 (en) 2012-02-02 2017-08-31 Idorsia Pharmaceuticals Ltd 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
UY34632A (es) 2012-02-24 2013-05-31 Novartis Ag Compuestos de oxazolidin- 2- ona y usos de los mismos
US9618514B2 (en) 2012-09-17 2017-04-11 Agios Pharmaceuticals, Inc Methods of evaluating patients using E-cadherin and vimentin
DK2906555T3 (en) * 2012-10-15 2017-02-06 Pfizer Ireland Pharmaceuticals Process for the preparation of voriconazole and analogs thereof
US9296733B2 (en) 2012-11-12 2016-03-29 Novartis Ag Oxazolidin-2-one-pyrimidine derivative and use thereof for the treatment of conditions, diseases and disorders dependent upon PI3 kinases
SG11201504022RA (en) 2012-11-21 2015-06-29 Agios Pharmaceuticals Inc Glutamase inhibitors and method of use
WO2014079011A1 (en) 2012-11-22 2014-05-30 Agios Pharmaceuticals, Inc. Heterocyclic compounds for inhibiting glutaminase and their methods of use
WO2014141104A1 (en) * 2013-03-14 2014-09-18 Novartis Ag 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant idh
WO2014190451A1 (zh) * 2013-05-28 2014-12-04 中国医学科学院肿瘤医院 辅助诊断肺腺癌患者的试剂盒
WO2014190449A1 (zh) * 2013-05-28 2014-12-04 中国医学科学院肿瘤医院 辅助诊断非小细胞肺癌患者的试剂盒
WO2015003355A2 (en) 2013-07-11 2015-01-15 Agios Pharmaceuticals, Inc. Therapeutically active compounds and their methods of use
CN105473560B (zh) * 2013-07-11 2020-01-17 安吉奥斯医药品有限公司 治疗活性化合物及其使用方法
WO2015006591A1 (en) 2013-07-11 2015-01-15 Agios Pharmaceuticals, Inc. 2,4- or 4,6-diaminopyrimidine compounds as idh2 mutants inhibitors for the treatment of cancer
US9724350B2 (en) 2013-07-11 2017-08-08 Agios Pharmaceuticals, Inc. N,6-bis(aryl or heteroaryl)-1,3,5-triazine-2,4-diamine compounds as IDH2 mutants inhibitors for the treatment of cancer
WO2015003360A2 (en) 2013-07-11 2015-01-15 Agios Pharmaceuticals, Inc. Therapeutically active compounds and their methods of use
US9579324B2 (en) 2013-07-11 2017-02-28 Agios Pharmaceuticals, Inc Therapeutically active compounds and their methods of use
CN105658649B (zh) 2013-07-22 2019-03-22 爱杜西亚药品有限公司 1-(哌嗪-1-基)-2-([1,2,4]三唑-1-基)-乙酮衍生物
US20150031627A1 (en) 2013-07-25 2015-01-29 Agios Pharmaceuticals, Inc Therapeutically active compounds and their methods of use
PL3052476T3 (pl) 2013-09-30 2021-01-11 Guangzhou Innocare Pharma Tech Co., Ltd. Podstawione nikotynoimidowe inhibitory btk oraz sposób ich wytwarzania i zastosowanie w leczeniu raka, stanu zapalnego i chorób automunnologicznych
RS63733B1 (sr) 2013-10-18 2022-12-30 Celgene Quanticel Research Inc Inhibitori bromodomena
EP3060550B1 (en) * 2013-10-21 2019-05-15 Merck Patent GmbH Heteroaryl compounds as btk inhibitors and uses thereof
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
UA121211C2 (uk) 2014-03-14 2020-04-27 Аджіос Фармасьютикалз, Інк. Фармацевтична композиція, що містить тверду дисперсію, та спосіб лікування гострої мієлогенної/мієлоїдної лейкемії (гмл)
AU2015231053B2 (en) * 2014-03-21 2019-04-11 Les Laboratoires Servier Compounds and their methods of use
AR099789A1 (es) 2014-03-24 2016-08-17 Actelion Pharmaceuticals Ltd Derivados de 8-(piperazin-1-il)-1,2,3,4-tetrahidro-isoquinolina
TW201613916A (en) 2014-06-03 2016-04-16 Gilead Sciences Inc TANK-binding kinase inhibitor compounds
EP3517536B1 (en) 2014-09-26 2021-05-05 Gilead Sciences, Inc. Aminotriazine derivatives useful as tank-binding kinase inhibitor compounds
