AR072092A1 - Diazacarbazoles y metodos de uso - Google Patents

Diazacarbazoles y metodos de uso

Info

Publication number
AR072092A1
AR072092A1 ARP090102095A ARP090102095A AR072092A1 AR 072092 A1 AR072092 A1 AR 072092A1 AR P090102095 A ARP090102095 A AR P090102095A AR P090102095 A ARP090102095 A AR P090102095A AR 072092 A1 AR072092 A1 AR 072092A1
Authority
AR
Argentina
Prior art keywords
alkyl
cr14r15
heterocyclyl
heteroaryl
cycloalkyl
Prior art date
Application number
ARP090102095A
Other languages
English (en)
Original Assignee
Genentech 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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=41066724&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR072092(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Genentech Inc filed Critical Genentech Inc
Publication of AR072092A1 publication Critical patent/AR072092A1/es

Links

Classifications

    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/14—Ortho-condensed 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines 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
    • A61K31/501—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
    • A61K31/505—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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61K31/54—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 sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Son de utilidad como inhibidores de quinasas, m s espec¡ficamente son de utilidad como inhibidores de la checkpoint quinasa 1 (chk1), siendo as¡ utiles como agentes terapeuticos contra el c ncer. Tambien composiciones, m s espec¡ficamente composiciones farmaceuticas que comprenden estos compuestos y sus metodos de uso para tratar diversas formas de c ncer y trastornos hiperproliferativos, as¡ como metodo de uso de los compuestos para diagnosis o tratamiento in vitro in situ e in vivo de celulas de mam¡feros o condiciones patologicas asociadas. Reivindicacion 1: Un compuesto caracterizado porque tiene la formula (1), (2) o (3) o uno de sus solvatos, hidratos o sales: X es CR2 o N; Y es CR4 o N; Z es CR8 o N; con la condicion de que no m s de uno de X, Y y Z sea N al mismo tiempo; R2 es H, halo, CN, CF3, -OCF3, OH, -NO2, alquilo C1-5, -O(alquilo C1-5, -S(alquilo C1-5) o N(R22)2; R3 es H, halo, CN, -O-R9, -N(R22)-R9, -S(O)p-R9 o R9; p es 0, 1 o 2; R4 es H, halo, CN, CF3, -OCF3, OH, -NO2, -(CR14R15)nC(=Y')OR11, -(CR14R15)nC(=Y')NR11R12, -(CR14R15)nNR11R12, -(CR14R15)nOR11, - (CR14R15)nS(O)pR11, -(CR14R15)nNR12C(=Y')R11, -(CR14R15)nNR12C(=Y')OR11, -(CR14R15)nNR12C(=Y')NR11R12, -(CR14R15)nNR12SO2R11, -(CR14R15)nOC(=Y')R11, -(CR14R15)nOC(=Y')NR11R12, -(CR14R15)nS(O)2NR11R12, alquilo, alquenilo, alquinilo, cicloalquilo, heterociclilo, arilo