CN112805063B - 作为gabaa a5受体调节剂的双环衍生物 - Google Patents

作为gabaa a5受体调节剂的双环衍生物 Download PDF

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Publication number
CN112805063B
CN112805063B CN201980063431.3A CN201980063431A CN112805063B CN 112805063 B CN112805063 B CN 112805063B CN 201980063431 A CN201980063431 A CN 201980063431A CN 112805063 B CN112805063 B CN 112805063B
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methyl
fluorophenyl
methoxy
tetrahydro
triazol
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CN112805063A (zh
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G·斯扎博
G·I·图罗斯
O·埃利拉斯
B·I·卡罗尔伊
P·艾尔德尔伊
G·L·卡普斯
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Richter Gedeon Nyrt
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Richter Gedeon Nyrt
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    • 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
    • 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
    • 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
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41921,2,3-Triazoles
    • 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
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42Oxazoles
    • A61K31/422Oxazoles not condensed 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
    • A61K31/435Heterocyclic 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
    • A61K31/437Heterocyclic 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
    • 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
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • A61P25/00Drugs for disorders of the nervous system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D249/00Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/041,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D261/00Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • 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
    • C07D413/12Heterocyclic 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 linked by a chain containing hetero atoms as chain links

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
CN201980063431.3A 2018-09-28 2019-09-27 作为gabaa a5受体调节剂的双环衍生物 Active CN112805063B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
HUP1800333 2018-09-28
HU1800333A HU231223B1 (hu) 2018-09-28 2018-09-28 GABAA A5 receptor modulátor hatású biciklusos vegyületek
PCT/IB2019/058208 WO2020065597A1 (en) 2018-09-28 2019-09-27 Bicyclic derivatives as gabaa α5 receptor modulators

Publications (2)

Publication Number Publication Date
CN112805063A CN112805063A (zh) 2021-05-14
CN112805063B true CN112805063B (zh) 2024-02-23

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Country Link
US (1) US12370182B2 (https=)
EP (1) EP3856342B1 (https=)
JP (1) JP7480128B2 (https=)
KR (1) KR20210086631A (https=)
CN (1) CN112805063B (https=)
AR (1) AR116549A1 (https=)
AU (1) AU2019346147B2 (https=)
BR (1) BR112021005837A2 (https=)
CA (1) CA3113072A1 (https=)
EA (1) EA202190857A1 (https=)
HU (1) HU231223B1 (https=)
MX (1) MX2021003670A (https=)
TW (1) TWI868079B (https=)
UA (1) UA130217C2 (https=)
WO (1) WO2020065597A1 (https=)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4126858B1 (en) * 2020-03-26 2026-03-18 Richter Gedeon Nyrt. Dihydro-2-pyrrolo[3,4-c]pyridine derivatives as gabaa a5 receptor modulators
TWI901650B (zh) * 2020-03-26 2025-10-21 匈牙利商羅特格登公司 啶及吡啶并〔3,4-c〕嗒衍生物
HU231691B1 (hu) * 2021-09-29 2025-10-28 Richter Gedeon Nyrt GABAA ALFA5 receptor modulátor hatású biciklusos aminszármazékok

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101883769A (zh) * 2007-12-04 2010-11-10 弗·哈夫曼-拉罗切有限公司 异噁唑-吡嗪衍生物
CN102300863A (zh) * 2009-02-25 2011-12-28 弗·哈夫曼-拉罗切有限公司 具有乙基和乙烯基连接体的异*唑/邻-吡啶衍生物
CN103221402A (zh) * 2010-11-09 2013-07-24 霍夫曼-拉罗奇有限公司 三唑衍生物及其用于神经障碍的用途
WO2014001278A1 (en) * 2012-06-26 2014-01-03 Aniona Aps A phenyl triazole derivative and its use for modulating the gabaa receptor complex

