PE20221517A1 - Derivado de triazolopiridazina, metodo de preparacion del mismo, composicion farmaceutica del mismo y uso del mismo - Google Patents

Derivado de triazolopiridazina, metodo de preparacion del mismo, composicion farmaceutica del mismo y uso del mismo

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Publication number
PE20221517A1
PE20221517A1 PE2022001105A PE2022001105A PE20221517A1 PE 20221517 A1 PE20221517 A1 PE 20221517A1 PE 2022001105 A PE2022001105 A PE 2022001105A PE 2022001105 A PE2022001105 A PE 2022001105A PE 20221517 A1 PE20221517 A1 PE 20221517A1
Authority
PE
Peru
Prior art keywords
same
triazole
pharmaceutical composition
methoxy
preparation
Prior art date
Application number
PE2022001105A
Other languages
English (en)
Inventor
Yun Jin
Fei Wang
Jinhua Wu
Nanyang Chen
Yong Sun
Shuai Li
Original Assignee
Shanghai Simr Biotechnology Co Ltd
Shanghai Simrd Biotechnology Co Ltd
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 Shanghai Simr Biotechnology Co Ltd, Shanghai Simrd Biotechnology Co Ltd filed Critical Shanghai Simr Biotechnology Co Ltd
Publication of PE20221517A1 publication Critical patent/PE20221517A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61K31/50Pyridazines; Hydrogenated pyridazines
    • A61K31/5025Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic 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
    • A61K31/435Heterocyclic 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
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53831,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K31/54Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541Non-condensed thiazines containing further heterocyclic rings
    • 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
    • A61P21/00Drugs for disorders of the muscular or neuromuscular 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
    • 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
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • 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
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D519/00Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Landscapes

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

Abstract

SE REFIERE A COMPUESTOS DERIVADOS DE TRIAZOLOPIRIDAZINA DE FORMULA (I) DONDE R1, R2 Y Z SON TAL COMO SE DESCRIBEN EN EL PRESENTE DOCUMENTO. SON COMPUESTOS PREFERIDOS: 3-(7-METOXI-6-((1-METIL-1H-1,2,4-TRIAZOL-5-IL)METOXI)-[1,2,4]TRIAZOLO[4,3-B]PIRIDAZIN-3-IL)-5-METILISOXAZOL; 6-(((7-METOXI-3-(5-METILISOXAZOL-3-IL)-[1,2,4]TRIAZOLO[4,3-B]PIRIDAZIN-6-IL)OXI)METIL)-N-(2,2,2-TRIFLUOROETIL)NICOTINAMIDA; 3-(7-METOXI-6-(PIRIDIN-2-ILMETOXI)-[1,2,4]TRIAZOLO[4,3-B]PIRIDAZIN-3-IL)-5-(METOXIMETIL)ISOXAZOL; ENTRE OTROS. TAMBIEN SE REFIERE A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS SON AGONISTAS INVERSOS DEL RECEPTOR ALFA 5-GABA A SIENDO UTILES EN EL TRATAMIENTO DE LA ENFERMEDAD DE ALZHEIMER, SINDROME DE DOWN, ESCLEROSIS LATERAL AMIOTROFICA.
PE2022001105A 2019-12-16 2020-12-16 Derivado de triazolopiridazina, metodo de preparacion del mismo, composicion farmaceutica del mismo y uso del mismo PE20221517A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201911296884.9A CN112979655A (zh) 2019-12-16 2019-12-16 ***并哒嗪类衍生物、其制备方法、药物组合物和用途
PCT/CN2020/136998 WO2021121294A1 (zh) 2019-12-16 2020-12-16 ***并哒嗪类衍生物、其制备方法、药物组合物和用途

Publications (1)

Publication Number Publication Date
PE20221517A1 true PE20221517A1 (es) 2022-10-04

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PE2022001105A PE20221517A1 (es) 2019-12-16 2020-12-16 Derivado de triazolopiridazina, metodo de preparacion del mismo, composicion farmaceutica del mismo y uso del mismo