US10040791B2 (en) * 2014-10-01 2018-08-07 Daiichi Sankyo Company, Limited Isoxazole derivative as mutant isocitrate dehydrogenase 1 inhibitor
JP6901394B2 (ja) 2014-12-22 2021-07-14 ザ ユナイテッド ステイツ オブ アメリカ， アズ リプレゼンテッド バイ ザ セクレタリー， デパートメント オブ ヘルス アンド ヒューマン サービシーズ 癌の処置に有用な変異型ｉｄｈ１阻害剤
MY187614A (en) 2015-01-15 2021-10-04 Idorsia Pharmaceuticals Ltd Hydroxyalkyl-piperazine derivatives as cxcr3 receptor modulators
AR103399A1 (es) 2015-01-15 2017-05-10 Actelion Pharmaceuticals Ltd Derivados de (r)-2-metil-piperazina como moduladores del receptor cxcr3
AR104259A1 (es) 2015-04-15 2017-07-05 Celgene Quanticel Res Inc Inhibidores de bromodominio
PL3322706T3 (pl) 2015-07-16 2021-07-19 Array Biopharma, Inc. Podstawione związki pirazolo[1,5-a]pirydynowe jako inhibitory kinazy ret
CN107849059B (zh) * 2015-07-27 2020-04-28 伊莱利利公司 7-苯基乙基氨基-4h-嘧啶并[4,5-d][1,3]噁嗪-2-酮化合物及其作为突变体idh1抑制剂的用途
DK3362066T3 (da) 2015-10-15 2021-11-22 Les Laboratoires Servier Sas Kombinationsterapi til behandling af maligniteter
MD3362065T2 (ro) 2015-10-15 2024-08-31 Servier Lab Terapie combinată care conține ivosidenib, citarabină și daunorubicina sau idarubicina pentru tratarea leucemiei acute mielogene
MX2018007421A (es) 2015-12-17 2018-08-15 Gilead Sciences Inc Compuestos inhibidores de quinasa de union a tank.
WO2017140758A1 (en) 2016-02-19 2017-08-24 Debiopharm International S.A. Derivatives of 2-amino-4-(2-oxazolidinon-3-yl)-pyrimidine fused with a five-membered heteroaromatic ring in 5,6-position which are useful for the treatment of various cancers
CN109071429B (zh) 2016-03-22 2021-04-02 正大天晴药业集团股份有限公司 丙啶磺酰胺类化合物及其使用方法
AU2017252276A1 (en) 2016-04-18 2018-11-15 Celgene Quanticel Research, Inc. Therapeutic compounds
US10150754B2 (en) 2016-04-19 2018-12-11 Celgene Quanticel Research, Inc. Histone demethylase inhibitors
ES2805030T3 (es) 2016-07-14 2021-02-10 Bristol Myers Squibb Co Compuestos monocíclicos sustituidos con heteroarilo
TWI704148B (zh) 2016-10-10 2020-09-11 美商亞雷生物製藥股份有限公司 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物
JOP20190077A1 (ar) 2016-10-10 2019-04-09 Array Biopharma Inc مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret
US11168090B2 (en) 2017-01-18 2021-11-09 Array Biopharma Inc. Substituted pyrazolo[1,5-a]pyrazines as RET kinase inhibitors
TWI783057B (zh) * 2017-10-10 2022-11-11 美商絡速藥業公司 製備6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈的方法
EP3740486A1 (en) 2018-01-18 2020-11-25 Array Biopharma, Inc. Substituted pyrazolyl[4,3-c]pyridinecompounds as ret kinase inhibitors
CA3087578C (en) 2018-01-18 2023-08-08 Array Biopharma Inc. Substituted pyrazolo[3,4-d]pyrimidine compounds as ret kinase inhibitors
EP3740491A1 (en) 2018-01-18 2020-11-25 Array Biopharma, Inc. Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors
US11013734B2 (en) 2018-05-16 2021-05-25 Forma Therapeutics, Inc. Treating patients harboring an isocitrate dehydrogenase-1 (IDH-1) mutation
US11311527B2 (en) 2018-05-16 2022-04-26 Forma Therapeutics, Inc. Inhibiting mutant isocitrate dehydrogenase 1 (mIDH-1)
WO2019222551A1 (en) 2018-05-16 2019-11-21 Forma Therapeutics, Inc. Solid forms of ((s)-5-((1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl)amino)-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile
PT3720442T (pt) 2018-05-16 2023-03-13 Forma Therapeutics Inc Inibição de idh-1 mutante
US11013733B2 (en) 2018-05-16 2021-05-25 Forma Therapeutics, Inc. Inhibiting mutant isocitrate dehydrogenase 1 (mlDH-1)