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1237793B (it) * 1989-12-21 1993-06-17 Zambon Spa Composti attivi come inibitori dell'enzima hmg-coa reduttasi
CA2288789C (en) 1997-05-08 2009-07-21 Merck Sharp & Dohme Limited Substituted 1,2,4-triazolo[3,4-a]phthalazine derivatives as gaba alpha 5 ligands
GB9813576D0 (en) 1998-06-24 1998-08-19 Merck Sharp & Dohme Therapeutic agents
GB0017518D0 (en) 2000-07-17 2000-08-30 Merck Sharp & Dohme Therapeutic agents
JP4148672B2 (ja) * 2000-11-17 2008-09-10 武田薬品工業株式会社 イソオキサゾール誘導体
JP2003261545A (ja) * 2001-12-28 2003-09-19 Takeda Chem Ind Ltd 神経栄養因子産生・分泌促進剤
US7595395B2 (en) 2005-05-16 2009-09-29 Wisys Technology Foundation Gabaergic agents to treat memory deficits
US7790745B2 (en) 2005-10-21 2010-09-07 Bristol-Myers Squibb Company Tetrahydroisoquinoline LXR Modulators
US8106077B2 (en) 2006-05-24 2012-01-31 Eli Lilly And Company Compounds and methods for modulating FXR
WO2008157270A1 (en) 2007-06-13 2008-12-24 Smithkline Beecham Corporation Farnesoid x receptor agonists
UA100132C2 (en) 2007-12-04 2012-11-26 Ф. Хоффманн-Ля Рош Аг Isoxazolo-pyridine derivatives
US7943619B2 (en) 2007-12-04 2011-05-17 Hoffmann-La Roche Inc. Isoxazolo-pyridazine derivatives
US8222246B2 (en) 2009-04-02 2012-07-17 Hoffmann-La Roche Inc. Substituted isoxazoles
AU2010244552A1 (en) * 2009-05-05 2011-09-29 F. Hoffmann-La Roche Ag Isoxazole-pyrazole derivatives
MX2011011484A (es) 2009-05-07 2011-11-18 Hoffmann La Roche Derivados de isoxazol-piridina como moduladores del acido gamma-aminobutirico.
GB2474120B (en) * 2009-10-01 2011-12-21 Amira Pharmaceuticals Inc Compounds as Lysophosphatidic acid receptor antagonists
GB201016088D0 (en) * 2010-09-24 2010-11-10 Phase Focus Ltd Improvements in imaging
MX341471B (es) 2010-11-05 2016-08-22 Hoffmann La Roche Uso de compuestos farmaceuticos activos para el tratamiento de estados patologicos del sistema nervioso central.
EP2638035B1 (en) 2010-11-09 2014-12-17 F.Hoffmann-La Roche Ag Triazole derivatives as ligands for Gaba receptors
AU2011329233A1 (en) * 2010-11-15 2013-05-23 Abbvie Deutschland Gmbh & Co Kg NAMPT and ROCK inhibitors
EP2545964A1 (en) 2011-07-13 2013-01-16 Phenex Pharmaceuticals AG Novel FXR (NR1H4) binding and activity modulating compounds
US8604062B2 (en) 2011-10-20 2013-12-10 Hoffman-La Roche Inc. Process for the preparation of isoxazolyl-methoxy nicotinic acids
AR088989A1 (es) 2011-11-30 2014-07-23 Hoffmann La Roche Derivados biciclicos de dihidroisoquinolin-1-ona
CA2876778A1 (en) 2012-06-26 2014-01-03 Saniona Aps A phenyl triazole derivative and its use for modulating the gabaa receptor complex
CN107108610B (zh) 2014-12-30 2019-06-04 豪夫迈·罗氏有限公司 用于治疗和预防肝炎b病毒感染的新的四氢吡啶并嘧啶和四氢吡啶并吡啶化合物
WO2017133521A1 (zh) 2016-02-01 2017-08-10 山东轩竹医药科技有限公司 Fxr受体激动剂
ES2910110T3 (es) * 2016-12-08 2022-05-11 Hoffmann La Roche Nuevos derivados de isoxazolil-éter como PAM de alfa 5 GABA A

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101883769A (zh) * 2007-12-04 2010-11-10 弗·哈夫曼-拉罗切有限公司 异噁唑-吡嗪衍生物
CN102300863A (zh) * 2009-02-25 2011-12-28 弗·哈夫曼-拉罗切有限公司 具有乙基和乙烯基连接体的异*唑/邻-吡啶衍生物
CN103221402A (zh) * 2010-11-09 2013-07-24 霍夫曼-拉罗奇有限公司 三唑衍生物及其用于神经障碍的用途
WO2014001278A1 (en) * 2012-06-26 2014-01-03 Aniona Aps A phenyl triazole derivative and its use for modulating the gabaa receptor complex

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Publication number Publication date
AR116549A1 (es) 2021-05-19
EP3856342A1 (en) 2021-08-04
US12370182B2 (en) 2025-07-29
MX2021003670A (es) 2021-08-19
CN112805063A (zh) 2021-05-14
BR112021005837A2 (pt) 2021-07-27
TW202035403A (zh) 2020-10-01
EA202190857A1 (ru) 2021-06-23
JP7480128B2 (ja) 2024-05-09
WO2020065597A1 (en) 2020-04-02
AU2019346147A1 (en) 2021-05-20
UA130217C2 (uk) 2025-12-24
HUP1800333A2 (hu) 2020-04-28
KR20210086631A (ko) 2021-07-08
CA3113072A1 (en) 2020-04-02
TWI868079B (zh) 2025-01-01
AU2019346147B2 (en) 2025-01-09
JP2022502366A (ja) 2022-01-11
EP3856342B1 (en) 2025-12-10
EP3856342C0 (en) 2025-12-10
HU231223B1 (hu) 2022-01-28
US20210386718A1 (en) 2021-12-16

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