o heteroarilo, en donde dicho alquilo, alquenilo, alquinilo, cicloalquilo, heterociclilo, arilo y heteroarilo est n opcionalmente sustituidos con uno a cuatro grupos R13, cada n es, de modo independiente, 0-5; R5 es H, halo, CN, CF3, -OCF3, OH, -NO2, -(CR14R15)nC(=Y')OR11, -(CR14R15)nC(=Y')NR11R12, -(CR14R15)nNR12C(=Y')R11, -(CR14R15)nNR11R12, -(CR14R15)nOR11, - (CR14R15)nS(O)pR11, -(CR14R15)nNR12C(=Y')OR11, -(CR14R15)nNR12C(=Y')NR11R12, -(CR14R15)nNR12SO2R11, -(CR14R15)nOC(=Y')R11, -(CR14R15)nOC(=Y')NR11R12, -(CR14R15)nS(O)2NR11R12, alquilo, alquenilo, alquinilo, cicloalquilo, heterociclilo, arilo, heteroarilo, en donde dicho alquilo, alquenilo, alquinilo, cicloalquilo, heterociclilo, arilo y heteroarilo est n opcionalmente sustituidos con uno a cuatro grupos R13; R6 es H, CN, -CF3, -OCF3, halo, -C(=Y')OR11, -C(=Y')NR11R12, -OR11, -OC(=Y')R11, -NR11R12, NR12C(=Y')R11, -NR12C(=Y')NR11R12, -NR12S(O)qR11, -SR11, -S(O)R11, -S(O)2R11, -OC(=Y')NR11R12, -S(O)2NR11R12, alquilo, alquenilo, alquinilo, cicloalquilo, heterociclilo, arilo o heteroarilo, en donde dicho alquilo, alquenilo, alquinilo, cicloalquilo, heterociclilo, arilo y heteroarilo est n opcionalmente sustituidos con uno a cuatro grupos R13; R7 es H, OH, CN, O(alquilo C1-3) o alquilo C1-4, en donde cada dicho alquilo est  opcionalmente sustituido con uno a tres grupos seleccionados, de modo independiente, de halo, N(R22)2 u OR22; R8 es H, halo, CN, NO2, N(R22)2, OH, O(alquilo C1-3) o alquilo C1-3, en donde cada dicho alquilo est  opcionalmente sustituido con uno a tres grupos fluor; cada R9 es, de modo independiente, alquilo, alquenilo, alquinilo, cicloalquilo, heterociclilo, arilo, heteroarilo, en donde cada miembro de R9 est  sustituido, de modo independiente, con uno a tres grupos R10; cada R10 es, de modo independiente, H, CN, -CF3, -OCF3, -NO2, halo, R11, -OR11, -NR12C(=Y')R11, -NR12C(=NR12)R11, -NR12S(O)qR11, -SR11, -NR11R12, oxo, -C(=Y')OR11, -C(=Y')NR11R12, -S(O)qR11, -NR2C(=Y')OR11, -NR12C(=Y')NR11R12, -OC(=Y')R11, -OC(=Y')NR11R12 o -S(O)2NR11R12, cada q es, de modo independiente, 1 o 2; R11 y R12 son, de modo independiente, H, alquilo, cicloalquilo, heterociclilo, arilo o heteroarilo, en donde dicho alquilo, cicloalquilo, heterociclilo, arilo y heteroarilo est n opcionalmente sustituidos con uno a cuatro grupos R13, en donde dos grupos geminales R13 se toman juntos opcionalmente con el  tomo al que est n unidos para formar un anillo de 3-6 miembros con 0-2 hetero tomos adicionales seleccionados de O, S y N, donde dicho anillo est  opcionalmente sustituido con uno a cuatro grupos