US10980788B2 (en) 2018-06-08 2021-04-20 Agios Pharmaceuticals, Inc. Therapy for treating malignancies
WO2020055672A1 (en) 2018-09-10 2020-03-19 Array Biopharma Inc. Fused heterocyclic compounds as ret kinase inhibitors
EP3845531A4 (en) * 2018-09-30 2021-11-24 Applied Pharmaceutical Science, Inc. SUBSTITUTED PYRAZOLE-CONDENSED RING DERIVATIVES, METHOD FOR THEIR PRODUCTION AND USE THEREOF
AU2019394519B2 (en) 2018-12-07 2025-02-13 Sunshine Lake Pharma Co., Ltd. RET inhibitors, pharmaceutical compositions and uses thereof
EP3891149A4 (en) 2018-12-07 2022-09-07 Sunshine Lake Pharma Co., Ltd. RET INHIBITOR, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
CN112851664B (zh) * 2019-11-12 2024-03-29 浙江海正药业股份有限公司 吡唑[1,5-a]吡啶-3-腈化合物及其在医药上的用途
WO2021162070A1 (ja) * 2020-02-14 2021-08-19 東レ株式会社 核酸製造用モノマーの製造方法
CN113461670B (zh) * 2020-03-31 2024-08-09 南京天印健华医药科技有限公司 作为转染期间重排激酶抑制剂的新的化合物
CN111606848A (zh) * 2020-06-05 2020-09-01 广西民族大学 一种氟二苯基取代吡啶类化合物的制备方法
WO2022029068A1 (en) * 2020-08-04 2022-02-10 F. Hoffmann-La Roche Ag Pyridinone compounds for the treatment of autoimmune disease
US11351149B2 (en) 2020-09-03 2022-06-07 Pfizer Inc. Nitrile-containing antiviral compounds
CN114437107B (zh) * 2020-11-06 2025-04-04 江苏先声药业有限公司 哌嗪类化合物及其应用
WO2023142641A1 (zh) * 2022-01-25 2023-08-03 成都苑东生物制药股份有限公司 一种吡啶类衍生物、其制备方法及用途
CN116768797A (zh) * 2022-03-16 2023-09-19 成都苑东生物制药股份有限公司 一种吡唑类衍生物、其制备方法及用途
WO2024148274A1 (en) * 2023-01-05 2024-07-11 Apellis Pharmaceuticals, Inc. Complement inhibition
CN117582438A (zh) * 2023-07-24 2024-02-23 成都硕德药业有限公司 吡啶类衍生物的药物组合物、制备方法及用途

Family Cites Families (141)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2390529A (en) 1942-02-03 1945-12-11 Ernst A H Friedheim Hydrazino-1,3,5-triazino derivatives of substituted phenylarsenic compounds
NL125847C (es) 1963-02-15
BE754242A (fr) 1970-07-15 1971-02-01 Geigy Ag J R Diamino-s-triazines et dinitro-s-triazines
US3867383A (en) 1971-03-29 1975-02-18 Ciba Geigy Corp Monoanthranilatoanilino-s-triazines
CH606334A5 (es) 1974-06-21 1978-10-31 Ciba Geigy Ag
JPS58186682A (ja) 1982-04-27 1983-10-31 日本化薬株式会社 セルロ−ス又はセルロ−ス含有繊維材料の染色法
DE3512630A1 (de) 1985-04-06 1986-10-23 Hoechst Ag, 6230 Frankfurt Verfahren zum faerben oder bedrucken von cellulosefasern oder cellulosemischfasern
US5041443A (en) 1989-02-21 1991-08-20 Dainippon Pharmaceutical Co., Ltd. Medicament for treating cerebral insufficiency diseases, novel 2-(1-piperazinyl)-4-phenylcycloalkanopyrimidine derivatives, and process for the production thereof
US5021421A (en) 1989-03-03 1991-06-04 Dainippon Pharmaceutical Co., Ltd. 2-(1-Piperazinyl)-4-phenylcycloalkanopyridine derivatives, processes for the production thereof, and pharmaceutical composition containing the same
JPH0499768A (ja) 1990-08-17 1992-03-31 Dainippon Pharmaceut Co Ltd ４―（４―フェニルピリジン―２―イル）ピペラジン―１―オキシド誘導体
JPH05140126A (ja) 1991-11-26 1993-06-08 Hokko Chem Ind Co Ltd トリアゾール誘導体および除草剤
EP0629622B1 (en) 1992-02-28 1998-11-11 Zenyaku Kogyo Kabushikikaisha S-triazine derivative and remedy for estrogen-dependent diseases containing the same as active ingredient
IL115420A0 (en) 1994-09-26 1995-12-31 Zeneca Ltd Aminoheterocyclic derivatives
IL117580A0 (en) 1995-03-29 1996-07-23 Merck & Co Inc Inhibitors of farnesyl-protein transferase and pharmaceutical compositions containing them
FR2735127B1 (fr) 1995-06-09 1997-08-22 Pf Medicament Nouvelles piperazines heteroaromatiques utiles comme medicaments.
