CN109563075B - Tlr7/8拮抗剂及其用途 - Google Patents

Tlr7/8拮抗剂及其用途 Download PDF

Info

Publication number
CN109563075B
CN109563075B CN201780049341.XA CN201780049341A CN109563075B CN 109563075 B CN109563075 B CN 109563075B CN 201780049341 A CN201780049341 A CN 201780049341A CN 109563075 B CN109563075 B CN 109563075B
Authority
CN
China
Prior art keywords
compound
methyl
piperidin
ring
quinoline
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
CN201780049341.XA
Other languages
English (en)
Chinese (zh)
Other versions
CN109563075A (zh
Inventor
B.A.舍雷尔
陈晓玲
E.克莱里
N.布鲁格
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Patent GmbH
Original Assignee
Merck Patent GmbH
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 Merck Patent GmbH filed Critical Merck Patent GmbH
Publication of CN109563075A publication Critical patent/CN109563075A/zh
Application granted granted Critical
Publication of CN109563075B publication Critical patent/CN109563075B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/14Heterocyclic 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
    • 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
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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
    • A61K31/4375Heterocyclic 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
    • 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
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545Non 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
    • 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
    • A61K31/435Heterocyclic 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
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/4709Non-condensed quinolines and containing further 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
    • A61K31/495Heterocyclic 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
    • A61K31/498Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • 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
    • A61K31/4995Pyrazines or piperazines forming part of bridged 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
    • A61K31/535Heterocyclic 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
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • 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
    • A61P19/00Drugs for skeletal disorders
    • A61P19/06Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • 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
    • 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
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07D215/00Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/04Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D215/00Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/12Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D215/00Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/12Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D215/14Radicals substituted by oxygen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D215/00Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/18Halogen atoms or nitro radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D241/00Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40Benzopyrazines
    • C07D241/42Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/04Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D451/00Heterocyclic 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
    • C07D451/02Heterocyclic 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 not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • 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
    • 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
    • C07D471/08Bridged systems
    • 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
    • C07D471/10Spiro-condensed systems
    • 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
    • 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
    • C07D487/08Bridged systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Epidemiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Diabetes (AREA)
  • Dermatology (AREA)
  • Urology & Nephrology (AREA)
  • Immunology (AREA)
  • Psychiatry (AREA)
  • Obesity (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Psychology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
CN201780049341.XA 2016-08-08 2017-08-07 Tlr7/8拮抗剂及其用途 Active CN109563075B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662371917P 2016-08-08 2016-08-08
US62/371917 2016-08-08
PCT/US2017/045671 WO2018031434A1 (en) 2016-08-08 2017-08-07 Tlr7/8 antagonists and uses thereof

Publications (2)

Publication Number Publication Date
CN109563075A CN109563075A (zh) 2019-04-02
CN109563075B true CN109563075B (zh) 2022-09-30

Family

ID=59656207

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201780049341.XA Active CN109563075B (zh) 2016-08-08 2017-08-07 Tlr7/8拮抗剂及其用途

Country Status (13)