R18; R11 y R12 se toman opcionalmente junto con el  tomo de N unido para formar un anillo de 4-7 miembros con 0-2 hetero tomos adicionales seleccionados de O, S y N, donde dicho anillo est  opcionalmente sustituido con uno a cuatro grupos R13; cada R13 es, de modo independiente, halo, CN, CF3, -OCF3, -NO2, oxo, -(CR14R15)nC(=Y')R16, -(CR14R15)nC(=Y')OR16, -(CR14R15)nC(=Y')NR16R17, -(CR14R15)nNR16R17, -(CR14R15)nOR16, -(CR14R15)nSR16, -(CR14R15)nNR16C(=Y')R17, -(CR14R15)nNR16C(=Y')OR17, -(CR14R15)nNR17C(=Y')NR16R17, -(CR14R15)nNR17SO2R16, -(CR14R15)OC(=Y')R16, -(CR14R15)nOC(=Y')NR16R17, -(CR14R15)nS(O)R16, -(CR14R15)nS(O)2R16, - (CR14R15)nS(O)2NR16R17 o R16; R14 y R15 est n seleccionados, de modo independiente, de H, alquilo, cicloalquilo, heterociclilo, arilo o heteroarilo, en donde dicho alquilo, cicloalquilo, heterociclilo, arilo y heteroarilo est n opcionalmente sustituidos con uno a cuatro grupos R18; R16 y R17 son de modo independiente, H, alquilo, cicloalquilo, heterociclilo, arilo o heteroarilo, en donde dicho alquilo, cicloalquilo, heterociclilo, arilo y heteroarilo est n opcionalmente sustituidos con uno a cuatro grupos R18; R16 y R17 se toman junto con el  tomo de N unido para formar un anillo de 5-6 miembros con 0-2 hetero tomos adicionales seleccionados de O, S y N, donde dicho anillo est  opcionalmente sustituido con uno a cuatro grupos R18; cada R18 es, de modo independiente, H, alquilo, cicloalquilo, heterociclilo, arilo, heteroarilo, halo, CN, CF3, -OCF3, -NO2, oxo, -(CR19R20)nC(=Y')R23, -(CR19R20)nC(=Y')OR23, -(CR19R20)nC(=Y')NR23R24, -(CR19R20)nNR23R24, -(CR19R20)nOR23, -(CR19R20)n-SR23, -(CR19R20)nNR24C(=Y')R23, -(CR19R20)nNR24C(=Y')OR23, -(CR19R20)nNR22C(=Y')NR23R24, -(CR19R20)nNR24SO2R23, -(CR19R20)nOC(=Y')R23, -(CR19R20)nOC(=Y')NR23R24, -(CR19R20)nS(O)R23, -(CR19R20)nS(O)2R23 o -(CR19R20)nS(O)2NR23R24, en donde dicho alquilo, cicloalquilo, heterociclilo, arilo y heteroarilo est n opcionalmente sustituidos con uno a cuatro grupos R21; R19 y R20 son, de modo independiente, H, alquilo, cicloalquilo, heterociclilo, arilo o heteroarilo, en donde dicho alquilo, cicloalquilo, heterociclilo, arilo y heteroarilo est n opcionalmente sustituidos con uno a cuatro grupos R25; R23 y R24 son, de modo independiente, H, alquilo, cicloalquilo, heterociclilo, arilo o heteroarilo, en donde dicho alquilo, cicloalquilo, heterociclilo, arilo y heteroarilo est n opcionalmente sustituidos con uno a cuatro grupos R21; R23 y R24 se toman opcionalmente junto con el  tomo de N unido para formar un anillo de 5-6 miembros con 0-2 hetero tomos adicionales seleccionados de O, S y N, donde dicho anillo est  opcionalmente sustituido con uno a cuatro