ES2100129B1 (es) 1995-10-11 1998-02-16 Medichem Sa Nuevos compuestos aminopiridinicos policiclicos inhibidores de acetilcolinesterasa, procedimiento para su preparacion y su utilizacion.
EP0880501A1 (en) 1996-02-02 1998-12-02 Zeneca Limited Heterocyclic compounds useful as pharmaceutical agents
GB9602166D0 (en) 1996-02-02 1996-04-03 Zeneca Ltd Aminoheterocyclic derivatives
US5807876A (en) 1996-04-23 1998-09-15 Vertex Pharmaceuticals Incorporated Inhibitors of IMPDH enzyme
JPH09291034A (ja) 1996-02-27 1997-11-11 Yoshitomi Pharmaceut Ind Ltd 縮合ピリジン化合物およびその医薬としての用途
US6262113B1 (en) 1996-03-20 2001-07-17 Smithkline Beecham Corporation IL-8 receptor antagonists
BR9709105A (pt) 1996-05-20 1999-08-03 Darwin Discovery Ltd Sulfonamidas de quinolina como inibidoras de tnf e como inobidoras de pde-iv
US5984882A (en) 1996-08-19 1999-11-16 Angiosonics Inc. Methods for prevention and treatment of cancer and other proliferative diseases with ultrasonic energy
CA2271744A1 (en) 1996-11-14 1998-05-22 Isao Hashiba Cyanoethylmelamine derivatives and process for producing the same
US6399358B1 (en) 1997-03-31 2002-06-04 Thomas Jefferson University Human gene encoding human chondroitin 6-sulfotransferase
JPH11158073A (ja) 1997-09-26 1999-06-15 Takeda Chem Ind Ltd アデノシンａ３拮抗剤
CA2315715C (en) 1997-12-22 2010-06-22 Bayer Corporation Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas
US7517880B2 (en) 1997-12-22 2009-04-14 Bayer Pharmaceuticals Corporation Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas
WO2000002864A1 (en) 1998-07-10 2000-01-20 Martens Juergen Precusors for pna-monomers
PT2316475T (pt) 1998-08-06 2017-12-21 Univ Duke Uricase tetramérica isolada
US6783965B1 (en) 2000-02-10 2004-08-31 Mountain View Pharmaceuticals, Inc. Aggregate-free urate oxidase for preparation of non-immunogenic polymer conjugates
UY25842A1 (es) 1998-12-16 2001-04-30 Smithkline Beecham Corp Antagonistas de receptores de il-8
AU5379900A (en) 1999-06-07 2000-12-28 Shire Biochem Inc. Thiophene integrin inhibitors
US6596772B1 (en) 1999-08-27 2003-07-22 Sugen, Inc. Phosphate mimics and methods of treatment using phosphatase inhibitors
CA2385589A1 (en) 1999-09-17 2001-03-22 Bing-Yan Zhu Inhibitors of factor xa
CA2385592C (en) 1999-09-17 2011-01-11 Bing-Yan Zhu Benzamides and related inhibitors of factor xa
JP2003519143A (ja) 1999-12-28 2003-06-17 ファーマコピーア，インコーポレーティッド ピリミジン及びトリアジン系キナーゼ阻害剤
ATE311366T1 (de) 2000-02-29 2005-12-15 Millennium Pharm Inc Benzamide und ähnliche inhibitoren vom faktor xa
KR20030024799A (ko) * 2000-07-20 2003-03-26 뉴로젠 코포레이션 캡사이신 수용체 리간드
JP4113323B2 (ja) 2000-08-07 2008-07-09 富士フイルム株式会社 アゾ色素及びそれを含むインクジェット記録用インク、並びにインクジェット記録方法
US6525091B2 (en) 2001-03-07 2003-02-25 Telik, Inc. Substituted diarylureas as stimulators for Fas-mediated apoptosis
JP2004534017A (ja) 2001-04-27 2004-11-11 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 Ｂａｃｅのインヒビター
CN100457726C (zh) 2001-06-11 2009-02-04 比奥维特罗姆股份公开公司 取代的磺酰胺化合物、其制备方法及其作为治疗cns疾病、肥胖和ⅱ型糖尿病的药物的应用
EP1397142A4 (en) 2001-06-19 2004-11-03 Bristol Myers Squibb Co PYRIMIDINE PHOSPHODIESTERASE (PDE) INHIBITORS 7
ATE485281T1 (de) 2001-08-17 2010-11-15 Basf Se Triazinderivate und deren verwendung als sonnenschutzmittel
JP4753336B2 (ja) 2001-09-04 2011-08-24 日本化薬株式会社 新規アリル化合物及びその製法
US6878196B2 (en) 2002-01-15 2005-04-12 Fuji Photo Film Co., Ltd. Ink, ink jet recording method and azo compound
