EA029568B8 - Бигетероарильные соединения и их применения - Google Patents

Бигетероарильные соединения и их применения

Info

Publication number
EA029568B8
EA029568B8 EA201592060A EA201592060A EA029568B8 EA 029568 B8 EA029568 B8 EA 029568B8 EA 201592060 A EA201592060 A EA 201592060A EA 201592060 A EA201592060 A EA 201592060A EA 029568 B8 EA029568 B8 EA 029568B8
Authority
EA
Eurasian Patent Office
Prior art keywords
compounds
biheteroaryl compounds
biheteroaryl
formula
diseases
Prior art date
Application number
EA201592060A
Other languages
English (en)
Other versions
EA201592060A1 (ru
EA029568B1 (ru
Inventor
Кевин С. Чэнь
Литин Дун
Энтони Эстрада
Пол Гиббонс
Малкольм Хуэстис
Терри Келлар
Вэнь Лю
Джозеф П. Лиссикатос
Чаню Ма
Алан Оливеро
Снахель Патель
Даниэль Шор
Майкл Сиу
Original Assignee
Ф.Хоффманн-Ля Рош Аг
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 Ф.Хоффманн-Ля Рош Аг filed Critical Ф.Хоффманн-Ля Рош Аг
Publication of EA201592060A1 publication Critical patent/EA201592060A1/ru
Publication of EA029568B1 publication Critical patent/EA029568B1/ru
Publication of EA029568B8 publication Critical patent/EA029568B8/ru

Links

Classifications

    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/535—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
    • A61K31/535—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
    • A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged 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
    • A61K31/55—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
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
    • 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—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
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/14—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof
    • 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
    • C07D471/08—Bridged systems
    • 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
    • C07D471/18—Bridged 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
    • C07D487/08—Bridged 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
    • C07D487/12—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 three hetero rings
    • C07D487/14—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
    • C07D487/12—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 three hetero rings
    • C07D487/18—Bridged systems
    • 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
    • C07D491/08—Bridged systems
    • 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
    • C07D495/08—Bridged 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Abstract

В изобретении предложены соединения формулы I-I, их воплощения и соли для лечения заболеваний (например, нейродегенеративных заболеваний). Все переменные R, R, R, X, X, A и Cy в формуле I-I имеют значение, определенное в данном документе.
EA201592060A 2013-05-01 2014-04-30 Бигетероарильные соединения и их применения EA029568B8 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361817966P 2013-05-01 2013-05-01
PCT/CN2014/076654 WO2014177060A1 (en) 2013-05-01 2014-04-30 Biheteroaryl compounds and uses thereof

Publications (3)

Publication Number Publication Date
EA201592060A1 EA201592060A1 (ru) 2016-02-29
EA029568B1 EA029568B1 (ru) 2018-04-30
EA029568B8 true EA029568B8 (ru) 2018-08-31

Family

ID=51841525

Family Applications (3)

Application Number Title Priority Date Filing Date
EA201991064A EA038235B1 (ru) 2013-05-01 2014-04-30 Бигетероарильные соединения и их применения
EA201592060A EA029568B8 (ru) 2013-05-01 2014-04-30 Бигетероарильные соединения и их применения
EA201792471A EA033084B1 (ru) 2013-05-01 2014-04-30 Бигетероарильные соединения и их применения

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EA201991064A EA038235B1 (ru) 2013-05-01 2014-04-30 Бигетероарильные соединения и их применения

Family Applications After (1)

Application Number Title Priority Date Filing Date
EA201792471A EA033084B1 (ru) 2013-05-01 2014-04-30 Бигетероарильные соединения и их применения

Country Status (23)