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US (1) US20230136194A1 (es)
EP (1) EP4079734A4 (es)
JP (1) JP7417742B2 (es)
KR (1) KR20220140710A (es)
CN (2) CN112979655A (es)
AU (1) AU2020410470B2 (es)
BR (1) BR112022011946A2 (es)
CA (1) CA3161739A1 (es)
CO (1) CO2022009489A2 (es)
IL (1) IL293959A (es)
MX (1) MX2022007426A (es)
PE (1) PE20221517A1 (es)
WO (1) WO2021121294A1 (es)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
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CN117069725A (zh) * 2022-05-10 2023-11-17 上海赛默罗生物科技有限公司 咪唑并哒嗪取代苯环类衍生物、制备方法、药物组合物及用途
CN114591352B (zh) * 2022-05-11 2022-09-09 上海赛默罗生物科技有限公司 一种***并哒嗪类化合物及其应用
CN114773352B (zh) * 2022-06-20 2023-03-17 上海赛默罗生物科技有限公司 制备取代的烟酰胺的方法
CN116008443B (zh) * 2023-03-28 2023-06-30 上海赛默罗生物科技有限公司 α5-GABAA受体调节剂类药物中有关物质的检测方法

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9112504D0 (en) 1991-06-11 1991-07-31 Merck Sharp & Dohme Cell line
WO1994013799A1 (en) 1992-12-10 1994-06-23 Merck Sharp & Dohme Limited Stably transfected cell lines expressing gaba-a receptors
GB9718254D0 (en) * 1997-08-28 1997-11-05 Merck Sharp & Dohme Therapeutic agents
GB9723999D0 (en) * 1997-11-13 1998-01-14 Merck Sharp & Dohme Therapeutic use
US6110915A (en) * 1997-12-18 2000-08-29 Merck & Co., Inc. Antiemetic use of triazolo-pyridazine derivatives
GB2345443A (en) * 1999-01-08 2000-07-12 Merck Sharp & Dohme Use of triazolo-pyridazines for treating premenstrual syndrome
WO2005041971A1 (en) * 2003-10-21 2005-05-12 Merck & Co., Inc. Triazolo-pyridazine compounds and derivatives thereof useful in the treatment of neuropathic pain
US7943619B2 (en) * 2007-12-04 2011-05-17 Hoffmann-La Roche Inc. Isoxazolo-pyridazine derivatives
US10206921B2 (en) 2009-06-03 2019-02-19 The Regents Of The University Of California Methods and compositions for treating a subject for central nervous system (CNS) injury
US20150374705A1 (en) 2012-02-14 2015-12-31 Shanghai Institues for Biological Sciences Substances for treatment or relief of pain
US9371282B2 (en) 2013-05-17 2016-06-21 Centrexion Therapeutics Corporation Somatostatin receptor subtype 4 (SSTR4) agonists
CN106854207B (zh) 2015-12-08 2019-10-29 上海赛默罗生物科技有限公司 呔嗪类衍生物、其制备方法、药物组合物和用途
CN107344938B (zh) * 2016-05-06 2022-05-06 上海赛默罗生物科技有限公司 吡唑-三嗪类衍生物、其制备方法、药物组合物和用途
CN107344936B (zh) * 2016-05-06 2022-06-03 上海赛默罗生物科技有限公司 ***哒嗪类衍生物、其制备方法、药物组合物和用途
AU2019233183B2 (en) * 2018-03-12 2024-02-01 Shanghai SIMR Biotechnology Co., Ltd Phthalazine isoxazole alkoxy derivatives, preparation method thereof, pharmaceutical composition and use thereof
CN110256441A (zh) * 2019-06-24 2019-09-20 江苏君若医药有限公司 一种巴瑞克替尼的制备方法

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Publication number Publication date
CA3161739A1 (en) 2021-06-24
BR112022011946A2 (pt) 2022-09-06
MX2022007426A (es) 2022-07-27
AU2020410470A1 (en) 2022-07-28
IL293959A (en) 2022-08-01
JP2023508858A (ja) 2023-03-06
JP7417742B2 (ja) 2024-01-18
CO2022009489A2 (es) 2022-07-08
EP4079734A4 (en) 2023-01-25
US20230136194A1 (en) 2023-05-04
CN114302886B (zh) 2024-03-22
AU2020410470B2 (en) 2023-07-27
WO2021121294A1 (zh) 2021-06-24
KR20220140710A (ko) 2022-10-18
CN114302886A (zh) 2022-04-08
CN112979655A (zh) 2021-06-18
EP4079734A1 (en) 2022-10-26

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