US20040067234A1 (en) 2002-07-11 2004-04-08 Paz Einat Isocitrate dehydrogenase and uses thereof
EP2256108B1 (en) 2002-07-18 2016-03-23 Janssen Pharmaceutica NV Substituted triazine kinase inhibitors
JP2004083610A (ja) 2002-08-22 2004-03-18 Fuji Photo Film Co Ltd インクセット、インクカートリッジ、記録方法、プリンター及び記録物
JP2004107220A (ja) 2002-09-13 2004-04-08 Mitsubishi Pharma Corp ＴＮＦ−α産生抑制剤
AR042052A1 (es) 2002-11-15 2005-06-08 Vertex Pharma Diaminotriazoles utiles como inhibidores de proteinquinasas
WO2004050033A2 (en) 2002-12-02 2004-06-17 Arqule, Inc. Method of treating cancers
ATE527278T1 (de) 2002-12-16 2011-10-15 Genmab As Humane monoklonale antikörper gegen interleukin 8 (il-8)
AU2004204778B2 (en) 2003-01-10 2008-05-22 Threshold Pharmaceuticals, Inc. Treatment of cancer with 2-deoxyglucose
US7358262B2 (en) 2003-01-29 2008-04-15 Whitehead Institute For Biomedical Research Identification of genotype-selective anti-tumor agents
WO2004073619A2 (en) 2003-02-14 2004-09-02 Smithkline Beecham Corporation Ccr8 antagonists
WO2004074438A2 (en) 2003-02-14 2004-09-02 Smithkline Beecham Corporation Ccr8 antagonists
DE602004027171D1 (de) 2003-04-11 2010-06-24 High Point Pharmaceuticals Llc Verbindungen mit Aktivität an der 11Beta-Hydroxasteroiddehydrogenase
WO2005013982A1 (en) * 2003-08-06 2005-02-17 Vertex Pharmaceuticals Incorporated Aminotriazole compounds useful as inhibitors of protein kinases
JP4948173B2 (ja) 2003-10-10 2012-06-06 ニツポネツクス・インコーポレーテツド 過剰増殖性疾患治療用ピリミジン誘導体
JP4099768B2 (ja) 2003-11-10 2008-06-11 富士電機デバイステクノロジー株式会社 電子写真感光体および該電子写真感光体に起因する干渉縞有無の判定方法
US20070196395A1 (en) 2003-12-12 2007-08-23 Mackerell Alexander Immunomodulatory compounds that target and inhibit the py'binding site of tyrosene kinase p56 lck sh2 domain
EP1708712A1 (en) 2003-12-24 2006-10-11 Scios, Inc. Treatment of malignant gliomas with tgf-beta inhibitors
JP2005264016A (ja) 2004-03-19 2005-09-29 Fuji Photo Film Co Ltd インクジェット記録用インク、インクセット及びインクジェット記録方法
US7335770B2 (en) 2004-03-24 2008-02-26 Reddy U5 Therapeutics, Inc. Triazine compounds and their analogs, compositions, and methods
GB0412526D0 (en) 2004-06-05 2004-07-14 Leuven K U Res & Dev Type 2 diabetes
TW200626155A (en) 2004-09-20 2006-08-01 Xenon Pharmaceuticals Inc Heterocyclic derivatives and their use as therapeutic agents
EP1805142A4 (en) 2004-09-23 2009-06-10 Reddy Us Therapeutics Inc PYRIDINE-BASED COMPOUNDS, PROCESS FOR THEIR PREPARATION AND COMPOSITIONS CONTAINING SAME
WO2006038594A1 (ja) 2004-10-04 2006-04-13 Ono Pharmaceutical Co., Ltd. Ｎ型カルシウムチャネル阻害薬
US20100160324A1 (en) 2004-12-30 2010-06-24 Astex Therapeutics Limited Pyrazole derivatives as that modulate the activity of cdk, gsk and aurora kinases
EP1924573A1 (en) 2005-01-25 2008-05-28 AstraZeneca AB B-raf inhibitors
HU229626B1 (hu) 2005-04-11 2014-03-28 Savient Pharmaceuticals Urát oxidáz változat és alkalmazása
JP5904569B2 (ja) 2005-06-08 2016-04-13 ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 癌治療を受けている患者の同定、判定および処置のための方法
GB0513702D0 (en) 2005-07-04 2005-08-10 Sterix Ltd Compound
UA100358C2 (xx) 2005-08-26 2012-12-25 Мерк Сероно Са Похідні піразину та їх застосування
US8133900B2 (en) 2005-11-01 2012-03-13 Targegen, Inc. Use of bi-aryl meta-pyrimidine inhibitors of kinases
TW200815426A (en) * 2006-06-28 2008-04-01 Astrazeneca Ab New pyridine analogues II 333
US20100297673A1 (en) 2006-09-20 2010-11-25 Reddy Us Therapeutics Methods and compositions for upregulation of peroxiredoxin activity