Country Link
US (8) US9266862B2 (ru)
EP (1) EP2991978A4 (ru)
JP (4) JP6229042B2 (ru)
KR (2) KR101836431B1 (ru)
CN (2) CN105431420B (ru)
AR (1) AR096151A1 (ru)
AU (2) AU2014261894C1 (ru)
BR (1) BR112015027055B1 (ru)
CA (1) CA2911051C (ru)
CL (1) CL2015003147A1 (ru)
CR (2) CR20200177A (ru)
EA (3) EA038235B1 (ru)
HK (1) HK1219276A1 (ru)
IL (2) IL296526A (ru)
MA (3) MA38624A1 (ru)
MX (1) MX2015015130A (ru)
MY (1) MY182082A (ru)
PE (2) PE20161063A1 (ru)
PH (1) PH12015502410A1 (ru)
SG (2) SG11201509027WA (ru)
TW (3) TW201800403A (ru)
UA (1) UA121016C2 (ru)
WO (1) WO2014177060A1 (ru)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2870049C (en) * 2012-05-03 2020-12-29 Charles Baker-Glenn Pyrazole aminopyrimidine derivatives as lrrk2 modulators
BR112015016395A2 (pt) * 2013-01-18 2017-07-11 Hoffmann La Roche pirazóis 3-substituídos e uso como inibidores de dlk
IL296526A (en) * 2013-05-01 2022-11-01 Hoffmann La Roche Biheteroaryl compounds and their uses
RU2015147601A (ru) * 2013-05-01 2017-06-05 Ф. Хоффманн-Ля Рош Аг С-связанные гетероциклоалкилзамещенные пиримидины и их применения
MX2016008110A (es) * 2013-12-20 2016-08-19 Hoffmann La Roche Derivados de pirazol como inhibidores de la cinasa de cremallera de leucina dual (dlk) y usos de los mismos.
CN104926716A (zh) * 2015-06-10 2015-09-23 哈尔滨工业大学 吡啶衍生物2,6-二[(6-甲氧基吡啶-2-基)甲基]吡啶及其合成方法
CA3035195A1 (en) * 2016-08-29 2018-03-08 Michael J. Soth Inhibitors of dual leucine zipper (dlk) kinase for the treatment of disease
AU2017371084B2 (en) 2016-12-08 2022-04-28 Board Of Regents, The University Of Texas System Bicyclo[1.1.1]pentane inhibitors of dual leucine zipper (DLK) kinase for the treatment of disease
EP3652178B1 (en) 2017-07-14 2024-01-24 F. Hoffmann-La Roche AG Bicyclic ketone compounds and methods of use thereof
RU2020114670A (ru) 2017-10-11 2021-11-12 Ф. Хоффманн-Ля Рош Аг Бициклические соединения для применения в качестве ингибиторов rip1 киназы
US11180480B2 (en) * 2017-10-17 2021-11-23 Sensorion Synthesis of 4-aminopyrimidine compounds
CA3078688A1 (en) 2017-10-31 2019-05-09 F. Hoffmann-La Roche Ag Bicyclic sulfones and sulfoxides and methods of use thereof
CN112074519A (zh) 2018-04-20 2020-12-11 豪夫迈·罗氏有限公司 作为rip1激酶抑制剂用于治疗e.g.肠易激综合征（ibs）的n-[4-氧代-2,3-二氢-1,5-苯并氧氮杂-3-基]-5,6-二氢-4h-吡咯并[1,2-b]吡唑-2-甲酰胺衍生物和有关化合物
AR119673A1 (es) 2019-01-11 2022-01-05 Hoffmann La Roche Compuestos bicíclicos de cetona y métodos para utilizarlos
CA3128416A1 (en) * 2019-01-31 2020-08-06 The National Institutes of Pharmaceutical R&D Co., Ltd. Aromatic ring or heteroaromatic ring compounds, preparation method therefor and medical use thereof
US11560366B2 (en) 2019-10-21 2023-01-24 Board Of Regents, The University Of Texas System Bicyclo[1.1.1]pentane inhibitors of dual leucine zipper (DLK) kinase for the treatment of disease
MX2023003759A (es) * 2020-10-02 2023-04-24 Genentech Inc Proceso para la preparacion de compuestos de biheteroarilo y formas cristalinas de estos.
AU2022340743A1 (en) * 2021-09-01 2024-03-14 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Mixed lineage kinase inhibitors and methods of use
WO2023067550A1 (en) * 2021-10-20 2023-04-27 Yousef Najajreh Allosteric inhibitor compounds for overcoming cancer resistance