Country Link
US (4) US10947214B2 (enExample)
EP (2) EP4198031A1 (enExample)
JP (1) JP7125385B2 (enExample)
KR (2) KR102635885B1 (enExample)
CN (1) CN109563075B (enExample)
AU (1) AU2017311047B2 (enExample)
DK (1) DK3497094T3 (enExample)
ES (1) ES2944573T3 (enExample)
IL (1) IL264676B (enExample)
MX (1) MX390698B (enExample)
RU (1) RU2758686C2 (enExample)
SG (1) SG11201900947RA (enExample)
WO (1) WO2018031434A1 (enExample)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SMT202400141T1 (it) 2015-12-17 2024-05-14 Merck Patent Gmbh 8-ciano-5-piperidino-chinoline come antagonisti di tlr7/8 e loro usi per trattamento di disturbi immunitari
JP7125385B2 (ja) 2016-08-08 2022-08-24 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング Tlr7/8アンタゴニストおよびそれらの使用
BR112019007450A2 (pt) 2016-10-14 2020-07-07 Precision Biosciences, Inc. meganucleases modificadas específicas para sequências de reconhecimento no genoma do vírus da hepatite b
EP3538513A1 (en) * 2016-11-11 2019-09-18 Dynavax Technologies Corporation Toll-like receptor antagonist compounds and methods of use
CA3086172A1 (en) 2017-12-19 2019-06-27 Merck Patent Gmbh Tlr7/8 antagonists and uses thereof
EP3728282B1 (en) 2017-12-20 2023-11-22 Institute of Organic Chemistry and Biochemistry ASCR, V.V.I. 2'3' cyclic dinucleotides with phosphonate bond activating the sting adaptor protein
CN111566120B (zh) 2017-12-20 2023-09-29 捷克共和国有机化学与生物化学研究所 活化sting转接蛋白的具有膦酸酯键的3’3’环状二核苷酸
JP7328977B2 (ja) 2018-02-12 2023-08-17 エフ. ホフマン-ラ ロシュ アーゲー ウイルス感染の処置および予防のための新規のスルホン化合物および誘導体
TWI818007B (zh) 2018-04-06 2023-10-11 捷克科學院有機化學與生物化學研究所 2'3'-環二核苷酸
TWI833744B (zh) 2018-04-06 2024-03-01 捷克科學院有機化學與生物化學研究所 3'3'-環二核苷酸
US11142750B2 (en) 2018-04-12 2021-10-12 Precision Biosciences, Inc. Optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome
PE20210131A1 (es) 2018-06-05 2021-01-19 Hoffmann La Roche COMPUESTOS TETRAHIDRO-1H-PIRAZINO[2,1-a]ISOINDOLILQUINOLINA PARA EL TRATAMIENTO DE ENFERMEDADES AUTOINMUNES
EP3807270B1 (en) 2018-06-12 2023-09-13 F. Hoffmann-La Roche AG Novel heteroaryl heterocyclyl compounds for the treatment of autoimmune disease
EP3826724B1 (en) * 2018-07-23 2022-10-05 F. Hoffmann-La Roche AG Novel piperazine compounds for the treatment of autoimmune disease
WO2020048583A1 (en) 2018-09-04 2020-03-12 F. Hoffmann-La Roche Ag Benzothiazole compounds for the treatment of autoimmune diseases
EP3847173B1 (en) 2018-09-06 2023-04-12 F. Hoffmann-La Roche AG Novel pyrazolopyridine compounds for the treatment of autoimmune disease
US11548884B2 (en) 2018-09-06 2023-01-10 Hoffmann-La Roche Inc. Cyclic amidine compounds for the treatment of autoimmune disease
CN113271938A (zh) * 2018-11-30 2021-08-17 林伯士拉克许米公司 Tyk2抑制剂和其用途
EP4051387B1 (en) 2019-10-31 2025-02-19 F. Hoffmann-La Roche AG Hydropyrazino[1,2-d][1,4]diazepine compounds for the treatment of autoimmune disease
CN114667286A (zh) * 2019-11-19 2022-06-24 豪夫迈·罗氏有限公司 用于治疗自身免疫性疾病的三氮杂三环类化合物
US12486273B2 (en) 2019-11-19 2025-12-02 Hoffmann-La Roche Inc. Hydro-1H-pyrrolo[1,2-a]pyrazine compounds for the treatment of autoimmune disease
WO2021099406A1 (en) 2019-11-20 2021-05-27 F. Hoffmann-La Roche Ag Spiro(isobenzofuranazetidine) compounds for the treatment of autoimmune disease
EP4069693B1 (en) * 2019-12-03 2024-03-20 F. Hoffmann-La Roche AG Hydropyrido[1,2-alpha]pyrazine compounds for the treatment of autoimmune diseases
ES3022990T3 (en) 2019-12-06 2025-05-29 Prec Biosciences Inc Optimized engineered meganucleases having specificity for a recognition sequence in the hepatitis b virus genome
CN116546984A (zh) * 2020-09-28 2023-08-04 耶鲁大学 5-ht2a受体的选择性激动剂及其使用方法
TWI861488B (zh) 2021-04-16 2024-11-11 美商基利科學股份有限公司 噻吩并吡咯化合物
KR20240056747A (ko) 2021-09-10 2024-04-30 길리애드 사이언시즈, 인코포레이티드 티에노피롤 화합물
CN115073369A (zh) * 2022-05-31 2022-09-20 汉瑞药业(荆门)有限公司 一种5-溴喹啉-8-甲醛的制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015057659A1 (en) * 2013-10-14 2015-04-23 Eisai R&D Management Co., Ltd. Selectively substituted quinoline compounds
WO2015057655A1 (en) * 2013-10-14 2015-04-23 Eisai R&D Management Co., Ltd. Selectively substituted quinoline compounds
WO2017106607A1 (en) * 2015-12-17 2017-06-22 Merck Patent Gmbh Polycyclic tlr7/8 antagonists and use thereof in the treatment of immune disorders