US7906555B2 (en) 2006-10-26 2011-03-15 Arizona Board Of Regents On Behalf Of The University Of Arizona Aquaporin modulators and methods of using them for the treatment of edema and fluid imbalance
HUP0600810A3 (en) 2006-10-27 2008-09-29 Richter Gedeon Nyrt New sulfonamide derivatives as bradykinin antagonists, process and intermediates for their preparation and pharmaceutical compositions containing them
PE20081229A1 (es) * 2006-12-01 2008-08-28 Merck & Co Inc Antagonistas de receptor de orexina de diazepam sustituido
CN101679371A (zh) 2006-12-04 2010-03-24 艾美罗股份公司 作为腺苷受体拮抗剂的取代的嘧啶
RU2452484C2 (ru) 2006-12-08 2012-06-10 Милленниум Фармасьютикалз, Инк. Стандартные лекарственные препараты и способы лечения тромбоза пероральным введением ингибитора фактора ха
WO2008076883A2 (en) 2006-12-15 2008-06-26 Abraxis Bioscience, Inc. Triazine derivatives and their therapeutical applications
US8258295B2 (en) 2007-04-30 2012-09-04 Prometic Biosciences Inc. Triazine derivatives, compositions containing such derivatives, and methods of treatment of cancer and autoimmune diseases using such derivatives
US20090029992A1 (en) 2007-06-11 2009-01-29 Agoston Gregory E Substituted pyrazole compounds
US8299057B2 (en) 2007-07-20 2012-10-30 Nerviano Medical Sciences S.R.L. Substituted indazole derivatives active as kinase inhibitors
AU2008279097B2 (en) 2007-07-25 2013-05-02 Bristol-Myers Squibb Company Triazine kinase inhibitors
TW200906818A (en) 2007-07-31 2009-02-16 Astrazeneca Ab Chemical compounds
CL2008002998A1 (es) * 2007-10-10 2009-11-20 Takeda Pharmaceuticals Co Compuestos derivados de piperazina-1-carboxamida, inhibidor de faah; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento del dolor inflamatorio o neuropatico, ansiedad y depresion.
JP2011507910A (ja) 2007-12-21 2011-03-10 ユニバーシティー オブ ロチェスター 真核生物の寿命を変更するための方法
JP5277685B2 (ja) 2008-03-26 2013-08-28 富士ゼロックス株式会社 電子写真感光体、画像形成装置、プロセスカートリッジ及び画像形成方法
GB0805477D0 (en) 2008-03-26 2008-04-30 Univ Nottingham Pyrimidines triazines and their use as pharmaceutical agents
US20090281089A1 (en) 2008-04-11 2009-11-12 Genentech, Inc. Pyridyl inhibitors of hedgehog signalling
CN101575408B (zh) 2008-05-09 2013-10-30 Mca技术有限公司 用作阻燃剂和光稳定剂的聚三嗪基化合物
FR2932483A1 (fr) 2008-06-13 2009-12-18 Cytomics Systems Composes utiles pour le traitement des cancers.
TW201028381A (en) * 2008-07-14 2010-08-01 Shionogi & Co Pyridine derivative having ttk inhibition activity
US20100144722A1 (en) 2008-09-03 2010-06-10 Dr. Reddy's Laboratories Ltd. Novel heterocyclic compounds as gata modulators
CN102177251B (zh) 2008-09-03 2017-06-16 约翰·霍普金斯大学 恶性神经胶质瘤的异柠檬酸脱氢酶和其他基因的遗传改变
JP2010079130A (ja) 2008-09-29 2010-04-08 Fuji Xerox Co Ltd 電子写真感光体、プロセスカートリッジ、及び画像形成装置
EP2370417A2 (en) 2008-11-21 2011-10-05 Millennium Pharmaceuticals, Inc. Lactate salt of 4-[6-methoxy-7-(3-piperidin-1-yl-propoxy)quinazolin-4-yl]piperazine-1-carboxylic acid(4-isopropoxyphenyl)-amide and pharmaceutical compositions thereof for the treatment of cancer and other diseases or disorders
JP2010181540A (ja) 2009-02-04 2010-08-19 Fuji Xerox Co Ltd 電子写真感光体、プロセスカートリッジ、及び画像形成装置
KR101677778B1 (ko) 2009-02-06 2016-11-18 니뽄 신야쿠 가부시키가이샤 아미노피라진 유도체 및 의약
MX346801B (es) 2009-03-13 2017-03-31 Agios Pharmaceuticals Inc Métodos y composiciones para trastornos relacionados con la proliferación celular.