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US4485045A (en) 1981-07-06 1984-11-27 Research Corporation Synthetic phosphatidyl cholines useful in forming liposomes
EP0102324A3 (de) 1982-07-29 1984-11-07 Ciba-Geigy Ag Lipide und Tenside in wässriger Phase
US4544545A (en) 1983-06-20 1985-10-01 Trustees University Of Massachusetts Liposomes containing modified cholesterol for organ targeting
HUT35524A (en) 1983-08-02 1985-07-29 Hoechst Ag Process for preparing pharmaceutical compositions containing regulatory /regulative/ peptides providing for the retarded release of the active substance
US5004697A (en) 1987-08-17 1991-04-02 Univ. Of Ca Cationized antibodies for delivery through the blood-brain barrier
US5112596A (en) 1990-04-23 1992-05-12 Alkermes, Inc. Method for increasing blood-brain barrier permeability by administering a bradykinin agonist of blood-brain barrier permeability
US5268164A (en) 1990-04-23 1993-12-07 Alkermes, Inc. Increasing blood-brain barrier permeability with permeabilizer peptides
ATE191853T1 (de) 1992-07-27 2000-05-15 Us Health Zielgerichte liposome zur blut-hirne schranke
US6514221B2 (en) 2000-07-27 2003-02-04 Brigham And Women's Hospital, Inc. Blood-brain barrier opening
US20020065259A1 (en) 2000-08-30 2002-05-30 Schatzberg Alan F. Glucocorticoid blocking agents for increasing blood-brain barrier permeability
US7034036B2 (en) 2000-10-30 2006-04-25 Pain Therapeutics, Inc. Inhibitors of ABC drug transporters at the blood-brain barrier
DE10121982B4 (de) 2001-05-05 2008-01-24 Lts Lohmann Therapie-Systeme Ag Nanopartikel aus Protein mit gekoppeltem Apolipoprotein E zur Überwindung der Blut-Hirn-Schranke und Verfahren zu ihrer Herstellung
EP1554572B1 (en) 2001-07-25 2009-10-14 Raptor Pharmaceutical Inc. Compositions and methods for modulating blood-brain barrier transport
US20030162695A1 (en) 2002-02-27 2003-08-28 Schatzberg Alan F. Glucocorticoid blocking agents for increasing blood-brain barrier permeability
MXPA05001808A (es) 2002-09-30 2005-08-16 Bayer Pharmaceuticals Corp Derivados de azol-pirimidina condensados.
WO2004050062A2 (en) 2002-12-03 2004-06-17 Blanchette Rockefeller Neurosciences Institute Artificial low-density lipoprotein carriers for transport of substances across the blood-brain barrier
WO2005025511A2 (en) 2003-09-10 2005-03-24 Cedars-Sinai Medical Center Potassium channel mediated delivery of agents through the blood-brain barrier
GB0508471D0 (en) 2005-04-26 2005-06-01 Celltech R&D Ltd Therapeutic agents
JO2660B1 (en) * 2006-01-20 2012-06-17 نوفارتيس ايه جي Pi-3 inhibitors and methods of use
WO2008064244A2 (en) 2006-11-20 2008-05-29 The Trustees Of Columbia University In The City Of New York Phosphoinositide modulation for the treatment of neurodegenerative diseases
WO2008098058A1 (en) * 2007-02-06 2008-08-14 Novartis Ag Pi 3-kinase inhibitors and methods of their use
EP2178861B1 (en) 2007-07-19 2014-08-20 Merck Sharp & Dohme Corp. Heterocyclic amide compounds as protein kinase inhibitors
WO2009066084A1 (en) * 2007-11-21 2009-05-28 F. Hoffmann-La Roche Ag 2 -morpholinopyrimidines and their use as pi3 kinase inhibitors
US20100056609A1 (en) 2008-08-26 2010-03-04 Washington University Methods and compositions for inhibition of axonal degeneration by modulation of the dlk/jnk pathway
CN102202668A (zh) * 2008-10-31 2011-09-28 诺瓦提斯公司 磷脂酰肌醇-3-激酶(PI3K)抑制剂和mTOR抑制剂的组合产品
GB2465405A (en) 2008-11-10 2010-05-19 Univ Basel Triazine, pyrimidine and pyridine analogues and their use in therapy
SG179085A1 (en) * 2009-09-09 2012-04-27 Avila Therapeutics Inc Pi3 kinase inhibitors and uses thereof
CN104043126A (zh) 2009-10-22 2014-09-17 霍夫曼-拉罗奇有限公司 轴突变性的调节
GB201004200D0 (en) 2010-03-15 2010-04-28 Univ Basel Spirocyclic compounds and their use as therapeutic agents and diagnostic probes
CN103153994B (zh) 2010-05-24 2016-02-10 罗切斯特大学 双环杂芳基激酶抑制剂及使用方法
EP2683243A4 (en) * 2011-03-09 2014-12-03 Celgene Avilomics Res Inc PI3 KINASE INHIBITORS AND USES THEREOF
IL296526A (en) 2013-05-01 2022-11-01 Hoffmann La Roche Biheteroaryl compounds and their uses
CN103483345B (zh) 2013-09-25 2016-07-06 中山大学 Pi3k激酶抑制剂、包含其的药物组合物及其应用
JP5920747B1 (ja) 2015-04-07 2016-05-18 エイピーエス．エスエイ アプリケーションプログラムおよびカード