Family Cites Families (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE812911C (de) 1945-03-12 1951-09-06 Rhone Poulenc Sa Verfahren zur Herstellung von neuen substituierten Derivaten des Piperidins
CH578535A5 (en) 1973-05-11 1976-08-13 Ciba Geigy Ag Quinoline-3-carboxylic acid derivs - with e.g. analgesic, antinociceptive, antiinflammatory and antiallergic props
US4933447A (en) 1987-09-24 1990-06-12 Ss Pharmaceutical Co., Ltd. Quinoline derivatives
FR2798656B1 (fr) 1999-09-17 2004-12-17 Aventis Pharma Sa Derives de la quinolyl propyl piperidine, leur preparation et les compositions qui les contiennent
MXPA04004443A (es) 2001-11-14 2004-08-11 Merck Patent Gmbh Derivados de pirazol.
GB0206033D0 (en) * 2002-03-14 2002-04-24 Pfizer Ltd Compounds useful in therapy
WO2003105850A1 (en) * 2002-06-18 2003-12-24 Abbott Laboratories 2-aminoquinolines as melanin concentrating hormone receptor antagonists
PL375042A1 (en) 2002-08-12 2005-11-14 Takeda Pharmaceutical Company Limited Fused benzene derivative and use
MXPA05005111A (es) * 2002-11-12 2005-07-01 Pfizer Prod Inc Derivados de quinolina.
GB0227240D0 (en) 2002-11-21 2002-12-31 Glaxo Group Ltd Compounds
US20050124625A1 (en) 2003-10-21 2005-06-09 Salvati Mark E. Piperazine derivatives and their use as modulators of nuclear hormone receptor function
WO2005087749A1 (ja) 2004-03-15 2005-09-22 Kyowa Hakko Kogyo Co., Ltd. 2−アミノキナゾリン誘導体
US20060211752A1 (en) 2004-03-16 2006-09-21 Kohn Leonard D Use of phenylmethimazoles, methimazole derivatives, and tautomeric cyclic thiones for the treatment of autoimmune/inflammatory diseases associated with toll-like receptor overexpression
WO2005115361A2 (en) 2004-05-17 2005-12-08 Acadia Pharmaceuticals Inc. Androgen receptor modulators and method of treating disease using the same
US20070004679A1 (en) 2004-05-17 2007-01-04 Nathalie Schlienger Androgen receptor modulators and methods of treating disease using the same
WO2006009245A1 (ja) 2004-07-23 2006-01-26 Tanabe Seiyaku Co., Ltd. 含窒素縮合二環式化合物
GB0510810D0 (en) 2005-05-26 2005-06-29 Novartis Ag Organic compounds
GB0526042D0 (en) 2005-12-21 2006-02-01 Syngenta Participations Ag Chemical compounds
WO2007097289A1 (ja) 2006-02-20 2007-08-30 Takeda Pharmaceutical Company Limited 新規医薬
EP1903038A1 (de) 2006-09-07 2008-03-26 Bayer Schering Pharma Aktiengesellschaft N-(1-Hetaryl-piperidin-4-yl)-(het)arylamide als EP2-Rezeptor Modulatoren
JP2010504367A (ja) 2006-09-26 2010-02-12 グラクソ グループ リミテッド 性機能障害、認知障害、精神病性障害、不安、鬱病などを処置するための5ht1a受容体モジュレーターとしての5−{2−[4−(2−メチル−5−キノリニル)−l−ピペリジニル]エチル}キノリノン誘導体
CL2008001002A1 (es) 2007-04-11 2008-10-17 Actelion Pharmaceuticals Ltd Compuestos derivados de oxazolidinona; composicion farmaceutica que comprende a dichos compuestos; y su uso para preparar un medicamento para tratar una infeccion bacteriana.
ES2485492T3 (es) 2007-06-05 2014-08-13 Sanofi Derivados de di(hetero)arilciclohexano, su preparación, su uso y composiciones farmacéuticas que los comprenden
MX2010012104A (es) 2008-05-12 2011-04-05 Amnestix Inc Compuestos para mejorar el aprendizaje y la memoria.
JP2011526931A (ja) 2008-07-03 2011-10-20 エグゼリクシス, インコーポレイテッド Cdkモジュレーター
BRPI0918496A2 (pt) 2008-09-02 2019-09-24 Novartis Ag composto inibidor bicíclico de quinase, uso do mesmo, composição farmacêutica e método para inibir a atividade da quinase pim em uma célula
CA2745041C (en) 2008-12-01 2017-08-22 Kai Schiemann 2, 5-diamino-substituted pyrido [4, 3-d] pyrimidines as autotaxin inhibitors against cancer
BRPI1008383A2 (pt) 2009-02-11 2016-02-23 Univ California composto, composição farmacêutica, método para prevenir, inibir ou tratar uma condição, e, uso de um composto