CA2760929C (en) 2009-05-04 2018-01-02 Agios Pharmaceuticals, Inc. Pkm2 activators for use in the treatment of cancer
WO2010130638A1 (en) 2009-05-14 2010-11-18 Evotec Ag Sulfonamide compounds, pharmaceutical compositions and uses thereof
BRPI1010881A2 (pt) 2009-06-08 2016-05-31 California Capital Equity Llc derivados de triazina e suas aplicações terapêuticas.
AU2010258974A1 (en) 2009-06-09 2012-01-12 California Capital Equity, Llc Pyridil-triazine inhibitors of hedgehog signaling
CN102573481A (zh) 2009-06-09 2012-07-11 加利福尼亚资本权益有限责任公司 脲基苯基取代的三嗪衍生物及其治疗应用
SG177434A1 (en) 2009-06-29 2012-02-28 Agios Pharmaceuticals Inc Therapeutic compounds and compositions
JP2013503846A (ja) * 2009-09-01 2013-02-04 ファイザー・インク ベンズイミダゾール誘導体
US20120189670A1 (en) 2009-09-14 2012-07-26 Kirkpatrick D Lynn Pharmaceutical compositions and formulations including inhibitors of the pleckstrin homology domain and methods for using same
JP5473851B2 (ja) 2009-09-30 2014-04-16 富士フイルム株式会社 高分子フィルム、位相差フィルム、偏光板及び液晶表示装置
US8652534B2 (en) 2009-10-14 2014-02-18 Berry Pharmaceuticals, LLC Compositions and methods for treatment of mammalian skin
WO2011050210A1 (en) 2009-10-21 2011-04-28 Agios Pharmaceuticals, Inc. Methods and compositions for cell-proliferation-related disorders
EP2947073B1 (en) 2009-10-22 2019-04-03 Fibrotech Therapeutics Pty Ltd Fused ring analogues of anti-fibrotic agents
WO2011072174A1 (en) 2009-12-09 2011-06-16 Agios Pharmaceuticals, Inc. Therapeutically active compounds for use in the treatment of cancer characterized as having an idh mutation
NZ578968A (en) 2010-02-10 2011-03-31 Allans Sheetmetal And Engineering Services Fuel feed system for a pellet fire
WO2011143160A2 (en) 2010-05-10 2011-11-17 The Johns Hopkins University Metabolic inhibitor against tumors having an idh mutation
US10064885B2 (en) 2010-07-09 2018-09-04 Massachusetts Institute Of Technology Metabolic gene, enzyme, and flux targets for cancer therapy
US20130184222A1 (en) 2010-07-16 2013-07-18 Agios Pharmaceuticals, Inc Therapeutically active compositions and their methods of use
BR112013009117A2 (pt) 2010-10-21 2016-07-19 Biomarin Pharm Inc sal tosilato de (8s,9r)-5-fluor-8-(4-fluorefenil)-9-(1-metil-1h-1,2,4-triazol-5-il)-8,9-diidro-2h-pirido[4,3,2-de]ftalazin-3(7h)-ona, método para preparar uma forma cristalina e uso do mesmo,composição farmacêutica e método para tratar um câncer ou um sintoma do mesmo.
CA2819333A1 (en) 2010-11-29 2012-06-07 Galleon Pharmaceuticals, Inc. Novel compounds as respiratory stimulants for treatment of breathing control disorders or diseases
TWI549947B (zh) 2010-12-29 2016-09-21 阿吉歐斯製藥公司 治療化合物及組成物
CA2834692A1 (en) 2011-05-03 2012-11-08 Agios Pharmaceuticals, Inc. Pyruvate kinase activators for use in therapy
TWI555737B (zh) 2011-05-24 2016-11-01 拜耳知識產權公司 含有硫醯亞胺基團之４－芳基－ｎ－苯基－１，３，５－三氮雜苯－２－胺
CN102827170A (zh) * 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
CN102827073A (zh) 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
CN103649074B (zh) 2011-07-07 2016-05-11 默克专利股份公司 用于治疗癌症的取代的氮杂环
EP2729146B1 (en) 2011-07-08 2017-03-08 Helmholtz-Zentrum für Infektionsforschung GmbH Medicament for treatment of liver cancer
CN102659765B (zh) 2011-12-31 2014-09-10 沈阳药科大学 嘧啶及三嗪类化合物的制备方法和应用
UA117451C2 (uk) 2012-01-06 2018-08-10 Аджиос Фармасьютікалз, Інк. Терапевтично активні сполуки і способи їх застосування
CA2860858A1 (en) 2012-01-19 2013-07-25 Agios Pharmaceuticals, Inc. Therapeutically active compounds and their methods of use
US9474779B2 (en) 2012-01-19 2016-10-25 Agios Pharmaceuticals, Inc. Therapeutically active compositions and their methods of use
EP2634259A1 (en) 2012-03-01 2013-09-04 Deutsches Krebsforschungszentrum Means and methods for the determination of (D)-2-hydroxyglutarate (D2HG)