Also Published As

Publication number Publication date
CR20150589A (es) 2015-12-07
AU2014261894B2 (en) 2018-10-18
US20160052940A1 (en) 2016-02-25
PH12015502410A1 (en) 2016-02-22
AU2019200249A1 (en) 2019-01-31
NZ750661A (en) 2020-11-27
US20200171029A1 (en) 2020-06-04
MA38624A1 (fr) 2017-02-28
CA2911051A1 (en) 2014-11-06
EA201592060A1 (ru) 2016-02-29
CN110003178A (zh) 2019-07-12
TWI710558B (zh) 2020-11-21
JP2018035187A (ja) 2018-03-08
UA121016C2 (uk) 2020-03-25
MA42164A1 (fr) 2019-01-31
JP2016518383A (ja) 2016-06-23
US10028954B2 (en) 2018-07-24
CN110003178B (zh) 2022-02-25
CA2911051C (en) 2021-08-17
BR112015027055B1 (pt) 2023-09-26
TWI622587B (zh) 2018-05-01
AU2014261894C1 (en) 2019-07-11
SG10201707002VA (en) 2017-10-30
US20140328805A1 (en) 2014-11-06
IL242164B (en) 2021-04-29
US20160158234A1 (en) 2016-06-09
JP6229042B2 (ja) 2017-11-08
CN105431420A (zh) 2016-03-23
US20170239246A9 (en) 2017-08-24
TW201506018A (zh) 2015-02-16
EP2991978A1 (en) 2016-03-09
BR112015027055A2 (pt) 2017-07-25
US9266862B2 (en) 2016-02-23
KR20160003241A (ko) 2016-01-08
EA029568B1 (ru) 2018-04-30
KR102002265B1 (ko) 2019-07-19
CN105431420B (zh) 2019-08-13
KR20180026806A (ko) 2018-03-13
JP6655052B2 (ja) 2020-02-26
TW201841907A (zh) 2018-12-01
US11129832B2 (en) 2021-09-28
KR101836431B1 (ko) 2018-03-09
WO2014177060A1 (en) 2014-11-06
PE20200447A1 (es) 2020-02-28
JP2020079264A (ja) 2020-05-28
EA038235B1 (ru) 2021-07-28
HK1219276A1 (zh) 2017-03-31
US10010549B2 (en) 2018-07-03
EP2991978A4 (en) 2016-09-14
MY182082A (en) 2021-01-18
US20180117044A1 (en) 2018-05-03
USRE47848E1 (en) 2020-02-11
IL296526A (en) 2022-11-01
NZ712934A (en) 2020-10-30
SG11201509027WA (en) 2015-12-30
US20200188397A1 (en) 2020-06-18
EA201792471A1 (ru) 2018-04-30
MA48577A1 (fr) 2021-03-31
US20180133219A1 (en) 2018-05-17
CL2015003147A1 (es) 2016-06-17
CR20200177A (es) 2020-06-28
PE20161063A1 (es) 2016-10-22
MX2015015130A (es) 2016-02-18
AR096151A1 (es) 2015-12-09
BR112015027055A8 (pt) 2020-01-14
TW201800403A (zh) 2018-01-01
JP2023011775A (ja) 2023-01-24
AU2019200249B2 (en) 2020-10-15
EA201991064A1 (ru) 2020-02-28
EA033084B1 (ru) 2019-08-30
AU2014261894A1 (en) 2015-10-29
MA42164B1 (fr) 2019-12-31

Similar Documents

Publication Publication Date Title
PH12015502410A1 (en) Biheteroaryl compounds and uses thereof
PH12014502398A1 (en) Pesticidal compositions and processes related thereto
UA116648C2 (uk) Фумарати як проліки та їх застосування при лікуванні різних захворювань
PH12015501393A1 (en) Pesticidal compositions and processes related thereto
TR201813877T4 (tr) Spi̇nal müsküler atrofi̇ni̇n tedavi̇ edi̇lmesi̇ne yöneli̇k bi̇leşi̇kler.
MX2015002040A (es) Baricitinib deuterado.
TN2014000138A1 (en) Substituted benzylindazoles for use as bub1 kinase inhibitors in the treatment of hyperproliferative diseases.
GEP20186933B (en) Substituted dihydroisoquinoline compounds
MX2015001720A (es) Hetero-azepinonas sustituidas.
MX2016006432A (es) Tetrahidro-benzodiazepinonas.
IN2015DN00598A (ru)
NZ710444A (en) Compositions and methods for treating neurodegenerative diseases and cardiomyopathy
EA201400178A1 (ru) Лечение рака молочной железы
PH12017501071A1 (en) Dihydropyrimidin-2-one compounds and medical use thereof
MX2015008829A (es) Momelotinib deuterado.
MX2015016332A (es) Inhibidores de alk biciclicos fusionados.
SG10201900954SA (en) Heterocycles as Modulators of Kinase Activity
PH12016501183A1 (en) Novel compound for treatment of severe hypoglycemia
GEP201706636B (en) Galactagogue compositions based on phosphatidylserine
PH12016501184A1 (en) Novel compound for treatment of severe hypoglycemia
PH12016501182A1 (en) Novel compound for treatment of severe hypoglycemia
EP2994156A4 (en) Compounds, compositions and methods for the treatment of diseases through inhibiting tgf- activity
MX2015012610A (es) Pacritinib deuterizado.
EA201401045A1 (ru) Соединения для лечения заболеваний, связанных с ишемией-реперфузией
IN2014KN01772A (ru)

Legal Events

Date Code Title Description
MM4A Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s)

Designated state(s): AM AZ BY KZ KG TJ TM