CN114206830B - 作为Kv7钾通道开放剂的醇衍生物 - Google Patents

作为Kv7钾通道开放剂的醇衍生物 Download PDF

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Publication number
CN114206830B
CN114206830B CN202080051950.0A CN202080051950A CN114206830B CN 114206830 B CN114206830 B CN 114206830B CN 202080051950 A CN202080051950 A CN 202080051950A CN 114206830 B CN114206830 B CN 114206830B
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difluoromethoxy
phenyl
ethyl
trifluoromethoxy
hydroxy
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Chinese (zh)
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CN114206830A (zh
Inventor
A.G.森斯
M·罗特兰德
K·拉森
王小芳
D·达斯
洪建�
陈曙辉
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H Lundbeck AS
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H Lundbeck AS
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/08—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • 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
    • A61P25/04—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
    • A61P25/06—Antimigraine agents
    • 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
    • A61P25/18—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
    • A61P25/22—Anxiolytics
    • 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
    • A61P25/24—Antidepressants
    • 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
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/26—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being saturated and containing rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/42—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
    • C07C255/44—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms at least one of the singly-bound nitrogen atoms being acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Epidemiology (AREA)
  • Psychology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)
CN202080051950.0A 2019-08-02 2020-07-30 作为Kv7钾通道开放剂的醇衍生物 Active CN114206830B (zh)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
EP19189750.3 2019-08-02
EP19189750 2019-08-02
CN2019107341230 2019-08-09
CN201910734123 2019-08-09
EP19191887 2019-08-15
EP19191887.9 2019-08-15
PCT/EP2020/071520 WO2021023617A1 (en) 2019-08-02 2020-07-30 Alcohol derivatives as kv7 potassium channel openers

Publications (2)

Publication Number Publication Date
CN114206830A CN114206830A (zh) 2022-03-18
CN114206830B true CN114206830B (zh) 2024-07-30

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CN202080051950.0A Active CN114206830B (zh) 2019-08-02 2020-07-30 作为Kv7钾通道开放剂的醇衍生物

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EP (2) EP4461725A3 (enExample)
JP (2) JP7720829B2 (enExample)
KR (1) KR102957984B1 (enExample)
CN (1) CN114206830B (enExample)
AU (1) AU2020325517B2 (enExample)
BR (1) BR112021006324A2 (enExample)
CA (1) CA3148719A1 (enExample)
CL (1) CL2022000221A1 (enExample)
CO (1) CO2022000080A2 (enExample)
CR (1) CR20220028A (enExample)
DO (1) DOP2022000026A (enExample)
EC (1) ECSP22008993A (enExample)
ES (1) ES2989376T3 (enExample)
GE (2) GEAP202415862A (enExample)
HR (1) HRP20241444T1 (enExample)
HU (1) HUE069310T2 (enExample)
IL (1) IL290193B2 (enExample)
JO (1) JOP20220017A1 (enExample)
MA (1) MA56708B1 (enExample)
MX (1) MX2022001063A (enExample)
PE (1) PE20220345A1 (enExample)
PH (1) PH12022550192A1 (enExample)
PL (1) PL4007634T3 (enExample)
RS (1) RS66130B1 (enExample)
SM (1) SMT202400445T1 (enExample)
WO (1) WO2021023617A1 (enExample)
ZA (1) ZA202109598B (enExample)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2989376T3 (es) * 2019-08-02 2024-11-26 H Lundbeck As Derivados de alcohol como abridores del canal de potasio Kv7
AU2024310446A1 (en) * 2023-06-27 2026-01-22 Saniona A/S Kv7 modulators
WO2026132415A1 (en) * 2024-12-20 2026-06-25 Saniona A/S Kv7 modulators

Citations (1)

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WO2006033844A2 (en) * 2004-09-15 2006-03-30 Bristol-Myers Squibb Company 4-arylspirocycloalkyl-2-aminopyrimidine carboxamide kcnq potassium channel modulators

