AR093512A1 - Derivados heterociclicos como moduladores de la actividad de cinasas - Google Patents

Derivados heterociclicos como moduladores de la actividad de cinasas

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Publication number
AR093512A1
AR093512A1 ARP130104220A ARP130104220A AR093512A1 AR 093512 A1 AR093512 A1 AR 093512A1 AR P130104220 A ARP130104220 A AR P130104220A AR P130104220 A ARP130104220 A AR P130104220A AR 093512 A1 AR093512 A1 AR 093512A1
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AR
Argentina
Prior art keywords
dihydropyrazinyl
atoms
independently
hal
dihydroxy
Prior art date
Application number
ARP130104220A
Other languages
English (en)
Inventor
R Huck Bayard
Chen Xiaoling
Xiao Yufang
Lan Ruoxi
Original Assignee
Merck Patent Gmbh
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Publication date
Application filed by Merck Patent Gmbh filed Critical Merck Patent Gmbh
Publication of AR093512A1 publication Critical patent/AR093512A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02Heterocyclic 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
    • C07D498/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic 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
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53831,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • A61P27/06Antiglaucoma agents or miotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D475/00Heterocyclic compounds containing pteridine ring systems
    • C07D475/06Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N2005/1092Details
    • A61N2005/1098Enhancing the effect of the particle by an injected agent or implanted device

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Rheumatology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pathology (AREA)
  • Radiology & Medical Imaging (AREA)
  • Hospice & Palliative Care (AREA)
  • Endocrinology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Psychiatry (AREA)
  • Reproductive Health (AREA)
  • Dermatology (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

La presente proporciona derivados de imidazol-piperidinilo de la fórmula (1) y su fabricación y uso para el tratamiento de enfermedades hiperproliferativas tales como el cáncer. Reivindicación 1: Compuestos de acuerdo con la fórmula (1), y sales farmacéuticamente aceptables, solvatos, solvatos de sales, tautómeros o estereoisómeros, incluyendo mezclas de los mismos en todas las proporciones, en donde: X¹ es N o CH; X² es CH₂ o NH; X³ es CH₂ o CO; X⁴ es O, CH₂ o NH; W es N o CH; R¹ es Ar o Het; R² es [C(R³)₂]ₚHet¹ o [C(R³)₂]ₚN(R³)₂; R³ es H o alquilo con 1, 2, 3 ó 4 átomos de C, que está opcionalmente sustituido; Ar es fenilo que está insustituido o mono, di o trisustituido con Hal, A, fenilo, CON(R³)₂, COOR³, NHCOA, NHSO₂A, CHO, COA, SO₂N(R³)₂, SO₂A, [C(R³)₂]ₚOR³, [C(R³)₂]ₚN(R³)₂ y/o [C(R³)₂]ₚCN; Het es furilo, tienilo, pirrolilo, imidazolilo, pirazolilo, oxazolilo, isoxazolilo, oxadiazolilo, tiazolilo, triazolilo, tetrazolilo, piridilo, pirimidilo, piridazinilo, pirazinilo, indolilo, isoindolilo, benzoimidazolilo, indazolilo o quinolilo, que está insustituido o mono, di o trisustituido con Hal, A, [C(R³)₂]ₚOR³, [C(R³)₂]ₚN(R³)₂, NO₂, CN, [C(R³)₂]ₚCOOR³, CON(R³)₂, NR³COA, NR³SO₂A, SO₂N(R³)₂, S(O)ₘA y/o O[C(R³)₂]qN(R³)₂; Het¹ es dihidropirrolilo, pirrolidinilo, azetidinilo, oxetanilo, tetrahidroimidazolilo, dihidropirazolilo, tetrahidropirazolilo, tetrahidrofuranoilo, dihidropiridilo, tetrahidropiridilo, piperidinilo, azepanilo, morfolinilo, hexahidropiridazinilo, hexahidropirimidinilo, [1,3]dioxolanilo, tetrahidropiranilo, piridilo o piperazinilo, que está insustituido o mono o disustituido con A; A es alquilo ramificado o no ramificado con 1 - 10 átomos de C, en donde uno o dos grupos CH y/o CH₂ no adyacentes pueden estar reemplazados por átomos de N, O y/o S y en donde 1 - 7 átomos de H pueden estar reemplazados por F o Cl; Hal es F, Cl, Br o I; cada m es independientemente 0, 1 ó 2; cada n es independientemente 0, 1 ó 2; cada p es independientemente 0, 1, 2, 3 ó 4; cada q es independientemente 2, 3 ó 4.
ARP130104220A 2012-11-16 2013-11-15 Derivados heterociclicos como moduladores de la actividad de cinasas AR093512A1 (es)

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US201261727298P 2012-11-16 2012-11-16

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US (3) US9580443B2 (es)
EP (1) EP2920178B1 (es)
JP (1) JP6386467B2 (es)
CN (1) CN105051043B (es)
AR (1) AR093512A1 (es)
AU (1) AU2013344552B2 (es)
CA (1) CA2890288A1 (es)
ES (1) ES2620119T3 (es)
IL (1) IL238825B (es)
WO (1) WO2014078637A1 (es)

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US20170015679A1 (en) 2017-01-19
US20180072757A1 (en) 2018-03-15
US9580443B2 (en) 2017-02-28
CN105051043A (zh) 2015-11-11
AU2013344552A1 (en) 2015-04-23
JP2016500065A (ja) 2016-01-07
AU2013344552B2 (en) 2018-03-15
US20150274750A1 (en) 2015-10-01
IL238825A0 (en) 2015-06-30
ES2620119T3 (es) 2017-06-27
US10287300B2 (en) 2019-05-14
IL238825B (en) 2019-10-31
US9850255B2 (en) 2017-12-26
JP6386467B2 (ja) 2018-09-05
CA2890288A1 (en) 2014-05-22
EP2920178A1 (en) 2015-09-23
EP2920178B1 (en) 2016-12-21
CN105051043B (zh) 2017-05-10
WO2014078637A1 (en) 2014-05-22

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