US8415333B2 (en) 2009-02-24 2013-04-09 Respiratorious Ab Bronchodilating diazaheteroaryls
NO2453895T3 (enExample) 2009-07-16 2018-10-20
US20120214803A1 (en) 2011-02-18 2012-08-23 Vifor (International) Ag Novel Sulfonaminoquinoline Hepcidin Antagonists
JP2013075834A (ja) 2011-09-29 2013-04-25 Kowa Co Tlr9阻害活性を有するピラゾロピリミジン−7−アミン誘導体
WO2013060881A1 (en) 2011-10-27 2013-05-02 Vereniging Voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek En Patientenzorg Pyridopyrimidines and their therapeutic use
WO2014086453A1 (en) 2012-12-07 2014-06-12 Merck Patent Gmbh Azaheterobicyclic compounds
HUE040645T2 (hu) 2013-06-26 2019-03-28 Abbvie Inc BTK-inhibitor primer karboxamidok
US20170050936A1 (en) * 2013-08-23 2017-02-23 Neupharma, Inc. Certain chemical entities, compositions, and methods
CN104557913B (zh) 2013-10-28 2017-02-08 上海汇伦生命科技有限公司 吡啶并嘧啶类化合物,其制备方法和用途
WO2015088045A1 (en) 2013-12-13 2015-06-18 Takeda Pharmaceutical Company Limited Pyrrolo[3,2-c]pyridine derivatives as tlr inhibitors
US9695171B2 (en) 2013-12-17 2017-07-04 Pfizer Inc. 3,4-disubstituted-1 H-pyrrolo[2,3-b]pyridines and 4,5-disubstituted-7H-pyrrolo[2,3-c]pyridazines as LRRK2 inhibitors
CA2947526A1 (en) 2014-02-05 2015-08-13 Stereokem, Inc. (Usa) Expedient synthesis of sitagliptin
JP6377245B2 (ja) 2014-03-24 2018-08-22 グアンドン ジョンシェン ファーマシューティカル カンパニー リミテッド Smo阻害剤としてのキノリン誘導体
CN104945377A (zh) * 2014-03-24 2015-09-30 南京明德新药研发股份有限公司 作为smo抑制剂的喹啉衍生物
SI3134402T1 (sl) 2014-04-22 2020-08-31 F. Hoffmann-La Roche Ag 4-amino-imidazokinolinske spojine
GB201411236D0 (en) 2014-06-25 2014-08-06 Takeda Pharmaceutical Novel compounds
RU2719446C2 (ru) 2014-11-03 2020-04-17 Айомет Фарма Лтд Фармацевтическое соединение
UY36390A (es) * 2014-11-05 2016-06-01 Flexus Biosciences Inc Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido), sus métodos de síntesis y composiciones farmacéuticas que los contienen
MX2017006302A (es) 2014-11-13 2018-02-16 Glaxosmithkline Biologicals Sa Derivados de adenina que son utiles en el tratamiento de enfermedades alergicas u otras afecciones inflamatorias.
WO2016087593A1 (en) 2014-12-05 2016-06-09 Syngenta Participations Ag Novel fungicidal quinolinylamidines
MA41169A (fr) 2014-12-17 2017-10-24 Acraf Composés antibactériens à large spectre d'activité
WO2017004405A1 (en) 2015-07-01 2017-01-05 Northwestern University Substituted quinazoline compounds and uses thereof for modulating glucocerebrosidase activity
WO2017031427A1 (en) 2015-08-19 2017-02-23 3-V Biosciences, Inc. COMPOUNDS AND METHODS FOR INHIBITING mTOR
US20190119236A1 (en) * 2016-02-23 2019-04-25 Portola Pharmaceuticals, Inc. Compounds for binding proprotein convertase subtilisin/kexin type 9 (pcsk9)
JP7125385B2 (ja) 2016-08-08 2022-08-24 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング Tlr7/8アンタゴニストおよびそれらの使用
ES2959782T3 (es) * 2016-12-20 2024-02-28 Fmc Corp Oxadiazoles fungicidas
US11050028B2 (en) * 2017-01-24 2021-06-29 Universal Display Corporation Organic electroluminescent materials and devices
ES2965044T3 (es) 2017-07-18 2024-04-10 Merck Patent Gmbh Antagonistas de TLR7/8 y sus usos
CA3086172A1 (en) 2017-12-19 2019-06-27 Merck Patent Gmbh Tlr7/8 antagonists and uses thereof
EP3830080A1 (en) 2018-07-31 2021-06-09 Merck Patent GmbH Tlr7/8 antagonists and uses thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015057659A1 (en) * 2013-10-14 2015-04-23 Eisai R&D Management Co., Ltd. Selectively substituted quinoline compounds
WO2015057655A1 (en) * 2013-10-14 2015-04-23 Eisai R&D Management Co., Ltd. Selectively substituted quinoline compounds
WO2017106607A1 (en) * 2015-12-17 2017-06-22 Merck Patent Gmbh Polycyclic tlr7/8 antagonists and use thereof in the treatment of immune disorders