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US6893858B2 (en) 2000-05-26 2005-05-17 Bristol-Myers Squibb Company Human kcnq5 potassium channel, methods and compositions thereof
WO2001096540A2 (en) 2000-06-11 2001-12-20 Dupont Pharmaceuticals Company Hepatitis c protease exosite for inhibitor design
US7790770B2 (en) * 2005-11-23 2010-09-07 Bristol-Myers Squibb Company Heterocyclic CETP inhibitors
US20090118285A1 (en) 2006-02-07 2009-05-07 H. Lundbeck A/S Use of kcnq-openers for treating or reducing the symptoms of schizophrenia
WO2007104717A1 (en) * 2006-03-15 2007-09-20 Neurosearch A/S Quinazolinones and their use as potassium channels activators
CN101790374A (zh) 2007-08-01 2010-07-28 H.隆德贝克有限公司 Kcnq钾通道开放剂用于减轻多巴胺能系统受到干扰的障碍或病症的症状或治疗这种障碍或病症的用途
TW201024286A (en) * 2008-11-27 2010-07-01 Neurosearch As Novel compounds
EP2928860A1 (en) * 2012-12-10 2015-10-14 H. Lundbeck A/S New positive allosteric modulators of nicotinic acetylcholine receptor
WO2014145852A2 (en) * 2013-03-15 2014-09-18 Knopp Biosciences Llc Imidazo(4,5-b) pyridin-2-yl amides as kv7 channel activators
ES2749103T3 (es) * 2014-09-12 2020-03-19 Knopp Biosciences Llc Benzoimidazol-1,2-ilamidas como activadores del canal Kv7
JP2017095366A (ja) 2015-11-18 2017-06-01 持田製薬株式会社 新規ビアリールアミド誘導体
CN105663136A (zh) * 2016-01-15 2016-06-15 河北中医学院 法舒地尔作为制备选择性Kv7离子通道激活剂药物的应用
US10590067B2 (en) * 2018-02-20 2020-03-17 H. Lundbeck A/S Alcohol derivatives of carboxamides as Kv7 potassium channel openers
ES3032221T3 (en) * 2018-02-20 2025-07-16 H Lundbeck As Alcohol derivatives as kv7 potassium channel openers
ES2989376T3 (es) * 2019-08-02 2024-11-26 H Lundbeck As Derivados de alcohol como abridores del canal de potasio Kv7
US12508239B2 (en) * 2019-08-02 2025-12-30 H. Lundbeck A/S Alcohol derivatives as Kv7 potassium channel openers for use in epilepsy or seizures

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
WO2006033844A2 (en) * 2004-09-15 2006-03-30 Bristol-Myers Squibb Company 4-arylspirocycloalkyl-2-aminopyrimidine carboxamide kcnq potassium channel modulators

Non-Patent Citations (1)

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Title
From Pan-Reactive KV7 Channel Opener to Subtype Selective Opener/Inhibitor by Addition of a Methyl Group;Sigrid Marie Blom et al;《Plos One》;第9卷(第6期);全文 *

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RS66130B1 (sr) 2024-11-29
EP4007634C0 (en) 2024-10-02
MX2022001063A (es) 2022-02-14
ES2989376T3 (es) 2024-11-26
HUE069310T2 (hu) 2025-02-28
EP4461725A3 (en) 2025-01-15
CL2022000221A1 (es) 2022-10-07
KR20220041084A (ko) 2022-03-31
JP7897992B2 (ja) 2026-07-30
JOP20220017A1 (ar) 2023-01-30
GEP20247629B (en) 2024-06-10
BR112021006324A2 (pt) 2022-02-15
CO2022000080A2 (es) 2022-01-17
DOP2022000026A (es) 2022-03-31
PH12022550192A1 (en) 2022-11-21
CR20220028A (es) 2022-03-02
MA56708B1 (fr) 2024-12-31
JP7720829B2 (ja) 2025-08-08
IL290193B1 (en) 2024-08-01
CN114206830A (zh) 2022-03-18
ECSP22008993A (es) 2022-03-31
ZA202109598B (en) 2024-04-24
AU2020325517A1 (en) 2022-02-24
KR102957984B1 (ko) 2026-04-27
EP4461725A2 (en) 2024-11-13
GEAP202415862A (en) 2024-01-25
IL290193A (en) 2022-03-01
SMT202400445T1 (it) 2024-11-15
JP2022543203A (ja) 2022-10-11
PL4007634T3 (pl) 2024-11-25
AU2020325517B2 (en) 2025-08-28
IL290193B2 (en) 2024-12-01
WO2021023617A1 (en) 2021-02-11
JP2025160211A (ja) 2025-10-22
PE20220345A1 (es) 2022-03-14
CA3148719A1 (en) 2021-02-11
EP4007634B1 (en) 2024-10-02
EP4007634A1 (en) 2022-06-08
HRP20241444T1 (hr) 2024-12-20

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