grupos R21; cada R21 es, de modo independiente, H, alquilo, cicloalquilo, heterociclilo, arilo, heteroarilo, halo, CN, CF3, -OCF3, -NO2, oxo, -C(=Y')R25, -C(=Y')OR25, -C(=Y')NR25R26, -NR25R26, -OR25, -SR25, -NR26C(=Y')R25, -NR26C(=Y')OR25, -NR22C(=Y')NR25R26, -NR26SO2R25, -OC(=Y')R25, -OC(=Y')NR25R26, -S(O)R25, -S(O)2R25, o -S(O)2NR25R26, en donde dicho alquilo, cicloalquilo, heterociclilo, arilo, y heteroarilo est n opcionalmente sustituidos con uno a cuatro grupos R25; cada R25 y R26 es, de modo independiente, H, alquilo, cicloalquilo, heterociclilo, arilo, o heteroarilo, en donde dicho, alquilo, cicloalquilo, heterociclilo, arilo o heteroarilo est  opcionalmente sustituido con uno a cuatro grupos seleccionados de halo, -CN, -OCF3, -CF3, -NO2, -alquilo C1-6, -OH, oxo, -SH, -O(alquilo C1-6), -S(alquilo C1-6), -NH2, -NH(alquilo C1-6), -N(Alquilo C1-6)2, -SO2(alquilo C1-6), -CO2H, -CO2(alquilo C1-6), -C(O)NH2, -C(O)NH(alquilo C1-6), -C(O)N(alquilo C1-6)2, -N(alquil C1-6)C(O)(alquilo C1-6), -NHC(O)(alquilo C1-6), -NHSO2(alquilo C1-6), -N(alquil C1-6)SO2(alquilo C1-6), -SO2NH2, -SO2NH(alquilo C1-6), -SO2N(alquilo C1-6)2, -OC(O)NH2, -OC(O)NH(alquilo C1-6), -OC(O)N(alquilo C1-6)2, -NHC(O)NH(alquilo C1-6, NHC(O)N(alquilo C1-6)2, -N(alquil C1-6)C(O)NH(alquilo C1-6), -N(alquil C1-6)C(O)N(alquilo C1-6)2, -NHC(O)NH(alquilo C1-6), -NHC(O)N(alquilo C1-6)2, -NHC(O)O(alquilo C1-6) y -N(alquil C1-6)C(O)O(alquilo C1-6); R25 y R26 se toman opcionalmente junto con el  tomo de N unido para formar un anillo de 5-6 miembros con 0-2 hetero tomos adicionales seleccionados de O, S y N, donde dicho anillo est  opcionalmente sustituido con uno a cuatro grupos seleccionados de halo, CN, -OCF3, CF3, -NO2, -alquilo C1-6, -OH, oxo, -SH, -O(alquilo C1-6), -S(alquilo C1-6), -NH2, -NH(alquilo C1-6), -N(alquilo C1-6)2, -SO2(alquilo C1-6), -CO2H, -CO2(alquilo C1-6), -C(O)NH2, -C(O)NH(alquilo C1-6), -C(O)N(alquilo C1-6)2, -N(alquil C1-6)C(O)(alquilo C1-6), -NHC(O)(alquilo C1-6), -NHSO2(alquilo C1-6), -N(alquil C1-6)SO2(alquilo C1-6), -SO2NH2, -SO2NH(alquilo C1-6), -SO2N(alquilo C1-6)2, -OC(O)NH2, -OC(O)NH(alquilo C1-6), -OC(O)N(alquilo C1-6)2, -NHC(O)NH(alquilo C1-6), -NHC(O)N(alquilo C1-6)2, -N(alquil C1-6)C(O)NH(alquilo C1-6), -N(alquil C1-6)C(O)N(alquilo C1-6)2, -NHC(O)NH(alquilo C1-6), -NHC(O)N(alquilo C1-6)2, -NHC(O)O(alquilo C1-6) y -N(alquil C1-6)C(O)O(alquilo C1-6); Y' es, de modo independiente, O, NR22 o S; y cada R22 es, de modo independiente, H o alquilo C1-5.
ARP090102095A 2008-06-11 2009-06-10 Diazacarbazoles y metodos de uso AR072092A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US6074608P 2008-06-11 2008-06-11
US14800109P 2009-01-28 2009-01-28