Also Published As

Publication number Publication date
DK3497094T3 (da) 2023-05-15
US20210002255A1 (en) 2021-01-07
AU2017311047A1 (en) 2019-03-21
EP4198031A1 (en) 2023-06-21
US20210002256A1 (en) 2021-01-07
US20180037570A1 (en) 2018-02-08
NZ750485A (en) 2025-03-28
EP3497094A1 (en) 2019-06-19
CN109563075A (zh) 2019-04-02
MX390698B (es) 2025-03-11
RU2019105719A (ru) 2020-09-11
CA3033240A1 (en) 2018-02-15
KR20190038616A (ko) 2019-04-08
BR112019000696A2 (pt) 2019-04-24
KR20240019867A (ko) 2024-02-14
JP2019527718A (ja) 2019-10-03
WO2018031434A1 (en) 2018-02-15
AU2017311047B2 (en) 2021-07-22
MX2019001096A (es) 2019-07-04
RU2758686C2 (ru) 2021-11-01
KR102635885B1 (ko) 2024-02-14
ES2944573T3 (es) 2023-06-22
EP3497094B1 (en) 2023-02-15
JP7125385B2 (ja) 2022-08-24
RU2019105719A3 (enExample) 2020-10-16
SG11201900947RA (en) 2019-02-27
IL264676B (en) 2022-04-01
US10947214B2 (en) 2021-03-16
US11512069B2 (en) 2022-11-29
US20240383876A1 (en) 2024-11-21

Similar Documents

Publication Publication Date Title
CN109563075B (zh) Tlr7/8拮抗剂及其用途
JP7754865B2 (ja) Tlr7/8アンタゴニストおよびそれらの使用
US10544122B2 (en) TLR7/8 antagonists and uses thereof
CA3033240C (en) Tlr7/8 antagonists and uses thereof
BR112019000696B1 (pt) Antagonistas de tlr7/8, seu uso, composição farmacêutica, e kit

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant