CN109111400A - The preparation and application of phenylchinoline ketone and flavone derivative - Google Patents
The preparation and application of phenylchinoline ketone and flavone derivative Download PDFInfo
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- CN109111400A CN109111400A CN201710488414.7A CN201710488414A CN109111400A CN 109111400 A CN109111400 A CN 109111400A CN 201710488414 A CN201710488414 A CN 201710488414A CN 109111400 A CN109111400 A CN 109111400A
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- compound
- ketone
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- -1 phenylchinoline ketone Chemical class 0.000 title claims abstract description 69
- 150000002212 flavone derivatives Chemical class 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title abstract description 32
- 230000000302 ischemic effect Effects 0.000 claims abstract description 9
- 230000006931 brain damage Effects 0.000 claims abstract description 7
- 231100000874 brain damage Toxicity 0.000 claims abstract description 7
- 208000029028 brain injury Diseases 0.000 claims abstract description 7
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 5
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 93
- 230000000694 effects Effects 0.000 claims description 18
- 208000024827 Alzheimer disease Diseases 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 8
- 239000012453 solvate Substances 0.000 claims description 8
- WZJYKHNJTSNBHV-UHFFFAOYSA-N benzoquinoline Natural products C1=CN=C2C3=CC=CC=C3C=CC2=C1 WZJYKHNJTSNBHV-UHFFFAOYSA-N 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 206010015037 epilepsy Diseases 0.000 claims description 5
- 206010034010 Parkinsonism Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
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- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 208000027089 Parkinsonian disease Diseases 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 239000000651 prodrug Substances 0.000 claims description 3
- 229940002612 prodrug Drugs 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
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- 125000000217 alkyl group Chemical group 0.000 description 6
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- 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
- A61K31/47—Quinolines; Isoquinolines
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- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic 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
- C07D215/16—Heterocyclic 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/60—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2
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- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/60—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2
- C07D311/62—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2 with oxygen atoms directly attached in position 3, e.g. anthocyanidins
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- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Compd | hH3R (IC50, nM) | Compd | hH3R (IC50, nM) |
I-1 | 2.41 | II-1 | 8.41 |
I-2 | 2.94 | II-2 | 10.46 |
I-3 | 0.97 | II-3 | 0.18 |
I-4 | 1.23 | II-4 | 0.34 |
I-5 | 0.69 | II-5 | 7.15 |
I-6 | 0.40 | II-6 | 6.05 |
I-7 | 12.82 | II-7 | 3.87 |
I-8 | 15.43 | II-8 | 4.30 |
I-9 | 0.30 | Clobenpropit | 1.15 |
I-10 | 0.19 |
Rank | Number of animals | Incubation period (min) |
Model group | 8 | 3.56±0.88 |
Control group | 8 | 10.11±6.69 |
I-3 group | 8 | 13.64±5.76 |
I-6 group | 8 | 14.49±7.17 |
I-9 group | 8 | 15.11±8.19 |
II-4 group | 8 | 17.86±9.53 |
II-7 group | 8 | 14.39±8.69 |
Claims (6)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710488414.7A CN109111400B (en) | 2017-06-23 | 2017-06-23 | Preparation and application of phenylquinolinone and flavonoid derivatives |
PCT/CN2018/089970 WO2018233483A1 (en) | 2017-06-23 | 2018-06-05 | Preparation and use of phenylquinolinone and flavonoid derivatives |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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CN111533721A (en) * | 2020-05-15 | 2020-08-14 | 浙江大学 | Benzopyrone or quinolinone compounds and application thereof |
CN114599362A (en) * | 2019-10-15 | 2022-06-07 | 杭州百诚医药科技股份有限公司 | Use of phenylquinolinone and flavonoid derivatives for treating neuropathic pain |
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WO2022113008A1 (en) | 2020-11-27 | 2022-06-02 | Richter Gedeon Nyrt. | Histamine h3 receptor antagonists/inverse agonists for the treatment of autism spectrum disorder |
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CN114599362A (en) * | 2019-10-15 | 2022-06-07 | 杭州百诚医药科技股份有限公司 | Use of phenylquinolinone and flavonoid derivatives for treating neuropathic pain |
CN111533721A (en) * | 2020-05-15 | 2020-08-14 | 浙江大学 | Benzopyrone or quinolinone compounds and application thereof |
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WO2018233483A1 (en) | 2018-12-27 |
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