Publications (1)

Publication Number Publication Date
AR072092A1 true AR072092A1 (es) 2010-08-04

Family

ID=41066724

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP090102095A AR072092A1 (es) 2008-06-11 2009-06-10 Diazacarbazoles y metodos de uso

Country Status (21)

Country Link
US (3) US8501765B2 (es)
EP (2) EP2300475B1 (es)
JP (2) JP5599784B2 (es)
KR (1) KR101710732B1 (es)
CN (2) CN102119163A (es)
AR (1) AR072092A1 (es)
AU (1) AU2009258124C1 (es)
BR (1) BRPI0909954A2 (es)
CA (1) CA2725754C (es)
CL (1) CL2010001415A1 (es)
DK (1) DK2300475T3 (es)
ES (1) ES2529361T3 (es)
HK (1) HK1149933A1 (es)
IL (1) IL209754A0 (es)
MX (1) MX2010013627A (es)
PE (2) PE20110365A1 (es)
PH (1) PH12013502369A1 (es)
RU (2) RU2515972C2 (es)
TW (2) TW201512199A (es)
WO (1) WO2009151598A1 (es)
ZA (1) ZA201008483B (es)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ565378A (en) 2005-06-29 2011-03-31 Threshold Pharmaceuticals Inc Phosphoramidate alkylator prodrugs
CA2725754C (en) * 2008-06-11 2017-05-23 Hazel Joan Dyke Diazacarbazoles and methods of use
AR072084A1 (es) * 2008-06-12 2010-08-04 Sanofi Aventis Derivados de azacarbolinas, su preparacion y su utilizacion terapeutica como inhibidores de las quinasas pim
FR2950891B1 (fr) * 2009-10-06 2012-11-09 Sanofi Aventis Derives d'azacarbolines 9h-pyrrolo[2,3-b:5,4-c']dipyridine, leur preparation et leur utilisation therapeutique
AU2009342734A1 (en) * 2009-03-24 2011-10-13 Sanofi 9H-pyrrolo[2,3-b: 5,4-c'] dipyridine azacarboline derivatives, preparation thereof, and therapeutic use thereof
US20110183938A1 (en) * 2009-12-16 2011-07-28 Genentech, Inc. 1,7-diazacarbazoles and methods of use
EP2640386B1 (en) 2010-11-16 2017-01-18 Array Biopharma Inc. Combination of checkpoint kinase 1 inhibitors and wee 1 kinase inhibitors
CN102503959B (zh) * 2011-10-25 2015-04-08 南方医科大学 一种稠三环类化合物及其制备方法、以及含该类化合物的药物组合物及其应用
WO2013068755A1 (en) * 2011-11-09 2013-05-16 Cancer Research Technology Limited 5-(pyridin-2-yl-amino)-pyrazine-2-carbonitrile compounds and their therapeutic use
US9254299B2 (en) 2011-12-22 2016-02-09 Threshold Pharmaceuticals, Inc. Administration of hypoxia activated prodrugs in combination with Chk1 inhibitors for treating cancer
CN104662018B (zh) 2012-04-20 2017-10-24 阿迪维纳斯治疗有限公司 取代的杂双环化合物、组合物及其医疗应用
EP2671881A1 (en) 2012-06-07 2013-12-11 Syngenta Participations AG. Pesticidally active pyridyl- and pyrimidyl- substituted thiazole derivatives
CA2938626A1 (en) 2013-07-26 2015-01-29 John Rothman Compositions to improve the therapeutic benefit of bisantrene
US10071109B2 (en) 2013-11-06 2018-09-11 Molecular Templates, Inc. Predictive biomarker for hypoxia-activated prodrug therapy
CA2946538A1 (en) 2014-04-04 2015-10-08 Del Mar Pharmaceuticals Use of dianhydrogalactitol and analogs or derivatives thereof to treat non-small-cell carcinoma of the lung and ovarian cancer
CN107118207B (zh) * 2017-05-22 2020-10-02 苏州东南药业股份有限公司 一类cdk抑制剂的制备方法
SG11202010882XA (en) 2018-05-04 2020-11-27 Incyte Corp Salts of an fgfr inhibitor
US11485734B2 (en) 2018-10-02 2022-11-01 Northwestern University Beta-carbolines as positive allosteric modulators of the human serotonin receptor 2C (5-HT2C)
EP3894403A1 (en) * 2018-12-13 2021-10-20 Intervet International B.V. Process for preparing 1-[(3r,4s)-4-cyanotetrahydropyran-3-yl]-3-[(2-fluoro-6-methoxy-4-pyridyl)amino]p yrazole-4-carboxamide