EP2824099A4 (en) 2012-03-09 2015-11-11 Carna Biosciences Inc NOVEL TRIAZINE DERIVATIVE
WO2014015422A1 (en) 2012-07-27 2014-01-30 Ontario Institute For Cancer Research Cellulose-based nanoparticles for drug delivery
US9579324B2 (en) 2013-07-11 2017-02-28 Agios Pharmaceuticals, Inc Therapeutically active compounds and their methods of use
WO2015003360A2 (en) 2013-07-11 2015-01-15 Agios Pharmaceuticals, Inc. Therapeutically active compounds and their methods of use
US20150031627A1 (en) 2013-07-25 2015-01-29 Agios Pharmaceuticals, Inc Therapeutically active compounds and their methods of use

Also Published As

Publication number Publication date
US20140213580A1 (en) 2014-07-31
EP2721019A4 (en) 2014-11-19
AU2012269648A1 (en) 2014-01-16
MX2013014922A (es) 2014-02-11
US9856279B2 (en) 2018-01-02
EP2721019B1 (en) 2018-08-08
JP2014519518A (ja) 2014-08-14
CA2839675C (en) 2019-06-11
AU2012269648B2 (en) 2017-04-20
MX345928B (es) 2017-02-23
WO2012171337A1 (en) 2012-12-20
EP2721019A1 (en) 2014-04-23
CA2839675A1 (en) 2012-12-20
TW201317215A (zh) 2013-05-01
ES2694160T3 (es) 2018-12-18
US20160229876A1 (en) 2016-08-11
TWI628165B (zh) 2018-07-01
CN102827073A (zh) 2012-12-19
JP6152098B2 (ja) 2017-06-21

Similar Documents

Publication Publication Date Title
AR086977A1 (es) Derivados heterociclicos nitrogenados utiles para el tratamiento del cancer y composiciones farmaceuticas que los contienen
AR119698A2 (es) Compuesto amida n-urea sustituida derivado de aminoácido
AR110139A1 (es) COMPUESTOS MONO Y ESPIROCÍCLICOS QUE CONTIENEN CICLOBUTANO Y AZETIDINA COMO INHIBIDORES DE LA INTEGRINA aV
AR087760A1 (es) Heterociclilaminas como inhibidores de pi3k
AR086676A1 (es) Derivados de alcoholes 1-fenil-2-piridinil alquilicos como inhibidores de fosfodiesterasa
AR062677A1 (es) Derivados de biaril-sulfonamida, procesos de produccion y composiciones farmaceuticas que los comprenden
AR088029A1 (es) Compuestos de pirimidina sustituidos, composiciones farmaceuticas que los contienen y uso de los mismos para el tratamiento del dolor, accidentes cerebrovasculares, epilepsia y otras enfermedades del sistema nervioso central
AR087311A1 (es) Quinolinas sustituidas y su uso como medicamentos
ES2606197T3 (es) Moduladores pirrolidina de GPR40
AR092306A1 (es) Antibacterianos de fenicol
AR058769A1 (es) Inhibidores de peptidil-deformilasa(pdf),utiles para el tratamiento de la tuberculosis y composiciones farmaceuticas que los contienen.
AR090548A1 (es) Azaheterociclobencilaminas biciclicas como inhibidores de pi3k
AR105845A1 (es) Compuestos de heteroarilo bicíclicos fusionados como moduladores de la función irak4
AR110153A1 (es) ÁCIDOS PROPIÓNICOS 3-SUSTITUIDOS COMO INHIBIDORES DE LA INTEGRINA aV
AR092959A1 (es) Derivados de nucleosidos 2-metil sustituidos y metodos de uso de los mismos para el tratamiento de enfermedades virales
AR086546A1 (es) Derivados de 7h-purin-8(9h)-ona como inhibidores de jak
AR090041A1 (es) Aril dihidropiridinona y piperidinona como inhibidores de mgat2
AR087591A1 (es) Derivados de ciclohexil azetidina como inhibidores de jak
AR082153A1 (es) N-sulfonilbenzamidas utiles como inhibidor del canal de sodio
AR096241A1 (es) Inhibidores de acc y usos de los mismos
AR102492A1 (es) Cromanos sustituidos y métodos para su uso
AR085893A1 (es) Pirrolopirazina-amidas de piperidina espirociclica como moduladores de los canales ionicos
AR095192A1 (es) Quinolina y quinazolinamidas como modulares de canales de sodio
AR091981A1 (es) Dihidropiridona p1 como inhibidores del factor xia
AR089865A1 (es) Derivados de bencimidazol e imidazopiridinas como moduladores de canales de sodio

Legal Events

Date Code Title Description
FB Suspension of granting procedure