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001068648A1 (en) 2000-03-15 2001-09-20 Aventis Pharma Deutschland Gmbh Substituted beta-carbolines with ikb-kinase inhibiting activity
AU3741801A (en) * 2000-03-15 2001-09-24 Aventis Pharma Gmbh Substituted beta-carbolines with ikb-kinase inhibiting activity
GB0116966D0 (en) * 2001-07-11 2001-09-05 Pharma Mar Sa Anittumoral compounds
GB0121941D0 (en) 2001-09-11 2001-10-31 Astrazeneca Ab Chemical compounds
US9248124B2 (en) * 2001-11-07 2016-02-02 Millennium Pharmaceuticals, Inc. Use of inhibitors of IκB kinase for the treatment of cancer
BRPI0407544A (pt) * 2003-02-17 2006-02-14 Pharmacia Italia Spa derivados de pirazol tetracìclicos como inibidores da cinase, processo para a sua preparação e composições farmacêuticas que os compreendem
SE0401655D0 (sv) 2004-06-24 2004-06-24 Astrazeneca Ab New compounds
WO2006131552A1 (de) * 2005-06-09 2006-12-14 Boehringer Ingelheim International Gmbh Alpha-carboline als cdk-1 inhibitoren
US8119655B2 (en) * 2005-10-07 2012-02-21 Takeda Pharmaceutical Company Limited Kinase inhibitors
AU2007313961A1 (en) 2006-10-09 2008-05-08 Takeda Pharmaceutical Company Limited Kinase inhibitors
CA2666130A1 (en) 2006-10-09 2008-04-17 Takeda San Diego, Inc. Kinase inhibitors
EP2170886A1 (en) * 2007-07-02 2010-04-07 Cancer Research Technology Limited 9h-pyrimido[4,5-b]indoles, 9h-pyrido[4',3':4,5]pyrrolo[2,3-d]pyridines, and 9h-1,3,6,9-tetraaza-fluorenes as chk1 kinase function inhibitors
US8133506B2 (en) 2008-03-12 2012-03-13 Aptalis Pharmatech, Inc. Drug delivery systems comprising weakly basic drugs and organic acids
WO2009129401A1 (en) 2008-04-16 2009-10-22 Takeda Pharmaceutical Company Limited Kinase inhibitors
CA2725754C (en) * 2008-06-11 2017-05-23 Hazel Joan Dyke Diazacarbazoles and methods of use
AR072084A1 (es) 2008-06-12 2010-08-04 Sanofi Aventis Derivados de azacarbolinas, su preparacion y su utilizacion terapeutica como inhibidores de las quinasas pim
WO2010015589A1 (en) 2008-08-05 2010-02-11 Nycomed Gmbh Benzyl-substituted tetracyclic heterocyclic compounds as pde5 inhibitors
AU2009342734A1 (en) 2009-03-24 2011-10-13 Sanofi 9H-pyrrolo[2,3-b: 5,4-c'] dipyridine azacarboline derivatives, preparation thereof, and therapeutic use thereof

Also Published As

Publication number Publication date
DK2300475T3 (en) 2014-12-08
EP2706059A1 (en) 2014-03-12
JP5599784B2 (ja) 2014-10-01
US20110118230A1 (en) 2011-05-19
US20150087630A1 (en) 2015-03-26
IL209754A0 (en) 2011-02-28
WO2009151598A8 (en) 2010-05-06
PE20110365A1 (es) 2011-07-11
ES2529361T3 (es) 2015-02-19
PE20140609A1 (es) 2014-05-22
WO2009151598A1 (en) 2009-12-17
TWI466886B (zh) 2015-01-01
PH12013502369A1 (en) 2015-09-21
MX2010013627A (es) 2010-12-21
CA2725754C (en) 2017-05-23
HK1149933A1 (en) 2011-10-21
RU2013156074A (ru) 2015-06-27
US9216980B2 (en) 2015-12-22
CN104059066A (zh) 2014-09-24
AU2009258124A1 (en) 2009-12-17
CN102119163A (zh) 2011-07-06
AU2009258124C1 (en) 2016-01-07
AU2009258124A2 (en) 2011-01-20
TW201512199A (zh) 2015-04-01
US20130261104A1 (en) 2013-10-03
EP2300475B1 (en) 2014-11-05
RU2010154105A (ru) 2012-07-20
US8501765B2 (en) 2013-08-06
BRPI0909954A2 (pt) 2015-11-03
KR20110015697A (ko) 2011-02-16
ZA201008483B (en) 2012-03-28
JP2011522889A (ja) 2011-08-04
JP2015028027A (ja) 2015-02-12
AU2009258124B2 (en) 2015-01-29
EP2300475A1 (en) 2011-03-30
TW201011023A (en) 2010-03-16
RU2515972C2 (ru) 2014-05-20
CL2010001415A1 (es) 2011-05-06
CA2725754A1 (en) 2009-12-17
KR101710732B1 (ko) 2017-02-27

Similar Documents

Publication Publication Date Title
AR072092A1 (es) Diazacarbazoles y metodos de uso
AR062468A1 (es) Compuestos de azabenzofuranil y metodos de uso
AR062469A1 (es) Compuestos de azabenzotiofeno y azabenzofurano como inhibidores de la quinasa mek, una composicion farmaceutica que los comprende y el uso de estos en el tratamiento de trastornos inflamatorios e hiperproliferativos.
AR064031A1 (es) Compuestos de azaindolilo y metodos de uso
RU2011103434A (ru) Изоиндолоны и способы их применения
AR080264A1 (es) Inhibidores ns5a de vhc
RU2011103454A (ru) Бициклические гетероциклы в качестве ингибиторов киназы мек
AR081848A1 (es) Inhibidores de la proteina ns5a del vhc
AR069803A1 (es) 5- anilinoimiazopiridinas y metodos de uso
AR072063A1 (es) Mimeticos de glucocorticoides metodos para su fabricacion, composiciones farmaceuticas y usos de los mismos
FI3442947T3 (fi) Amiinisubstituoituja aryyli- tai heteroaryyliyhdisteitä EHMT1- ja EHMT2-inhibiittoreina
AR047981A1 (es) Inhibidores de caspasa y sus usos correspondientes
AR082974A1 (es) Derivados de azabenzotiazol, composiciones farmaceuticas que los contienen, metodo para prepararlos y uso de los mismos para tratar enfermedades inflamatorias
AR067116A1 (es) Compuestos derivados de piperazina utiles como agentes herbicidas y procedimiento para combatir el crecimiento indeseado de plantas.
AR046792A1 (es) Fenilalanina-amidas sustituidas por heteroaroilo, un procedimiento para su preparacion, utilizacion de las mismas como herbicidas y productos fitosa-nitarios que los contienen como principio activo
AR063240A1 (es) Derivados de n-aril pirazol,composiciones farmaceuticas que los contienen y usos para el tratamiento de la diabetes tipo2,y enfermedades relacionadas.
AR084768A1 (es) Moduladores de la senda de complemento y usos de los mismos
AR081331A1 (es) Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos
AR069488A1 (es) Derivados quirales de 2-(bencilsulfinil)-tiazol y derivados de 2-[ (1 h-pirazol-4-ilmetil)sulfinil ] -tiazol, procedimientos para su preparacion, asi como su uso como herbicidas y reguladores del crecimiento de plantas y composiciones en base al compuesto
CO6251243A2 (es) Nuevos inhibidores macrocíclicos de la replicación del virus de hepatitis c
AR062666A1 (es) Benzotriazoles como moduladores de quinasas
AR069637A1 (es) Derivados de pirazinas
AR080263A1 (es) Inhibidores ns5a de vhc
AR071281A1 (es) Derivados de naftiridina moduladores de receptores trl, composiciones farmaceuticas que los contienen y uso de los mismos en el tratamiento de enfermedades autoinmunes, dermatologicas y respiratorias.
AR046767A1 (es) Inhibidores heterociclil amino de 11-beta-hidroxiesteroide deshidrogenasa tipo 1

Legal Events

Date Code Title Description
FB Suspension of granting procedure